Amenorrhoea

Question 1

How do you know if a woman is ovulating?

Answer 1

-Regular menstrual cycle
-Progesterone from corpus luteum (7 days before period so Day 21)
-Serial progesterone testing if irregular (urine): progesterone increases as oestrogen increases

Question 2

Hormones in control of menstruation

Answer 2

-FSH
-LH
-Prolactin
-Testosterone
-Thyroid
-Oestrogen

Question 3

Classes of amenorrhoea

Answer 3

-Primary: defined as the failure to establish menstruation by 15 years of age in girls with normal secondary sexual characteristics (such as breast development), or by 13 years of age in girls with no secondary sexual characteristics
=Girls who have not established menstruation within 3 years of the start of breast development (thelarche), or within 5 years if breast budding occurred before the age of 10.

-Secondary: cessation of menstruation for 3-6 months in women with previously normal and regular menses, or 6-12 months in women with previous oligomenorrhoea/ infrequent irregular

Question 4

Causes of primary amenorrhoea

Answer 4

-Gonadal dysgenesis (e.g. Turner’s syndrome)= the most common causes
-Testicular feminisation
-Congenital malformations of the genital tract
-Functional hypothalamic amenorrhoea (e.g. secondary to anorexia)
-Congenital adrenal hyperplasia
-Imperforate hymen
-Hypogonadotropic hypogonadism
-Hypergonadotropic hypogonadism

Question 5

Causes of secondary amenorrhoea

Answer 5

-Pregnancy
-Hypothalamic amenorrhoea (e.g. secondary stress, excessive exercise)
-Polycystic ovarian syndrome (PCOS)
-Hyperprolactinaemia
-Premature ovarian failure/ Menopause
-Thyrotoxicosis*
-Sheehan’s syndrome
-Asherman’s syndrome (intrauterine adhesions)

Question 6

Hypothalamic and pituitary causes of secondary amenorrhoea

Answer 6

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

Question 7

History in primary amenorrhoea

Answer 7

-History of pubertal development, particularly breast development and appearance of pubic hair.
-Sexual history and contraception (to exclude pregnancy or a contraceptive cause of amenorrhoea. Consider the possibility of sexual abuse).
-Cyclical lower abdominal pain (suggesting haematocolpos, caused by a genital tract malformation).
-Stress, depression, weight loss, disturbance of perception of weight or shape, level of exercise, and chronic systemic illness (suggesting hypothalamic dysfunction).
-Headache, visual disturbance, or galactorrhoea (suggesting prolactinoma).
-Anosmia (suggesting Kallman syndrome).
-Past medical history: head injury or infection, medication, surgery, chemotherapy, radiotherapy, or chronic illness.
-Age at menarche of mother and sisters (family history of late menarche suggests constitutional delay of puberty).
-Family history of genetic anomalies (for example, androgen insensitivity [46XY female]).

Question 8

History in secondary amenorrhoea

Answer 8

-Exclude pregnancy, lactation, menopause
-Contraceptive use (extended-cycle combined oral contraceptives, injectable progesterone, implantable etonogestrel, and levonorgestrel intrauterine systems may cause amenorrhoea).
-Hot flushes and vaginal dryness (suggesting premature ovarian insufficiency [POI] or natural menopause).
-Headaches, visual disturbances, or galactorrhoea (suggesting a pituitary tumour).
-Acne, hirsutism, and weight gain (suggesting polycystic ovary syndrome [PCOS]).
-Stress, depression, weight loss, disturbance of perception of weight or shape, level of exercise, and chronic systemic illness (suggesting hypothalamic dysfunction).
-Symptoms of thyroid and other endocrine disease.
-A history of obstetric or surgical procedures (such as endometrial curettage) that may have resulted in intrauterine adhesions.
-A history of chemotherapy and pelvic radiotherapy (which can cause POI); and cranial radiotherapy, head injury, or major obstetric haemorrhage (which can cause hypopituitarism).
-Drugs (such as antipsychotics, which can cause increased prolactin levels) and illicit drug use (in particular cocaine and opiates, which can cause hypogonadism).
-A family history of cessation of menses before 40 years of age (suggesting POI).

