Hyperprolactinaemia–Hypogonadism Syndromes

Hyperprolactinaemia is a common cause of ovarian dysfunction: infertility, amenorrhoea, oligomenorrhoea, menorrhagia, or regular menstruation with anovulation or a deficient luteal phase. Galactorrhoea occurs only in the minority of these patients, and its incidence depends upon the enthusiasm with which it is searched for by medical practitioners. On average, it appears to occur in between 20% and 30% of hyperprolactinaemic patients and, of all the patients with secondary amenorrhoea, some 30% appear to have hyperprolactinaemia. Bromocriptine, a dopamine receptor agonist, acts as a functional analogue of the prolactininhibiting factor of the hypothalamus directly on the pituitary cells to lower prolactin secretion, returning circulating prolactin levels to normal. Normalization of prolactin levels is associated with a prompt return of gonadal function to normal. Normal ovulatory menstruation returns rapidly, usually within two months of commencement of therapy, though occasionally longer intervals of up to seven months may be required. Responsiveness to clomiphene also returns. Clinical hypogonadism usually recurs if the drug therapy is stopped. Women with hyperprolactinaemic infertility are highly fertile while being treated with bromocriptine, but there is a danger of rapid enlargement of any pre–existing pituitary tumour when such patients become pregnant. Consideration must be given to primary therapy directed at any existing pituitary tumour before conception occurs. Bromocriptine is not teratogenic and, in the doses required to treat hyperprolactinaemia, side effects are usually encountered only at the start of treatment. Such initial side effects may be avoided by starting the therapy with low dosage and increasing it slowly to the usually effective dosage of from 5 mg/day to 7.5 mg/day, although higher doses may be required. In men, hyperprolactinaemia is usually associated with relative or absolute impotence, and only rarely with accompanying galactorrhoea. As in women, these symptoms disappear rapidly on lowering the prolactin levels with bromocriptine. The introduction of bromocriptine has heralded a major change in the management of the hyperprolactinaemia –hypogonadism syndromes and resulted in safer and easier treatment of many cases of infertility, menstrual disorders and, to a lesser extent, of impotence. Gonadotrophin therapy is now rarely indicated, and only when the pituitary gonadotrophin reserve is demonstrably reduced in the presence of normal or low circulating prolactin levels. At present, bromocriptine therapy is the treatment of choice for hyperprolactinaemia.