dihydroergotoxine and Hyperprolactinemia

The PRL-inhibiting and ovulation-inducing effects of hydergine were studied in 18 patients with hyperprolactinemic ovulatory disturbances. The women were divided into 2 groups of 9 each. Those in group A had basal serum PRL levels higher than 100 micrograms/L, and those in group B had basal serum PRL levels lower than 100 micrograms/L. Serum PRL levels in both groups were determined before and hourly for 8 h after a single oral dose of either 2 mg hydergine or placebo. Hydergine induced a significant (P less than 0.01) decrease in the serum PRL level, compared with placebo, in both groups. The fall in mean serum PRL in group A was significant (P less than 0.05) 300 min after hydergine administration, and the concentration remained low at 480 min, at 45.5% of the mean baseline value. However, the serum PRL concentration did not reach the normal PRL range in any group A patient. Chronic treatment with this drug (2 mg, 3 times daily, for 4-12 weeks) in 5 patients from group A normalized the serum PRL concentration in only 1 patient and did not induce ovulation in any patient. In group B, also, hydergine administration significantly (P less than 0.01) reduced the mean serum PRL concentration within 240 min, and it declined further to within the normal range. The mean maximal reduction was to 56.4% of the baseline value at 360 min. All of the group B women received chronic treatment (2 mg, 3 times daily, for 4-104 weeks); repeated ovulation was induced in 7 (78%). Seven pregnancies ensued in 6 of the women in whom ovulation had been induced, and 4 normal infants were delivered. There were no side-effects, such as nausea and vomiting, during these trials. These data indicate that hydergine has PRL inhibitory activity and is useful in the treatment of hyperprolactinemic anovulatory patients whose basal serum PRL concentrations are below 100 micrograms/L.

Topics: Adolescent; Adult; Anovulation; Bromocriptine; Dihydroergotoxine; Dose-Response Relationship, Drug; Female; Humans; Hyperprolactinemia; Prolactin; Random Allocation

Osteocalcin (OC) concentration, a specific index of bone formation, was measured in 29 female patients with microprolactinoma (serum prolactin, PRL: 105 +/- 10.9 ng/ml; mean +/- SE). Mean OC levels were significantly lower than in controls (1.7 +/- 0.2 vs 5.1 +/- 0.3 ng/ml; p less than 0.001), being below the normal range in 28 out of 29 patients. All patients were treated with dopaminergic agents (dihydroergocriptine, bromocriptine or cabergoline). After treatment mean serum PRL levels were significantly reduced (12 +/- 3.1 ng/ml; p less than 0.001), a full normalization being obtained in 26 patients. There were no significant differences in both basal and after treatment PRL levels among patients treated with different drugs, although a greater PRL decrease was induced by cabergoline. Serum OC levels significantly increased after 12 month therapy (4.7 +/- 0.6 ng/ml, p less than 0.001), a normal concentration being reached in 14 of 29 cases. During treatment there were no significant differences in serum estradiol and PRL concentrations between patients who normalized or not their OC levels, while the reduction in PRL levels with respect to baseline was more pronounced in the former group. The absolute increase in OC levels positively correlated with serum PRL decrements (p less than 0.01). It is noteworthy that serum OC normalized in 1/10 patients during dihydroergocriptine, 3/8 during bromocriptine and 10/11 during cabergoline. Four patients, previously treated with dihydroergocriptine and bromocriptine without normalizing OC and PRL levels, underwent a second course of therapy with cabergoline and then normalized OC concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Antineoplastic Agents; Bone Density; Cabergoline; Dihydroergotoxine; Dopamine Agents; Ergolines; Estradiol; Female; Humans; Hyperprolactinemia; Osteocalcin; Pituitary Neoplasms; Prolactin; Prolactinoma