Physiology + Gynaecology & Genitourinary Flashcards
What are the hormones of the hypothalamic-pituitary-gonadal axis?
The hypothalamus releases gonadotrophin-releasing hormone (GnRH). GnRH stimulates the anterior pituitary to produce luteinising hormone (LH) and follicle-stimulating hormone (FSH).
LH and FSH stimulate the development of follicles in the ovaries. The theca granulosa cells around the follicles secrete oestrogen. Oestrogen has a negative feedback effect on the hypothalamus and anterior pituitary to suppress the release of GnRH, LH and FSH.
What type of hormone is oestrogen and what are its functions?
Oestrogen is a steroid sex hormone produced by the ovaries in response to LH and FSH. The most prevalent and active version is 17-beta oestradiol. It acts on tissues with oestrogen receptors to promote female secondary sexual characteristics.
It stimulates:
- Breast tissue development
- Growth and development of the female sex organs (vulva, vagina and uterus) at puberty
- Blood vessel development in the uterus
- Development of the endometrium
What type of hormone is Progesterone and what are its functions?
Progesterone is a steroid sex hormone produced by the corpus luteum after ovulation. When pregnancy occurs, progesterone is produced mainly by the placenta from 10 weeks gestation onwards. Progesterone acts on tissues that have previously been stimulated by oestrogen.
Progesterone acts to:
- Thicken and maintain the endometrium
- Thicken the cervical mucus
- Increase the body temperature
What changes occur in female puberty? What are the hormonal changes?
In childhood, girls have relatively little GnRH, LH, FSH, oestrogen and progesterone in their system. During puberty, these hormones start to increase sequentially, causing the development of female secondary sexual characteristics, the onset of the menstrual cycle and the ability to conceive children.
Puberty starts age 8 – 14 in girls and 9 – 15 in boys. It takes about 4 years from start to finish. Girls have their pubertal growth spurt earlier in puberty than boys.
In girls, puberty starts with the development of breast buds, followed by pubic hair and finally the onset of menstrual periods. The first episode of menstruation is called menarche. Menstrual periods usually begin about two years from the start of puberty.
Growth hormone (GH) increases initially, causing a spurt in growth during the initial phases of puberty.
The hypothalamus starts to secrete GnRH, initially during sleep, then throughout the day in the later stages of puberty. GnRH stimulates the release of FSH and LH from the pituitary gland. FSH and LH stimulate the ovaries to produce oestrogen and progesterone. FSH levels plateau about a year before menarche. LH levels continue to rise, and spike just before they induce menarche.
What factors may speed up or delay puberty in females?
Overweight children tend to enter puberty at an earlier age. Aromatase is an enzyme found in adipose (fat) tissue, that is important in the creation of oestrogen. Therefore, the more adipose tissue present, the higher the quantity of the enzyme responsible for oestrogen creation.
There may be delayed puberty in girls with low birth weight, chronic disease or eating disorders, or athletes.
What are the tanner stages of puberty for females?
Stage 1:
Under 10
No pubic hair
No Breast Development
Stage 2:
10 – 11
Light and thin hair
Breast buds form behind the areola
Stage 3:
11 – 13
Coarse and curly
Breast begins to elevate beyond the areola
Stage 4:
13 – 14
Adult like but not reaching the thigh
Areolar mound forms and projects from surrounding breast
Stage 5:
Above 14
Hair extending to the medial thigh
Areolar mounds reduce, and adult breasts form
What are the 2 phases of the menstrual cycle and when do they occur?
The menstrual cycle consists of two phases: the follicular phase and the luteal phase.
The follicular phase is from the start of menstruation to the moment of ovulation (the first 14 days in a 28-day cycle). The luteal phase is from the moment of ovulation to the start of menstruation (the final 14 days of the cycle).
How do follices mature in the ovaries, when independent of the menstrual cycle?
From puberty, the ovaries have a finite number of cells that have the potential to develop into eggs. These cells are called oocytes. Granulosa cells surround the oocytes, forming structures called follicles.
