Physiology + Gynaecology & Genitourinary Flashcards

Question

How do the placenta and umbilical cord develop?

Answer 1

When the blastocyst implants on the endometrium, the outermost layer, called the syncytiotrophoblast, grows into the endometrium. It forms finger-like projections called chorionic villi. The chorionic villi contain fetal blood vessels. The chorionic villi nearest the connecting stalk of the developing embryo are the most vascular and contain mesoderm. This area is called the chorion frondosum. The cells in the chorion frondosum proliferate and become the placenta. The connecting stalk becomes the umbilical cord. Placental development is usually complete by 10 weeks gestation.

Answer 2

Trophoblast invasion of the endometrium sends signals to the spiral arteries in that area, reducing their vascular resistance and making them more fragile. The blood flow to these arteries increases, and eventually they break down, leaving pools of blood called lacunae (lakes). Maternal blood flows from the uterine arteries, into these lacunae, and back out through the uterine veins. Lacunae form at around 20 weeks gestation. These lacunae surround the chorionic villi, separated by the placental membrane. Oxygen, carbon dioxide and other substances can diffuse across the placental membrane between the maternal and fetal blood. When the process of forming lacunae is inadequate, the woman can develop pre-eclampsia. Pre-eclampsia is caused by high vascular resistance in the spiral arteries. High vascular resistance in the spiral arteries results in a sharp rise in maternal blood pressure, and leads to a number of complications in the mother and fetus.

Answer 3

1. Respiration The placenta is the only source of oxygen for the fetus. Fetal haemoglobin has a higher affinity for oxygen than adult haemoglobin. The fetal haemoglobin is more attractive to oxygen molecules than the maternal haemoglobin. As a result, when maternal blood and fetal blood are nearby in the placenta, oxygen is drawn off the maternal haemoglobin, across the placental membrane, onto the fetal haemoglobin. Carbon dioxide, hydrogen ions, bicarbonate and lactic acid are also exchanged in the placenta, allowing the fetus to maintain a healthy acid-base balance. 2. Nutrition All of the nutrition for the fetus comes from the mother. This nutrition is mostly in the form of glucose, which is used for energy and growth. The placenta can also transfer vitamins and minerals to the fetus, as well as potentially harmful substances if the mother is consuming medications, alcohol, caffeine or cigarette smoke. 3. Excretion The placenta performs a similar function to kidneys in a child or adult, filtering waste products from the fetus. These waste products include urea and creatinine. 4. Endocrine - Human Chorionic Gonadotrophin: The syncytiotrophoblast produces hCG. hCG levels increase in early pregnancy, plateau at around ten weeks gestation, then start to fall. HCG helps to maintain the corpus luteum until the placenta can take over the production of oestrogen and progesterone. HCG can cause symptoms of nausea and vomiting in early pregnancy. Higher levels of hCG occur with multiple pregnancy (e.g. twins) and molar pregnancy. Pregnancy tests look for hCG as a marker of pregnancy. - Oestrogen: The placenta produces oestrogen, which helps to soften tissues and make them more flexible. Oestrogen allows the muscles and ligaments of the uterus and pelvis to expand, and the cervix to become soft and ready for birth. It also enlarges and prepares the breasts and nipples for breastfeeding. - Progesterone: The placenta mostly takes over the production of progesterone by five weeks gestation. The role of progesterone is to maintain the pregnancy. It causes relaxation of the uterine muscles (preventing contraction and labour) and maintains the endometrium. It causes side effects by relaxing other muscles, such as the lower oesophageal sphincter (causing heartburn), the bowel (causing constipation) and the blood vessels (causing hypotension, headaches and skin flushing). It also raises the body temperature between 0.5 and 1 degree Celsius. 5. Immunity The mother’s antibodies can transfer across the placenta to the fetus during pregnancy. These antibodies allow the fetus to benefit from the long term immunity of the mother during the pregnancy and shortly after birth. An example of this is with recurrent genital herpes, where the mother’s antibodies to the herpes virus cross the placenta and protect the baby during labour and delivery, preventing infection during birth. This protection does not occur during an initial episode of genital herpes, as the mother has not yet started producing sufficient antibodies against the herpes virus to offer the fetus protection.

Answer 4

The anterior pituitary gland produces more ACTH, prolactin and melanocyte stimulating hormone in pregnancy. - Higher ACTH levels cause a rise in steroid hormones, particularly cortisol and aldosterone. Higher steroid levels lead to an improvement in most autoimmune conditions and a susceptibility to diabetes and infections. - Increased prolactin acts to suppress FSH and LH, causing reduced FSH and LH levels. - Increased melanocyte stimulating hormone causes increased pigmentation of the skin during pregnancy, resulting in skin changes such as linea nigra and melasma. TSH remains normal, but T3 and T4 levels rise. HCG levels rise, roughly doubling every 48 hours until they plateau around 8 – 12 weeks, then gradually start to fall. Progesterone levels rise throughout pregnancy. Progesterone acts to maintain the pregnancy, prevent contractions and suppress the mother’s immune reaction to fetal antigens. The corpus luteum produces progesterone until ten weeks gestation. The placenta produces it during the remainder of the pregnancy. Oestrogen rises throughout pregnancy, produced by the placenta.

Answer 5

The size of the uterus increases from around 100g to 1.1kg during pregnancy. There is hypertrophy of the myometrium and the blood vessels in the uterus. Increased oestrogen may cause cervical ectropion and increased cervical discharge. Oestrogen also causes hypertrophy of the vaginal muscles and increased vaginal discharge. The changes in the vagina prepare it for delivery, however they make bacterial and candidal infection (thrush) more common. Before delivery, prostaglandins break down collagen in the cervix, allowing it to dilate and efface during childbirth.

Answer 6

There are several cardiovascular changes during pregnancy: - Increased blood volume - Increased plasma volume - Increased cardiac output, with increased stroke volume and heart rate - Decreased peripheral vascular resistance - Decreased blood pressure in early and middle pregnancy, returning to normal by term - Varicose veins can occur due to peripheral vasodilation and obstruction of the inferior vena cava by the uterus - Peripheral vasodilation also causes flushing and hot sweats Respiratory Changes - Tidal volume and respiratory rate increase in later pregnancy, to meet the increased oxygen demands.

Answer 7

A number of changes in the kidneys happen during pregnancy: - Increased blood flow to the kidneys - Increased glomerular filtration rate (GFR) - Increased aldosterone leads to increased salt and water reabsorption and retention - Increased protein excretion from the kidneys (normal is up to 0.3g in 24 hours) - Dilatation of the ureters and collecting system, leading to a physiological hydronephrosis (more right-sided)

Answer 8

There is increased red blood cell production in pregnancy, leading to higher iron, folate and B12 requirements. Plasma volume increases more than red blood cell volume, leading to a lower concentration of red blood cells. High plasma volume means the haemoglobin concentration and red cell concentration (haematocrit) fall in pregnancy, resulting in anaemia. Clotting factors such as fibrinogen and factor 7, 8 and 10 increase in pregnancy, making women hyper-coagulable. This increases the risk of venous thromboembolism (blood clots developing in the veins). Pregnant women are more likely to develop deep vein thrombosis and pulmonary embolism. There are a few other changes you may find on blood results: - Increased white blood cells - Decreased platelet count - Increased ESR and D-dimer - Increased alkaline phosphatase (ALP), up to 4 times normal, due to secretion by the placenta - Reduced albumin due to loss of proteins in the kidneys - Calcium requirements increase, but so does gut absorption of calcium, meaning calcium levels remain stable

Answer 9

Several changes to skin are normal in pregnancy: - Increased skin pigmentation due to increased melanocyte stimulating hormone, with linea nigra and melasma - Striae gravidarum (stretch marks on the expanding abdomen) - General itchiness (pruritus) can be normal, but can indicate obstetric cholestasis - Spider naevi - Palmar erythema Postpartum hair loss is normal, and usually improves within six months.

Answer 10

1. The first stage is from the onset of labour (true contractions) until 10cm cervical dilatation. 2. The second stage is from 10cm cervical dilatation to delivery of the baby. 3. The third stage is from delivery of the baby to delivery of the placenta.

Answer 11

Prostaglandins act like local hormones, triggering specific effects in local tissues. Tissues throughout the entire body contain and respond to prostaglandins. They play a crucial role in menstruation and labour by stimulating contraction of the uterine muscles. They also have a role in the ripening of the cervix before delivery. One key prostaglandin to be aware of is prostaglandin E2. Pessaries containing prostaglandin E2 (dinoprostone) can be used to induce labour.

Answer 12

Braxton-Hicks contractions are occasional irregular contractions of the uterus. They are usually felt during the second and third trimester. Women can experience temporary and irregular tightening or mild cramping in the abdomen. These are not true contractions, and they do not indicate the onset of labour. They do not progress or become regular. Staying hydrated and relaxing can help reduce Braxton-Hicks contractions.

Answer 13

The first stage of labour is from the onset of labour (true contractions) until the cervix is fully dilated to 10cm. It involves cervical dilation (opening up) and effacement (getting thinner from front to back). The “show” refers to the mucus plug in the cervix, that prevents bacteria from entering the uterus during pregnancy, falling out and creating space for the baby to pass through. The first stage has three phases: 1. Latent phase: From 0 to 3cm dilation of the cervix. This progresses at around 0.5cm per hour. There are irregular contractions. 2. Active phase: From 3cm to 7cm dilation of the cervix. This progresses at around 1cm per hour, and there are regular contractions. 3. Transition phase: From 7cm to 10cm dilation of the cervix. This progresses at around 1cm per hour, and there are strong and regular contractions.

Answer 14

The second stage of labour lasts from 10cm dilatation of the cervix to delivery of the baby. The success of the second stage depends on “the three Ps”: power, passenger and passage. 1. Power: the strength of the uterine contractions. 2. Passenger: the four descriptive qualities of the fetus: - Size: particularly the size of the head as this is the largest part. - Attitude: the posture of the fetus. For example, how the back is rounded and how the head and limbs are flexed. - Lie: the position of the fetus in relation to the mother’s body: * Longitudinal lie – the fetus is straight up and down. * Transverse lie – the fetus is straight side to side. * Oblique lie – the fetus is at an angle. - Presentation: the part of the fetus closest to the cervix: *Cephalic presentation – the head is first. *Shoulder presentation – the shoulder is first. *Breech presentation – the legs are first. This can be: > Complete breech – with hips and knees flexed (like doing a cannonball jump into a pool) > Frank breech – with hips flexed and knees extended, bottom first > Footling breech – with a foot hanging through the cervix 3. Passage: the size and shape of the passageway, mainly the pelvis.

Answer 15

1. Engagement 2. Descent: Obstetricians describe the position of the baby’s head in relation to the mother’s ischial spines during the descent phase. Descent is measured in centimetres, from: -5: when the baby is high up at around the pelvic inlet 0: when the head is at the ischial spines (this is when the head is “engaged”) +5: when the fetal head has descended further out 3. Flexion 4. Internal Rotation 5. Extension 6. Restitution and external rotation 7. Expulsion

Answer 16

The third stage of labour is from the completed birth of the baby to the delivery of the placenta. Physiological management is where the placenta is delivered by maternal effort without medications or cord traction. Active management of the third stage is where the midwife or doctor assist in delivery of the placenta. Active management shortens the third stage and reduces the risk of bleeding. Haemorrhage, or more than a 60-minute delay in delivery of the placenta, should prompt active management. Active management can be associated with nausea and vomiting. Active management involves giving a dose of intramuscular oxytocin to help the uterus contract and expel the placenta. Careful traction is applied to the umbilical cord to guide the placenta out of the uterus and vagina.

Answer 17

1. Primary amenorrhoea is when the patient has never developed periods. This can be due to: - Abnormal functioning of the hypothalamus or pituitary gland (hypogonadotropic hypogonadism) - Abnormal functioning of the gonads (hypergonadotropic hypogonadism) - Imperforate hymen or other structural pathology 2. Secondary amenorrhoea is when the patient previously had periods that subsequently stopped. This can be due to: - Pregnancy (the most common cause) - Menopause - Physiological stress due to excessive exercise, low body weight, chronic disease or psychosocial factors - Polycystic ovarian syndrome - Medications, such as hormonal contraceptives - Premature ovarian insufficiency (menopause before 40 years) - Thyroid hormone abnormalities (hyper or hypothyroid) - Excessive prolactin, from a prolactinoma - Cushing’s syndrome

Answer 18

Irregular menstrual periods indicate anovulation (a lack of ovulation) or irregular ovulation. This occurs due to disruption of the normal hormonal levels in the menstrual cycle, or ovarian pathology. It can be due to: - Extremes of reproductive age (early periods or perimenopause) - Polycystic ovarian syndrome - Physiological stress (excessive exercise, low body weight, chronic disease and psychosocial factors) - Medications, particularly progesterone only contraception, antidepressants and antipsychotics - Hormonal imbalances, such as thyroid abnormalities, Cushing’s syndrome and high prolacti

Answer 19

Intermenstrual bleeding (IMB) refers to any bleeding that occurs between menstrual periods. This is a red flag that should make you consider cervical and other cancers, although other causes are more common. The key causes of intermenstrual bleeding are: - Hormonal contraception - Cervical ectropion, polyps or cancer - Sexually transmitted infection - Endometrial polyps or cancer - Vaginal pathology, including cancers - Pregnancy - Ovulation can cause spotting in some women - Medications, such as SSRIs and anticoagulants

Answer 20

Dysmenorrhoea describes painful periods. The causes are: - Primary dysmenorrhoea (no underlying pathology) - Endometriosis or adenomyosis - Fibroids - Pelvic inflammatory disease - Copper coil - Cervical or ovarian cancer

Answer 21

Menorrhagia refers to heavy menstrual bleeding. This can be caused by: - Dysfunctional uterine bleeding (no identifiable cause) - Extremes of reproductive age - Fibroids - Endometriosis and adenomyosis - Pelvic inflammatory disease (infection) - Contraceptives, particularly the copper coil - Anticoagulant medications - Bleeding disorders (e.g. Von Willebrand disease) - Endocrine disorders (diabetes and hypothyroidism) - Connective tissue disorders - Endometrial hyperplasia or cancer - Polycystic ovarian syndrome

Answer 22

Postcoital bleeding (PCB) refers to bleeding after sexual intercourse. This is a red flag that should make you consider cervical and other cancers, although other causes are more common. Often no cause is found. The key causes are: - Cervical cancer, ectropion or infection - Trauma - Atrophic vaginitis - Polyps - Endometrial cancer - Vaginal cancer

Answer 23

Pelvic pain can be acute or chronic. The presentation of pelvic pain varies significantly. A detailed history and examination are usually able to identify the cause. There are a large number of possible causes, including: - Urinary tract infection - Dysmenorrhoea (painful periods) - Irritable bowel syndrome (IBS) - Ovarian cysts - Endometriosis - Pelvic inflammatory disease (infection) - Ectopic pregnancy - Appendicitis - Mittelschmerz (cyclical pain during ovulation) - Pelvic adhesions - Ovarian torsion - Inflammatory bowel disease (IBD)

Answer 24

-Bacterial vaginosis -Candidiasis (thrush) -Chlamydia -Gonorrhoea -Trichomonas vaginalis -Foreign body -Cervical ectropion -Polyps -Malignancy -Pregnancy -Ovulation (cyclical) -Hormonal contraception

Answer 25

Pruritus vulvae refers to itching of the vulva and vagina. There are a large number of causes: - Irritants such as soaps, detergents and barrier contraception - Atrophic vaginitis - Infections such as candidiasis (thrush) and pubic lice - Skin conditions such as eczema - Vulval malignancy - Pregnancy-related vaginal discharge - Urinary or faecal incontinence - Stress

Answer 26

Primary amenorrhoea is defined as not starting menstruation: - By 13 years when there is no other evidence of pubertal development - By 15 years of age where there are other signs of puberty, such as breast bud development

Answer 27

Hypogonadism refers to a lack of the sex hormones, oestrogen and testosterone, that normally rise before and during puberty. A lack of these hormones causes a delay in puberty. The lack of sex hormones is fundamentally due to one of two reasons: 1. Hypogonadotropic hypogonadism: a deficiency of LH and FSH 2. Hypergonadotropic hypogonadism: a lack of response to LH and FSH by the gonads (the testes and ovaries)

Answer 28

Hypogonadotropic hypogonadism involves deficiency of LH and FSH, leading to deficiency of the sex hormones (oestrogen). LH and FSH are gonadotrophins produced by the anterior pituitary gland in response to gonadotropin releasing hormone (GnRH) from the hypothalamus. Since no gonadotrophins are simulating the ovaries, they do not respond by producing sex hormones (oestrogen). A deficiency of LH and FSH is the result of abnormal functioning of the hypothalamus or pituitary gland. This could be due to: - Hypopituitarism (under production of pituitary hormones) - Damage to the hypothalamus or pituitary, for example, by radiotherapy or surgery for cancer - Significant chronic conditions can temporarily delay puberty (e.g. cystic fibrosis or inflammatory bowel disease) - Excessive exercise or dieting can delay the onset of menstruation in girls - Constitutional delay in growth and development is a temporary delay in growth and puberty without underlying physical pathology - Endocrine disorders such as growth hormone deficiency, hypothyroidism, Cushing’s or hyperprolactinaemia - Kallman syndrome

Answer 29

Hypergonadotropic hypogonadism is where the gonads fail to respond to stimulation from the gonadotrophins (LH and FSH). Without negative feedback from the sex hormones (oestrogen), the anterior pituitary produces increasing amounts of LH and FSH. Consequently, you get high gonadotrophins and low sex hormones Hypergonadotropic hypogonadism is the result of abnormal functioning of the gonads. This could be due to: - Previous damage to the gonads (e.g. torsion, cancer or infections such as mumps) - Congenital absence of the ovaries - Turner’s syndrome (XO)

Answer 30

Kallman syndrome is a genetic condition causing hypogonadotrophic hypogonadism, with failure to start puberty. It is associated with a reduced or absent sense of smell (anosmia).

Answer 31

Congenital adrenal hyperplasia is caused by a congenital deficiency of the 21-hydroxylase enzyme. This causes underproduction of cortisol and aldosterone, and overproduction of androgens from birth. It is a genetic condition inherited in an autosomal recessive pattern. In a small number of cases, it involves a deficiency of 11-beta-hydroxylase rather than 21-hydroxylase. In severe cases, the neonate is unwell shortly after birth, with electrolyte disturbances and hypoglycaemia. In mild cases, female patients can present later in childhood or at puberty with typical features: - Tall for their age - Facial hair - Absent periods (primary amenorrhoea) - Deep voice - Early puberty

Answer 32

Androgen insensitivity syndrome is a condition where the tissues are unable to respond to androgen hormones (e.g. testosterone), so typical male sexual characteristics do not develop. It results in a female phenotype, other than the internal pelvic organs. Patients have normal female external genitalia and breast tissue. Internally there are testes in the abdomen or inguinal canal, and an absent uterus, upper vagina, fallopian tubes and ovaries.

