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Journal de pharmacologie 1983

[Dopaminergic agents in the treatment of hyperprolactinemia].

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R Mornex
B Hugues

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概要

The treatment of hyperprolactinemia with dopaminergic agents is directly correlated with the improvement of the knowledge about hypothalamic control of prolactin secretion. Since 1963 it is wellknown that the hypothalamus acts on this activity of the pituitary gland with a tonic inhibition. A prolactin inhibiting factor (PIF) was suspected for this control and the tubero-infundibular dopaminergic system was considered to modulate the secretion of PIF. In fact a lot of experience demonstrated a direct control of dopamine on pituitary gland itself (fig. 1). Ergot alkaloids are the most useful dopaminergic drugs. They derive from 6 methyl 9 ergoline (fig. 2) and, in the main group of 12 ergocryptine molecules, alpha-ergocryptine and ergocornine are the most potent (fig. 3). Bromocryptine (2 alpha-bromoergocryptine, BEC) is a compound (fig. 4) with a magnification of the effect on prolactin secretion and loss of uterotonic and vasoconstrictive effects. This drug acts directly on normal pituitary cells and on adenomas in vitro. The inhibition of secretion is first seen, followed by inhibition of synthesis. Transplanted tumors (MtTW15) are sensible to ergocornine but not to BEC. The oral administration of the drug is followed by an increase in serum concentration (fig. 5) maximum at 3 hours. The decrease of prolactin is progressive and prolonged until the 7th hour. Some similarities between the structure of dopamine and bromocryptine may explain the effect of the drug (fig. 6). Hyperprolactinemia constitutes a frequent clinical syndrome with amenorrhea-galactorrhea and sterility. The cause is a pituitary tumor composed of prolactin secreting cells. All the clinical and biological manifestations are due to high prolactin secretion and the surgical ablation of the adenoma is followed by complete cure. This result is obtained frequently in microadenomas. The medical treatment of hyperprolactinemia with BEC was initiated in 71 by Lutterbeck. Since that time a lot of clinical experiences give the same kind of results: Improvement in 100% of galactorrhea, 90% of amenorrhea and 80% of fertility. These results are now wellknown and the secondary effects of the drug are quite limited. The development of pregnancy in a patient suspected of a pituitary adenoma is a major problem which is now clearly solved. In a survey of the literature Nillius found 146 patients in this situation with only 5.6% of complication. Our experience with 18 patients is confirmative. Moreover we found after delivery a decrease of serum prolactin (fig. 7).(ABSTRACT TRUNCATED AT 400 WORDS)

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