Anna Mattei

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.

Enlargement of a prolactin-secreting pituitary microadenoma during bromocriptine treatment. Case report.

Summary. A patient with prolactin‐secreting pituitary microadenoma was treated with bromocriptine, 5 mg daily for 1 year. Despite normalization of prolactin levels throughout the treatment period, partial destruction of the sellar floor with growth of the adenoma into sphenoidal sinus were evident in a control tomography performed at the end of the treatment.

Visual field defects and reduced visual acuity during pregnancy in two patients with prolactinoma: Rapid regression of symptoms under bromocriptine. Case reports

This 38-year-old woman had three previous spontaneous uneventful pregnancies, the last in 1975; she had had amenorrhoea since 1977 when her plasma prolactin was 200 ng/ml. Tomography of the pituitary fossa suggested the existence of a micro-adenoma, and the patient was followed up without any treatment until May 1982 when she had bromocriptine therapy in order to achieve pregnancy. At that time plasma prolactin was 260 ng/ml. After 4 weeks of treatment (5 mg/day) the patient became pregnant, and bromocriptine was withdrawn at the time of the positive pregnancy test. The pregnancy progressed uneventfully with repeated normal visual fields until 30 weeks gestation when a lower quadrant nasal visual field defect occurred in the presence of a plasma prolactin level of 330 ng/ml. Bromocriptine was immediately restarted (5 mg/day) and after 3 and 5 weeks, respectively, visual fields first improved and then became normal (Fig. 1). Prolactin levels were checked at 1, 3 and 5 weeks of treatment and varied between 45 and 22 ng/ml. The patient gave birth to a normal baby at 38 weeks and no further complications ensued. She is still being treated with the same dose of bromocriptine.

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.

Antiserotonin treatment of hyperprolactinemic amenorrhea: long-term follow-up with metergoline, methysergide, and cyproheptadine.

Twenty patients affected by hyperprolactinemic amenorrhea-galactorrhea have been treated with one or more of the following serotonin antagonists: metergoline, methysergide, and cyproheptadine. Among the 11 patients without evidence of pituitary tumor resumption of menses was observed in five, two of whom had ovulatory cycles; one patient became pregnant; ovulations occurred only during treatment with metergoline. In the group of nine patients with enlarged sellae, three experienced isolated episodes of bleeding, while two had three and four menses each, respectively; all cycles were anovulatory. Plasma prolactin levels and galactorrhea were favorably affected by treatment only in a minority of amenorrhea-galactorrhea patients with and without tumors.

Effect of Fenfluramine Oral Administration on Serum Prolactin Levels in Healthy and Hyperprolactinemic Women

The effects of two different doses (40 and 80 mg orally) of fenfluramine on serum prolactin (PRL) levels have been evaluated in healthy and hyperprolactinemic women and compared with those of the potent dopamine antagonist sulpiride (100 mg i.m.). The lower fenfluramine dose resulted in a significant PRL rise in healthy women (n = 16) but not in hyperprolactinemics (n = 14). A dose-response effect was shown between 40 and 80 mg in control subjects (n = 7); in 4 hyperprolactinemics the higher dose also failed to increase PRL levels. Sulpiride resulted in a much greater PRL response. Since fenfluramine at the low doses used does not seem to exert antidopaminergic action, it is suggested that the mild PRL stimulation observed be mediated by the known brain serotoninergic activation induced by the drug.

Enlargement of a prolactin‐secreting pituitary microadenoma during bromocriptine treatment

Summary. A patient with prolactin-secreting pituitary microadenoma was treated with bromocriptine, 5 mg daily for 1 year. Despite normalization of prolactin levels throughout the treatment period, partial destruction of the sellar floor with growth of the adenoma into sphenoidal sinus were evident in a control tomography performed at the end of the treatment.

Metergoline Treatment of Hyperprolactinemic States

The ergoline derivative metergoline was administered at the daily dose of 12mg for 1 to 28 months to 41 hyperprolactinemic women (20 with a normal sella turcica according to tomography, 16 with radiologic evidence of pituitary microadenoma, and 5 with macroadenoma). Serum prolactin (PRL) concentration was reduced by treatment to below 50% of pretreatment values in 29 patients, with actual normalization (serum PRL

Efficacy of Placebo in the Treatment of Patients with Amenorrhea

Thirty-two amenorrheic patients were treated with a tablet oral placebo preparation for a period varying from 30 to 180 days. Another 24 amenorrheic patients were also treated with a placebo administered i.m. for a period varying from 30 to 120 days. As a consequence of the treatment, 27 patients (48%) had menstrual bleedings. The progestogen withdrawal test responsive patients were more responsive to placebo (73 vs. 14% in the progestogen withdrawal test nonresponsive, p < 0.001). The time lag between starting the medication and the first bleeding varied between 4 and 120 days with a mean value of 33.9 (SD 26.3). Oral placebo was more effective than the intramuscular form (56 vs. 38%, p < 0.05).

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.