Answer 33

Structural pathology in the pelvic organs can prevent menstruation. If the ovaries are unaffected, there will be typical secondary sexual characteristics, but no menstrual periods. There may be cyclical abdominal pain as menses build up but are unable to escape through the vagina. Structural pathology that can cause primary amenorrhoea include: - Imperforate hymen - Transverse vaginal septae - Vaginal agenesis - Absent uterus - Female genital mutilation

Answer 34

Assessment aims to look for evidence of puberty and to assess for possible underlying causes. The first step is to take a detailed history of their general health, development, family history, diet and lifestyle. Examination is required to assess height, weight, stage of pubertal development and features of any underlying conditions. The threshold for initiating investigations is no evidence of pubertal changes in a girl aged 13. Investigation can also be considered when there is some evidence of puberty but no progression after two years. Initial investigations assess for underlying medical conditions: - Full blood count and ferritin for anaemia - U&E for chronic kidney disease - Anti-TTG or anti-EMA antibodies for coeliac disease Hormonal blood tests assess for hormonal abnormalities: - FSH and LH will be low in hypogonadotropic hypogonadism and high in hypergonadotropic hypogonadism - Thyroid function tests - Insulin-like growth factor I is used as a screening test for GH deficiency - Prolactin is raised in hyperprolactinaemia - Testosterone is raised in polycystic ovarian syndrome, androgen insensitivity syndrome and congenital adrenal hyperplasia Genetic testing with a microarray test to assess for underlying genetic conditions: - Turner’s syndrome (XO) Imaging can be useful: - Xray of the wrist to assess bone age and inform a diagnosis of constitutional delay - Pelvic ultrasound to assess the ovaries and other pelvic organs - MRI of the brain to look for pituitary pathology and assess the olfactory bulbs in possible Kallman syndrome

Answer 35

Management of primary amenorrhoea involves establishing and treating the underlying cause. Where necessary, replacement hormones can induce menstruation and improve symptoms. Patients with constitutional delay in growth and development may only require reassurance and observation. Where the cause is due to stress or low body weight secondary to diet and exercise, treatment involves a reduction in stress, cognitive behavioural therapy and healthy weight gain. Where the cause is due to an underlying chronic or endocrine condition, management involves optimising treatment for that condition. In patients with hypogonadotrophic hypogonadism, such as hypopituitarism or Kallman syndrome, treatment with pulsatile GnRH can be used to induce ovulation and menstruation. This has the potential to induce fertility. Alternatively, where pregnancy is not wanted, replacement sex hormones in the form of the combined contraceptive pill may be used to induce regular menstruation and prevent the symptoms of oestrogen deficiency. In patients with an ovarian cause of amenorrhoea, such as polycystic ovarian syndrome, damage to the ovaries or absence of the ovaries, the combined contraceptive pill may be used to induce regular menstruation and prevent the symptoms of oestrogen deficiency.

Answer 36

Secondary amenorrhea is defined as no menstruation for more than three months after previous regular menstrual periods. Consider assessment and investigation after three to six months. In women with previously infrequent irregular periods, consider investigating after six to twelve months.

Answer 37

-Pregnancy is the most common cause -Menopause and premature ovarian failure -Hormonal contraception (e.g. IUS or POP) -Hypothalamic or pituitary pathology -Ovarian causes such as polycystic ovarian syndrome -Uterine pathology such as Asherman’s syndrome -Thyroid pathology -Hyperprolactinaemia The hypothalamus reduces the production of GnRH in response to significant physiological or psychological stress. This leads to hypogonadotropic hypogonadism and amenorrhoea. The hypothalamus responds this way to prevent pregnancy in situations where the body may not be fit for it, for example: -Excessive exercise (e.g. athletes) -Low body weight and eating disorders -Chronic disease -Psychological stress Pituitary causes of secondary amenorrhoea include: -Pituitary tumours, such as a prolactin-secreting prolactinoma -Pituitary failure due to trauma, radiotherapy, surgery or -Sheehan syndrome

Answer 38

High prolactin levels act on the hypothalamus to prevent the release of GnRH. Without GnRH, there is no release of LH and FSH. This causes hypogonadotropic hypogonadism. Only 30% of women with a high prolactin level will have galactorrhea (breast milk production and secretion). The most common cause of hyperprolactinaemia is a pituitary adenoma secreting prolactin. Where there are high prolactin levels, a CT or MRI scan of the brain is used to assess for a pituitary tumour. Often there is a microadenoma that will not appear on the initial scan, and follow up scans are required to identify tumours that may develop later. Often no treatment is required for hyperprolactinaemia. Dopamine agonists such as bromocriptine or cabergoline can be used to reduce prolactin production. These medications treat hyperprolactinaemia, Parkinson’s disease and acromegaly.

Answer 39

Assessment of secondary amenorrhoea involves: 1.Detailed history and examination to assess for potential causes 2. Hormonal blood tests 3. Ultrasound of the pelvis to diagnose polycystic ovarian syndrome Hormone Tests: - Beta human chorionic gonadotropin (HCG) urine or blood tests are required to diagnose or rule out pregnancy. - Luteinising hormone and follicle-stimulating hormone: *High FSH suggests primary ovarian failure *High LH, or LH:FSH ratio, suggests polycystic ovarian syndrome -Prolactin can be measured to assess for hyperprolactinaemia, followed by an MRI to identify a pituitary tumour. - Thyroid stimulating hormone (TSH) can screen for thyroid pathology. This is followed by T3 and T4 when the TSH is abnormal. *Raised TSH and low T3 and T4 indicate hypothyroidism *Low TSH and raised T3 and T4 indicate hyperthyroidism - Raise testosterone indicates polycystic ovarian syndrome, androgen insensitivity syndrome or congenital adrenal hyperplasia.

Answer 40

Management of secondary amenorrhoea involves establishing and treating the underlying cause. Where necessary, replacement hormones can induce menstruation and improve symptoms. *It is worth remembering that women with polycystic ovarian syndrome require a withdrawal bleed every 3 – 4 months to reduce the risk of endometrial hyperplasia and endometrial cancer. Medroxyprogesterone for 14 days, or regular use of the combined oral contraceptive pill, can be used to stimulate a withdrawal bleed.*

Answer 41

Osteoporosis Patients with amenorrhoea associated with low oestrogen levels are at increased risk of osteoporosis. Where the amenorrhoea lasts more than 12 months, treatment is indicated to reduce the risk of osteoporosis: - Ensure adequate vitamin D and calcium intake - Hormone replacement therapy or the combined oral contraceptive pill

Answer 42

Premenstrual syndrome (PMS) describes the psychological, emotional and physical symptoms that occur during the luteal phase of the menstrual cycle, particularly in the days prior to the onset of menstruation. These symptoms can be distressing and significantly impact quality of life. Most women will experience some of the symptoms of premenstrual syndrome. The critical aspects are the severity of the symptoms, and the impact these symptoms have on the woman’s functioning and quality of life. The symptoms of PMS resolve once menstruation begins. Symptoms are not present before menarche, during pregnancy or after menopause. These are key things to note when you take a history. Cause: Premenstrual syndrome is though to the caused by fluctuation in oestrogen and progesterone hormones during the menstrual cycle. The exact mechanism is not known, but it may be due to increased sensitivity to progesterone or an interaction between the sex hormones and the neurotransmitters serotonin and GABA.

Answer 43

There is a long list of symptoms that can occur with premenstrual syndrome, and these will vary with the individual. Common symptoms include: -Low mood -Anxiety -Mood swings -Irritability -Bloating -Fatigue -Headaches -Breast pain -Reduced confidence -Cognitive impairment -Clumsiness -Reduced libido These symptoms can occur in the absence of menstruation after a hysterectomy, endometrial ablation or on the Mirena coil, as the ovaries continue to function and the hormonal cycle continues. They can also occur in response to the combined contraceptive pill or cyclical hormone replacement therapy containing progesterone, and this is described as progesterone-induced premenstrual disorder. When features are severe and have a significant effect on quality of life, this is called premenstrual dysphoric disorder.

Answer 44

Diagnosis is made based on a symptom diary spanning two menstrual cycles. The symptom diary should demonstrate cyclical symptoms that occur just before, and resolve after, the onset of menstruation. A definitive diagnosis may be made, under the care of a specialist, by administering a GnRH analogues to halt the menstrual cycle and temporarily induce menopause, to see if the symptoms resolve.

Answer 45

The following management options can be initiated in primary care: - General healthy lifestyle changes, such as improving diet, exercise, alcohol, smoking, stress and sleep - Combined contraceptive pill (COCP): those containing drospirenone first line (i.e. Yasmin). Drospironone as some antimineralocortioid effects, similar to spironolactone. Continuous use of the pill, as opposed to cyclical use, may be more effective. - SSRI antidepressants - Cognitive behavioural therapy (CBT) Severe cases should be managed by a multidisciplinary team, involving GPs, gynaecologists, psychologists and dieticians. - Continuous transdermal oestrogen (patches) can be used to improve symptoms. - Progestogens are required for endometrial protection against endometrial hyperplasia when using oestrogen. This can be in the form of low dose cyclical progestogens (e.g. norethisterone) to trigger a withdrawal bleed, or the Mirena coil. - GnRH analogues can be used to induce a menopausal state. They are very effective at controlling symptoms; however, they are reserved for severe cases due to the adverse effects (e.g. osteoporosis). Hormone replacement therapy can be used to add back the hormones to mitigate these effects. - Hysterectomy and bilateral oophorectomy can be used to induce menopause where symptoms are severe and medical management has failed. Hormone replacement therapy will be required, particularly in women under 45 years. - Danazole and tamoxifen are options for cyclical breast pain, initiated and monitored by a breast specialist. - Spironolactone may be used to treat the physical symptoms of PMS, such as breast swelling, water retention and bloating.

Answer 46

Heavy menstrual bleeding is also called menorrhagia. On average, women lose 40 ml of blood during menstruation. Excessive menstrual blood loss involves more than an 80 ml loss. The volume of blood loss is rarely measured in practice. The diagnosis is based on symptoms, such as changing pads every 1 – 2 hours, bleeding lasting more than seven days and passing large clots. A diagnosis can be made based on a self-report of “very heavy periods”. Heavy menstrual periods can have a significant impact on quality of life.

Answer 47

-Dysfunctional uterine bleeding (no identifiable cause) -Extremes of reproductive age -Fibroids -Endometriosis and adenomyosis -Pelvic inflammatory disease (infection) -Contraceptives, particularly the copper coil -Anticoagulant medications -Bleeding disorders (e.g. Von Willebrand disease) -Endocrine disorders (diabetes and hypothyroidism) -Connective tissue disorders -Endometrial hyperplasia or cancer -Polycystic ovarian syndrome

Answer 48

1. Pelvic examination with a speculum and bimanual should be performed, unless there is straightforward history heavy menstrual bleeding without other risk factors or symptoms, or they are young and not sexually active. This is mainly to assess for fibroids, ascites and cancers. 2. Full blood count should be performed in all women with heavy menstrual bleeding, to look for iron deficiency anaemia. 3. Outpatient hysteroscopy should be arranged if there is: - Suspected submucosal fibroids - Suspected endometrial pathology, such as endometrial hyperplasia or cancer - Persistent intermenstrual bleeding 4. Pelvic and transvaginal ultrasound should be arranged if the is: - Possible large fibroids (palpable pelvic mass) - Possible adenomyosis (associated pelvic pain or tenderness on examination) - Examination is difficult to interpret (e.g. obesity) - Hysteroscopy is declined Additional tests to consider in women with additional features: - Swabs if there is evidence of infection (e.g. abnormal discharge or suggestive sexual history) - Coagulation screen if there is a family history of clotting disorders (e.g. Von Willebrand disease) or periods have been heavy since menarche - Ferritin if they are clinically anaemic - Thyroid function tests if there are additional features of hypothyroidism

Answer 49

1. Start by excluding underlying pathology such as anaemia, fibroids, bleeding disorders and cancer. Where causes are identified, these should be managed initially. For example, menorrhagia caused by a copper coil should resolve when the coil is removed. 2. The next step is to establish whether contraception is required or acceptable. * When the woman does not want contraception; treatment can be used during menstruation for symptomatic relief, with: - Tranexamic acid when no associated pain (antifibrinolytic – reduces bleeding) - Mefenamic acid when there is associated pain (NSAID – reduces bleeding and pain) *Management when contraception is wanted or acceptable: - Mirena coil (first line) - Combined oral contraceptive pill - Cyclical oral progestogens, such as norethisterone 5mg three times daily from day 5 – 26 (although this is associated with progestogenic side effects and an increased risk of venous thromboembolism) - Progesterone only contraception may also be tried, as it can suppress menstruation. This could be the progesterone-only pill or a long-acting progesterone (e.g. depo injection or implant). 3. Referral to secondary care for further investigation and management is indicated if treatment is unsuccessful, symptoms are severe or there are large fibroids (more than 3 cm). 4. The final options when medical management has failed are endometrial ablation and hysterectomy. - Endometrial ablation involves destroying the endometrium. The first generation of ablative techniques involved a hysteroscopy and direct destruction of the endometrium. This has been replaced by second generation, non-hysteroscopic techniques that are safer and faster. A typical example of one of these techniques involves passing a specially designed balloon into the endometrial cavity and filling it with high-temperature fluid that burns the endometrial lining. This is called balloon thermal ablation.

Answer 50

Fibroids are benign tumours of the smooth muscle of the uterus. They are also called uterine leiomyomas. They are very common, affecting 40-60% of women in later reproductive years, and are more common in black women compared with other ethnic groups. They are oestrogen sensitive, meaning they grow in response to oestrogen. Types - Intramural means within the myometrium (the muscle of the uterus). As they grow, they change the shape and distort the uterus. - Subserosal means just below the outer layer of the uterus. These fibroids grow outwards and can become very large, filling the abdominal cavity. - Submucosal means just below the lining of the uterus (the endometrium). - Pedunculated means on a stalk.

Answer 51

Fibroids are often asymptomatic. They can present in several ways: - Heavy menstrual bleeding (menorrhagia) is the most frequent presenting symptom - Prolonged menstruation, lasting more than 7 days - Abdominal pain, worse during menstruation - Bloating or feeling full in the abdomen - Urinary or bowel symptoms due to pelvic pressure or fullness - Deep dyspareunia (pain during intercourse) - Reduced fertility Abdominal and bimanual examination may reveal a palpable pelvic mass or an enlarged firm non-tender uterus.

Answer 52

- Hysteroscopy is the initial investigation for submucosal fibroids presenting with heavy menstrual bleeding. - Pelvic ultrasound is the investigation of choice for larger fibroids. - MRI scanning may be considered before surgical options, where more information is needed about the size, shape and blood supply of the fibroids.

Answer 53

For fibroids less than 3 cm, the medical management is the same as with heavy menstrual bleeding: - Mirena coil (1st line) – fibroids must be less than 3cm with no distortion of the uterus - Symptomatic management with NSAIDs and tranexamic acid - Combined oral contraceptive - Cyclical oral progestogens For fibroids more than 3 cm, women need referral to gynaecology for investigation and management. Medical management options are: - Symptomatic management with NSAIDs and tranexamic acid - Mirena coil – depending on the size and shape of the fibroids and uterus - Combined oral contraceptive - Cyclical oral progestogens GnRH agonists, such as goserelin (Zoladex) or leuprorelin (Prostap), may be used to reduce the size of fibroids before surgery. They work by inducing a menopause-like state (stimulating then desensitising the GnRH receptors in the pituitary gland) and reducing the amount of oestrogen maintaining the fibroid. Usually, GnRH agonists are only used short term, for example, to shrink a fibroid before myomectomy.

Answer 54

Surgical options for managing smaller fibroids with heavy menstrual bleeding are: - Endometrial ablation: can be used to destroy the endometrium. Second generation, non-hysteroscopic techniques are used, such as balloon thermal ablation. This involves inserting a specially designed balloon into the endometrial cavity and filling it with high-temperature fluid that burns the endometrial lining of the uterus. - Resection of submucosal fibroids during hysteroscopy - Hysterectomy: involves removing the uterus and fibroids. Hysterectomy may be by laparoscopy (keyhole surgery), laparotomy or vaginal approach. The ovaries may be removed or left depending on patient preference, risks and benefits Surgical options for larger fibroids are: - Uterine artery embolisation: a surgical option for larger fibroids, performed by interventional radiologists. The radiologist inserts a catheter into an artery, usually the femoral artery. This catheter is passed through to the uterine artery under X-ray guidance. Once in the correct place, particles are injected that cause a blockage in the arterial supply to the fibroid. This starves the fibroid of oxygen and causes it to shrink. - Myomectomy: involves surgically removing the fibroid via laparoscopic (keyhole) surgery or laparotomy (open surgery). Myomectomy is the only treatment known to potentially improve fertility in patients with fibroids. - Hysterectomy

Answer 55

There are several potential complications of fibroids: - Heavy menstrual bleeding, often with iron deficiency anaemia - Reduced fertility - Pregnancy complications, such as miscarriages, premature labour and obstructive delivery - Constipation - Urinary outflow obstruction and urinary tract infections - Red degeneration of the fibroid - Torsion of the fibroid, usually affecting pedunculated fibroids - Malignant change to a leiomyosarcoma is very rare (<1%)

Answer 56

Red degeneration refers to ischaemia, infarction and necrosis of the fibroid due to disrupted blood supply. Red degeneration is more likely to occur in larger fibroids (above 5 cm) during the second and third trimester of pregnancy. Red degeneration may occur as the fibroid rapidly enlarges during pregnancy, outgrowing its blood supply and becoming ischaemic. It may also occur due to kinking in the blood vessels as the uterus changes shape and expands during pregnancy. Red degeneration presents with severe abdominal pain, low-grade fever, tachycardia and often vomiting. Management is supportive, with rest, fluids and analgesia. *Look out for the pregnant woman with a history of fibroids presenting with severe abdominal pain and a low-grade fever in your exams. The diagnosis is likely to be red degeneration.*

Answer 57

Endometriosis is a condition where there is ectopic endometrial tissue outside the uterus. A lump of endometrial tissue outside the uterus is described as an endometrioma. Endometriomas in the ovaries are often called “chocolate cysts”. Adenomyosis refers to endometrial tissue within the myometrium (muscle layer) of the uterus.

Answer 58

The exact cause of endometriosis is not clear, but there are several theories. No specific genes have been found to cause endometriosis; however, there does seem to be a genetic component to developing the condition. One notable theory for the cause of ectopic endometrial tissue is that during menstruation, the endometrial lining flows backwards, through the fallopian tubes and out into the pelvis and peritoneum. This is called retrograde menstruation. The endometrial tissue then seeds itself around the pelvis and peritoneal cavity. Other possible methods for endometrial tissue exiting the uterus have been proposed: - Embryonic cells destined to become endometrial tissue may remain in areas outside the uterus during the development of the fetus, and later develop into ectopic endometrial tissue. - There may be spread of endometrial cells through the lymphatic system, in a similar way to the spread of cancer. - Cells outside the uterus somehow change, in a process called metaplasia, from typical cells of that organ into endometrial cells.

Answer 59

Endometriosis can be asymptomatic in some cases, or present with a number of symptoms: - Cyclical abdominal or pelvic pain - Deep dyspareunia (pain on deep sexual intercourse) - Dysmenorrhoea (painful periods) - Infertility - Cyclical bleeding from other sites, such as haematuria There can also be cyclical symptoms relating to other areas affected by the endometriosis: - Urinary symptoms - Bowel symptoms Examination may reveal: - Endometrial tissue visible in the vagina on speculum examination, particularly in the posterior fornix - A fixed cervix on bimanual examination - Tenderness in the vagina, cervix and adnexa

Answer 60

The main symptom of endometriosis is pelvic pain. The cells of the endometrial tissue outside the uterus respond to hormones in the same way as endometrial tissue in the uterus. During menstruation, as the endometrial tissue in the uterus sheds its lining and bleeds, the same thing happens in the endometrial tissue elsewhere in the body. This causes irritation and inflammation of the tissues around the sites of endometriosis. This results in the cyclical, dull, heavy or burning pain that occurs during menstruation in patients with endometriosis. Deposits of endometriosis in the bladder or bowel can lead to blood in the urine or stools. Localised bleeding and inflammation can lead to adhesions. Inflammation causes damage and development of scar tissue that binds the organs together. For example, the ovaries may be fixed to the peritoneum, or the uterus may be fixed to the bowel. Adhesions can also occur after abdominal surgery. Adhesions lead to a chronic, non-cyclical pain that can be sharp, stabbing or pulling and associated with nausea. Endometriosis can lead to reduced fertility. Often it is not clear why women with endometriosis struggle to get pregnant. It may be due to adhesions around the ovaries and fallopian tubes, blocking the release of eggs or kinking the fallopian tubes and obstructing the route to the uterus. Endometriomas in the ovaries may also damage eggs or prevent effective ovulation.

Answer 61

Pelvic ultrasound may reveal large endometriomas and chocolate cysts. Ultrasound scans are often unremarkable in patients with endometriosis. Patients with suspected endometriosis need referral to a gynaecologist for laparoscopy. Laparoscopic surgery is the gold standard way to diagnose abdominal and pelvic endometriosis. A definitive diagnosis can be established with a biopsy of the lesions during laparoscopy. Laparoscopy has the added benefit of allowing the surgeon to remove deposits of endometriosis and potentially improve symptoms.

