Session 23. Reproductive endocrinology
In order to show evidence of prolactin changes specifically related to drug use, pregnancy or the simple effect of time, the evolution of plasma prolactin (PRL) levels were studied in 176 hyperprolactinemic women (87 carrying a prolactinoma) over a mean period of four years (range between 6-180 months). Clinical presentation of the patients was amenorrhea for 110 oligomenorrhea for 37 while 29 had normal but anovulator; cycles. 107 patients underwent 191 cycles of medical tretament (mean length
... tament (mean length 11 months; range 2-43), 73 got pregnant spontaneously or during drug intake while in 38 subjects spontaneous evolution of plasma prolactin concentration was evaluated over a mean period of 19 months (range 6-72). Evaluation of prolactin changes after medical treatment pregnancy or just waiting periods showed a significant lower mean PRL level only in the idiopathic group of patients after pregnancy. PRL trend of the individual values in both groups of patients indicate that: pregnancy normalizes prolactin concentration in 49% of patients and medical therapy is linked with a normalization rate of 27%. 131. Dose-dependent suppression of serum Prolactin by cabergoline in hyperprolactinemic patients: a placebo controlled, randomized, double blind multicentre study Cabergoline is a novel dopamine agonist with very longlasting (7-14 days) Prolactin (PRL)-lowering activity after oral administration. We have investigated the efficacy and tolerability of a range of doses of cabergoline in suppressing Prolactin in hyperprolactanemic women. Patients and methods. This was a multi-centre, prospective, randomized, double-blind study involving 188 women with hyperprolactinemia secondary to a microprolactinoma (n=113, 60.1%), ideopathic disease (n=67, 35.6%), empty sella syndrome (n=5, 2.7%), or following failed surgery for prolactinoma (n=3, 1.6%). The mean age was 31.8 years (range 16-46). Patients received either placebo (n=20) or cabergoline 0.125 mg (n=43), 0.5 mg (n=42), 0.75 mg (n=42) or 1 mg (n=41) twice weekly for four weeks, the first week's treatment being half dose; There were no significant differences in age, diagnosis r previous therapy abstracts of the II Joint ESCO-ESHRE Meeting, Milan, 1990 between the 5 treatment groups; mean (± SEM) pre-treatment prolactins were 65.0 ± 6.3, 90.8 ± 14.8, 92.7 ± 13.8, 129.0 ± 20.1 and 70.0 ± 6.6 ng:ml respectively. Results; After 4 weeks treatment PRL was suppressed to below half the pre-treatment level in 5%,60%,90%,95% and 98%, and completely normalized in 0%, 30%, 74%, and 95% of patients taking placebo or cabergoline (0.125 mg, 0.5 mg, 0.75 mg and 1 mg twice weekly respectively, showing a dose-response relationship among cabergoline doses (Armitage test: p«0.01). In contrast, at these doses, adverse effects were reported in 45%, 44%, 50% and 58% of patients with no evident dose relationship. Over 95% of reported side effects were relatively trivial, most frequently transient nausea, headache and dizziness. Severe adverse events including dizziness, nausea, headache and fatigue occurred in 13 patients taking cabergoline (7.7%) but treatment had to be discontinued in only one patient who experienced severe dizziness. Conclusions. Cabergoline is effective in normalizing PRL in hyperprolactinemia at doses of 0.5 -1.0 mg twice weekly. Its tolerability and simple administration schedule represent a significant therapeutic advance in the management of hyperprolactinemia. Parlodel LAR in the chronic treatment of hyperprolactinaemic patients Parlodel LAR, a new injectable long-acting form of bromocriptine, was administered to 78 patients (63 women and 15 men) affected by prolactinomas. At the CT-Scan/NMR macroadenoma was present in 31n8 patients (pts). The initial dose of Pardlodel LAR was 25mg in 8 pts, 50mg in 62 and l00mg in the other 8 pts. AU pts received repeated injections of Parlodel LAR at the dose of 25-200mg every 28-60 days for 3-48 months. In every patient clinical evaluation, PRL plasma levels, tumor size evaluation and visual field (VF) examination were monitored. A marked decrease in PRL plasma levels was achieved in all patients whereas PRL normalization in 45n8 pts after the first injection of Parlodel LAR. Eighteen of 78 pts also had bromocriptin plasma levels assessed after the first injection of Parlodel LAR 25mg, 50mg or 100mg (6 pts/dose) to assess the dose proportionality of this injectable bromocriptin preparation. Fifteen of 18 pts ,ormalized PRL plasma levels independently of the dose. The duration of PRL suppression/normalization lasted 7 to 60 days with a positive correlation between the length of efficacy and the initial dose used. At the CT -Scan/NMR a marked tumor shrinkage (20-60%) was observed in 19/31 pts with macroprolactinoma within the first 28 days after the first dose of Parlodel LAR 50mg. After 6-12 month's therapy complete disappearance of the pituitary tumor was documented in 3/31 pts. Three of the 4 pts who had VF defects obtained a complete and quick normalization of their VF within 12-72 hours after the first injection of Parlodel LAR. The clinical symptoms/signs recorded in 72(18 pts regressed in 69n2 pts after 14-700 days treatment. No important side effects were reported except in 2 cases. Patients' compliance was very good due to the therapeutic 41 abstracts of the II Joint ESCO-ESHRE Meeting, Milan, 1990 efficacy, good tolerability and long-lasting action of Parlodel The use of an urinary LH rapid assay seems effective in LAR. Therefore, in conclusion, Parlodel LAR could be considered raising the pregnancy rate of CC therapy in infertile patients. the frrst choice treatment in pts with prolactinoma.