Question 9

Initial investigations of amenorrhoea

Answer 9

-Exclude pregnancy with urinary or serum bHCG
-Full blood count, urea & electrolytes, coeliac screen, thyroid function tests (TSH)
-Gonadotrophins
=Low levels indicate a hypothalamic cause where as raised levels suggest an ovarian problem (e.g. Premature ovarian failure)
=Raised if gonadal dysgenesis (e.g. Turner’s syndrome)
-Prolactin: >1000 warrant pituitary MRI, drug review
-Androgen levels
=Raised levels may be seen in PCOS, total testosterone if features of androgen excess: androgen insensitivity, CAH, Cushing’s, androgen secreting tumour
-Oestradiol

-Pelvic ultrasound (if the presence of a vagina and uterus cannot be confirmed by physical examination, or in place of a pelvic examination in young girls who are not sexually active).
=If present and normal secondary characteristics: outflow obstruction (imperforate/transverse vaginal septum) or PCOS
=Present with no secondary: Turner’s 46XO, gonadal agenesis 46XX/XY
=Absent/abnormal: androgen insensitivity syndrome

Question 10

Management of secondary amenorrhoea

Answer 10

-Exclude pregnancy, lactation, and menopause (in women 40 years of age or older)
-Treat the underlying cause

Question 11

What is hypogonadism?

Answer 11

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:

-Hypogonadotropic hypogonadism: a deficiency of LH and FSH
-Hypergonadotropic hypogonadism: a lack of response to LH and FSH by the gonads (the testes and ovaries)

Question 12

What is hypogonadotropic hypogonadism?

Answer 12

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). Therefore, “hypogonadotropism” causes “hypogonadism”.
A deficiency of LH and FSH is the result of abnormal functioning of the hypothalamus or pituitary gland.

Question 13

Causes of hypogonadotropic hypogonadism

Answer 13

-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

Question 14

What is hypergonadotropic hypogonadism?

Answer 14

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 (“hypergonadotropic”) and low sex hormones (“hypogonadism”).
Hypergonadotropic hypogonadism is the result of abnormal functioning of the gonads

Question 15

Causes of hypergonadotropic hypogonadism

Answer 15

-Previous damage to the gonads (e.g. torsion, cancer or infections such as mumps)
-Congenital absence of the ovaries
-Turner’s syndrome (XO)

Question 16

Overview of Kallman syndrome

Answer 16

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).

It is usually inherited as an X-linked recessive trait. Kallmann’s syndrome is thought to be caused by failure of GnRH-secreting neurons to migrate to the hypothalamus.

The clue given in many questions is lack of smell (anosmia) in a boy with delayed puberty.

-Features
‘delayed puberty’
hypogonadism, cryptorchidism
anosmia
sex hormone levels are low
LH, FSH levels are inappropriately low/normal
patients are typically of normal or above-average height

Cleft lip/palate and visual/hearing defects are also seen in some patients

Management
testosterone supplementation
gonadotrophin supplementation may result in sperm production if fertility is desired later in life

Question 17

Overview of congenital adrenal hyperplasia

Answer 17

-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. The deficiency in cortisol production leads to compensatory overproduction of adrenocorticotropic hormone (ACTH) by the anterior pituitary. Elevated ACTH levels increase the production of adrenal androgens, which can result in the virilization of female infants and affect genital development.
-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 (5%) rather than 21-hydroxylase (90%).

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, shorter adult as early epiphyseal closure
=Facial hair
=Absent periods (primary amenorrhoea)
=Deep voice
=Early puberty (precocious)
=Virilisation (female infants present with ambiguous genitalia due to excessive androgen exposure in utero, male appear normal at birth)
=Salt-wasting crisis: dehydration, hypotension, electrolyte imbalance
=Infertility

-Diagnosis: ACTH stimulation testing

-M: glucocorticoid replacement to reduce ACTH, in cases of mineralocorticoid deficiency fludrocortisone is also prescribed

Question 18

Overview of Androgen Insensitivity syndrome

Answer 18

Androgen insensitivity syndrome is a condition where the tissues are unable to respond to androgen hormones due to lack of androgen receptors (e.g. testosterone), so typical male sexual characteristics do not develop (testicular feminisation syndrome)
-It results in a female phenotype, other than the internal pelvic organs as extra androgens converted into oestrogen. X-linked recessive, mutation to androgen receptor gene on X chromosome. Genetically XY 46XY

-P: 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. 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 (undescended testes cause groin swellings). Androgen insensitivity syndrome often presents in infancy with inguinal hernias containing testes. Alternatively, it presents at puberty with primary amenorrhoea.

-I: raised LH, normal/raised FSH, normal/raised testosterone after puberty, raised oestrogen levels. Buccal smear or chromosomal analysis 46XY

-M: 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.