Answer 62

Initial management involves: - Establishing a diagnosis - Providing a clear explanation - Listening to the patient, establishing their ideas, concerns and expectations and building a partnership - Analgesia as required for pain (NSAIDs and paracetamol first line) Hormonal management options can be tried before establishing a definitive diagnosis with laparoscopy. Cyclical pain can be treated with hormonal medications that stop ovulation and reduce endometrial thickening. This can be achieved using: - Combined oral contractive pill, which can be used back to back without a pill-free period if helpful - Progesterone only pill - Medroxyprogesterone acetate injection (e.g. Depo-Provera) - Nexplanon implant - Mirena coil The cyclical pain tends to improve after the menopause when the female sex hormones are reduced. Therefore, another treatment option for endometriosis is to induce a menopause-like state using GnRH agonists. Examples of GnRH agonists are goserelin (Zoladex) or leuprorelin (Prostap). They shut down the ovaries temporarily and can be useful in treating pain in many women. However, inducing the menopause has several side effects, such as hot flushes, night sweats and a risk of osteoporosis. Surgical management options: - Laparoscopic surgery to excise or ablate the endometrial tissue and remove adhesions (adhesiolysis) - Hysterectomy and bilateral salpingo-opherectomy is the final surgical option. During the procedure, the surgeon will attempt to remove as much of the endometriosis as possible. Importantly, this is still not guaranteed to resolve symptoms. Removing the ovaries induces menopause, and this stops ectopic endometrial tissue responding to the menstrual cycle. Infertility secondary to endometriosis can be treated with surgery. The aim is to remove as much of the endometriosis as possible, treat adhesions and return the anatomy to normal. This improves fertility in some but not all women with endometriosis. Laparoscopic treatment may improve fertility. Hormonal therapies may improve symptoms but not fertility.

Answer 63

Adenomyosis refers to endometrial tissue inside the myometrium (muscle layer of the uterus). It is more common in later reproductive years and those that have had several pregnancies (multiparous). It occurs in around 10% of women overall. It may occur alone, or alongside endometriosis or fibroids. The cause is not fully understood, and multiple factors are involved, including sex hormones, trauma and inflammation. The condition is hormone-dependent, and symptoms tend to resolve after menopause, similarly to endometriosis and fibroids.

Answer 64

Adenomyosis typically presents with: - Painful periods (dysmenorrhoea) - Heavy periods (menorrhagia) - Pain during intercourse (dyspareunia) It may also present with infertility or pregnancy-related complications. Around a third of patients are asymptomatic. Examination can demonstrate an enlarged and tender uterus. It will feel more soft than a uterus containing fibroids.

Answer 65

Transvaginal ultrasound of the pelvis is the first-line investigation for suspected adenomyosis. MRI and transabdominal ultrasound are alternative investigations where transvaginal ultrasound is not suitable. The gold standard is to perform a histological examination of the uterus after a hysterectomy. However, this is not usually a suitable way of establishing the diagnosis for obvious reasons.

Answer 66

Management of adenomyosis will depend on symptoms, age and plans for pregnancy. NICE recommend the same treatment for adenomyosis as for heavy menstrual bleeding. *When the woman does not want contraception; treatment can be used during menstruation for symptomatic relief, with: - Tranexamic acid when there is no associated pain (antifibrinolytic – reduces bleeding) - Mefenamic acid when there is associated pain (NSAID – reduces bleeding and pain) *Management when contraception is wanted or acceptable: - Mirena coil (first line) - Combined oral contraceptive pill - Cyclical oral progestogens - Progesterone only medications such as the pill, implant or depot injection may also be helpful. Other options are that may be considered by a specialist include: - GnRH analogues to induce a menopause-like state - Endometrial ablation - Uterine artery embolisation - Hysterectomy

Answer 67

Adenomyosis is associated with: - Infertility - Miscarriage - Preterm birth - Small for gestational age - Preterm premature rupture of membranes - Malpresentation - Need for caesarean section - Postpartum haemorrhage

Answer 68

Menopause is a retrospective diagnosis, made after a woman has had no periods for 12 months. It is defined as a permanent end to menstruation. On average, women experience the menopause around the age of 51 years, although this can vary significantly. Menopause is a normal process affecting all women reaching a suitable age. Menopause is caused by a lack of ovarian follicular function, resulting in changes in the sex hormones associated with the menstrual cycle: - Oestrogen and progesterone levels are low - LH and FSH levels are high, in response to an absence of negative feedback from oestrogen 1. Menopause is the point at which menstruation stops. 2. Postmenopause describes the period from 12 months after the final menstrual period onwards. 3. Perimenopause refers to the time around the menopause, where the woman may be experiencing vasomotor symptoms and irregular periods. Perimenopause includes the time leading up to the last menstrual period, and the 12 months afterwards. This is typically in women older than 45 years. Premature menopause is menopause before the age of 40 years. It is the result of premature ovarian insufficiency.

Answer 69

Inside the ovaries, the process of primordial follicles maturing into primary and secondary follicles is always occurring, independent of the menstrual cycle. At the start of the menstrual cycle, FSH stimulates further development of the secondary follicles. As the follicles grow, the granulosa cells that surround them secrete increasing amounts of oestrogen. The process of the menopause begins with a decline in the development of the ovarian follicles. Without the growth of follicles, there is reduced production of oestrogen. Oestrogen has a negative feedback effect on the pituitary gland, suppressing the quantity of LH and FSH produced. As the level of oestrogen falls in the perimenopausal period, there is an absence of negative feedback on the pituitary gland, and increasing levels of LH and FSH. The failing follicular development means ovulation does not occur (anovulation), resulting in irregular menstrual cycles. Without oestrogen, the endometrium does not develop, leading to a lack of menstruation (amenorrhoea). Lower levels of oestrogen also cause the perimenopausal symptoms.

Answer 70

A lack of oestrogen in the perimenopausal period leads to symptoms of: - Hot flushes - Emotional lability or low mood - Premenstrual syndrome - Irregular periods - Joint pains - Heavier or lighter periods - Vaginal dryness and atrophy - Reduced libido

Answer 71

A lack of oestrogen increases the risk of certain conditions: - Cardiovascular disease and stroke - Osteoporosis - Pelvic organ prolapse - Urinary incontinence

Answer 72

A diagnosis of perimenopause and menopause can be made in women over 45 years with typical symptoms, without performing any investigations. An FSH blood test may help with the diagnosis in: - Women under 40 years with suspected premature menopause - Women aged 40 – 45 years with menopausal symptoms or a change in the menstrual cycle

Answer 73

Fertility gradually declines after 40 years of age. However, women should still consider themselves fertile. Pregnancy after 40 is associated with increased risks and complications. Women need to use effective contraception for: - Two years after the last menstrual period in women under 50 - One year after the last menstrual period in women over 50 Hormonal contraceptives do not affect the menopause, when it occurs or how long it lasts, although they may suppress and mask the symptoms. This can make diagnosing menopause in women on hormonal contraception more difficult. Good contraceptive options (UKMEC 1) for women approaching the menopause are: - Barrier methods - Mirena or copper coil - Progesterone only pill - Progesterone implant - Progesterone depot injection (under 45 years)* - Sterilisation The combined oral contraceptive pill is UKMEC 2 (the advantages generally outweigh the risks) after aged 40, and can be used up to age 50 years if there are no other contraindications. Consider combined oral contraceptive pills containing norethisterone or levonorgestrel in women over 40, due to the relatively lower risk of venous thromboembolism compared with other options. *It is worth making a note and remembering two key side effects of the progesterone depot injection (e.g. Depo-Provera): weight gain and reduced bone mineral density (osteoporosis). These side effects are unique to the depot and do not occur with other forms of contraception. Reduced bone mineral density makes the depot unsuitable for women over 45 years.*

Answer 74

Vasomotor symptoms are likely to resolve after 2 – 5 years without any treatment. Management of symptoms depends on the severity, personal circumstances and response to treatment. Options include: - No treatment - Hormone replacement therapy (HRT) - Tibolone, a synthetic steroid hormone that acts as continuous combined HRT (only after 12 months of amenorrhoea) - Clonidine, which act as agonists of alpha-adrenergic and imidazoline receptors - Cognitive behavioural therapy (CBT) - SSRI antidepressants, such as fluoxetine or citalopram - Testosterone can be used to treat reduced libido (usually as a gel or cream) - Vaginal oestrogen cream or tablets, to help with vaginal dryness and atrophy (can be used alongside systemic HRT) - Vaginal moisturisers, such as Sylk, Replens and YES

Answer 75

Premature ovarian insufficiency is defined as menopause before the age of 40 years. It is the result of a decline in the normal activity of the ovaries at an early age. It presents with early onset of the typical symptoms of the menopause. Premature ovarian insufficiency is characterised by hypergonadotropic hypogonadism. Under-activity of the gonads (hypogonadism) means there is a lack of negative feedback on the pituitary gland, resulting in an excess of the gonadotropins (hypergonadotropism). Hormonal analysis will show: - Raised LH and FSH levels (gonadotropins) - Low oestradiol levels

Answer 76

- Idiopathic (the cause is unknown in more than 50% of cases) - Iatrogenic, due to interventions such as chemotherapy, radiotherapy or surgery (i.e. oophorectomy) - Autoimmune, possibly associated with coeliac disease, adrenal insufficiency, type 1 diabetes or thyroid disease - Genetic, with a positive family history or conditions such as Turner’s syndrome - Infections such as mumps, tuberculosis or cytomegalovirus

Answer 77

Premature ovarian insufficiency presents with irregular menstrual periods, lack of menstrual periods (secondary amenorrhea) and symptoms of low oestrogen levels, such has hot flushes, night sweats and vaginal dryness.

Answer 78

Premature ovarian insufficiency can be diagnosed in women younger than 40 years with typical menopausal symptoms plus elevated FSH. The FSH level needs to be persistently raised (more than 25 IU/l) on two consecutive samples separated by more than four weeks to make a diagnosis. The results are difficult to interpret in women taking hormonal contraception.

Answer 79

Women with premature ovarian failure are at higher risk of multiple conditions relating to the lack of oestrogen, including: - Cardiovascular disease - Stroke - Osteoporosis - Cognitive impairment - Dementia - Parkinsonism

Answer 80

Management involves hormone replacement therapy (HRT) until at least the age at which women typically go through menopause. HRT reduces the cardiovascular, osteoporosis, cognitive and psychological risks associated with premature menopause. It is worth noting there is still a small risk of pregnancy in women with premature ovarian failure, and contraception is still required. There are two options for HRT in women with premature ovarian insufficiency: 1. Traditional hormone replacement therapy: associated with a lower blood pressure compared with the combined oral contraceptive pill. 2. Combined oral contraceptive pill: may be more socially acceptable (less stigma for younger women) and additionally acts as contraception. Hormone replacement therapy before the age of 50 is not considered to increase the risk of breast cancer compared with the general population, as women would ordinarily produce the same hormones at this age. There may be an increased risk of venous thromboembolism with HRT in women under 50 years. The risk of VTE can be reduced by using transdermal methods (i.e. patches)

Answer 81

Hormone replacement therapy (HRT) is used in perimenopausal and postmenopausal women to alleviate symptoms associated with menopause. These symptoms are associated with a decline in the level of oestrogen. Exogenous oestrogen is given to alleviate the symptoms. Progesterone needs to be given (in addition to oestrogen) to women that have a uterus. The primary purpose of adding progesterone is to prevent endometrial hyperplasia and endometrial cancer secondary to “unopposed” oestrogen. Women that still have periods should go on cyclical HRT, with cyclical progesterone and regular breakthrough bleeds. Not all menopausal women require hormone replacement therapy. Women have often tried non-hormonal methods of controlling their symptoms before seeking help from their GP. HRT can offer very effective relief from symptoms, and in the majority of women the benefits will outweigh the risks.

Answer 82

Non-hormonal treatments may be tried initially, or used when there are contraindications to HRT. Options include: - Lifestyle changes such as improving the diet, exercise, weight loss, smoking cessation, reducing alcohol, reducing caffeine and reducing stress - Cognitive behavioural therapy (CBT) - Clonidine, which is an agonist of alpha-adrenergic and imidazoline receptors - SSRI antidepressants (e.g. fluoxetine) - Venlafaxine, which is a selective serotonin norepinephrine reuptake inhibitor (SNRI) - Gabapentin

Answer 83

Clonidine act as an agonist of alpha-2 adrenergic receptors and imidazoline receptors in the brain. It lowers blood pressure and reduces the heart rate, and is also used as an antihypertensive medication. It can be helpful for vasomotor symptoms and hot flushes, particularly where there are contraindications to using HRT. Common side effects of clonidine are dry mouth, headaches, dizziness and fatigue. Sudden withdrawal can result in rapid increases in blood pressure and agitation.

Answer 84

Patients might try alternative remedies, although they are not generally recommended as the safety and efficacy is unclear. They can have significant side effects and interact with other medications. These alternative remedies are intended to manage the vasomotor symptoms, such as hot flushes: - Black cohosh, which may be a cause of liver damage - Dong quai, which may cause bleeding disorders - Red clover, which may have oestrogenic effects that would be concerning with oestrogen sensitive cancers - Evening primrose oil, which has significant drug interactions and is linked with clotting disorders and seizures - Ginseng may be used for mood and sleep benefits

Answer 85

1. Replacing hormones in premature ovarian insufficiency, even without symptoms 2. Reducing vasomotor symptoms such as hot flushes and night sweats 3. Improving symptoms such as low mood, decreased libido, poor sleep and joint pain 4. Reducing risk of osteoporosis in women under 60 years

Answer 86

In women under 60 years, the benefits of HRT generally outweigh the risks. The key benefits to inform women of include: - Improved vasomotor and other symptoms of menopause (including mood, urogenital and joint symptoms) - Improved quality of life - Reduced the risk of osteoporosis and fractures Risks of HRT Women may be concerned about the risks of HRT. It is crucial to put these into perspective. In women under 60 years, the benefits generally outweigh the risks. Specific treatment regimes significantly reduce the risks associated with HRT. The risks of HRT are more significant in older women and increase with a longer duration of treatment. The principal risks of HRT are: - Increased risk of breast cancer (particularly combined HRT – oestrogen-only HRT has a lower risk) - Increased risk of endometrial cancer - Increased risk of venous thromboembolism (2 – 3 times the background risk) - Increased risk of stroke and coronary artery disease with long term use in older women - The evidence is inconclusive about ovarian cancer, and if there is an increase in risk, it is minimal These risks do not apply to all women: - The risks are not increased in women under 50 years compared with other women their age - There is no risk of endometrial cancer in women without a uterus - There is no increased risk of coronary artery disease with oestrogen-only HRT (the risk may even be lower with HRT) Ways to reduce the risks: - The risk of endometrial cancer is greatly reduced by adding progesterone in women with a uterus - The risk of VTE is reduced by using patches rather than pills

Answer 87

- Undiagnosed abnormal bleeding - Endometrial hyperplasia or cancer - Breast cancer - Uncontrolled hypertension - Venous thromboembolism - Liver disease - Active angina or myocardial infarction - Pregnancy

Answer 88

Before initiating HRT, there are a few things to check and consider: - Take a full history to ensure there are no contraindications - Take a family history to assess the risk of oestrogen dependent cancers (e.g. breast cancer) and VTE - Check the body mass index (BMI) and blood pressure - Ensure cervical and breast screening is up to date - Encourage lifestyle changes that are likely to improve symptoms and reduce risks Choosing the HRT Formulation There are three steps to consider when choosing the HRT formulation: Step 1: Do they have local or systemic symptoms? - Local symptoms: use topical treatments such as topical oestrogen cream or tablets - Systemic symptoms: use systemic treatment Step 2: Does the woman have a uterus? - No uterus: use continuous oestrogen-only HRT - Has uterus: add progesterone (combined HRT) Step 3: Have they had a period in the past 12 months? - Perimenopausal: give cyclical combined HRT - Postmenopausal (more than 12 months since last period): give continuous combined HRT

Answer 89

Oestrogen is the critical component of HRT for reducing the symptoms of menopause. There are two options for delivering systemic oestrogen: 1. Oral (tablets) eg Elleste Solo or Premarin 2. Transdermal (patches or gels) eg Evorel or Estradot: Patches are more suitable for women with poor control on oral treatment, higher risk of venous thromboembolism, cardiovascular disease and headaches. Progesterone is added to HRT to reduce the risk of endometrial hyperplasia and endometrial cancer. Progesterone is only required in women that have a uterus. Women without a uterus do not need progesterone, and can have oestrogen-only HRT. 1. Cyclical progesterone, given for 10 – 14 days per month, is used for women that have had a period within the past 12 months. Cycling the progesterone allows patients to have a monthly breakthrough bleed during the oestrogen-only part of the cycle, similar to a period. 2. Continuous progesterone is used when the woman has not had a period in the past: a. 24 months if under 50 years b. 12 months if over 50 years Using continuous combined HRT before postmenopause can lead to irregular breakthrough bleeding and investigation for other underlying causes of bleeding. You can switch from cyclical to continuous HRT after at least 12 months of treatment in women over 50, and 24 months in women under 50. Switch from cyclical to continuous HRT during the withdrawal bleed. Continuous HRT has better endometrial protection than cyclical HRT. There are three options for delivering progesterone for endometrial protection: 1. Oral (tablets) 2. Transdermal (patches) 3. Intrauterine system (e.g. Mirena coil) Cyclical combined HRT options include sequential tablets (eg Elleste-Duet, Clinorette or Femoston) or patches (Evorel Sequi or FemSeven Sequi) containing continuous oestrogen with progesterone added for specific periods during the cycle. The Mirena coil is licensed for four years for endometrial protection, after which time it needs replacing. The Mirena coil has the added benefits of contraception and treating heavy menstrual periods. It can cause irregular bleeding and spotting in the first few months after insertion. This usually settles with time and many women become amenorrhoeic.

Answer 90

The terms around progesterone can be confusing. There are some key definitions to remember: 1. Progestogens refer to any chemicals that target and stimulate progesterone receptors 2. Progesterone is the hormone produced naturally in the body 3. Progestins are synthetic progestogens There are two significant progestogen classes used in HRT. If the woman experiences side effects, consider switching the progestogen class. They can be described as C19 and C21 progestogens, referring to the chemical structure and number of carbon atoms in the molecule. C19 progestogens are derived from testosterone, and are more “male” in their effects. Examples are norethisterone, levonorgestrel and desogestrel. These may be helpful for women with reduced libido. C21 progestogens are derived from progesterone, and are more “female” in their effects. Examples are progesterone, dydrogesterone and medroxyprogesterone. These may be helpful for women with side effects such as depressed mood or acne.

Answer 91

Tibolone is a synthetic steroid that stimulates oestrogen and progesterone receptors. It also weakly stimulates androgen receptors. The effects on androgen receptors mean tibolone can be helpful for patients with reduced libido. Tibolone is used as a form of continuous combined HRT. Women need to be more than 12 months without a period (24 months if under 50 years). They would be expected not to have breakthrough bleeding. Tibolone can cause irregular bleeding, resulting in further investigations to exclude other causes.

Answer 92

1. Follow up three months after initiating HRT to review symptom and side effects 2. Side effects often settle with time, so it is worth persisting for at least three months with each regime 3. It takes 3 – 6 months of treatment to gain the full effects 4. Problematic or irregular bleeding is an indication for referral to a specialist 5. Ensure the woman has appropriate contraception eg Mirena coil or Progesterone only pill, given in addition to HRT 6. Stop oestrogen-containing contraceptives or HRT 4 weeks before major surgery 7. Consider other causes of symptoms where they persist despite HRT (e.g. thyroid, liver disease and diabetes)

Answer 93

The oestrogen and progesterone components of HRT cause different side effects. 1. Oestrogenic side effects: - Nausea and bloating - Breast swelling - Breast tenderness - Headaches - Leg cramps 2. Progestogenic side effects: - Mood swings - Bloating - Fluid retention - Weight gain - Acne and greasy skin Where patients experience side effects, it is worth changing the type of HRT or the route of administration (switch between patches and pills). Patients with progestogenic side effects may do better switching to an HRT with a different form of progesterone. For example, patients with acne and mood swings may do better with a dydrogesterone progesterone (e.g. Femoston). In contrast, patients with reduced libido may do better with a norethisterone progesterone (e.g. Elleste-Duet). Progestogenic side effects can be avoided altogether by using a Mirena coil for endometrial protection. Unscheduled bleeding can occur in the first 3 – 6 months of HRT (in women with a uterus). If unscheduled bleeding continues, consider referral for investigations, particularly regarding endometrial cancer.

Answer 94

Polycystic ovarian syndrome (PCOS) is a common condition causing metabolic and reproductive problems in women. There are characteristic features of multiple ovarian cysts, infertility, oligomenorrhea, hyperandrogenism and insulin resistance.

