BROMOCRIPTINE AND OESTROGEN MODULATION OF GONADOTROPHIN RELEASE IN NORMO-AND HYPERPROLACTINAEMIC PATIENTS WITH AMENORRHOEA

Effects of oestradiol, bromocriptine, and bromocriptine plus oestradiol, on basal and GnRH stimulated gonadotrophin concentrations were studied in normo-(group 1, n= 7) and hyperprolactinaemic (group 2, n= 6) patients with secondary amenorrhoea. Before drug administration, hyper-responsiveness of LH, but normal FSH responses to GnRH were observed in most patients. Oral administration of 2 mg oestradiol for 4 days resulted in increased 17β-oestradiol levels in plasma in normal women (n= 6) in the early follicular phase of the cycle, and in groups 1 and 2. During oestradiol administration plasma LH concentration increased significantly and there was an increase of LH and FSH responses to GnRH in normal subjects, but not in amenorrhoeic women. In groups 1 and 2 basal FSH levels were suppressed but no change in GnRH stimulated gonadotrophin responses was seen. Bromocriptine (5 mg per day for 5 days) significantly decreased prolactin concentrations and increased 17β-oestradiol levels in plasma in group 2 but not in group 1. The mean plasma 17β-oestradiol concentration had increased to levels similar to those obtained during oestradiol administration alone. The mean LH response to GnRH was suppressed in group 2, but not in group 1. Basal and GnRH-stimulated plasma FSH concentrations were not changed by bromocriptine treatment. Compared with the GnRH induced LH response during bromocriptine alone, bromocriptine treatment plus oestradiol administration resulted in a significantly increased LH response in group 2. This was not found in group 1. The present results suggest that there is an increased dopamine activity and inhibition of GnRH at the hypothalamic level and a relative dopamine deficiency at the pituitary level in hyperprolactinaemic patients. Normoprolac-tinaemic patients with hypothalamic amenorrhoea have increased dopaminergic activity at the hypothalamic, as well as the, pituitary level, or alternatively that the LH release is not influenced by dopamine in these patients. Finally bromocriptine sensitizes LH-secreting cells to GnRH in hyperprolactinaemic, but not in normoprolactinaemic, patients.