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 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 42:13 :6 years), in whom the T-score L2 -L4 ranged between 21 and 22.5 S.D., were used as a control group (group 2). Serum PRL, FSH, LH and 17b-estradiol (E2) levels were evaluated at baseline and after 3 and 6 months of treatment. In all subjects, PRL responsiveness to TRH (200 mg 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 74:42 5:0 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 ð100:1^47:7 mIU=l; P , 0:05Þ and 6 months ð81:5^30:2 mIU=l; P , 0:001Þ: 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 ð770:5^47:4 mIU=l; P , 0:001Þ and it was significantly lower than in group 2 ð1068:1^301:8 mIU=l; P ¼ 0:02Þ: 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.

Effects of Neonatal Exposure to Diethylstilbestrol, Tamoxifen, and Toremifene on the BALB/c Mouse Mammary Gland1

“…Further studies are underway to establish the contribution of PRL to this phenotype. Indeed, a role for PRL is supported by the findings of Aoki Mdel et al [64], who recently demonstrated that TAM induces apoptosis in lactotrophs, while a separate study showed that administration of the antiestrogen, raloxifene, to postmenopausal women suppressed levels of serum PRL [65]. Taken together, these findings suggest that higher doses of TAM may restrict mammary development through a negative impact on pituitary cell number or function.…”

Effects of clomiphene and raloxifene on gonadotrophin secretion in postmenopausal women: evidence of nongenomic action

“…2 Serum levels (mean ± SEM) of FSH and LH in experiments (Exp) in which oestrogen-deprived postmenopausal women were treated with (a) raloxifene (R) or clomiphene (Cl) plus E2 (Group 1, n = 8), or (b) E2 plus R or Cl (Group 2, n = 8). In particular, in postmenopausal women, raloxifene at the dose of 120 mg /day for 1 week had no significant effects on basal gonadotrophin levels (Malacara et al, 2001), while at 60 mg /day raloxifene induced a significant decrease in basal FSH values at 3 months (Reindollar et al, 2002) or no change in FSH and LH values at 3 and 6 months (Lasco et al, 2002). *P < 0·05, **P < 0·01, ***P < 0·001 (difference from D0), +P < 0·05 (difference from D20).…”

“…In terms of hormonal secretion, clomiphene in oestrogen-deprived postmenopausal women demonstrates mainly oestrogenic activities suppressing basal and GnRH-induced gonadotrophin secretion, an effect that can be reversed by oestrogen pretreatment (Hashimoto et al ., 1976a;Messinis & Templeton, 1990). Little is known about the effects of this agent on basal gonadotrophin secretion because data are limited and conflicting (Baker et al ., 1998;Lasco et al ., 2002;Reindollar et al ., 2002). Little is known about the effects of this agent on basal gonadotrophin secretion because data are limited and conflicting (Baker et al ., 1998;Lasco et al ., 2002;Reindollar et al ., 2002).…”

Genetic Variation in Candidate Osteoporosis Genes, Bone Mineral Density, and Fracture Risk: The Study of Osteoporotic Fractures

“…High prolactin levels have been associated with osteopenia, decreased bone density, and increased osteoporosis risk, possibly as a result of a reduction in estrogen levels [40, 41]. In addition, long-term administration of raloxifene, which has been shown to decrease fracture risk in postmenopausal women with osteoporosis, decreases serum prolactin levels [42]. …”