Answer 95

The Rotterdam criteria are used for making a diagnosis of polycystic ovarian syndrome. A diagnosis requires at least two of the three key features: 1. Oligoovulation or anovulation, presenting with irregular or absent menstrual periods 2. Hyperandrogenism, characterised by hirsutism and acne 3. Polycystic ovaries on ultrasound (or ovarian volume of more than 10cm3)

Answer 96

Women with polycystic ovarian syndrome present with some key features: - Oligomenorrhoea or amenorrhoea - Infertility - Obesity (in about 70% of patients with PCOS) - Hirsutism - Acne - Hair loss in a male pattern In addition to the presenting features, women may also experience: - Insulin resistance and diabetes - Acanthosis nigricans: thickened, rough skin, typically found in the axilla and on the elbows. It has a velvety texture. It occurs with insulin resistance - Cardiovascular disease - Hypercholesterolaemia - Endometrial hyperplasia and cancer - Obstructive sleep apnoea - Depression and anxiety - Sexual problems

Answer 97

- Medications, such as phenytoin, ciclosporin, corticosteroids, testosterone and anabolic steroids - Ovarian or adrenal tumours that secrete androgens - Cushing’s syndrome - Congenital adrenal hyperplasia

Answer 98

Insulin resistance is a crucial part of PCOS. When someone is resistant to insulin, their pancreas has to produce more insulin to get a response from the cells of the body. Insulin promotes the release of androgens from the ovaries and adrenal glands. Therefore, higher levels of insulin result in higher levels of androgens (such as testosterone). Insulin also suppresses sex hormone-binding globulin (SHBG) production by the liver. SHBG normally binds to androgens and suppresses their function. Reduced SHBG further promotes hyperandrogenism in women with PCOS. The high insulin levels contribute to halting the development of the follicles in the ovaries, leading to anovulation and multiple partially developed follicles (seen as polycystic ovaries on the scan). Diet, exercise and weight loss help reduce insulin resistance.

Answer 99

The following blood tests can diagnose PCOS and exclude other pathology that may have a similar presentation: - Testosterone (Raised) - Sex hormone-binding globulin - Luteinizing hormone (raised, with a raised LH:FSH ratio) - Follicle-stimulating hormone - Prolactin (may be mildly elevated in PCOS) - Thyroid-stimulating hormone Hormonal blood tests typically show: - Raised insulin - Normal or raised oestrogen levels Pelvic ultrasound is required when suspecting PCOS. A transvaginal ultrasound is the gold standard for visualising the ovaries. The follicles may be arranged around the periphery of the ovary, giving a “string of pearls” appearance. The diagnostic criteria are either: - 12 or more developing follicles in one ovary - Ovarian volume of more than 10cm3 (even without the presence of cysts) Pelvic ultrasound is not reliable in adolescents for the diagnosis of PCOS. The screening test of choice for diabetes in patients with PCOS is a 2-hour 75g oral glucose tolerance test (OGTT). An OGTT is performed in the morning prior to having breakfast. It involves taking a baseline fasting plasma glucose, giving a 75g glucose drink and then measuring plasma glucose 2 hours later. It tests the ability of the body to cope with a carbohydrate meal. The results are: - Impaired fasting glucose: 6.1 – 6.9 mmol/l (before the glucose drink) - Impaired glucose tolerance: plasma glucose at 2 hours of 7.8 – 11.1 mmol/l - Diabetes: plasma glucose at 2 hours above 11.1 mmol/l

Answer 100

It is crucial to reduce the risks associated with obesity, type 2 diabetes, hypercholesterolaemia and cardiovascular disease. These risks can be reduced by: - Weight loss - Low glycaemic index, calorie-controlled diet - Exercise - Smoking cessation - Antihypertensive medications where required - Statins where indicated (QRISK >10%) Patients should be assessed and managed for the associated features and complications, such as: - Endometrial hyperplasia and cancer - Infertility - Hirsutism - Acne - Obstructive sleep apnoea - Depression and anxiety Weight loss is a significant part of the management of PCOS. Weight loss alone can result in ovulation and restore fertility and regular menstruation, improve insulin resistance, reduce hirsutism and reduce the risks of associated conditions. Orlistat may be used to help weight loss in women with a BMI above 30. Orlistat is a lipase inhibitor that stops the absorption of fat in the intestines.

Answer 101

Women with polycystic ovarian syndrome have several risk factors for endometrial cancer: - Obesity - Diabetes - Insulin resistance - Amenorrhoea Under normal circumstances, the corpus luteum releases progesterone after ovulation. Women with PCOS do not ovulate (or ovulate infrequently), and therefore do not produce sufficient progesterone. They continue to produce oestrogen and do not experience regular menstruation. Consequently, the endometrial lining continues to proliferate under the influence of oestrogen, without regular shedding during menstruation. This is similar to giving unopposed oestrogen in women on hormone replacement therapy. It results in endometrial hyperplasia and a significant risk of endometrial cancer. Women with extended gaps between periods (more than three months) or abnormal bleeding need to be investigated with a pelvic ultrasound to assess the endometrial thickness. Cyclical progestogens should be used to induce a period prior to the ultrasound scan. If the endometrial thickness is more than 10mm, they need to be referred for a biopsy to exclude endometrial hyperplasia or cancer. Options for reducing the risk of endometrial hyperplasia and endometrial cancer are: 1. Mirena coil for continuous endometrial protection 2. Inducing a withdrawal bleed at least every 3 – 4 months with either: - Cyclical progestogens (e.g. medroxyprogesterone acetate 10mg once a day for 14 days) - Combined oral contraceptive pill

Answer 102

Weight loss is the initial step for improving fertility. Losing weight can restore regular ovulation. A specialist may initiate other options where weight loss fails. These include: - Clomifene - Laparoscopic ovarian drilling: involves laparoscopic surgery. The surgeon punctures multiple holes in the ovaries using diathermy or laser therapy. This can improve the woman’s hormonal profile and result in regular ovulation and fertility. - In vitro fertilisation (IVF) Metformin and letrozole may also help restore ovulation under the guidance of a specialist; however, the evidence to support their use is not clear. Women that become pregnant require screening for gestational diabetes. Screening involves an oral glucose tolerance test, performed before pregnancy and at 24 – 28 weeks gestation

Answer 103

Weight loss may improve the symptoms of hirsutism. Women are likely to have already explored options for hair removal, such as waxing, shaving and plucking. 1. Co-cyprindiol (Dianette) is a combined oral contraceptive pill licensed for the treatment of hirsutism and acne. It has an anti-androgenic effect, works as a contraceptive and will also regulate periods. The downside is a significantly increased risk of venous thromboembolism. For this reason, co-cyprindiol is usually stopped after three months of use. 2. Topical eflornithine can be used to treat facial hirsutism. It usually takes 6 – 8 weeks to see a significant improvement. The hirsutism will return within two months of stopping eflornithine. Other options that may be considered by a specialist experienced in treating hirsutism include: - Electrolysis - Laser hair removal - Spironolactone (mineralocorticoid antagonist with anti-androgen effects) - Finasteride (5α-reductase inhibitor that decreases testosterone production) - Flutamide (non-steroidal anti-androgen) - Cyproterone acetate (anti-androgen and progestin)

Answer 104

The combined oral contraceptive pill is first-line for acne in PCOS. Co-cyprindiol may be the best option as it has anti-androgen effects; however, there is a significantly increased risk of venous thromboembolism. Other standard treatments for acne include: - Topical adapalene (a retinoid) - Topical antibiotics (e.g. clindamycin 1% with benzoyl peroxide 5%) - Topical azelaic acid 20% - Oral tetracycline antibiotics (e.g. lymecycline)

Answer 105

Most ovarian cysts are asymptomatic. Cysts are often found incidentally on pelvic ultrasound scans. Occasionally, ovarian cysts can cause vague symptoms of: -Pelvic pain -Bloating -Fullness in the abdomen -A palpable pelvic mass (particularly with very large cysts such as mucinous cystadenomas) -Ovarian cysts may present with acute pelvic pain if there is ovarian torsion, haemorrhage or rupture of the cyst.

Answer 106

1. Follicular cysts represent the developing follicle. When these fail to rupture and release the egg, the cyst can persist. Follicular cysts are the most common ovarian cyst, they are harmless and tend to disappear after a few menstrual cycles. Typically they have thin walls and no internal structures, giving a reassuring appearance on the ultrasound. 2. Corpus luteum cysts occur when the corpus luteum fails to break down and instead fills with fluid. They may cause pelvic discomfort, pain or delayed menstruation. They are often seen in early pregnancy.

Answer 107

1. Serous Cystadenoma: These are benign tumours of the epithelial cells. 2. Mucinous Cystadenoma: These are also benign tumour of the epithelial cells. They can become huge, taking up lots of space in the pelvis and abdomen. 3. Endometrioma: These are lumps of endometrial tissue within the ovary, occurring in patients with endometriosis. They can cause pain and disrupt ovulation. 4. Dermoid Cysts / Germ Cell Tumours: These are benign ovarian tumours. They are teratomas, meaning they come from the germ cells and may contain various tissue types, such as skin, teeth, hair and bone. They are particularly associated with ovarian torsion. 5. Sex Cord-Stromal Tumours: These are rare tumours, that can be benign or malignant. They arise from the stroma (connective tissue) or sex cords (embryonic structures associated with the follicles). There are several types, including Sertoli–Leydig cell tumours and granulosa cell tumours.

Answer 108

The key to managing ovarian cysts is to establish whether they are benign or malignant. Take a detailed history and examination for features that may suggest malignancy: -Abdominal bloating -Reduce appetite -Early satiety -Weight loss -Urinary symptoms -Pain -Ascites -Lymphadenopathy Assess for risk factors for ovarian malignancy: -Age -Postmenopause -Increased number of ovulations -Obesity -Hormone replacement therapy -Smoking -Breastfeeding (protective) -Family history and BRCA1 and BRCA2 genes The number of times a woman has ovulated during her life correlates with her risk of ovarian cancer. More ovulations increases the risk of ovarian cancer. Factors that will reduce the number of ovulations are: -Later onset of periods (menarche) -Early menopause -Any pregnancies -Use of the combined contraceptive pill

Answer 109

Premenopausal women with a simple ovarian cyst less than 5cm on ultrasound (usually found incidentally on pelvic US) do not need further investigations. Blood tests for tumour markers may be indicated. CA125 is the tumour marker to remember for ovarian cancer. It contributes to the overall impression of whether an ovarian cyst is related to cancer and forms part of the risk of malignancy index. Women under 40 years with a complex ovarian mass require tumour markers for a possible germ cell tumour: - Lactate dehydrogenase (LDH) - Alpha-fetoprotein (α-FP) - Human chorionic gonadotropin (HCG)

Answer 110

CA125 is a tumour marker for epithelial cell ovarian cancer. It is not very specific, and there are many non-malignant causes of a raised CA125: - Endometriosis - Fibroids - Adenomyosis - Pelvic infection - Liver disease - Pregnancy

Answer 111

The risk of malignancy index (RMI) estimates the risk of an ovarian mass being malignant, taking account of three things: 1. Menopausal status 2. Ultrasound findings 3. CA125 level

Answer 112

Possible ovarian cancer (complex cysts or raised CA125) requires a two-week wait referral to a gynaecological oncology specialist. Possible dermoid cysts require referral to a gynaecologist for further investigation and consideration of surgery. Simple ovarian cysts in premenopausal women can be managed based on their size: - Less than 5cm cysts will almost always resolve within three cycles. They do not require a follow-up scan. - 5cm to 7cm: Require routine referral to gynaecology and yearly ultrasound monitoring. - More than 7cm: Consider an MRI scan or surgical evaluation as they can be difficult to characterise with ultrasound. Cysts in postmenopausal women generally require correlation with the CA125 result and referral to a gynaecologist. When there is a raised CA125, this should be a two-week wait suspected cancer referral. Simple cysts under 5cm with a normal CA125 may be monitored with an ultrasound every 4 – 6 months. Persistent or enlarging cysts may require surgical intervention (usually with laparoscopy). Surgery may involve removing the cyst (ovarian cystectomy), possibly along with the affected ovary (oophorectomy).

Answer 113

Consider complications when patients present with acute onset pain. The main complications are: - Torsion - Haemorrhage into the cyst - Rupture, with bleeding into the peritoneum

Answer 114

Meig’s syndrome involves a triad of: 1. Ovarian fibroma (a type of benign ovarian tumour) 2. Pleural effusion 3. Ascites Meig’s syndrome typically occurs in older women. Removal of the tumour results in complete resolution of the effusion and ascites. *It is worth remembering Meig’s syndrome for your MCQ exams. Look out for the woman presenting with a pleural effusion and an ovarian mass.*

Answer 115

No, unless they also have other features of the condition. A diagnosis of PCOS requires at least two of: -Anovulation -Hyperandrogenism -Polycystic ovaries on ultrasound

Answer 116

Ovarian torsion is a condition where the ovary twists in relation to the surrounding connective tissue, fallopian tube and blood supply (the adnexa). Ovarian torsion is usually due to an ovarian mass larger than 5cm, such as a cyst or a tumour. It is more likely to occur with benign tumours. It is also more likely to occur during pregnancy. Ovarian torsion can also happen with normal ovaries in younger girls before menarche (the first period), when girls have longer infundibulopelvic ligaments that can twist more easily. Twisting of the adnexa and blood supply to the ovary leads to ischaemia. If the torsion persists, necrosis will occur, and the function of that ovary will be lost. Therefore, ovarian torsion is an emergency, where a delay in treatment can have significant consequences. Prompt diagnosis and management is essential.

Answer 117

The main presenting feature is sudden onset severe unilateral pelvic pain. The pain is constant, gets progressively worse and is associated with nausea and vomiting. The pain is not always severe, and ovarian torsion can take a milder and more prolonged course. Occasionally, the ovary can twist and untwist intermittently, causing pain that comes and goes. On examination there will be localised tenderness. There may be a palpable mass in the pelvis, although the absence of a mass does not exclude the diagnosis.

Answer 118

- Pelvic ultrasound is the initial investigation of choice. Transvaginal is ideal, but transabdominal can be used where transvaginal is not possible. It may show “whirlpool sign”, free fluid in pelvis and oedema of the ovary. - Doppler studies may show a lack of blood flow. The definitive diagnosis is made with laparoscopic surgery.

Answer 119

Patients need emergency admission under gynaecology for urgent investigation and management. Depending on the duration and severity of the illness they require laparoscopic surgery to either: 1. Un-twist the ovary and fix it in place (detorsion) 2. Remove the affected ovary (oophorectomy) The decision whether to save the ovary or remove it is made during the surgery, based on a visual inspection of the ovary. Laparotomy may be required where there is a large ovarian mass or malignancy is suspected.

Answer 120

A delay in treating ovarian torsion can result in loss of function of that ovary. The other ovary can usually compensate, so fertility is not typically affected. Where this is the only functioning ovary, loss of function leads to infertility and menopause. Where a necrotic ovary is not removed, it may become infected, develop an abscess and lead to sepsis. Additionally it may rupture, resulting in peritonitis and adhesions.

Answer 121

Asherman’s syndrome is where adhesions (sometimes called synechiae) form within the uterus, following damage to the uterus. Usually Asherman’s syndrome occurs after a pregnancy-related dilatation and curettage procedure, for example in the treatment of retained products of conception (removing placental tissue left behind after birth). It can also occur after uterine surgery (e.g. myomectomy) or several pelvic infection (e.g. endometritis). Endometrial curettage (scraping) can damage the basal layer of the endometrium. This damaged tissue may heal abnormally, creating scar tissue (adhesions) connecting areas of the uterus that are generally not connected. There may be adhesions binding the uterine walls together, or within the endocervix, sealing it shut. These adhesions form physical obstructions and distort the pelvic organs, resulting in menstruation abnormalities, infertility and recurrent miscarriages. Adhesions may be found incidentally during hysteroscopy. Asymptomatic adhesions are not classified as Asherman’s syndrome.

Answer 122

Asherman’s syndrome typically presents following recent dilatation and curettage, uterine surgery or endometritis with: 1. Secondary amenorrhoea (absent periods) 2. Significantly lighter periods 3. Dysmenorrhoea (painful periods) It may also present with infertility.

Answer 123

There are several options for establishing a diagnosis of intrauterine adhesions: 1. Hysteroscopy is the gold standard investigation, and can involve dissection and treatment of the adhesions 2. Hysterosalpingography, where contrast is injected into the uterus and imaged with xrays 3. Sonohysterography, where the uterus is filled with fluid and a pelvic ultrasound is performed 4. MRI scan

Answer 124

Management is by dissecting the adhesions during hysteroscopy. Reoccurrence of the adhesions after treatment is common.

Answer 125

Cervical ectropion can also be called cervical ectopy or cervical erosion. Cervical ectropion occurs when the columnar epithelium of the endocervix (the canal of the cervix) has extended out to the ectocervix (the outer area of the cervix). The lining of the endocervix becomes visible on examination of the cervix using a speculum. This lining has a different appearance to the normal endocervix. The cells of the endocervix (columnar epithelial cells) are more fragile and prone to trauma. They are more likely to bleed with sexual intercourse. This means cervical ectropion often presents with postcoital bleeding. Cervical ectropion is associated with higher oestrogen levels, and therefore, is more common in younger women, the combined contraceptive pill and pregnancy.

Answer 126

The transformation zone is the border between the columnar epithelium of the endocervix (the canal), and the stratified squamous epithelium of the ectocervix (the outer area of the cervix visible on speculum examination). When the transformation zone is located on the ectocervix, it is visible during speculum examination as a border between the two epithelial types.

Answer 127

Many cervical ectropion are asymptomatic, and they are found incidentally during speculum examination for other reasons, for example, smear tests. Ectropion may present with increased vaginal discharge, vaginal bleeding or dyspareunia (pain during sex). Intercourse is a common cause of minor trauma to the ectropion, triggering episodes of postcoital bleeding. Examination of the cervix will reveal a well-demarcated border between the redder, velvety columnar epithelium extending from the os (opening), and the pale pink squamous epithelium of the ectocervix. This border is the transformation zone.

Answer 128

Asymptomatic ectropion require no treatment. Ectropion will typically resolve as the patient gets older, stops the pill or is no longer pregnant. Having a cervical ectropion is not a contraindication to the combined contraceptive pill. Problematic bleeding is an indication for the treatment of cervical ectropion. Treatment involves cauterisation of the ectropion using silver nitrate or cold coagulation during colposcopy.

Answer 129

Nabothian cysts are fluid-filled cysts often seen on the surface of the cervix. They are also called nabothian follicles or mucinous retention cysts. They are usually up to 1cm in size, but rarely can be more extensive. They are harmless and unrelated to cervical cancer. The columnar epithelium of the endocervix (the canal) produces cervical mucus. When the squamous epithelium of the ectocervix slightly covers the mucus-secreting columnar epithelium, the mucus becomes trapped and forms a cyst. This can happen after childbirth, minor trauma to the cervix or cervicitis secondary to infection.

Answer 130

Nabothian cysts are often found incidentally on a speculum examination. They do not typically cause any symptoms. Rarely, when they are very large, they may cause a feeling of fullness in the pelvis. Nabothian cysts appear as smooth rounded bumps on the cervix, usually near to os (opening). They can range in size from 2mm to 30mm, and have a whitish or yellow appearance.

Answer 131

Where the diagnosis is clear, women can be reassured, and no treatment is required. They do not cause any harm and often resolve spontaneously. If the diagnosis is uncertain, women can be referred for colposcopy to examine in detail. Occasionally they may be excised or biopsied to exclude other pathology. Rarely they may be treated during colposcopy to relieve symptoms.

Answer 132

Pelvic organ prolapse refers to the descent of pelvic organs into the vagina. Prolapse is the result of weakness and lengthening of the ligaments and muscles surrounding the uterus, rectum and bladder. 1. Uterine Prolapse: where the uterus itself descends into the vagina. 2. Vault Prolapse: occurs in women that have had a hysterectomy, and no longer have a uterus. The top of the vagina (the vault) descends into the vagina. 3. Rectocele: caused by a defect in the posterior vaginal wall, allowing the rectum to prolapse forwards into the vagina. Rectoceles are particularly associated with constipation. Women can develop faecal loading in the part of the rectum that has prolapsed into the vagina. Loading of faeces results in significant constipation, urinary retention (due to compression on the urethra) and a palpable lump in the vagina. Women may use their fingers to press the lump backwards, correcting the anatomical position of the rectum, and allowing them to open their bowels. 4. Cystocele: caused by a defect in the anterior vaginal wall, allowing the bladder to prolapse backwards into the vagina. Prolapse of the urethra is also possible (urethrocele). Prolapse of both the bladder and the urethra is called a cystourethrocele.

