Pietro Rampini

Treatment of hyperprolactinemic states with different drugs: a study with bromocriptine, metergoline, and lisuride *

One hundred ninety-one hyperprolactinemic patients (78 women and 13 men; 54 with pituitary macroadenoma, 53 with microadenoma, and 84 with idiopathic disease) were treated for 2 to 48 months with one or two of the following prolactin (PRL)-lowering drugs: bromocriptine, metergoline, and lisuride. All of the three drugs used were highly effective in lowering PRL levels and restoring gonadal function both in females and in males in the majority of patients with either idiopathic or tumorous disease. In poorly responsive patients, increasing the drug doses resulted in further PRL lowering for all the three drugs. Mild side effects were frequently encountered with initiation of drug treatment but spontaneously subsided in most cases; severe side effects, necessitating stopping of the treatment, occurred in only 12 instances, but changing of the drug allowed PRL-lowering treatment to be continued in 11 of them.

Serum prolactin and ovarian function after discontinuation of drug treatment for hyperprolactinaemia: a study with bromocriptine and metergoline

Serum prolactin (PRL) was estimated for up to 2 months after discontinuation of therapy with either bromocriptine (n=33; 15 with idiopathic disease, 12 with pituitary microadenoma, and six with macro‐adenoma) or metergoline (n=23; 11 with idiopathic disease, and 12 with microadenoma) that had been administered for 8–30 months. Only five patients treated with bromocriptine and two treated with metergoline had PRL levels that remained normal or below 50% of pretreatment values. Among the patients followed‐up for up to 12 months, four showed a fall in PRL at 3–4 months, but this was followed by a rise in one patient. Five patients showing persistently lower or normal PRL after drug withdrawal were retested with thyrotrophin‐releasing hormone; the two responsive women also had a normal response before treatment. Of 10 patients followed for 9 months, three had persistently normal PRL levels. Amenorrhoea and anovulation recurred, with some delay, in all the patients showing PRL rebound except one. Medical treatment of hyperprolactinaemia only rarely results in permanent benefit.

Effects of Chronic Prazosin Treatment on the Renin—Angiotensin—Aldosterone System in Man

Abstract: The effects of chronic prazosin treatment (3 mg/day for three weeks) on plasma renin activity (PRA) and plasma aldosterone (PA) levels were evaluated in 12 hypertensive patients, under conditions of metabolic balance. After three weeks of drug administration no significant change occurred in PRA as well as PA levels, with respect to pretreatment values, both in basal conditions and following 2 hours of ambulation. No change was observed in heart rate, while a fall in both systolic (P < 0.02) and diastolic (P < 0.05) blood pressure occurred in supine as well as in deambulation‐stimulated condition. A mild increase in body weight (P < 0.05) and a decrease in serum sodium (P < 0.05) was induced by prazosin treatment. These findings are in keeping with the pharmacologic properties of prazosin, which is a selective blocker of postsynaptic alpha adrenoreceptors and therefore lowers vascular resistance without reflex sympathetic overactivity. The moderate volume expansion after prazosin does not appear to be aldosterone mediated.

Restoration of Cyclic Ovarian Function by Metergoline Treatment in a Patient with a Prolactin-Secreting Pituitary Microadenoma

A patient with amenorrhea due to a prolactin-secreting pituitary microadenoma was treated with the antiserotoninergic drug metergoline for 8 months. The first menstruation occurred after 1 month of therapy, and it was followed by regular menses by the 3rd month. Presumptive evidence of ovulation was obtained in at least some instances by serum progesterone and gonadotropin determination. Serum prolactin was only slightly lowered by treatment. The patient had menses and possibly ovulation in the 2 months following drug withdrawal. Metergoline might restore ovarian function in hyperprolactinemic amenorrhea either by prolactin suppression or perhaps by direct stimulation of gonadotropin release.

Effects of ibopamine on serum prolactin and growth hormone levels in hyperprolactinemic and acromegalic subjects

The effects of oral doses (100, 200, and 400 mg) of a dopamine derivative, ibopamine, on serum prolactin (PRL) and growth hormone (GH) levels were evaluated in hyperprolactinemic patients, some of whom also were acromegalic. There was dose‐related lowering of PRL levels. The highest dose was as effective as 500 mg L‐dopa, although the duration of action was shorter, with a decrease to below 50% of basal PRL values in all patients. Serum GH did not rise in nonacromegalic subjects, but it fell after 400 mg ibopamine in the L‐dopa‐sensitive acromegalic patients. These data suggest, but do not prove, that ibopamine is able to directly stimulate pituitary dopamine receptors.

Prolactin response to the dopamine antagonists sulpiride and domperidone. Further evidence for pituitary dopamine deficiency in hyperprolactinemic disorders of different etiology.

The PRL response to the dopamine antagonists sulpiride (100 mg i.m.) or domperidone (2 or 8 mg i.v.) was evaluated in healthy controls and in 148 patients with different hyperprolactinemic disorders (50 with idiopathic hyperprolactinemia, 58 with microprolactinoma, 19 with macroprolactinoma, 2 with empty sella, 8 with acromegaly, 7 with organic lesions of the hypothalamus, and 4 with idiopathic hypopituitarism of presumed hypothalamic origin). Mean PRL response to both drugs was significantly lower in all groups of patients than in controls, and significantly higher in subjects with idiopathic hyperprolactinemia than in those with pituitary adenomas or hypothalamic disease. Absent or impaired PRL responses were found in 38% of idiopathic patients, in 91.5% of microprolactinomas and in all of the patients with either macroprolactinoma, acromegaly, or hypothalamic disorders. Since the PRL response to dopamine antagonists depends on the presence of an endogenous dopaminergic tone, it is suggested that these figures reflect the incidence of major dopamine deficiency at pituitary lactotrophs in different hyperprolactinemic states. These data suggest that the pathophysiology of hyperprolactinemia in many patients with idiopathic disease is different from that of microprolactinoma. However, the finding of a normal PRL response to sulpiride in some subjects with radiologically or surgically proven microprolactinoma indicates that this test has no diagnostic value in the individual case.

Hyperprolactinemic Primary Amenorrhea: Case Report with Successful Prolactin-Lowering Treatment and Review of the Literature

A 19-year-old girl with primary amenorrhea, galactorrhea, and hyperprolactinemia is described. Her high serum prolactin levels (95 ng/ml) did not increase after thyrotropin-releasing hormone and sulpiride, but markedly decreased after acute bromocriptine and metergoline administration. The results of other pituitary function tests were normal. Tomography of the sella turcica and CT scan of the skull were also normal. The patient was treated with metergoline, a prolactin-lowering drug which is believed to act as a serotonin antagonist, for 30 months. Serum prolactin rapidly decreased after institution of treatment, with actual normalization (less than 20 ng/ml) by the 3rd month. At this time the low serum luteinizing hormone levels began to rise and fluctuate in the normal follicular range. Galactorrhea disappeared, and menarche occurred during the 15th month of treatment. 15 further menstrual bleedings ensued over the following 15 months, albeit at irregular time intervals; ovulation was suggested by finding elevated serum progesterone levels in the presumed luteal phase by about 1 year following the menarche. The available data on 38 patients with primary amenorrhea and hyperprolactinemia reported in the literature are reviewed. 15 of them were treated with bromocriptine, and either pregnancy or cyclic menses occurred in 11. Hyperprolactinemic primary amenorrhea may be more common than previously recognized, and it may probably be successfully treated by prolactin-lowering drugs or by surgical ablation of a pituitary adenoma in a high percentage of cases.