Follicles go through four key stages of development in the ovaries:
1. Primordial follicles
2. Primary follicles
3. Secondary follicles
4. Antral follicles (also known as Graafian follicles)
The process of primordial follicles maturing into primary and secondary follicles is always occurring, independent of the menstrual cycle. Once the follicles reach the secondary follicle stage, they develop the receptors for follicle stimulating hormone (FSH). Further development after the secondary follicle stage requires stimulation from FSH.
What changes occur during the follicular phase 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 oestradiol (oestrogen). The oestradiol has a negative feedback effect on the pituitary gland, reducing the quantity of LH and FSH produced. The rising oestrogen also causes the cervical mucus to become more permeable, allowing sperm to penetrate the cervix around the time of ovulation.
One of the follicles will develop further than the others and become the dominant follicle. Luteinising hormone (LH) spikes just before ovulation, causing the dominant follicle to release the ovum (an unfertilised egg) from the ovary. Ovulation happens 14 days before the end of the menstrual cycle, for example, day 14 of a 28-day cycle, or day 16 of a 30-day cycle.
What changes occur during the luteal phase of the menstrual cycle?
After ovulation, the follicle that released the ovum collapses and becomes the corpus luteum. The corpus luteum secretes high levels of progesterone, which maintains the endometrial lining. This progesterone also causes the cervical mucus to become thick and no longer penetrable. The corpus luteum also secretes a small amount of oestrogen.
When fertilisation occurs, the syncytiotrophoblast of the embryo secretes human chorionic gonadotrophin (HCG). HCG maintains the corpus luteum. Without hCG, the corpus luteum degenerates. Pregnancy tests check for hCG to confirm a pregnancy.
When there is no fertilisation of the ovum, and no production of hCG, the corpus luteum degenerates and stops producing oestrogen and progesterone. This fall in oestrogen and progesterone causes the endometrium to break down and menstruation to occur. Additionally, the stromal cells of the endometrium release prostaglandins. Prostaglandins encourage the endometrium to break down and the uterus to contract. Menstruation starts on day 1 of the menstrual cycle. The negative feedback from oestrogen and progesterone on the hypothalamus and pituitary gland ceases, allowing the levels of LH and FSH to begin to rise, and the cycle to restart.
What is the structure of a primordial follicle? What do they contain?
Primordial follicles each contain a primary oocyte. The oocytes are the germ cells (first generation of sex cell) that eventually undergo meiosis to become the mature ovum, ready for fertilisation. They contain the full 46 chromosomes. These primordial follicles and oocytes spend the majority of their lives in a resting state inside the ovaries, waiting for their time to develop. The primary oocyte is contained within the pregranulosa cells, surrounded by the outer basal lamina layer.
How do primordial follicles develop into primary follicles?
Primordial follicles grow and become primary follicles. These primary follicles have three layers:
1. The primary oocyte in the centre
2. The zona pellucida
3. The cuboidal shaped granulosa cells - secrete the material that becomes the zona pellucida. They also secrete oestrogen.
As the follicles grow larger, they develop a further surrounding layer called the theca folliculi. The inner layer of the theca folliculi is called the theca interna. The theca interna secretes androgen hormones. The outer layer, called the theca externa, is made up of connective tissue cells containing smooth muscle and collagen.
How do primary follicles develop into secondary follicles?
As primary follicles become secondary follicles, they grow larger and develop small fluid-filled gaps between the granulosa cells. Once the follicles reach the secondary follicle stage, they have receptors for follicle stimulating hormone (FSH). Further development after the secondary follicle stage requires stimulation from FSH. At the start of the menstrual cycle, FSH stimulates further development of the secondary follicles.
How do secondary follicles develop into antral follicles?
With further development, the secondary follicle develops a single large fluid-filled area within the granulosa cells called the antrum. Antrum refers to a natural chamber within a structure. This is the antral follicle stage. This antrum fills with increasing amounts of fluid, making the follicle expand rapidly. The corona radiata is made of granulosa cells, and surrounds the zona pellucida and the oocyte.
At this point, one of the follicles becomes the dominant follicle. The other follicles start to degrade, while the dominant follicle grows to become a mature follicle. This follicle bulges through the wall of the ovary.
How does ovulation occur?