Answer 133

Pelvic organ prolapse is the result of weak and stretched muscles and ligaments. The factors that can contribute to this include: 1. Multiple vaginal deliveries 2, Instrumental, prolonged or traumatic delivery 3. Advanced age and postmenopause status 4. Obesity 5. Chronic respiratory disease causing coughing 6. Chronic constipation causing straining

Answer 134

Typical presenting symptoms are: - A feeling of “something coming down” in the vagina - A dragging or heavy sensation in the pelvis - Urinary symptoms, such as incontinence, urgency, frequency, weak stream and retention - Bowel symptoms, such as constipation, incontinence and urgency - Sexual dysfunction, such as pain, altered sensation and reduced enjoyment Women may have identified a lump or mass in the vagina, and often will already be pushing it back up themselves. They may notice the prolapse will become worse on straining or bearing down.

Answer 135

Ideally, the patient should empty their bladder and bowel before examination of a prolapse. When examining for pelvic organ prolapse, various positions may be attempted, including the dorsal and left lateral position. A Sim’s speculum is a U-shaped, single-bladed speculum that can be used to support the anterior or posterior vaginal wall while the other vaginal walls are examined. It is held on the anterior wall to examine for a rectocele, and the posterior wall for a cystocele. The women can be asked to cough or “bear down” to assess the full descent of the prolapse.

Answer 136

The severity of a uterine prolapse can be graded using the pelvic organ prolapse quantification (POP-Q) system: Grade 0: Normal Grade 1: The lowest part is more than 1cm above the introitus Grade 2: The lowest part is within 1cm of the introitus (above or below) Grade 3: The lowest part is more than 1cm below the introitus, but not fully descended Grade 4: Full descent with eversion of the vagina A prolapse extending beyond the introitus can be referred to as uterine procidentia.

Answer 137

There are three options for management: 1. Conservative management Conservative management is appropriate for women that are able to cope with mild symptoms, do not tolerate pessaries or are not suitable for surgery. Conservative management involves: - Physiotherapy (pelvic floor exercises) - Weight loss - Lifestyle changes for associated stress incontinence, such as reduced caffeine intake and incontinence pads - Treatment of related symptoms, such as treating stress incontinence with anticholinergic mediations - Vaginal oestrogen cream 2. Vaginal pessary Vaginal pessaries are inserted into the vagina to provide extra support to the pelvic organs. They can create a significant improvement in symptoms and can easily be removed and replaced if they cause any problems. There are many types of pessary: - Ring pessaries are a ring shape, and sit around the cervix holding the uterus up - Shelf and Gellhorn pessaries consist of a flat disc with a stem, that sits below the uterus with the stem pointing downwards - Cube pessaries are a cube shape - Donut pessaries consist of a thick ring, similar to a doughnut - Hodge pessaries are almost rectangular. One side is hooked around the posterior aspect of the cervix and the other extends into the vagina. Women often have to try a few types of pessary before finding the correct comfort and symptom relief. Pessaries should be removed and cleaned or changed periodically (e.g. every four months). They can cause vaginal irritation and erosion over time. Oestrogen cream helps protect the vaginal walls from irritation. 3. Surgery Surgery is the definitive option for treating a pelvic organ prolapse. There are many methods for surgical correction of a prolapse, including hysterectomy. Surgery can be very successful in correcting the problem. Possible complications of pelvic organ prolapse surgery include: - Pain, bleeding, infection, DVT and risk of anaesthetic - Damage to the bladder or bowel - Recurrence of the prolapse - Altered experience of sex

Answer 138

Mesh repairs have been the subject of a lot of controversy over recent years. Mesh repairs involve inserting a plastic mesh to support the pelvic organs. After review, NICE recommend that mesh procedures should be avoided entirely. Potential complications associated with mesh repairs are: -Chronic pain -Altered sensation -Dyspareunia (painful sex) for the women or her partner -Abnormal bleeding -Urinary or bowel problems Women presenting with possible complications of mesh repair should be referred to a specialist for assessment and management.

Answer 139

Urinary incontinence refers to the loss of control of urination. There are two types of urinary incontinence, urge incontinence and stress incontinence. Establishing the type of incontinence is essential, as this will determine the management. 1. Urge Incontinence Urge incontinence is caused by overactivity of the detrusor muscle of the bladder. Urge incontinence is also known as overactive bladder. The typical description is of suddenly feeling the urge to pass urine, having to rush to the bathroom and not arriving before urination occurs. Women with urge incontinence are very conscious about always having access to a toilet, and may avoid activities or places where they may not have easy access. This can have a significant impact on their quality of life, and stop them doing work and leisure activities. 2. Stress Incontinence The pelvic floor consists of a sling of muscles that support the contents of the pelvic. There are three canals through the centre of the female pelvic floor: the urethral, vaginal and rectal canals. When the muscles of the pelvic floor are weak, the canals become lax, and the organs are poorly supported within the pelvis. Stress incontinence is due to weakness of the pelvic floor and sphincter muscles. This allows urine to leak at times of increased pressure on the bladder. The typical description of stress incontinence is urinary leakage when laughing, coughing or surprised.

Answer 140

Mixed incontinence refers to a combination of urge incontinence and stress incontinence. It is crucial to identify which of the two is having the more significant impact and address this first. Overflow incontinence can occur when there is chronic urinary retention due to an obstruction to the outflow of urine. Chronic urinary retention results in an overflow of urine, and the incontinence occurs without the urge to pass urine. It can occur with anticholinergic medications, fibroids, pelvic tumours and neurological conditions such as multiple sclerosis, diabetic neuropathy and spinal cord injuries. Overflow incontinence is more common in men, and rare in women. Women with suspected overflow incontinence should be referred for urodynamic testing and specialist management.

Answer 141

- Increased age - Postmenopausal status - Increased BMI - Previous pregnancies and vaginal deliveries - Pelvic organ prolapse - Pelvic floor surgery - Neurological conditions, such as multiple sclerosis - Cognitive impairment and dementia

Answer 142

A medical history should distinguish between the types of incontinence. Try to differentiate between urinary leakage with coughing or sneezing (stress incontinence), and incontinence due to a sudden urge to pass urine with loss of control on the way to the toilet (urge incontinence). Assess for modifiable lifestyle factors that can contribute to symptoms: - Caffeine consumption - Alcohol consumption - Medications - Body mass index (BMI) Assess the severity by asking about: - Frequency of urination - Frequency of incontinence - Night-time urination - Use of pads and changes of clothing Examination should assess the pelvic tone and examine for: - Pelvic organ prolapse - Atrophic vaginitis - Urethral diverticulum - Pelvic masses During the examination, ask the patient to cough and watch for leakage from the urethra. The strength of the pelvic muscle contractions can be assessed during a bimanual examination by asking the woman to squeeze against the examining fingers. This can be graded using the modified Oxford grading system: 0: No contraction 1: Faint contraction 2: Weak contraction 3: Moderate contraction with some resistance 4: Good contraction with resistance 5: Strong contraction, a firm squeeze and drawing inwards

Answer 143

1. A bladder diary should be completed, tracking fluid intake and episodes of urination and incontinence over at least three days. There should be a mix of work and leisure days. 2. Urine dipstick testing should be performed to assess for infection, microscopic haematuria and other pathology. 3. Post-void residual bladder volume should be measured using a bladder scan to assess for incomplete emptying. 4. Urodynamic testing can be used to investigate patients with urge incontinence not responding to first-line medical treatments, difficulties urinating, urinary retention, previous surgery or an unclear diagnosis. It is not always required where the diagnosis is possible based on the history and examination. Patients need to stop taking any anticholinergic and bladder related medications around five days before the tests. A thin catheter is inserted into the bladder, and another into the rectum. These two catheters can measure the pressures in the bladder and rectum for comparison. The bladder is filled with liquid, and various outcome measures are taken: - Cystometry measures the detrusor muscle contraction and pressure - Uroflowmetry measures the flow rate - Leak point pressure is the point at which the bladder pressure results in leakage of urine. The patient is asked to cough, move or jump when the bladder is filled to various capacities. This assesses for stress incontinence. - Post-void residual bladder volume tests for incomplete emptying of the bladder Video urodynamic testing involves filling the bladder with contrast and taking xray images as the bladder is emptied. Theses are only performed where necessary and not a routine part of urodynamic testing.

Answer 144

Management of stress incontinence involves: - Avoiding caffeine, diuretics and overfilling of the bladder - Avoid excessive or restricted fluid intake - Weight loss (if appropriate) - Supervised pelvic floor exercises for at least three months before considering surgery: Pelvic floor exercises are used to strengthen the muscles of the pelvic floor. They increase the tone and improve the support for the bladder and bowel. Pelvic floor exercises should be supervised by an appropriate professional, such as a specialist nurse or physiotherapist. Women should aim for at least eight contractions, three times daily. - Surgery - Duloxetine is an SNRI antidepressant used second line where surgery is less preferred Surgical options to treat stress incontinence include: 1. Tension-free vaginal tape (TVT) procedures involve a mesh sling looped under the urethra and up behind the pubic symphysis to the abdominal wall. This supports the urethra, reducing stress incontinence. 2. Autologous sling procedures work similarly to TVT procedures but a strip of fascia from the patient’s abdominal wall is used rather than tape 3. Colposuspension involves stitches connecting the anterior vaginal wall and the pubic symphysis, around the urethra, pulling the vaginal wall forwards and adding support to the urethra 4. Intramural urethral bulking involves injections around the urethra to reduce the diameter and add support Where the stress incontinence is caused by a neurological disorder or other surgical methods have failed, specialist centres may offer an operation to create an artificial urinary sphincter. This involves a pump inserted into the labia that inflates and deflates a cuff around the urethra, allowing women to control their continence manually.

Answer 145

Management of urge incontinence and overactive bladder involves: - Bladder retraining (gradually increasing the time between voiding) for at least six weeks is first-line - Anticholinergic medication, for example, oxybutynin, tolterodine and solifenacin: need to be used carefully, as they have anticholinergic side effects. These include dry mouth, dry eyes, urinary retention, constipation and postural hypotension. Importantly they can also lead to a cognitive decline, memory problems and worsening of dementia, which can be very problematic in older, more frail patients. - Mirabegron is an alternative to anticholinergic medications: less of an anticholinergic burden. However, it is worth noting that mirabegron is contraindicated in uncontrolled hypertension. Blood pressure needs to be monitored regularly during treatment. It works as a beta-3 agonist, stimulating the sympathetic nervous system, leading to raised blood pressure. This can lead to a hypertensive crisis and an increased risk of TIA and stroke. - Invasive procedures where medical treatment fails: Invasive options for overactive bladder that has failed to respond to retraining and medical management include 1. Botulinum toxin type A injection into the bladder wall 2. Percutaneous sacral nerve stimulation involves implanting a device in the back that stimulates the sacral nerves 3. Augmentation cystoplasty involves using bowel tissue to enlarge the bladder 4. Urinary diversion involves redirecting urinary flow to a urostomy on the abdomen

Answer 146

Atrophic vaginitis refers to dryness and atrophy of the vaginal mucosa related to a lack of oestrogen. Atrophic vaginitis can also be referred to as genitourinary syndrome of menopause. It occurs in women entering the menopause. The epithelial lining of the vagina and urinary tract responds to oestrogen by becoming thicker, more elastic and producing secretions. As women enter the menopause, oestrogen levels fall, resulting in the mucosa becoming thinner, less elastic and more dry. The tissue is more prone to inflammation. There are also changes in the vaginal pH and microbial flora that can contribute to localised infections. (Oestrogen also helps maintain healthy connective tissue around the pelvic organs, and a lack of oestrogen can contribute to pelvic organ prolapse and stress incontinence.)

Answer 147

Atrophic vaginitis presents in postmenopausal women with symptoms of: -Itching -Dryness -Dyspareunia (discomfort or pain during sex) -Bleeding due to localised inflammation You should also consider atrophic vaginitis in older women presenting with recurrent urinary tract infections, stress incontinence or pelvic organ prolapse. Treatment with topical oestrogen where appropriate may improve the symptoms of these conditions. It is worth asking about symptoms of vaginal dryness and discomfort, as women will often be reluctant to bring it up during a consultation. It is straightforward to treat and can make a big difference to their quality of life.

Answer 148

Examination of the labia and vagina will demonstrate: -Pale mucosa -Thin skin -Reduced skin folds -Erythema and inflammation -Dryness -Sparse pubic hair

Answer 149

Vaginal lubricants can help symptoms of dryness. Examples include Sylk, Replens and YES. Topical oestrogen can make a big difference in symptoms. Options include: - Estriol cream, applied using an applicator (syringe) at bedtime -Estriol pessaries, inserted at bedtime -Estradiol tablets (Vagifem), once daily -Estradiol ring (Estring), replaced every three months Topical oestrogen shares many contraindications with systemic HRT, such as breast cancer, angina and venous thromboembolism. It is unclear whether long term use of topical oestrogen increases the risk of endometrial hyperplasia and endometrial cancer. Women should be monitored at least annually, with a view of stopping treatment whenever possible.

Answer 150

The Bartholin’s glands are a pair glands located either side of the posterior part of the vaginal introitus (the vaginal opening). They are usually pea-sized and not palpable. They produce mucus to help with vaginal lubrication. When the ducts become blocked, the Bartholin’s glands can swell and become tender, causing a Bartholin’s cyst. The swelling is typically unilateral and forms a fluid-filled cyst between 1 – 4 cm. Cysts can become infected, forming a Bartholin’s abscess. A Bartholin’s abscess will be hot, tender, red and potentially draining pus.

Answer 151

Bartholin’s cysts will usually resolve with simple treatment such as good hygiene, analgesia and warm compresses. Incision is generally avoided, as the cyst will often reoccur. A biopsy may be required if vulval malignancy needs to be excluded (particularly in women over 40 years). A Bartholin’s abscess will require antibiotics. A swab of pus or fluid from the abscess can be taken to culture the infective organism and check the antibiotic sensitivities. E. coli is the most common cause. Send specific swabs for chlamydia and gonorrhoea. Surgical interventions may be required to treat a Bartholin’s abscess. There are two options for surgical management: 1. Word catheter (Bartholin’s gland balloon) – requires local anaesthetic, it is a small rubber tube with a balloon on the end. Local anaesthetic is used to numb the area. An incision is made, and any pus is drained from the abscess. The Word catheter is inserted into the abscess space, and inflated up to 3 ml with saline. The balloon fills the space and keeps the catheter in place. Fluid can drain around the catheter, preventing a cyst or abscess reoccurring. The tissue heals around the catheter, leaving a permanent hole. The catheter can be deflated and carefully removed at a later date, once epithelisation of the hole has occurred. 2. Marsupialisation – requires general anaesthetic, involves a general anaesthetic in a surgical theatre. An incision is made, and the abscess is drained. The sides of the abscess are sutured open. Suturing the abscess open allows continuous drainage of the area and prevents recurrence of the cyst or abscess.

Answer 152

Lichen sclerosis is a chronic inflammatory skin condition that presents with patches of shiny, “porcelain-white” skin. It commonly affects the labia, perineum and perianal skin in women. It can affect other areas, such as the axilla and thighs. It can also affect men, typically on the foreskin and glans of the penis. Lichen sclerosis is thought to be an autoimmune condition. It is associated with other autoimmune diseases, such as type 1 diabetes, alopecia, hypothyroid and vitiligo. The diagnosis of lichen sclerosis is usually made clinically, based on the history and examination findings. Where there is doubt, a vulval biopsy can confirm the diagnosis.

Answer 153

Lichen sclerosis may be confused with other conditions that include “lichen” in the name. Lichen refers to a flat eruption that spreads. It is important not to get lichen sclerosis confused with lichen simplex or lichen planus. Lichen simplex is chronic inflammation and irritation caused by repeated scratching and rubbing of an area of skin. This presents with excoriations, plaques, scaling and thickened skin. Lichen planus is an autoimmune condition that causes localised chronic inflammation with shiny, purplish, flat-topped raised areas with white lines across the surface called Wickham’s striae.

Answer 154

The typical presentation in your exams is a woman aged 45 – 60 years complaining of vulval itching and skin changes in the vulva. The condition may be asymptomatic, or present with several symptoms: -Itching -Soreness and pain possibly worse at night -Skin tightness -Painful sex (superficial dyspareunia) -Erosions -Fissures The Koebner phenomenon refers to when the signs and symptoms are made worse by friction to the skin. This occurs with lichen sclerosus. It can be made worse by tight underwear that rubs the skin, urinary incontinence and scratching. Changes affect the labia, perianal and perineal skin. There can be associated fissures, cracks, erosions or haemorrhages under the skin. The affected skin appears: -“Porcelain-white” in colour -Shiny -Tight -Thin -Slightly raised -There may be papules or plaques

Answer 155

Lichen sclerosis cannot be cured, but the symptoms can be effectively controlled. Lichen sclerosis is usually managed and followed up every 3 – 6 months by an experienced gynaecologist or dermatologist. 1. Potent topical steroids are the mainstay of treatment. The typical choice is clobetasol propionate 0.05% (dermovate). Steroids are used long term to control the symptoms of the condition. They also seem to reduce the risk of malignancy. Steroids are initially used once a day for four weeks, then gradually reduced in frequency every four weeks to alternate days, then twice weekly. When the condition flares patients can go back to using topical steroids daily until they achieve good control. A 30g tube should last at least three months. 2. Emollients should be used regularly, both with steroids initially and then as part of maintenance.

Answer 156

The critical complication to remember is a 5% risk of developing squamous cell carcinoma of the vulva. Other complications include: -Pain and discomfort -Sexual dysfunction -Bleeding -Narrowing of the vaginal or urethral openings

Answer 157

Female genital mutilation (FGM) involves surgically changing the genitals of a female for non-medical reasons. FGM is a cultural practice that usually occurs in girls before puberty. It is a form of child abuse and a safeguarding issue. Female genital mutilation is illegal as stated in the Female Genital Mutilation Act 2003, and there is a legal requirement for healthcare professionals to report cases of FGM to the police. FGM is a common cultural practice in many African countries. Somalia has the highest levels of FGM in any country. Other countries with high rates are Ethiopia, Sudan and Eritrea. It also occurs in Yemen, Kurdistan, Indonesia and various parts of South and Western Asia. There are four types of female genital mutilation: Type 1: Removal of part or all of the clitoris. Type 2: Removal of part or all of the clitoris and labia minora. The labia majora may also be removed. Type 3: Narrowing or closing the vaginal orifice (infibulation). Type 4: All other unnecessary procedures to the female genitalia.

Answer 158

It is important to recognise risk factors for FGM to identify and ideally prevent cases from occurring. Two key risk factors to bear in mind are coming from a community that practise FGM and having relatives affected by FGM. There are scenarios where it is worth considering the risk of FGM: - Pregnant women with FGM with a possible female child - Siblings or daughters of women or girls affected by FGM - Extended trips with infants or children to areas where FGM is practised - Women that decline examination or cervical screening - New patients from communities that practise FGM Women may also present with the complications of FGM.

Answer 159

Immediate complications include: -Pain -Bleeding -Infection -Swelling -Urinary retention -Urethral damage and incontinence Long term complications include: - Vaginal infections, such as bacterial vaginosis - Pelvic infections - Urinary tract infections - Dysmenorrhea (painful menstruation) - Sexual dysfunction and dyspareunia (painful sex) - Infertility and pregnancy-related complications - Significant psychological issues and depression - Reduced engagement with healthcare and screening

Answer 160

It is essential to educate patients and relatives that FGM is illegal in the UK. Discuss the health consequences of FGM. It is mandatory to report all cases of FGM in patients under 18 to the police. Other services should also be contacted: -Social services and safeguarding -Paediatrics -Specialist gynaecology or FGM services -Counselling In patients over 18, there needs to be careful consideration about whether to report cases to the police or social services. The RCOG recommends using a risk assessment tool to tackle this issue. The risk assessment includes considering whether the patient has female relatives that may be at risk. If the unborn child of a pregnant woman affected by FGM is considered to be at risk, a referral should be made. A de-infibulation surgical procedure may be performed by a specialist in FGM in cases of type 3 FGM. This aims to correct the narrowing or closure of the vaginal orifice, improve symptoms and try to restore normal function. Re-infibulation (re-closure of the vaginal orifice) could be requested after childbirth. Performing this procedure is illegal.

