Functional Delineation of Hyperprolactinemic-Amenorrhea1

Abstract

To account for the development of PRL [prolactin] hypersecretion and acyclic gonadotropin release, the separate functional activity of the pituitary and the ovary were assessed in 2 overlapping groups of patients with amenorrhea-galactorrhea and comparable levels of hyperprolactinemia. Group I was composed of 13 patients with a probable microadenoma and Group II was composed of 5 patients with surgically documented pituitary PRL-secreting microadenomata. Pituitary functional capacity was determined by alternating pulses of LRF [luteinizing hormone releasing factor] (10 .mu.g) and TRF [thyrotropin releasing factor] (200 .mu.g)-3 doses of each. When responses in the early follicular phase (EF) of normal women were used as a reference point there appeared to be a progressive decline in pituitary LH [luteinizing hormone] sensitivity (.DELTA. max to 1st pulse) and reserve (net integrated release during 2nd and 3rd pulses) from Group I to Group II patients. In contrast, there was an increase in pituitary sensitivity and reserve for FSH [follicle stimulating hormone] in both groups of patients. There exists a marked reduction of the LH/FSH ratio of the releasable gonadotropin of the pituitary. These functional aberrations were associated with normal basal concentrations of LH and FSH except in Group II patients in whom significantly lower levels of FSH were found. Basal E2 [estradiol] levels were significantly lower in both groups of patients. Under these conditions, the integrated (6 h) gonadotropin release induced by LRF appears to be biologically active as evidenced by an impressive rise in circulating E/2 levels. The smaller integrated gonadotropin release in Groups II patients was associated with a correspondingly smaller increase in E/2 levels. This finding strongly suggests that in humans, the presence of hyperprolactinemia, other than in the postpartum period, may not have a measurable effect on the ovarian response to endogenous gonadotropin stimulation. Basal TSH and its response to TRF was normal but PRL responses to TRF were markedly impaired in Group I and absent in Group II patients. These functional aberrations in the 3 reproductive hormones, LH, FSH and PRL, can be readily reversed by the reduction of PRL secretion either through an increase in dopamine activity such as the adminstration of 2-Bromo-.alpha.-ergocryptine (a dopamine agonist) or by the removal of the microadenoma by microsurgery. Based on previous experimental data and the functional changes in the pituitary and ovary observed in this study, it is suggested that a primary defect in the pituitary lactotrophs-hypothalamic dopamine system results in hyperprolactinemia, acyclic gonadotropin secretion and pituitary microadenoma.