The extent of hair growth varies between individuals, families and races, being more extensive in the Mediterranean and Asian populations. Soft vellous hair on the face and elsewhere is not sex-hormone dependent, nor is hair on the forearm or lower leg. Hair in the beard, moustache, breast, chest, axilla, abdominal midline, pubic and thigh areas is sex-hormone dependent. Any excess in the latter regions is thus usually a mark of increased ovarian or adrenal androgen production. Hair has a long growing cycle with spontaneous variations and clinical changes are therefore slow.
Oestrogens are converted to androgens in adipose tissue, which presumably explains the frequent coexistence of hirsuties and obesity without definable endocrine disease.
The complaint is common and often accompanied by severe anxiety and social stress. Important questions are:
AGE AND SPEED OF ONSET. Rapid progression and prepubertal or late onset suggest a more serious cause.
ACCOMPANYING VIRILIZATION (clitoromegaly, frontal balding, male phenotype, greasy skin, acne). This implies substantial androgen excess.
MENSTR VA TION. The greater the disruption the more likely a serious cause.
CAUSES AND INVESTIGATION
These are summarized.
The underlying cause should be removed in the rare instances where this is possible (e.g. drugs, adrenal or ovarian tumours). Other therapy is either local or systemic.
Plucking, bleaching, depilatory cream or wax and shaving may all help and are underused. Waxing is of especial value where the ‘bikini area’ is causing the concern. Electrolysis is slow and expensive.
Oestrogens (e.g. oral contraceptives) reduce free androgens by increasing SHBG levels when these are low. Prednisolone given in a reverse circadian manner (5 mg at night, 2.5 mg in the morning) may rarely improve hirsuties in polycystic ovarian syndrome when given alone, though is more effective in restoring regular menstruation. Cyproterone acetate (50-200 mg daily). is an antiandrogen but is also teratogenic and a weak glucocorticoid and progestogen. Given continuously it produces amenorrhoea, and so is normally given for days 1-14 of each cycle. In women of childbearing age, contraception is essential. Other agents of doubtful efficacy include spironolactone, bromocriptine and cimetidine.
Polycystic ovarian syndrome
This very common condition, originally known in its severe form as the Stein-Leventhal syndrome, is characterized by multiple ovarian cysts and by excess androgen production from the ovaries and adrenals, although whether the basic defect is in the ovary, adrenal or pituitary, remains unknown. The ovarian cysts represent arrested follicular development.
It is a common cause of amenorrhoea/oligomenorrhoea, hirsuties or acne, usually beginning shortly after menarche. It is sometimes associated with marked obesity, but weight may be normal. Mild virilization occurs in severe cases.
Recent studies have shown an association of polycystic ovarian syndrome with menstrual disturbance and hypertension and hyperlipidaemia; it appears that insulin resistance may form part of the mechanism of the syndrome.
The most accurate investigation is ovarian ultrasound, although a skilled observer is necessary and some apparently normal women show the abnormality. The typical ultrasonic features are those of a thickened capsule, multiple 3-5 mm cysts and a hyperechogenic stroma. Biochemically there are increased free androgens, though total testosterone may be normal. SHBG is low. The LH : FSH ratio is usually raised (>2: I) but the FSH is normal or low. Mild hyperprolactinaemia is common but rarely exceeds 1500 mU litre.”.
This depends upon whether the aim is to produce fertility, regularize periods or reduce hirsuties.
REVERS CIRCADIAN RHYTHM, prednisolone (2.5 mg in the morning,S mg on retiring) to suppress pituitary production of ACTH upon which adrenal androgens partly depend. Regular ovulatory cycles often ensue; hirsuties seldom respond to this treatment alone, but acne frequently does. Steroid instruction and a card must be supplied.
OESTROGENS/ORAL CONTRACEPTIVES FOR HIRSUTIES.
CYPROTERONE as above. For fertility, in addition to prednisolone:
CLOMIPHENE 50-200 mg daily from days 2-6 of cycle (or tamoxifen 10-40 mg daily) plus HCG 5000 U i.m. on day 12/13. This can occasionally cause ovarian hyperstimulation and specialist supervision is essential.
WEDGE RESECTION OR LASER SURGERY OF THE OVARY-rarely.
Mildly increased prolactin levels (400-600 mU litre:’) may be physiological, pathological or secondary to drug therapy (Table 16.19), while higher levels require a diagnosis. Not all patients with galactorrhoea have hyperprolactinaemia, but the other causes are poorly understood Cnormoprolactinaemic galactorrhoea’).
Hyperprolactinaemia per se usually presents with:
• Galactorrhoea, spontaneous or expressible (60% of cases)
• Oligomenorrhoea or amenorrhoea
• Decreased libido in both sexes
• Decreased potency
• Sub fertility
• Symptoms or signs of oestrogen or androgen deficiency-in the long term osteoporosis may result, especially in women
• In the peripubertal patient, as delayed or arrested puberty Additionally, headaches and/or visual field defects may be present if there is a pituitary tumour (more common in men).
Sleep (REM) phase
Production by tumours
Occurs in some acromegalies
Interference with stalk
Any hypothalamidpituitary tumour
Polycystic ovarian syndrome
Chest wall injury
Dopamine antagonists (e.g. metoclopramide and phenothiazines)
Once physiological and drug causes have been excluded:
AT LEAST THREE PROLACTIN LEVELS SHOULD BE MEASURED. Mean levels of >2000-3000 mU litre-I suggest a prolactinoma
A GOOD QUALITY SKULL X-RAY should be obtained.
VISUAL FIELDS should be checked.
ANTERIOR PITUITARY FUNCTION should be assessed if there is any clinical evidence of hypopituitarism or radiological evidence of tumour. Hypothyroidism must be excluded.
MRI OF THE PITUITARY is necessary (if available) if there is an obvious tumour, and desirable if not. MRI is more sensitive than CT though the latter should be used if MRI is not available.
Macroprolactinoma refers to tumours above 10 mm in diameter, microprolactinoma to smaller ones. The size of tumour may affect the choice of treatment.
Treatment is dependent upon circumstances and facilities. Hyperprolactinaemia should be reduced with bromocriptine, a dopamine agonist. Initial doses shouldbe small (e.g. 1 mg) and taken during food, beginning at bedtime. The dose should be gradually increased, usually to 2.5 mg three times daily, judged on clinical response and prolactin levels. Maintenance doses are 2.5-15 mg daily in divided doses. Side-effects include nausea and vomiting, dizziness and syncope, constipation and cold peripheries. Newer agents include lisuride. If a tumour is present this is likely to shrink with bromocriptine. Definitive therapy is controversial and will depend upon the size of the tumour, the patient’s wish for fertility and local facilities.
TRANS-SPHENOIDAL SURGERY often restores normoprolactinaemia but there is a considerable late recurrence rate (50% at 5 years). Bromocriptine may produce hardening of the tumour and surgery should not be delayed beyond 2-3 months’ treatment. RADIOTHERAPY is only slowly effective and can sometimes cause eventual hypopituitarism. It should, however, be used after surgery in larger turnours, especially where families are complete.
SMALL TUMOURS in asymptomatic patients without hypogonadism may need only observation.
RARELY, TUMOURS ENLARGE DURING PREGNANCY to produce headaches and visual defects. Bromocriptine should be restarted.
MICROPROLACTI OMAS. There is some evidence that some microprolactinomas may not recur after several years of dopamine agonist therapy.