Answer 161

The upper vagina, cervix, uterus and fallopian tubes develop from the paramesonephric ducts (Mullerian ducts). These are a pair of passageways along the outside of the urogenital region that fuse and mature to become the uterus, fallopian tubes, cervix and upper third of the vagina. Errors in their development lead to congenital structural abnormalities in the female pelvic organs. In a male fetus, anti-Mullerian hormone is produced, which suppresses the growth of the paramesonephric ducts, causing them to disappear.

Answer 162

A bicornuate uterus is where there are two “horns” to the uterus, giving the uterus a heart-shaped appearance. It can be diagnosed on a pelvic ultrasound scan. A bicornuate uterus may be associated with adverse pregnancy outcomes. However, successful pregnancies are generally expected. In most cases, no specific management is required. Typical complications include: -Miscarriage -Premature birth -Malpresentation

Answer 163

Imperforate hymen is where the hymen at the entrance of the vagina is fully formed, without an opening. Imperforate hymen may be discovered when the girl starts to menstruate, and the menses are sealed in the vagina. This causes cyclical pelvic pain and cramping that would ordinarily be associated with menstruation, but without any vaginal bleeding. An imperforate hymen can be diagnosed during a clinical examination. Treatment is with surgical incision to create an opening in the hymen. Theoretically, if an imperforate hymen is not treated retrograde menstruation could occur leading to endometriosis.

Answer 164

Transverse vaginal septae is caused by an error in development, where a septum (wall) forms transversely across the vagina. This septum can either be perforate (with a hole) or imperforate (completely sealed). Where it is perforate, girls will still menstruate, but can have difficulty with intercourse or tampon use. Where it is imperforate, it will present similarly to an imperforate hymen with cyclical pelvic symptoms without menstruation. Vaginal septae can lead to infertility and pregnancy-related complications. Diagnosis is by examination, ultrasound or MRI. Treatment is with surgical correction. The main complications of surgery are vaginal stenosis and recurrence of the septae.

Answer 165

Vaginal hypoplasia refers to an abnormally small vagina. Vaginal agenesis refers to an absent vagina. These occur due to failure of the Mullerian ducts to properly develop, and may be associated with an absent uterus and cervix. The ovaries are usually unaffected, leading to normal female sex hormones. The exception to this is with androgen insensitivity syndrome, where there are testes rather than ovaries. Management may involve the use of a vaginal dilator over a prolonged period to create an adequate vaginal size. Alternatively, vaginal surgery may be necessary.

Answer 166

Androgen insensitivity syndrome is a condition where cells are unable to respond to androgen hormones due to a lack of androgen receptors. It is an X-linked recessive genetic condition, caused by a mutation in the androgen receptor gene on the X chromosome. Extra androgens are converted into oestrogen, resulting in female secondary sexual characteristics. It was previously known as testicular feminisation syndrome. Patients with androgen insensitivity syndrome are genetically male, with XY sex chromosome. However, the absent response to testosterone and the conversion of additional androgens to oestrogen result in a female phenotype externally. Typical male sexual characteristics do not develop, and patients have normal female external genitalia and breast tissue. Patients have testes in the abdomen or inguinal canal, and absence of a uterus, upper vagina, cervix, fallopian tubes and ovaries. The female internal organs do not develop because the testes produce anti-Müllerian hormone, which prevents males from developing an upper vagina, uterus, cervix and fallopian tubes. The insensitivity to androgens also results in a lack of pubic hair, facial hair and male type muscle development. Patients tend to be slightly taller than the female average. Patients are infertile, and there is an increased risk of testicular cancer unless the testes are removed. There is also a condition called partial androgen insensitivity syndrome, where there the cells have a partial response to androgens. This presents with more ambiguous signs and symptoms, such as a micropenis or clitoromegaly, bifid scrotum, hypospadias and diminished male characteristics.

Answer 167

Androgen insensitivity syndrome often presents in infancy with inguinal hernias containing testes. Alternatively, it presents at puberty with primary amenorrhoea. The results of hormone tests are: -Raised LH -Normal or raised FSH -Normal or raised testosterone levels (for a male) -Raised oestrogen levels (for a male)

Answer 168

Management is coordinated by a specialist MDT, involving paediatrics, gynaecology, urology, endocrinology and clinical psychology. Medical input involves: -Bilateral orchidectomy (removal of the testes) to avoid testicular tumours -Oestrogen therapy -Vaginal dilators or vaginal surgery can be used to create an adequate vaginal length Generally, patients are raised as female, but this is sensitive and tailored to the individual. They are offered support and counselling to help them understand the condition and promote their psychological, social and sexual wellbeing.

Answer 169

Cancer of the cervix tends to affect younger women, peaking in the reproductive years. -80% of cervical cancers are squamous cell carcinoma. -Adenocarcinoma is the next most common type. -Very rarely there are other types, such as small cell cancer. Cervical cancer is strongly associated with human papillomavirus. Children aged 12 – 13 years are vaccinated against certain strains of HPV to reduce the risk of cervical cancer. Cervical screening with smear tests is used to screen for precancerous and cancerous changes to the cells of the cervix. Early detection of precancerous changes enables prompt treatment to prevent the development of cervical cancer.

Answer 170

The most common cause of cervical cancer is infection with human papillomavirus (HPV). HPV is also associated with anal, vulval, vaginal, penis, mouth and throat cancers. HPV is primarily a sexually transmitted infection. There are over 100 strains of HPV. The important ones to remember are type 16 and 18, as they are responsible for around 70% of cervical cancers and also the strains targeted with the HPV vaccine. There is no treatment for infection with HPV. Most cases resolve spontaneously within two years, while some will persist. P53 and pRb are tumour suppressor genes. They have a role in suppressing cancers from developing. HPV produces two proteins (E6 and E7) that inhibit these tumour suppressor genes. The E6 protein inhibits p53, and the E7 protein inhibits pRb. Therefore, HPV promotes the development of cancer by inhibiting tumour suppressor genes.

Answer 171

You can think of the risk factors for cervical cancer in terms of: 1. Increased risk of catching HPV 2. Later detection of precancerous and cancerous changes (non-engagement with screening) 3. Other risk factors 1. Increased risk of catching HPV occurs with: -Early sexual activity -Increased number of sexual partners -Sexual partners who have had more partners -Not using condoms 2. Non-engagement with cervical screening is a significant risk factor. Many cases of cervical cancer are preventable with early detection and treatment of precancerous changes. 3. Other risk factors are: - Smoking - HIV (patients with HIV are offered yearly smear tests) - Combined contraceptive pill use for more than five years - Increased number of full-term pregnancies - Family history - Exposure to diethylstilbestrol during fetal development (this was previously used to prevent miscarriages before 1971)

Answer 172

Cervical cancer may be detected during cervical smears in otherwise asymptomatic women. The presenting symptoms that should make you consider cervical cancer as a differential are: - Abnormal vaginal bleeding (intermenstrual, postcoital or post-menopausal bleeding) - Vaginal discharge - Pelvic pain - Dyspareunia (pain or discomfort with sex) These symptoms are non-specific, and in most cases, not caused by cervical cancer. The next step is to examine the cervix with a speculum. During examination, swabs can be taken to exclude infection. Where there is an abnormal appearance of the cervix suggestive of cancer, an urgent cancer referral for colposcopy should be made to assess further. Appearances that may suggest cervical cancer are: -Ulceration -Inflammation -Bleeding -Visible tumour The result of cervical screening should not be used to exclude cervical cancer where it is suspected for another reason, even if the smear result was normal.

Answer 173

Cervical intraepithelial neoplasia (CIN) is a grading system for the level of dysplasia (premalignant change) in the cells of the cervix. CIN is diagnosed at colposcopy (not with cervical screening - different to dyskaryosis). The grades are: CIN 1: mild dysplasia, affecting 1/3 the thickness of the epithelial layer, likely to return to normal without treatment CIN 2: moderate dysplasia, affecting 2/3 the thickness of the epithelial layer, likely to progress to cancer if untreated CIN 3: severe dysplasia, very likely to progress to cancer if untreated. This is sometimes called cervical carcinoma in situ.

Answer 174

Screening for cervical cancer aims to pick up precancerous changes in the epithelial cells of the cervix. It involves a cervical smear test, performed by a qualified person, often a practice nurse. The test consists of a speculum examination and collection of cells from the cervix using a small brush. The cells are deposited from the brush into a preservation fluid. This fluid is transported to a lab where the cells are examined under a microscope for precancerous changes (dyskaryosis). This way of transporting the cells is called liquid-based cytology. The samples are initially tested for high-risk HPV before the cells are examined. If the HPV test is negative (the person does not have HPV), the cells are not examined, the smear is considered negative, and the woman is returned to the routine screening program.

Answer 175

The cervical screening program involves performing a smear for women (and transgender men that still have a cervix): - Every three years aged 25 – 49 - Every five years aged 50 – 64 There are some notable exceptions to the program: -Women with HIV are screened annually -Women over 65 may request a smear if they have not had one since aged 50 -Women with previous CIN may require additional tests (e.g. test of cure after treatment) -Certain groups of immunocompromised women may have additional screening (e.g. women on dialysis, cytotoxic drugs or undergoing an organ transplant) -Pregnant women due a routine smear should wait until 12 weeks post-partum

Answer 176

Cytology results: 1. Inadequate 2. Normal 3. Borderline changes 4. Low-grade dyskaryosis 5. High-grade dyskaryosis (moderate) 6. High-grade dyskaryosis (severe) 7. Possible invasive squamous cell carcinoma 8. Possible glandular neoplasia Infections such as bacterial vaginosis, candidiasis and trichomoniasis may be identified and reported on the smear result. Actinomyces-like organisms are often discovered in women with an intrauterine device (coil). These do not require treatment unless they are symptomatic. Where the woman is symptomatic (e.g. pelvic pain or abnormal bleeding), removal of the intrauterine device may be considered. A summary of the management of smear results is: 1. Inadequate sample – repeat the smear after at least three months 2. HPV negative – continue routine screening 3. HPV positive with normal cytology – repeat the HPV test after 12 months 4. HPV positive with abnormal cytology – refer for colposcopy

Answer 177

A specialist performs colposcopy. It involves inserting a speculum and using equipment (a colposcope) to magnify the cervix. This allows the epithelial lining of the cervix to be examined in detail. During colposcopy, stains such as acetic acid and iodine solution can be used to differentiate abnormal areas. - Acetic acid causes abnormal cells to appear white. This appearance is described as acetowhite. This occurs in cells with an increased nuclear to cytoplasmic ratio (more nuclear material), such as cervical intraepithelial neoplasia and cervical cancer cells. - Schiller’s iodine test involves using an iodine solution to stain the cells of the cervix. Iodine will stain healthy cells a brown colour. Abnormal areas will not stain. A punch biopsy or large loop excision of the transformational zone can be performed during the colposcopy procedure to get a tissue sample. 1. Large Loop Excision of the Transformation Zone (LLETZ) procedure is also called a loop biopsy. It can be performed with a local anaesthetic during a colposcopy procedure. It involves using a loop of wire with electrical current (diathermy) to remove abnormal epithelial tissue on the cervix. The electrical current cauterises the tissue and stops bleeding. Bleeding and abnormal discharge can occur for several weeks following a LLETZ procedure. This varies between women. Intercourse and tampon use should be avoided after the procedure to reduce the risk of infection. Depending on the depth of the tissue removed from the cervix, the procedure may increase the risk of preterm labour. 2. Cone Biopsy is a treatment for cervical intraepithelial neoplasia (CIN) and very early-stage cervical cancer. It involves a general anaesthetic. The surgeon removes a cone-shaped piece of the cervix using a scalpel. This sample is sent for histology to assess for malignancy. The main risks of a cone biopsy are: -Pain -Bleeding -Infection -Scar formation with stenosis of the cervix -Increased risk of miscarriage and premature labour

Answer 178

Stage 1: Confined to the cervix. A = <5mm, B= 5mm-4cm Stage 2: Invades the uterus (2B) or upper 2/3 of the vagina (2A). Stage 3: Invades the pelvic wall (3B) or lower 1/3 of the vagina (3A) Stage 4: Invades the bladder, rectum or beyond the pelvis

Answer 179

Management of cervical cancer depends on the stage and the individual situation. The usual treatments are: 1. Cervical intraepithelial neoplasia and early-stage 1A: LLETZ or cone biopsy 2. Stage 1B – 2A: Radical hysterectomy and removal of local lymph nodes with chemotherapy and radiotherapy 3. Stage 2B – 4A: Chemotherapy and radiotherapy 4. Stage 4B: Management may involve a combination of surgery, radiotherapy, chemotherapy and palliative care The 5-year survival drops significantly with more advanced cervical cancer, from around 98% with stage 1A to around 15% with stage 4. Early detection makes a significant difference, which is one reason the screening program is so valuable and important. - Pelvic exenteration is an operation that may be used in advanced cervical cancer. It involves removing most or all of the pelvic organs, including the vagina, cervix, uterus, fallopian tubes, ovaries, bladder and rectum. It is a vast operation and has significant implications on quality of life. - Bevacizumab (Avastin) is a monoclonal antibody that may be used in combination with other chemotherapies in the treatment of metastatic or recurrent cervical cancer. It is also used in several other types of cancer. It targets vascular endothelial growth factor A (VEGF-A), which is responsible for the development of new blood vessels. Therefore, it reduces the development of new blood vessels. You may also come across this medication as a treatment for wet age-related macular degeneration, where it is injected directly into the patient eye to stop new blood vessels forming on the retina.

Answer 180

The HPV vaccine is ideally given to girls and boys before they become sexually active. The intention is to prevent them contracting and spreading HPV once they become sexually active. The current NHS vaccine is Gardasil, which protects against strains 6, 11, 16 and 18: -Strains 6 and 11 cause genital warts -Strains 16 and 18 cause cervical cancer

Answer 181

Endometrial cancer is cancer of the endometrium, the lining of the uterus. Around 80% of cases are adenocarcinoma. It is an oestrogen-dependent cancer, meaning that oestrogen stimulates the growth of endometrial cancer cells.

Answer 182

Endometrial hyperplasia is a precancerous condition involving thickening of the endometrium. The risk factors, presentation and investigations of endometrial hyperplasia are similar to endometrial cancer. Most cases of endometrial hyperplasia will return to normal over time. Less than 5% go on to become endometrial cancer. There are two types of endometrial hyperplasia to be aware of: -Hyperplasia without atypia -Atypical hyperplasia Endometrial hyperplasia may be treated by a specialist using progestogens, with either: - Intrauterine system (e.g. Mirena coil) - Continuous oral progestogens (e.g. medroxyprogesterone or levonorgestrel)

Answer 183

You can think of the risk factors for endometrial cancer in relation to the patient’s exposure to unopposed oestrogen. Unopposed oestrogen refers to oestrogen without progesterone. Unopposed oestrogen stimulates the endometrial cells and increases the risk of endometrial hyperplasia and cancer. The risk of endometrial cancer is associated with the amount of unopposed oestrogen the endometrium is exposed to during the patient’s life. Situations where there is increased exposure of unopposed oestrogen are: - Increased age - Earlier onset of menstruation - Late menopause - Oestrogen only hormone replacement therapy - No or fewer pregnancies - Obesity: a crucial risk factor because adipose tissue is the primary source of oestrogen in postmenopausal women. Adipose tissue contains aromatase, which is an enzyme that converts androgens such as testosterone into oestrogen. Androgens are produced mainly by the adrenal glands. In women with more adipose tissue, and therefore more aromatase enzyme, more of these androgens are converted to oestrogen. This extra oestrogen is unopposed in women that are not ovulating. - Polycystic ovarian syndrome: PCOS leads to increased exposure to unopposed oestrogen due to a lack of ovulation. Women with PCOS are less likely to ovulate and form a corpus luteum. Without developing a corpus luteum during the menstrual cycle, progesterone is not produced, and the endometrial lining has more exposure to unopposed oestrogen. For endometrial protection, women with PCOS should have one of: *The combined contraceptive pill *An intrauterine system (e.g. Mirena coil) *Cyclical progestogens to induce a withdrawal bleed. -Tamoxifen: has an anti-oestrogenic effect on breast tissue, but an oestrogenic effect on the endometrium. This increase the risk of endometrial cancer. Additional risk factors not related to unopposed oestrogen are: - Type 2 diabetes: may increase the risk of endometrial cancer due to the increased production of insulin. Insulin may stimulate the endometrial cells and increase the risk of endometrial hyperplasia and cancer. PCOS is also associated with insulin resistance and increased insulin production. Insulin resistance further adds to the risk of endometrial cancer in women with PCOS. - Hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome

Answer 184

Protective factors against endometrial cancer include: -Combined contraceptive pill -Mirena coil -Increased pregnancies -Cigarette smoking: Smoking appears to be protective against endometrial cancer in postmenopausal women by being anti-oestrogenic. Interestingly, it is not protective against other oestrogen dependent cancers, such as breast cancer (where it increases the risk). Smoking may have anti-oestrogenic effects in several ways: - Oestrogen may be metabolised differently in smokers - Smokers tend to be leaner, meaning they have less adipose tissue and aromatase enzyme - Smoking destroys oocytes (eggs), resulting in an earlier menopause

Answer 185

The number one presenting symptom of endometrial cancer to remember for your exams is postmenopausal bleeding. Any woman presenting with postmenopausal bleeding has endometrial cancer until proven otherwise Endometrial cancer may also present with: -Postcoital bleeding -Intermenstrual bleeding -Unusually heavy menstrual bleeding -Abnormal vaginal discharge -Haematuria -Anaemia -Raised platelet count

Answer 186

The referral criteria for a 2-week-wait urgent cancer referral for endometrial cancer is: - Postmenopausal bleeding (more than 12 months after the last menstrual period) NICE also recommends referral for a transvaginal ultrasound in women over 55 years with: - Unexplained vaginal discharge - Visible haematuria plus raised platelets, anaemia or elevated glucose levels

Answer 187

There are three investigations to remember for diagnosing and excluding endometrial cancer: 1. Transvaginal ultrasound for endometrial thickness (normal is less than 4mm post-menopause) 2. Pipelle biopsy, which is highly sensitive for endometrial cancer making it useful for excluding cancer: can be taken in the outpatient clinic. It involves a speculum examination and inserting a thin tube (pipelle) through the cervix into the uterus. This small tube fills with a sample of endometrial tissue that can be examined for signs of endometrial hyperplasia or cancer. Pipelle biopsy is a quicker and less invasive alternative to hysteroscopy for excluding cancer in lower-risk women. 3. Hysteroscopy with endometrial biopsy Depending on local guidelines, a normal transvaginal ultrasound (endometrial thickness < 4mm) and normal pipelle biopsy are sufficient to demonstrate a very low risk of endometrial cancer and discharge the patient.

Answer 188

Stage 1: Confined to the uterus Stage 2: Invades the cervix Stage 3: Invades the ovaries, fallopian tubes, vagina or lymph nodes Stage 4: Invades bladder, rectum or beyond the pelvis

Answer 189

The usual treatment for stage 1 and 2 endometrial cancer is a total abdominal hysterectomy with bilateral salpingo-oophorectomy, also known as a TAH and BSO (removal of uterus, cervix and adnexa). Other treatment options depending on the individual presentation include: -A radical hysterectomy involves also removing the pelvic lymph nodes, surrounding tissues and top of the vagina -Radiotherapy -Chemotherapy -Progesterone may be used as a hormonal treatment to slow the progression of the cancer

Answer 190

1. Epithelial Cell Tumours (tumours arising from the epithelial cells of the ovary) are the most common type. Subtypes of epithelial cell tumours include: -Serous tumours (the most common) -Endometrioid carcinomas -Clear cell tumours -Mucinous tumours -Undifferentiated tumours 2. Dermoid Cysts / Germ Cell Tumours: These are benign ovarian tumours. They are teratomas, meaning they come from the germ cells. They may contain various tissue types, such as skin, teeth, hair and bone. They are particularly associated with ovarian torsion. Germ cell tumours may cause raised alpha-fetoprotein (α-FP) and human chorionic gonadotrophin (hCG). 3. Sex Cord-Stromal Tumours: These are rare tumours, that can be benign or malignant. They arise from the stroma (connective tissue) or sex cords (embryonic structures associated with the follicles). There are several types, including Sertoli–Leydig cell tumours and granulosa cell tumours. 4. Metastases: Ovarian tumours may be due to metastasis from a cancer elsewhere. A Krukenberg tumour refers to a metastasis in the ovary, usually from a gastrointestinal tract cancer, particularly the stomach. Krukenberg tumours have characteristic “signet-ring” cells on histology, which look like signet rings on under a microscopy.