When there is a surge of luteinising hormone (LH) from the pituitary, it causes the smooth muscle of the theca externa to squeeze, and the follicle to burst. Follicular cells also release digestive enzymes that puncture a hole in the wall of the ovary, allowing the ovum to pass escape. The oocyte is released into the area surrounding the ovary. At this point, it is floating in the peritoneal cavity, but it is quickly swept up by the fimbriae of the fallopian tubes.
How is a corpus luteum formed?
Following ovulation, the leftover parts of the antral follicle collapse and turn a yellow colour. The collapsed follicle becomes the corpus luteum. The cells of the granulosa and theca interna become luteal cells. Luteal cells secrete steroid hormones, most notably progesterone.
The corpus luteum persists in response to human chorionic gonadotropin (HCG) from a fertilised blastocyst when pregnancy occurs. When fertilisation does not occur, the corpus luteum degenerates after 10 to 14 days.
What change occurs to the primary oocyte around the time of ovulation?
Just before and around the time of ovulation, the primary oocyte undergoes meiosis. This process splits the full 46 chromosomes in the oocyte (a diploid cell) into two, leaving only 23 chromosomes (a haploid cell). The other 23 chromosomes float off to the side and become something called a polar body. It is then a secondary oocyte.
The female egg (ovum) at this stage still has the surrounding layers from its time in the follicle. In the middle is the oocyte with the first polar body, surrounded by the zona pellucida and the granulosa cells that make up the corona radiata.
How does fertilisation occur?
When sperm from the male enters the fallopian tube via the vagina and uterus, they will attempt to penetrate the corona radiata and zona pellucida to fertilise the egg. Usually, only one sperm will get through before the surrounding layers shut the other sperm out.
When a sperm enters the egg, the 23 chromosomes of the egg multiply into two sets. One set of 23 chromosomes combine with the 23 chromosomes from the sperm to form a diploid set of 46 chromosomes, and the other set of 23 chromosomes float off to the side and create the second polar body.
How does a blastocyst develop from a fertilised egg?
The combination of the 23 chromosomes from the egg and 23 chromosomes from the sperm combine to form a fertilised cell called a zygote. This cell divides rapidly to create a mass of cells called the morula. During this process, the mass of cells travels along the fallopian tube toward the uterus.
While travelling, a fluid-filled cavity gathers within the group of cells, and it becomes a blastocyst. The blastocyst contains the main group of cells in the middle, called the embryoblast. Alongside the embryoblast is a fluid-filled cavity called the blastocele. Surrounding the embryoblast and the blastocele is an outer layer of cells called the trophoblast. At this point, it gradually loses the corona radiata and zona pellucida. When the blastocyst enters the uterus, it contains 100-150 cells.
How does the blastocyst implant into the endometrium?
When the blastocyst arrives at the uterus, 8 – 10 days after ovulation, it reaches the endometrium. The cells of the trophoblast (the outer layer of the blastocyst) undergo adhesion to the stroma (supportive outer tissue) of the endometrium. The outer layer of the trophoblast is called the syncytiotrophoblast. This layer forms projections into the stroma. The cells of the syncytiotrophoblast mix with the cells of the endometrium (stroma).
The cells of the stroma convert into a tissue called decidua that is specialised in providing nutrients to the trophoblast. When the blastocyst implants on the endometrium, the syncytiotrophoblast starts to produce human chorionic gonadotropin (HCG). This HCG is very important for maintaining the corpus luteum in the ovary, allowing it to continue producing progesterone and oestrogen.
How does a blastocyst develop into an embryo?
A week after fertilisation, the implanted blastocyst starts to differentiate into various types of cell. The cells of the embryoblast split in two, with the yolk sac on one side and the amniotic cavity on the other. The embryonic disc sits between the yolk sac and the amniotic cavity. The cells of the embryonic disc develop into the fetal pole, and eventually into the fetus.
The chorion surrounds this complex. The chorion has two layers: the cytotrophoblast and the syncytiotrophoblast. The cytotrophoblast is the inner layer and the syncytiotrophoblast is the outer layer, which is embedded in the endometrium.
Over a short time, a space called the chorionic cavity forms around the yolk sac, embryonic disc and amniotic sac. These structures are suspended from the chorion by the connecting stalk, which will eventually become the umbilical cord.
At around five weeks gestation, the embryonic disc develops into a fetal pole containing three layers: the ectoderm (outer layer), mesoderm (middle layer) and endoderm (inner layer). These three layers go on to become all the different tissues of the body.
