Menstrual disturbance is classified as:
· Amenorrhoea – absent menses for >6 months. This can be fur-ther subdivided into primary amenorrhoea (failure of menarche – the first appearance of periods– by age 16 years) or secondary amenorrhoea (cessation of menstrual periods for >6 months in women who have previously menstruated)
• Oligomenorrhoea – reduced menstrual frequency to <9 peri-ods/year
• Polymenorrhoea – frequent menstrual periods
• Menorrhagia – heavy menstrual periods.
Polymenorrhoea and menorrhagia can relate to hypothyroidism but usually reflect abnormal (dysfunctional) uterine bleeding (irregular bleeding, which is more common in adolescents and women approaching the menopause, and not caused by structural pathology). This is not considered further here as it is not usually managed by endocrinologists in clinical practice.
The causes of primary amenorrhoea, secondary amenorrhoea and oligomenorrhoea can be broadly divided into four groups:
1. Premature ovarian failure.
2. Disordered gonadotrophin secretion (hypogonadotrophic hypogonadism). This can be caused by hypothalamic–pituitary disease (Chapter 5), including hyperprolactinaemia, or hypo-thalamic amenorrhoea whereby low body weight (e.g. anorexia nervosa), intensive exercise, prolonged psychological stress or systemic illness lead to suppressed gonadotrophin pulsatility.
3. Hyperandrogenic disorders, including polycystic ovary syn-drome (PCOS; Chapter 26).
4. Structural disease (e.g. uterine adhesions, congenital absence of the uterus).
Symptoms of oestrogen deficiency (flushes, vaginal dryness and dyspareunia), androgen excess (hirsutism, acne), galactorrhoea, heavy exercise, weight change, emotional stress and systemic illness should be looked for. It is important to document the onset and duration of the menstrual disturbance.
This should include an evaluation of body habitus (e.g. anorexia nervosa, Turner’s syndrome), hyperandrogenism, secondary sexual characteristics (pubic and axillary hair, breast development), visual fields and anosmia.
These should initially be based on measurement of oestradiol, FSH and LH which will establish whether ovarian dysfunction is primary (raised gonadotrophins) or secondary (low–normal gonadotrophins) (Figure 25.1). FSH and LH should be measured in the follicular phase (days 0–5 of a period) to avoid the FSH/LH surge which can give the false impression of raised gonadotrophins. A pregnancy test may be indicated if the history is short, while a pelvic ultrasound helps exclude structural abnormalities and can show altered ovarian morphology (e.g. polycystic ovaries, ‘streak ovaries’ in Turner’s syndrome). Other tests may subsequently be needed depending on clinical suspicion and the pattern of the gonadotrophin results.
Treatment is directed at the underlying cause (e.g. weight gain in low body weight, dopamine agonists for prolactinomas). Oestrogen replacement will improve symptoms of oestrogen deficiency and protect against decline in bone mineral density. In women seeking pregnancy, fertility can be improved with cause-specific treatment (Chapter 30).
Premature ovarian failure
This group of disorders are characterised by amenorrhoea, oestrogen deficiency and raised gonadotrophins in women <40 years, due to loss of ovarian follicular function. Causes include:
• Chromosomal abnormalities (60%), especially Turner’s syndrome
• Autoimmune disease (20%)
• Iatrogenic – following surgery, chemotherapy or radiotherapy
This affects 1 in 2500 female births and results from complete or partial absence of one X chromosome; the most common karyotype is 45 XO. Affected patients are characterised by short stature and gonadal dysgenesis (>90% have premature ovarian failure). Clinical features include webbing of the neck, widened nipples, cubitus valgus and a short 4th metacarpal (Figure 25.2).
Optimisation of growth and puberty
This is achieved through use of high dose GH and oestrogen replacement. Oestrogen replacement is usually continued until an age at which menopause would normally be expected to occur.
Screening for and seeking to prevent complications
Patients with Turner’s syndrome have an increased risk of audiological (otitis media, sensorineural deafness), cardiac (hypertension, coarctation of the aorta, bicuspid aortic valve, aortic dissection), renal (congenital abnormalities), hepatic (raised liver enzymes, fatty liver disease), metabolic (hypothyroidism, type 2 diabetes), skeletal (osteoporosis) and neuropsychological (motor coordination, visuospatial) complications. These should be screened for with annual measurement of body mass index (BMI), blood pressure, HbA1c, thyroid function, liver and renal blood tests, echocardiography every 3–5 years, and bone density and hearing tests every 5 years.