Answer 191

Risk factors -Age (peaks age 60) -BRCA1 and BRCA2 genes (consider the family history) -Increased number of ovulations eg Early-onset of periods, Late menopause or No pregnancies -Obesity -Smoking -Recurrent use of clomifene Protective Factors Factors that stop ovulation or reduce the number of lifetime ovulations, reduce the risk: -Combined contraceptive pill -Breastfeeding -Pregnancy

Answer 192

Ovarian cancer often presents late due to the non-specific symptoms, resulting in a worse prognosis. More than 70% of patients with ovarian cancer present after it has spread beyond the pelvis. In older women, keep the possibility of ovarian cancer in mind and have a low threshold for considering further investigations. Symptoms that may indicate ovarian cancer include: -Abdominal bloating -Early satiety (feeling full after eating) -Loss of appetite -Pelvic pain -Urinary symptoms (frequency / urgency) -Weight loss -Abdominal or pelvic mass -Ascites An ovarian mass may press on the obturator nerve and cause referred hip or groin pain. The obturator nerve passes along the inside of the pelvic, lateral to the ovaries, where an ovarian mass can compress it.

Answer 193

Refer directly on a 2-week-wait referral if a physical examination reveals: -Ascites -Pelvic mass (unless clearly due to fibroids) -Abdominal mass Carry out further investigations before referral in women presenting with symptoms of possible ovarian cancer, starting with a CA125 blood test. This is particularly important in women over 50 years presenting with: -New symptoms of IBS / change in bowel habit -Abdominal bloating -Early satiety -Pelvic pain -Urinary frequency or urgency -Weight loss

Answer 194

The initial investigations in primary or secondary care are: - CA125 blood test (>35 IU/mL is significant) -Pelvic ultrasound The risk of malignancy index (RMI) estimates the risk of an ovarian mass being malignant, taking account of three things: -Menopausal status -Ultrasound findings -CA125 level Further investigations in secondary care include: -CT scan to establish the diagnosis and stage the cancer -Histology (tissue sample) using a CT guided biopsy, laparoscopy or laparotomy -Paracentesis (ascitic tap) can be used to test the ascitic fluid for cancer cells Women under 40 years with a complex ovarian mass require tumour markers for a possible germ cell tumour: -Alpha-fetoprotein (α-FP) -Human chorionic gonadotropin (HCG)

Answer 195

Stage 1: Confined to the ovary Stage 2: Spread past the ovary but inside the pelvis Stage 3: Spread past the pelvis but inside the abdomen Stage 4: Spread outside the abdomen (distant metastasis) Ovarian cancer will be managed by a specialist gynaecology oncology MDT. It usually involves a combination of surgery and chemotherapy.

Answer 196

Vulval cancer is rare compared with other gynaecological cancers. Around 90% are squamous cell carcinomas. Less commonly, they can be malignant melanomas.

Answer 197

-Advanced age (particularly over 75 years) -Immunosuppression -Human papillomavirus (HPV) infection -Lichen sclerosus -Around 5% of women with lichen sclerosus get vulval cancer.

Answer 198

Vulval intraepithelial neoplasia (VIN) is a premalignant condition affecting the squamous epithelium of the skin that can precede vulval cancer. - High grade squamous intraepithelial lesion is a type of VIN associated with HPV infection that typically occurs in younger women aged 35 – 50 years. - Differentiated VIN is an alternative type of VIN associated with lichen sclerosus and typically occurs in older women (aged 50 – 60 years). A biopsy is required to diagnose VIN. A specialist will coordinate management. Treatment options include: -Watch and wait with close followup -Wide local excision (surgery) to remove the lesion -Imiquimod cream -Laser ablation

Answer 199

Vulval cancer may be an incidental finding in older women, for example, during catheterisation in a patient with dementia. Vulval cancer may present with symptoms of: -Vulval lump -Ulceration -Bleeding -Pain -Itching -Lymphadenopathy in the groin Vulval cancer most frequently affects the labia majora, giving an appearance of: -Irregular mass -Fungating lesion -Ulceration -Bleeding

Answer 200

Suspected vulval cancer should be referred on a 2-week-wait urgent cancer referral. Establishing the diagnosis and staging involves: -Biopsy of the lesion -Sentinel node biopsy to demonstrate lymph node spread -Further imaging for staging (e.g. CT abdomen and pelvis) Management depends on the stage, and may involve: -Wide local excision to remove the cancer -Groin lymph node dissection -Chemotherapy -Radiotherapy

Answer 201

Bacterial vaginosis (BV) refers to an overgrowth of bacteria in the vagina, specifically anaerobic bacteria. It is not a sexually transmitted infection. It is caused by a loss of the lactobacilli “friendly bacteria” in the vagina. Bacterial vaginosis can increase the risk of women developing sexually transmitted infections. Lactobacilli are the main component of the healthy vaginal bacterial flora. These bacteria produce lactic acid that keeps the vaginal pH low (under 4.5). The acidic environment prevents other bacteria from overgrowing. When there are reduced numbers of lactobacilli in the vagina, the pH rises. This more alkaline environment enables anaerobic bacteria to multiply. Examples of anaerobic bacteria associated with bacterial vaginosis are: -Gardnerella vaginalis (most common) -Mycoplasma hominis -Prevotella species It is worth remembering that bacterial vaginosis can occur alongside other infections, including candidiasis, chlamydia and gonorrhoea.

Answer 202

There are a number of factors that increase the risk of developing bacterial vaginosis: -Multiple sexual partners (although it is not sexually transmitted) -Excessive vaginal cleaning (douching, use of cleaning products and vaginal washes) - Recent antibiotics -Smoking -Copper coil -Bacterial vaginosis occurs less frequently in women taking the combined pill or using condoms effectively.

Answer 203

The standard presenting feature of bacterial vaginosis is a fishy-smelling watery grey or white vaginal discharge. Half of women with BV are asymptomatic. Itching, irritation and pain are not typically associated with BV and suggest an alternative cause or co-occurring infection. A speculum examination can be performed to confirm the typical discharge, complete a high vaginal swab and exclude other causes of symptoms. Examination is not always required where the symptoms are typical, and the women is low risk of sexually transmitted infections.

Answer 204

Vaginal pH can be tested using a swab and pH paper. The normal vaginal pH is 3.5 – 4.5. BV occurs with a pH above 4.5. A standard charcoal vaginal swab can be taken for microscopy. This can be a high vaginal swab taken during a speculum examination or a self-taken low vaginal swab. Bacterial vaginosis gives “clue cells” on microscopy. Clue cells are epithelial cells from the cervix that have bacteria stuck inside them, usually Gardnerella vaginalis.

Answer 205

Asymptomatic BV does not usually require treatment. Additionally, it may resolve without treatment. - Metronidazole is the antibiotic of choice for treating bacterial vaginosis. Metronidazole specifically targets anaerobic bacteria. This is given orally, or by vaginal gel. -Clindamycin is an alternative but less optimal antibiotic choice. -Always assess the risk of additional pelvic infections, with swabs for chlamydia and gonorrhoea where appropriate. -Provide advice and information about measures that can reduce the risk of further episodes of bacterial vaginosis, such as avoiding vaginal irrigation or cleaning with soaps that may disrupt the natural flora. (Whenever prescribing metronidazole advise patients to avoid alcohol for the duration of treatment. Alcohol and metronidazole can cause a “disulfiram-like reaction”, with nausea and vomiting, flushing and sometimes severe symptoms of shock and angioedema.)

Answer 206

Bacterial vaginosis can increase the risk of catching sexually transmitted infections, including chlamydia, gonorrhoea and HIV. It is also associated with several complications in pregnant women: -Miscarriage -Preterm delivery -Premature rupture of membranes -Chorioamnionitis -Low birth weight -Postpartum endometritis

Answer 207

Vaginal candidiasis is commonly referred to as “thrush”. It refers to vaginal infection with a yeast of the Candida family. The most common is Candida albicans. Candida may colonise the vagina without causing symptoms. It then progresses to infection when the right environment occurs, for example, during pregnancy or after treatment with broad-spectrum antibiotics that alter the vaginal flora.

Answer 208

*Increased oestrogen (higher in pregnancy, lower pre-puberty and post-menopause) *Poorly controlled diabetes *Immunosuppression (e.g. using corticosteroids) *Broad-spectrum antibiotics

Answer 209

The symptoms of vaginal candidiasis are: - Thick, white discharge that does not typically smell - Vulval and vaginal itching, irritation or discomfort More severe infection can lead to: -Erythema -Fissures -Oedema -Pain during sex (dyspareunia) -Dysuria -Excoriation

Answer 210

Often treatment for candidiasis is started empirically, based on the presentation. Testing the vaginal pH using a swab and pH paper can be helpful in differentiating between bacterial vaginosis and trichomonas (pH > 4.5) and candidiasis (pH < 4.5). A high-vaginal charcoal swab with microscopy can confirm the diagnosis.

Answer 211

Treatment of candidiasis is with antifungal medications. These can be delivered in several ways: -Antifungal cream (i.e. clotrimazole) inserted into the vagina with an applicator -Antifungal pessary (i.e. clotrimazole) -Oral antifungal tablets (i.e. fluconazole) Canesten Duo is a standard over-the-counter treatment worth knowing. It contains a single fluconazole tablet and clotrimazole cream to use externally for vulval symptoms. Recurrent infections (more than 4 in a year) can be treated with an induction and maintenance regime over six months with oral or vaginal antifungal medications. This is an off-label use. Warn women that antifungal creams and pessaries can damage latex condoms and prevent spermicides from working, so alternative contraceptive is required for at least five days after use.

Answer 212

Chlamydia trachomatis is a gram-negative bacteria. It is an intracellular organism, meaning it enters and replicates within cells before rupturing the cell and spreading to others. Chlamydia is the most common sexually transmitted infection in the UK and a significant cause of infertility. Being young, sexually active and having multiple partners increase the risk of catching the infection. A large number of cases are asymptomatic (50% in men and 75% in woman). Asymptomatic patients can still pass the infection on.

Answer 213

Public Health England has set out a National Chlamydia Screening Programme (NCSP). This program aims to screen every sexually active person under 25 years of age for chlamydia annually or when they change their sexual partner. Everyone that tests positive should have a re-test three months after treatment. This re-testing is to ensure they have not contracted chlamydia again, rather than to check the treatment has worked. In general, when a patient attends a GUM clinic for STI screening, as a minimum, they are tested for: -Chlamydia -Gonorrhoea -Syphilis (blood test) -HIV (blood test)

Answer 214

There are two types of swabs involved in sexual health testing: 1. Charcoal swabs Charcoal swabs allow for microscopy (looking at the sample under the microscope), culture (growing the organism) and sensitivities (testing which antibiotics are effective against the bacteria). Charcoal swabs look like a long cotton bud that goes into a tube with a black transport medium at the end. The transport medium is called Amies transport medium, and contains a chemical solution for keeping microorganisms alive during transport. - Microscopy involves gram staining and examination under a microscope. A stain is used to highlight different types of bacteria with different colours. Charcoal swabs can be used for endocervical swabs and high vaginal swabs (HVS). Charcoal swabs can confirm: -Bacterial vaginosis -Candidiasis -Gonorrhoeae (specifically endocervical swab) -Trichomonas vaginalis (specifically a swab from the posterior fornix) -Other bacteria, such as group B streptococcus (GBS) 2. Nucleic acid amplification test (NAAT) swabs NAAT checks directly for the DNA or RNA of the organism. NAAT testing is used to test specifically for chlamydia and gonorrhoea. They are not useful for other pelvic infections (except where specifically testing for Mycoplasma genitalium). In women, a NAAT test can be performed on a vulvovaginal swab (a self-taken lower vaginal swab), an endocervical swab or a first-catch urine sample. The order of preference is endocervical, vulvovaginal, and then urine. In men, a NAAT test can be performed on a first-catch urine sample or a urethral swab. It is worth noting that the NAAT swabs will specify on the packet whether the swabs are for endocervical, vulvovaginal or urethral use. A specific kit is used for first-catch urine NAAT testing. Rectal and pharyngeal NAAT swabs can also be taken to diagnose chlamydia in the rectum and throat. Consider these swabs where anal or oral sex has occurred. Where gonorrhoea is suspected or demonstrated on a NAAT test, an endocervical charcoal swab is required for microscopy, culture and sensitivities.

Answer 215

The majority of cases of chlamydia in women are asymptomatic. Consider chlamydia in women that are sexually active and present with: -Abnormal vaginal discharge -Pelvic pain -Abnormal vaginal bleeding (intermenstrual or postcoital) -Painful sex (dyspareunia) -Painful urination (dysuria) Consider chlamydia in men that are sexually active and present with: -Urethral discharge or discomfort -Painful urination (dysuria) -Epididymo-orchitis -Reactive arthritis It is worth considering rectal chlamydia and lymphogranuloma venereum in patients presenting with anorectal symptoms, such as discomfort, discharge, bleeding and change in bowel habits.

Answer 216

Examination findings: -Pelvic or abdominal tenderness -Cervical motion tenderness (cervical excitation) -Inflamed cervix (cervicitis) -Purulent discharge Diagnosis Nucleic acid amplification tests (NAAT) are used to diagnose chlamydia. This can involve a: -Vulvovaginal swab -Endocervical swab -First-catch urine sample (in women or men) -Urethral swab in men -Rectal swab (after anal sex) -Pharyngeal swab (after oral sex)

Answer 217

First-line for uncomplicated chlamydia infection is doxycycline 100mg twice a day for 7 days. Doxycycline is contraindicated in pregnancy and breastfeeding. Alternatives options in pregnant or breastfeeding women are: -Azithromycin 1g stat then 500mg once a day for 2 days -Erythromycin 500mg four times daily for 7 days or Erythromycin 500mg twice daily for 14 days -Amoxicillin 500mg three times daily for 7 days A test of cure is not routinely recommended. However, a test of cure should be used for rectal cases of chlamydia, in pregnancy and where symptoms persist. Other factors to consider are: - Abstain from sex for seven days of treatment of all partners to reduce the risk of re-infection - Refer all patients to genitourinary medicine (GUM) for contact tracing and notification of sexual partners - Test for and treat any other sexually transmitted infections - Provide advice about ways to prevent future infection - Consider safeguarding issues and sexual abuse in children and young people (The guidelines previously recommended a single dose of azithromycin 1g orally as an alternative. This recommendation has been removed due to Mycoplasma genitalium resistance to azithromycin, and azithromycin being less effective for rectal chlamydia infection.)

Answer 218

There are a large number of complications from infection with chlamydia: -Pelvic inflammatory disease -Chronic pelvic pain -Infertility -Ectopic pregnancy -Epididymo-orchitis -Conjunctivitis -Lymphogranuloma venereum -Reactive arthritis Pregnancy-related complications include: -Preterm delivery -Premature rupture of membranes -Low birth weight -Postpartum endometritis -Neonatal infection (conjunctivitis and pneumonia)

Answer 219

Lymphogranuloma venereum (LGV) is a condition affecting the lymphoid tissue around the site of infection with chlamydia. It most commonly occurs in men who have sex with men (MSM). LGV occurs in three stages: 1. The primary stage involves a painless ulcer (primary lesion). This typically occurs on the penis in men, vaginal wall in women or rectum after anal sex. 2. The secondary stage involves lymphadenitis. This is swelling, inflammation and pain in the lymph nodes infected with the bacteria. The inguinal or femoral lymph nodes may be affected. 3. The tertiary stage involves inflammation of the rectum (proctitis) and anus. Proctocolitis leads to anal pain, change in bowel habit, tenesmus and discharge. Tenesmus is a feeling of needing to empty the bowels, even after completing a bowel motion. Doxycycline 100mg twice daily for 21 days is the first-line treatment for LGV. Erythromycin, azithromycin and ofloxacin are alternatives.

Answer 220

Chlamydia can infect the conjunctiva of the eye. Conjunctival infection is usually as a result of sexual activity, when genital fluid comes in contact with the eye, for example, through hand-to-eye spread. It presents with chronic erythema, irritation and discharge lasting more than two weeks. Most cases are unilateral. Chlamydial conjunctivitis occurs more frequently in young adults. It can also affect neonates with mothers infected with chlamydia. Gonococcal conjunctivitis is a crucial differential diagnosis and should be tested.

Answer 221

Neisseria gonorrhoeae is a gram-negative diplococcus bacteria. It infects mucous membranes with a columnar epithelium, such as the endocervix in women, urethra, rectum, conjunctiva and pharynx. It spreads via contact with mucous secretions from infected areas. Gonorrhoea is a sexually transmitted infection. Being young, sexually active and having multiple partners increases the risk of infection with gonorrhoea. Having other sexually transmitted infections, such as chlamydia or HIV, also increases the risk. There is a high level of antibiotic resistance to gonorrhoea. Traditionally ciprofloxacin or azithromycin was used to treat gonorrhoea. However, there are now high levels of resistance to these antibiotics.

Answer 222

Infection with gonorrhoea is more likely to be symptomatic than infection with chlamydia. 90% of men and 50% of women are symptomatic. The presentation will vary depending on the site. Female genital infections can present with: -Odourless purulent discharge, possibly green or yellow -Dysuria -Pelvic pain Male genital infections can present with: -Odourless purulent discharge, possibly green or yellow -Dysuria -Testicular pain or swelling (epididymo-orchitis) Rectal infection may cause anal or rectal discomfort and discharge, but is often asymptomatic. Pharyngeal infection may cause a sore throat, but is often asymptomatic. Prostatitis causes perineal pain, urinary symptoms and prostate tenderness on examination. Conjunctivitis causes erythema and a purulent discharge.

Answer 223

Nucleic acid amplification testing (NAAT) is used to detect the RNA or DNA of gonorrhoea. Genital infection can be diagnosed with endocervical, vulvovaginal or urethral swabs, or in a first-catch urine sample. Rectal and pharyngeal swab are recommended in all men who have sex with men (MSM), and in those with risk factors (e.g. anal and oral sex) or symptoms of infection in these areas. A standard charcoal endocervical swab should be taken for microscopy, culture and antibiotic sensitivities before initiating antibiotics. This is particularly important given the high rates of antibiotic resistance. ( NAAT swabs do not provide any information about the specific bacteria and their antibiotic sensitivities and resistance. This is why a standard charcoal swab for microscopy, culture and sensitivities is so essential, to guide the choice of antibiotics to use in treatment.)

Answer 224

Patients should be referred to GUM clinics (or local equivalent) to coordinate testing, treatment and contact tracing. Management depends on whether antibiotic sensitivities are known. For uncomplicated gonococcal infections: - A single dose of intramuscular ceftriaxone 1g if the sensitivities are NOT known - A single dose of oral ciprofloxacin 500mg if the sensitivities ARE known Different regimes are recommended for complicated infections, infections in other sites and pregnant women. Most regimes involve a single dose of intramuscular ceftriaxone. All patients should have a follow-up “test of cure” given the high antibiotic resistance. This is with NAAT testing if they are asymptomatic, or cultures where they are symptomatic. BASHH recommend a test of cure at least: -72 hours after treatment for culture -7 days after treatment for RNA NAAT -14 days after treatment for DNA NAAT Other factors to consider are: -Abstain from sex for seven days of treatment of all partners to reduce the risk of re-infection -Test for and treat any other sexually transmitted infections -Provide advice about ways to prevent future infection -Consider safeguarding issues and sexual abuse in children and young people

Answer 225

-Pelvic inflammatory disease -Chronic pelvic pain -Infertility -Epididymo-orchitis (men) -Prostatitis (men) -Conjunctivitis -Urethral strictures -Disseminated gonococcal infection -Skin lesions -Fitz-Hugh-Curtis syndrome (when PID causes swelling of the tissue around the liver) -Septic arthritis -Endocarditis A key complication to remember is gonococcal conjunctivitis in a neonate. Gonococcal infection is contracted from the mother during birth. Neonatal conjunctivitis is called ophthalmia neonatorum. This is a medical emergency and is associated with sepsis, perforation of the eye and blindness.