What tissues do the endoderm, mesoderm and ectoderm go on to develop?
Endoderm:
-GI tract
-Lungs
-Liver
-Pancreas
-Thyroid
-Reproductive system
Mesoderm:
-Heart
-Muscle
-Bone
-Connective tissue
-Blood
-Kidneys
Ectoderm:
-Skin
-Hair
-Nails
-Teeth
-CNS
How and when does the embryo develop into a foetus?
At around six weeks gestation, the fetal heart forms and starts to beat. The spinal cord and muscles also begin to develop. The embryo (fetal pole) is about 4mm in length.
At around eight weeks gestation, all the major organs have started to develop. From this point onwards the fetus matures and grows until birth.
How does the endometrium develop during the follicular phase?
During the follicular phase of the menstrual cycle, the endometrium thickens and gets ready for a fertilised egg to arrive. The myometrium sends off artery branches into the endometrium. Initially, these arteries grow straight outwards like plant shoots. As they continue to grow, they coil into a spiral. These thick-walled and coiled arteries are bunched together, making the endometrial tissue highly vascular. These are known as the spiral arteries.
How do the placenta and umbilical cord develop?
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.
How do the lacunae develop?
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.
What are the 5 functions of the placenta?
- 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. - 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. - 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. - 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. - 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.
What hormonal changes occur during pregnancy?
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.
What changes occur to the uterus, cervix and vagina during pregnancy?
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.
What cardiovascular and respiratory changes occur during pregnancy?
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.
What renal changes occur during pregnancy?
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)
What haematological and biochemical changes occur during pregnancy?
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
What skin and hair changes may occur during pregnancy?
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.
What are the 3 stages of labour?
- The first stage is from the onset of labour (true contractions) until 10cm cervical dilatation.
- The second stage is from 10cm cervical dilatation to delivery of the baby.
- The third stage is from delivery of the baby to delivery of the placenta.
What are the functions of prostaglandins in labour and delivery?
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.
What are Braxton-Hicks contractions?
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.
What happens during the first stage of labour?
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.
What happens during the second stage of labour? What factors does successful delivery depend on?
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.
- Power: the strength of the uterine contractions.
- 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
- Passage: the size and shape of the passageway, mainly the pelvis.
What are the 7 cardinal movements of labour?
- Engagement
- 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 - Flexion
- Internal Rotation
- Extension
- Restitution and external rotation
- Expulsion
What happens during the third stage of labour and delivery? What is the difference between active and physiological management?
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.
What are the two types of amenorrhoea and their possible causes?
- 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 - 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
What are the possible causes of irregular menstruation?
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
What are the possible causes of intermenstrual bleeding?
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
What are the possible causes of dysmenorrhoea?
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
What are the possible causes of menorrhagia?
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
What are the possible causes of postcoital bleeding?
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
What are the possible causes of pelvic pain?
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)
What are the possible causes of excessive, discoloured or foul-smelling discharge?
-Bacterial vaginosis
-Candidiasis (thrush)
-Chlamydia
-Gonorrhoea
-Trichomonas vaginalis
-Foreign body
-Cervical ectropion
-Polyps
-Malignancy
-Pregnancy
-Ovulation (cyclical)
-Hormonal contraception
What are the possible causes of pruritis vulvae?
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
What is the definition of primary amenorrhoea?
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
What are the types of hypogonadism?
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)
What is hypogonadotropic hypogonadism and what are the possible causes?
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
What is hypergonadotropic hypogonadism and what are the possible causes?
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)
What is Kallman’s syndrome?
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).
What is congenital adrenal hyperplasia? What are the typical features in females?
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
What is androgen insensitivity syndrome?
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.
Which structural pathologies can cause primary amenorrhoea?
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
How is primary amenorrhoea assessed? When should investigations be initiated and what might they be?
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
How is primary amenorrhoea managed?
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.
What is the definition of secondary amenorrhoea?
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.
What are the possible causes of secondary amenorrhoea?
-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
How does hyperprolactinaemia affect the menstrual cycle? What are the possible causes and treatments?
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.
How is secondary amenorrhoea assessed and investigated?