Question 19

Examples of structural pathology

Answer 19

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: cyclical pelvic pain and cramping with no vaginal bleeding, retrograde menstruation can lead to endometriosis
=Transverse vaginal septae: imperforate/perforate, surgery complications vaginal stenosis and recurrence
=Vaginal agenesis: failure of Mullerian ducts to develop, dilator
Absent uterus
Female genital mutilation

Question 20

Primary amenorrhoea assessment

Answer 20

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

Question 21

Management of primary amenorrhoea

Answer 21

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.

-Investigate and treat any underlying cause
-With primary ovarian insufficiency due to gonadal dysgenesis (e.g. Turner’s syndrome) are likely to benefit from hormone replacement therapy (e.g. to prevent osteoporosis etC)

Question 22

Overview of Hyperprolactinaemia

Answer 22

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.

Question 23

Hormone tests in secondary amenorrhoea

Answer 23

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.
=Raise 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.

Question 24

Presentation of PCOS

Answer 24

-5-20% women

-Oligomenorrhoea or amenorrhoea
-Infertility/sub
-Obesity (in about 70% of patients with PCOS)
-Hirsutism
-Acne
-Hair loss in a male pattern

-Insulin resistance and diabetes
-Acanthosis nigricans
-Cardiovascular disease
-Hypercholesterolaemia
-Endometrial hyperplasia and cancer
-Obstructive sleep apnoea
-Depression and anxiety
-Sexual problems

Question 25

Rotterdam criteria

Answer 25

-Oligoovulation or anovulation, presenting with irregular or absent menstrual periods
-Hyperandrogenism, characterised by hirsutism and acne
-Polycystic ovaries on ultrasound (or ovarian volume of more than 10cm3)

Question 26

PCOS Investigations

Answer 26

-Raised luteinising hormone
-Raised LH to FSH ratio (high LH compared with FSH)
-Raised testosterone
-Raised insulin
-Normal or raised oestrogen levels
-Sex hormone-binding globulin normal to low
-Prolactin (may be mildly elevated)
-TSH

-Pelvic/transvaginal USS: string of pearls, 12+ developing follicles in 1 ovary, ovarian volume >10cm cubed, not reliable in adolescents

-Screening: 2-hour 75g oral glucose tolerance test
=Impaired fasting glucose – fasting glucose of 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

Question 27

Management of PCOS

Answer 27

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.

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.

Question 28

Managing endometrial cancer risk in PCOS

Answer 28

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:

Mirena coil for continuous endometrial protection
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

Question 29

Managing infertility in PCOS

Answer 29

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
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.

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.

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.

Question 30

Managing hirsutism in PCOS

Answer 30

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.

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.

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)

Question 31

Management of acne in PCOS

Answer 31

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)

Question 32

Osteoporosis in amenorrhoea

Answer 32

Patients with amenorrhoea associated with low oestrogen levels are at risk 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

Question 33

Overview of Asherman’s syndrome

Answer 33

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.

Presentation
Asherman’s syndrome typically presents following recent dilatation and curettage, uterine surgery or endometritis with:

Secondary amenorrhoea (absent periods)
Significantly lighter periods
Dysmenorrhoea (painful periods)
It may also present with infertility.

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

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

Question 34

What is premature ovarian insufficiency?

Answer 34

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

Question 35

Causes of premature ovarian insufficiency

Answer 35

Idiopathic (the cause is unknown in more than 50% of cases)
Iatrogenic, due to interventions such as chemotherapy, radiotherapy or surgery (i.e. bilateral oophorectomy, hysterectomy)
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

Question 36

Presentation and associations of Premature Ovarian Insufficiency

Answer 36

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. Infertility, secondary amenorrhoea

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

Question 37

Diagnosis of POI

Answer 37

NICE guidelines on menopause (2015) say 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 25/30 IU/l) on two consecutive samples separated by more than 4-6 weeks to make a diagnosis. The results are difficult to interpret in women taking hormonal contraception. Low oestradiol <100

Question 38

Management of POI

Answer 38

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:

Traditional hormone replacement therapy
Combined oral contraceptive pill
Traditional hormone replacement therapy is associated with a lower blood pressure compared with the combined oral contraceptive pill. The combined pill may be more socially acceptable (less stigma for younger women) and additionally acts as contraception. COCP until 51

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).
it should be noted that HRT does not provide contraception, in case spontaneous ovarian activity resumes