Answer 226

Disseminated gonococcal infection (GDI) is a complication of untreated gonococcal infection, where the bacteria spreads to the skin and joints. It causes: -Various non-specific skin lesions -Polyarthralgia (joint aches and pains) -Migratory polyarthritis (arthritis that moves between joints) -Tenosynovitis -Systemic symptoms such as fever and fatigue

Answer 227

Mycoplasma genitalium (MG) is a bacteria that causes non-gonococcal urethritis. It is a sexually transmitted infection. There are developing problems with antibiotic resistance, particularly with azithromycin. Most cases of MG do not cause symptoms. The presentation is very similar to chlamydia, and patients may be infected with both organisms. Urethritis is a key feature. Mycoplasma genitalium infection may lead to: -Urethritis -Epididymitis -Cervicitis -Endometritis -Pelvic inflammatory disease -Reactive arthritis -Preterm delivery in pregnancy -Tubal infertility (blockage of fallopian tubes)

Answer 228

Traditional cultures are not helpful in isolating MG, as it is a very slow-growing organism. Therefore, testing involves nucleic acid amplification tests (NAAT) to look specifically for the DNA or RNA if the bacteria. The samples recommended are: -First urine sample in the morning for men -Vaginal swabs (can be self-taken) for women The guideline recommends checking every positive sample for macrolide resistance, and performing a “test of cure” after treatment in every positive patient.

Answer 229

The BASHH guidelines (2018) recommend a course of doxycycline followed by azithromycin for uncomplicated genital infections: -Doxycycline 100mg twice daily for 7 days then; -Azithromycin 1g stat then 500mg once a day for 2 days (unless it is known to be resistant to macrolides) Moxifloxacin is used as an alternative or in complicated infections. Azithromycin alone is used in pregnancy and breastfeeding (remember doxycycline is contraindicated).

Answer 230

Pelvic inflammatory disease (PID) is inflammation and infection of the organs of the pelvis, caused by infection spreading up through the cervix. It is a significant cause of tubular infertility and chronic pelvic pain. It is worth remembering the technical terms for the affected organs: -Endometritis is inflammation of the endometrium -Salpingitis is inflammation of the fallopian tubes -Oophoritis is inflammation of the ovaries -Parametritis is inflammation of the parametrium, which is the connective tissue around the uterus -Peritonitis is inflammation of the peritoneal membrane

Answer 231

Most cases of pelvic inflammatory disease are caused by one of the sexually transmitted pelvic infections: -Neisseria gonorrhoeae tends to produce more severe PID -Chlamydia trachomatis -Mycoplasma genitalium Pelvic inflammatory disease can less commonly be caused by non-sexually transmitted infections, such as: -Gardnerella vaginalis (associated with bacterial vaginosis) -Haemophilus influenzae (a bacteria often associated with respiratory infections) -Escherichia coli (an enteric bacteria commonly associated with urinary tract infections)

Answer 232

There risk factors for pelvic inflammatory disease are the same as any other sexually transmitted infection: - Not using barrier contraception - Multiple sexual partners - Younger age - Existing sexually transmitted infections - Previous pelvic inflammatory disease - Intrauterine device (e.g. copper coil)

Answer 233

Women may present with symptoms of: -Pelvic or lower abdominal pain -Abnormal vaginal discharge -Abnormal bleeding (intermenstrual or postcoital) -Pain during sex (dyspareunia) -Fever -Dysuria Examination findings may reveal: -Pelvic tenderness -Cervical motion tenderness (cervical excitation) -Inflamed cervix (cervicitis) -Purulent discharge -Patients may have a fever and other signs of sepsis.

Answer 234

Patients with pelvic inflammatory disease should have testing for causative organisms and other sexually transmitted infections: -NAAT swabs for gonorrhoea and chlamydia -NAAT swabs for Mycoplasma genitalium if available -HIV test -Syphilis test -A high vaginal swab can be used to look for bacterial vaginosis, candidiasis and trichomoniasis. A microscope can be used to look for pus cells on swabs from the vagina or endocervix. The absence of pus cells is useful for excluding PID. A pregnancy test should be performed on sexually active women presenting with lower abdominal pain to exclude an ectopic pregnancy. Inflammatory markers (CRP and ESR) are raised in PID and can help support the diagnosis.

Answer 235

Where appropriate patients should be referred to a genitourinary medicine (GUM) specialist service for management and contact tracing. Antibiotics are started empirically, before swab results are obtained, to avoid a delay and complications. One suggested outpatient regime (listed here to help your understanding and not as a guide to treatment) is: -A single dose of intramuscular ceftriaxone 1g (to cover gonorrhoea) -Doxycycline 100mg twice daily for 14 days (to cover chlamydia and Mycoplasma genitalium) -Metronidazole 400mg twice daily for 14 days (to cover anaerobes such as Gardnerella vaginalis) -Ceftriaxone and doxycycline will cover many other bacteria, including H. influenzae and E. coli. More severe cases, particularly where there are signs of sepsis or the patient is pregnant, require admission to hospital for IV antibiotics. Where a pelvic abscess develops, this may need drainage by interventional radiology or surgery.

Answer 236

-Sepsis -Abscess -Infertility -Chronic pelvic pain -Ectopic pregnancy -Fitz-Hugh-Curtis syndrome

Answer 237

Fitz-Hugh-Curtis syndrome is a complication of pelvic inflammatory disease. It is caused by inflammation and infection of the liver capsule (Glisson’s capsule), leading to adhesions between the liver and peritoneum. Bacteria may spread from the pelvis via the peritoneal cavity, lymphatic system or blood. Fitz-Hugh-Curtis syndrome results in right upper quadrant pain that can be referred to the right shoulder tip if there is diaphragmatic irritation. Laparoscopy can be used to visualise and also treat the adhesions by adhesiolysis.

Answer 238

Trichomonas vaginalis is a type of parasite spread through sexual intercourse. Trichomonas is classed as a protozoan, and is a single-celled organism with flagella. Flagella are appendages stretching from the body, similar to limbs. Trichomonas has four flagella at the front and a single flagellum at the back, giving a characteristic appearance to the organism. The flagella are used for movement, attaching to tissues and causing damage. Trichomonas is spread through sexual activity and lives in the urethra of men and women and the vagina of women. Trichomonas can increase the risk of: - Contracting HIV by damaging the vaginal mucosa - Bacterial vaginosis - Cervical cancer - Pelvic inflammatory disease - Pregnancy-related complications such as preterm delivery.

Answer 239

Up to 50% of cases of trichomoniasis are asymptomatic. When symptoms occur, they are non-specific: -Vaginal discharge -Itching -Dysuria (painful urination) -Dyspareunia (painful sex) -Balanitis (inflammation to the glans penis) -The typical description of the vaginal discharge is frothy and yellow-green, although this can vary significantly. It may have a fishy smell. Examination of the cervix can reveal a characteristic “strawberry cervix” (also called colpitis macularis). A strawberry cervix is caused by inflammation (cervicitis) relating to the trichomonas infection. There are tiny haemorrhages across the surface of the cervix, giving the appearance of a strawberry. Testing the vaginal pH will reveal a raised ph (above 4.5), similar to bacterial vaginosis.

Answer 240

The diagnosis can be confirmed with a standard charcoal swab with microscopy (examination under a microscope). Swabs should be taken from the posterior fornix of the vagina (behind the cervix) in women. A self-taken low vaginal swab may be used as an alternative. A urethral swab or first-catch urine is used in men.

Answer 241

Patients should be referred to a genitourinary medicine (GUM) specialist service for diagnosis, treatment and contact tracing. Treatment is with metronidazole.

Answer 242

The herpes simplex virus (HSV) is commonly responsible for both cold sores (herpes labialis) and genital herpes. There are two main strains, HSV-1 and HSV-2. Both strains are common in the UK, and many people are infected without experiencing any symptoms. After an initial infection, the virus becomes latent in the associated sensory nerve ganglia. Typically this is the trigeminal nerve ganglion with cold sores and the sacral nerve ganglia with genital herpes. The herpes simplex virus can also cause aphthous ulcers (small painful oral sores in the mouth), herpes keratitis (inflammation of the cornea in the eye) and herpetic whitlow (a painful skin lesion on a finger or thumb). The herpes simplex virus is spread through direct contact with affected mucous membranes or viral shedding in mucous secretions. The virus can be shed even when no symptoms are present, meaning it can be contracted from asymptomatic individuals. Asymptomatic shedding is more common in the first 12 months of infection and where recurrent symptoms are present. 1. HSV-1 is most associated with cold sores. It is often contracted initially in childhood (before five years), remains dormant in the trigeminal nerve ganglion and reactivates as cold sores, particularly in times of stress. Genital herpes caused by HSV-1 is usually contracted through oro-genital sex, where the virus spreads from a person with an oral infection to the person that develops a genital infection. 2. HSV-2 typically causes genital herpes and is mostly a sexually transmitted infection. It can also cause lesions in the mouth.

Answer 243

Ask about sexual contacts, including those with cold sores, to establish a possible source of transmission. They may have caught the infection from someone unaware they are infected and not experiencing any symptoms. The diagnosis can be made clinically based on the history and examination findings. A viral PCR swab from a lesion can confirm the diagnosis and causative organism.

Answer 244

Where appropriate, patients should be referred to a genitourinary medicine (GUM) specialist service. Aciclovir is used to treat genital herpes. There are various aciclovir regimes listed in the BNF, depending on the individual circumstances. Alternatives are valaciclovir and famciclovir. Additional measures, including to manage the symptoms include: -Paracetamol -Topical lidocaine 2% gel (e.g. Instillagel) -Cleaning with warm salt water -Topical vaseline -Additional oral fluids -Wear loose clothing -Avoid intercourse with symptoms

Answer 245

The main issue with genital herpes during pregnancy is the risk of neonatal herpes simplex infection contracted during labour and delivery. Neonatal herpes simplex infection has high morbidity and mortality. Neonatal infection should be avoided as much as possible and treated early if identified. After an initial infection with genital herpes, the woman will develop antibodies to the virus. During pregnancy, these antibodies can cross the placenta into the fetus. This gives the fetus passive immunity to the virus, and protects the baby during labour and delivery. Management of genital herpes in pregnancy depends on whether it is the first episode of genital herpes (primary infection) or recurrent genital herpes. Aciclovir is not known to be harmful in pregnancy. 1. Primary genital herpes contracted before 28 weeks gestation is treated with aciclovir during the initial infection. This is followed by regular prophylactic aciclovir starting from 36 weeks gestation onwards to reduce the risk of genital lesions during labour and delivery. Women that are asymptomatic at delivery can have a vaginal delivery (provided it is more than six weeks after the initial infection). Caesarean section is recommended when symptoms are present. 2. Primary genital herpes contracted after 28 weeks gestation is treated with aciclovir during the initial infection followed immediately by regular prophylactic aciclovir. Caesarean section is recommended in all cases to reduce the risk of neonatal infection. 3. Recurrent genital herpes in pregnancy, where the woman is known to have genital herpes before the pregnancy, carries a low risk of neonatal infection (0-3%), even if the lesions are present during delivery. Regular prophylactic aciclovir is considered from 36 weeks gestation to reduce the risk of symptoms at the time of delivery.

Answer 246

HIV is an RNA retrovirus. HIV-1 is the most common type. HIV-2 is mainly found in West Africa. The virus enters and destroys the CD4 T-helper cells of the immune system. An initial seroconversion flu-like illness occurs within a few weeks of infection. The infection is then asymptomatic until the condition progresses to immunodeficiency. Disease progression may occur years after the initial infection.

Answer 247

HIV is not transmitted through day-to-day activities, including kissing. It is spread through: - Unprotected anal, vaginal or oral sexual activity - Mother to child at any stage of pregnancy, birth or breastfeeding (called vertical transmission) - Mucous membrane, blood or open wound exposure to infected blood or bodily fluids (e.g., sharing needles, needle-stick injuries or blood splashed in an eye)

Answer 248

There is a long list of AIDS-defining illnesses associated with end-stage HIV infection. These occur where the CD4 count has dropped to a level that allows for unusual opportunistic infections and malignancies to appear. Examples of AIDS-defining illnesses include: -Kaposi’s sarcoma -Pneumocystis jirovecii pneumonia (PCP) -Cytomegalovirus infection -Candidiasis (oesophageal or bronchial) -Lymphomas -Tuberculosis

Answer 249

The fourth-generation laboratory test for HIV checks for antibodies to HIV and the p24 antigen. It has a window period of 45 days, meaning it can take up to 45 days after exposure to the virus for the test to turn positive. A negative result within 45 days of exposure is unreliable. More than 45 days after exposure, a negative result is reliable. Point-of-care tests for HIV antibodies give a result within minutes. They have a 90-day window period. Patients at risk of HIV can request home testing kits, either: -Self-sampling kits to be posted to the lab (fourth-generation tests for antibodies and the p24 antigen) -Point-of-care tests (antibodies only)

Answer 250

Specialist HIV, infectious disease or GUM centres manage patients with HIV. Treatment involves a combination of antiretroviral therapy (ART) medications. ART is offered to everyone diagnosed with HIV, irrespective of viral load or CD4 count. Some regimes involve only a single combination tablet, taken once daily, with the potential to suppress the infection completely. Genotypic resistance testing can establish the resistance of each HIV strain to different medications to help guide treatment. There are several classes of antiretroviral therapy medications: -Protease inhibitors (PI) -Integrase inhibitors (II) -Nucleoside reverse transcriptase inhibitors (NRTI) -Non-nucleoside reverse transcriptase inhibitors (NNRTI) -Entry inhibitors (EI) The usual starting regime is two NRTIs (e.g., tenofovir plus emtricitabine) plus a third agent (e.g., bictegravir). Treatment aims to achieve a normal CD4 count and undetectable viral load. Generally, when a patient has a normal CD4 and an undetectable viral load on ART, physical health problems (e.g., routine chest infections) are treated the same as those without HIV. When prescribing for patients on ART, be aware and carefully check for any medication interactions

Answer 251

Prophylactic co-trimoxazole is given to all HIV positive patients with a CD4 count under 200/mm3 to protect against pneumocystis jirovecii pneumonia (PCP). HIV infection increases the risk of developing cardiovascular disease. Patients with HIV have close monitoring of cardiovascular risk factors, such as blood lipids. Interventions to reduce the risk (e.g., statins) may be recommended. Yearly cervical smears are recommended in HIV as it increases the risk of human papillomavirus (HPV) infection and cervical cancer. Vaccinations should be up to date, including against influenza (yearly), pneumococcal, HPV and hepatitis A and B. Live vaccines (e.g., BCG and typhoid) are avoided.

Answer 252

The mother’s viral load will determine the mode of delivery: 1. Under 50 copies/ml = Normal vaginal delivery 2. Over 50 copies/ml = Consider a pre-labour caesarean section 3. Over 400 copies/ml = Pre-labour caesarean section is recommended IV zidovudine is given as an infusion during labour and delivery if the viral load is unknown or above 1000 copies/ml. Prophylaxis may be given to the baby, depending on the mother’s viral load: 1. Low-risk babies (mother’s viral load is under 50 copies per ml) are given zidovudine for 2-4 weeks 2. High-risk babies are given zidovudine, lamivudine and nevirapine for four weeks

Answer 253

HIV can be transmitted during breastfeeding. The risk is reduced if the mother’s viral load is undetectable but not eliminated. Therefore, the safest option is to avoid breastfeeding. However, if the mother is adamant and the viral load is undetectable, sometimes it is attempted with close monitoring by the HIV team.

Answer 254

Post-exposure prophylaxis (PEP) can be used after exposure to reduce the risk of transmission. PEP is not 100% effective and must be commenced within a short window of opportunity (less than 72 hours). The sooner it is started, the better. A risk assessment of the probability of developing HIV should be balanced against the side effects of PEP. PEP involves a combination of ART therapy. The current regime is emtricitabine/ tenofovir (Truvada) and raltegravir for 28 days. Pre-exposure prophylaxis (PrEP) is also available to take before exposure to reduce the risk of transmission. The usual choice is emtricitabine/tenofovir (Truvada).

Answer 255

Syphilis is caused by bacteria called Treponema pallidum. This bacteria is a spirochete, a type of spiral-shaped bacteria. The bacteria gets in through skin or mucous membranes, replicates and then disseminates throughout the body. It is mainly a sexually transmitted infection. The incubation period between the initial infection and symptoms is 21 days on average.

Answer 256

Syphilis can also be contracted through: - Oral, vaginal or anal sex involving direct contact with an infected area - Vertical transmission from mother to baby during pregnancy - Intravenous drug use - Blood transfusions and other transplants (although this is rare due to screening of blood products)

Answer 257

1. Primary syphilis involves a painless ulcer called a chancre at the original site of infection (usually on the genitals). 2. Secondary syphilis involves systemic symptoms, particularly of the skin and mucous membranes. These symptoms can resolve after 3 – 12 weeks and the patient can enter the latent stage. 3. Latent syphilis occurs after the secondary stage of syphilis, where symptoms disappear and the patient becomes asymptomatic despite still being infected. Early latent syphilis occurs within two years of the initial infection, and late latent syphilis occurs from two years after the initial infection onwards. 4. Tertiary syphilis can occur many years after the initial infection and affect many organs of the body, particularly with the development of gummas and cardiovascular and neurological complications. Neurosyphilis occurs if the infection involves the central nervous system, presenting with neurological symptoms.

Answer 258

Primary syphilis can present with: -A painless genital ulcer (chancre). This tends to resolve over 3 – 8 weeks. -Local lymphadenopathy Secondary syphilis typically starts after the chancre has healed, with symptoms of: -Maculopapular rash -Condylomata lata (grey wart-like lesions around the genitals and anus) -Low-grade fever -Lymphadenopathy -Alopecia (localised hair loss) -Oral lesions Tertiary syphilis can present with several symptoms depending on the affected organs. Key features to be aware of are: -Gummatous lesions (gummas are granulomatous lesions that can affect the skin, organs and bones) -Aortic aneurysms -Neurosyphilis: can occur at any stage if the infection reaches the central nervous system, and present with symptoms of: *Headache *Altered behaviour *Dementia *Tabes dorsalis (demyelination affecting the spinal cord posterior columns) *Ocular syphilis (affecting the eyes) *Paralysis *Sensory impairment Argyll-Robertson pupil is a specific finding in neurosyphilis. It is a constricted pupil that accommodates when focusing on a near object but does not react to light. They are often irregularly shaped. It is commonly called a “prostitutes pupil” due to the relation to neurosyphilis and because “it accommodates but does not react“.

Answer 259

Antibody testing for antibodies to the T. pallidum bacteria can be used as a screening test for syphilis. Patients with suspected syphilis or positive antibodies should be referred to a specialist GUM centre for further testing. Samples from sites of infection can be tested to confirm the presence of T. pallidum with: -Dark field microscopy -Polymerase chain reaction (PCR) -The rapid plasma reagin (RPR) and venereal disease research laboratory (VDRL) tests are two non-specific but sensitive tests used to assess for active syphilis infection. These tests assess the quantity of antibodies being produced by the body to an infection with syphilis. A higher number indicates a greater chance of active disease. These tests involve introducing a sample of serum to a solution containing antigens and assessing the reaction. A more significant reaction suggests a higher quantity of antibodies. The tests are non-specific, meaning they often produce false-positive results. There is a skill to both performing and interpreting the results of these tests.

Answer 260

All patients should be managed and followed up by a specialist service, such as GUM. As with all sexually transmitted infections, patients need: -Full screening for other STIs -Advice about avoiding sexual activity until treated -Contact tracing -Prevention of future infections A single deep intramuscular dose of benzathine benzylpenicillin (penicillin) is the standard treatment for syphilis. Alternative regimes and types of penicillin are used in different scenarios, for example, late syphilis and neurosyphilis. Ceftriaxone, amoxicillin and doxycycline are alternatives.

Answer 261

An endometrial polyp represents the extreme end of macroscopic hyperplasia of the endometrium when tissue grows so fast that parts of the endometrium are pushed into the cavity of the uterus. They may be a cause of menorrhagia and of post menopausal bleeding. All endometrial tissue must be examined histologically because of the association with endometrial carcinoma.