Effects of long-lasting raloxifene treatment on serum prolactin and gonadotropin levels in postmenopausal women

Abstract

Objective: To evaluate the effects of a 6 month administration of raloxifene hydrochloride, a selective estrogen receptor modulator which was recently approved for the prevention of osteoporosis, on serum gonadotropin and prolactin (PRL) levels and on TRH-stimulated PRL responsiveness in postmenopausal women who have not undergone estrogen replacement therapy. Design and methods: Sixteen healthy postmenopausal women were divided into two groups on the basis of their bone status, evaluated by dual energy X-ray absorptiometry at the lumbar level. Eight women (chronological age 52.4±4.1 (S.D.) years, menopausal age 42.4±3.9 years), in whom T-score L2-L4 was less than -2.5 S.D., were treated with raloxifene (60 mg p.o.) administered daily for 6 months (group 1), while the other eight women (chronological age 52.6±2.5 years, menopausal age 42.1± 3.6 years), in whom the T-score L2-L4 ranged between -1 and -2.5 S.D., were used as a control group (group 2). Serum PRL, FSH, LH and 17β-estradiol (E2) levels were evaluated at baseline and after 3 and 6 months of treatment. In all subjects, PRL responsiveness to TRH (200 μg i.v.) administration was evaluated at baseline and at the end of the study. Results: At baseline, mean PRL, LH and FSH levels were not significantly different in the two groups (PRL 133.6±21.7 vs 136.7±28.1 mIU/l (NS), LH 25.1±6.8 vs 24.4±6.7 mIU/ml (NS), FSH 74.4± 25.0 vs 71.1±24.1 mIU/ml (NS), in group 1 and group 2 respectively). No significant variations in serum FSH and LH values, in either group, or in serum PRL levels in group 2, were observed at the 3 and 6 month examinations. On the contrary, serum PRL values decreased significantly in group 1 after 3 months (100.1±47.7 mIU/l, P < 0.05) and 6 months (81.5±30.2 mIU/l, P < 0.001). At baseline, no significant differences were observed in the TRH-stimulated serum PRL peak between the groups (1015.4±30.5 vs 1030.2±25.7 mIU/l in group 1 and in group 2 respectively), while it decreased significantly at the 6 month examination in group 1 (770.5±47.4 mIU/l, P < 0.001) and it was significantly lower than in group 2 (1068.1±301.8 mIU/l, P = 0.02). Serum E2 was not detected at baseline and at each examination, in all patients. Conclusions: The decrease of PRL values induced by long-term raloxifene administration in postmenopausal women could be explained by a direct antiestrogenic effect of raloxifene on lactotrope cells or by the recently suggested increase of opiatergic tone on the hypothalamic-pituitary region.