Abnormal patterns of pulsatile luteinizing hormone secretion in women with hyperprolactinemia and amenorrhea: responses to bromocriptine.J Clin Endocrinol Metab. 1984 Nov; 59(5):941-8.JC
Pulsatile gonadotropin secretion was examined in seven women with hyperprolactinemia and amenorrhea by obtaining blood samples every 20 min for 24 h. When plasma PRL had returned to normal and menses had resumed during bromocriptine treatment, five women were restudied in an identical manner during the early to midfollicular stage of their cycles. Gonadotropin responses to a small dose of synthetic GnRH (25 ng/kg, iv) were measured after the initial 24-h study in each patient. In addition, low dose pulses of GnRH (25 ng/kg) were administered iv every 2 h for 88 h to three hyperprolactinemic women, and LH and FSH responses were determined. Before treatment with bromocriptine, mean +/- SE plasma gonadotropin concentrations (LH, 5.8 +/- 0.2 mIU/ml; FSH, 4.4 +/- 0.1 mIU/ml) were comparable to values during the follicular phase of normal menstrual cycles. LH pulse frequency during the pretreatment study in the hyperprolactinemic women (mean +/- SE, 7.6 +/- 1.2 pulses/24 h) was significantly less than that found during the early follicular stage of normal cycles (days 3-5; mean, 15.4 +/- 1.1 pulses/24 h). Mean +/- SE LH pulse amplitude before bromocriptine was 5.2 +/- 0.6 mIU/ml. The pattern of pulsatile LH secretion was highly variable before treatment and was characterized by prolonged periods (6-11 h) of low plasma LH concentrations. LH responses to GnRH were normal or increased (mean maximum increment in LH, 38.5 +/- 15.9; range, 4.3-125.2 mIU/ml), and no evidence of intermittent pituitary refractoriness was found during prolonged (88-h) administration of GnRH pulses. Treatment with bromocriptine was associated with the resumption of menses, and no significant change in mean gonadotropin concentrations. LH pulse frequency was increased (mean +/- SE = 10.2 +/- 1.0 pulses/24 h) and LH pulse amplitude was decreased (mean, 3.9 +/- 0.2 mIU/ml) in four of five patients receiving bromocriptine. Moreover, the pattern of pulsatile LH secretion was more uniform during treatment. We conclude that pituitary responsiveness to GnRH is not impaired in women with hyperprolactinemia and amenorrhea, and that periods of low LH secretion in these women are due to intermittent reductions in GnRH secretion. These observations suggest that the abnormal patterns of pulsatile gonadotropin secretion, and by inference GnRH secretion, are important factors in the etiology of amenorrhea associated with hyperprolactinemia.