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.
How is secondary amenorrhoea managed?
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.
What is the complication of amenorrhoea?
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
What is premenstrual syndrome and what is the causes?
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.
What are the presenting features of premenstrual syndrome? What is premenstrual dysphoric disorder?
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.
How is premenstrual syndrome diagnosed?
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.
How is premenstrual syndrome managed?
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.
What is the definition of menorrhagia?
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.
What are the possible causes of menorrhagia?
-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
How is menorrhagia investigated?
- 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.
- Full blood count should be performed in all women with heavy menstrual bleeding, to look for iron deficiency anaemia.
- Outpatient hysteroscopy should be arranged if there is:
- Suspected submucosal fibroids
- Suspected endometrial pathology, such as endometrial hyperplasia or cancer
- Persistent intermenstrual bleeding - 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
How is menorrhagia treated?
- 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.
- 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).
- 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).
- 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.
What are uterine leiomyomas (fibroids) and what are the types?
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.
What are the presenting features of fibroids (uterine leiomyomas)?
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.
How are fibroids (uterine leiomyomas) investigated?
- 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.
How are fibroids (uterine leiomyomas) medically managed?
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.
How are fibroids (uterine leiomyomas) surgically managed?
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
What are the potential complications of fibroids (uterine leiomyomas)?
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%)
What is red degeneration of fibroids?
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.
What is the difference between an endometrioma, a chocolate cyst and adenomysosis?
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.
What are the potential aetiologies of endometriosis?
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.
What are the presenting features of endometriosis?
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
What is the pathophysiology of endometriosis symptoms?
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.
How is endometriosis diagnosed?
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.
How is endometriosis managed?
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.
What is adenomysosis?
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.
What are the presenting features of adenomyosis?
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.
How is adenomyosis diagnosed?
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.
How is adenomyosis managed?
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
What are the obstetric implications of adenomysosis?
Adenomyosis is associated with:
- Infertility
- Miscarriage
- Preterm birth
- Small for gestational age
- Preterm premature rupture of membranes
- Malpresentation
- Need for caesarean section
- Postpartum haemorrhage
What is menopause? What are the differences between Menopause, Postmenopause and Perimenopause? When is menopause premature?
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
- Menopause is the point at which menstruation stops.
- Postmenopause describes the period from 12 months after the final menstrual period onwards.
- 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.
What is the physiology of menopause?
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.
What are the perimenopausal symptoms?
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
What are the risks associated with menopause?
A lack of oestrogen increases the risk of certain conditions:
- Cardiovascular disease and stroke
- Osteoporosis
- Pelvic organ prolapse
- Urinary incontinence
How is menopause diagnosed?
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
When should contraception be continued in menopausal women? Which options are best?
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.
How can the perimenopausal symptoms be managed?
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
What is premature ovarian insufficiency?
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
What are the causes of premature ovarian insufficiency?
- 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
What are the presenting features of premature ovarian insufficiency?
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.
How is premature ovarian insufficiency diagnosed?
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.
What are the associated risks with premature ovarian insufficiency?
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
How is premature ovarian insufficiency managed?
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)
When is hormone replacement therapy (HRT) given? What specific therapies are used in women with a uterus and those who still have periods?
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.
What non-hormonal treatment can be used to treat menopausal symptoms?
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
How does clonidine improve menopausal symptoms and what are the common side effects?
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.
What alternative remedies for menopausal symptoms might patients try?
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
What are the indications for HRT?
- Replacing hormones in premature ovarian insufficiency, even without symptoms
- Reducing vasomotor symptoms such as hot flushes and night sweats
- Improving symptoms such as low mood, decreased libido, poor sleep and joint pain
- Reducing risk of osteoporosis in women under 60 years
What are the benefits and risks of HRT?
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
What are the contraindications to HRT?
- Undiagnosed abnormal bleeding
- Endometrial hyperplasia or cancer
- Breast cancer
- Uncontrolled hypertension
- Venous thromboembolism
- Liver disease
- Active angina or myocardial infarction
- Pregnancy
What are important factors in the assessment for HRT? How are HRT formulations chosen?
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
What are the options for oestrogen and progesterone delivery in HRT?
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.
What are the types of progesterone treatment?
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.
