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

Abstract

These results demonstrate for the first time that in contrast to Cl, R does not exert oestrogenic effects on basal gonadotrophin secretion. Although the antioestrogenic action of these drugs was evident only after pretreatment with E2, both R and Cl stimulated GnRH-induced gonadotrophin secretion in oestrogen-deprived women. It is hypothesized that these two compounds sensitize the pituitary to GnRH through mechanisms not involving the oestrogen receptor complex (nongenomic).

Nuclear Receptors and Their Selective Pharmacologic Modulators

“…It has also been suggested that clomifene may inhibit the estradiol-dependent proliferation of endometrial epithelial cells by inhibiting the recruitment of SRC1 to ERa and thus estradioldependent ER transactivation (Amita et al, 2010). A summary of several clinical trials revealed that clomifene is as effective as tamoxifen in inducing ovulation for infertility management, although results from another study suggest that the actions on gonadotropin-releasing hormone levels may be nongenomic in nature (Garas et al, 2004;Steiner et al, 2005).…”

Oestradiol stimulates prolactin secretion in women through oestrogen receptors

“…It is possible therefore that various pathways can be involved in the control of PRL release from the pituitary lactotrophs. It has also been suggested that raloxifene and clomiphene, although binding to oestrogen receptors, can also affect the function of pituitary gonadotrophs via nongenomic mechanisms 13 . Nevertheless, regardless of all these mechanisms, it seems from the present data that the main pathway through which E2 stimulates PRL secretion is via the oestrogen receptors.…”

“…Changes in gonadotrophin values during these experiments have already been reported 13 . Basal hormone values were calculated as the mean of the values at −15 and 0 min.…”

“…Unlike the actions of raloxifene and clomiphene in various tissues, such as the endometrium and bones, 28,29 it is evident that in terms of PRL secretion they act similarly. However, regarding gonadotrophins these two compounds affect differentially FSH and LH secretion 13 . Also, the mechanism of action is different from that of PRL.…”

“…In terms of gonadotrophin secretion, clomiphene citrate acts as an oestrogenic compound in oestrogen‐deprived postmenopausal women and as an anti‐oestrogenic when the women are pretreated with oestrogen 11,12 . Raloxifene is a new anti‐oestrogenic drug that shows actions that are different from those of clomiphene regarding the secretion of gonadotrophins with no oestrogenic activity in postmenopausal women 13 . Data on the effects of these agents on PRL secretion are scanty and mainly based on experiments in animals 14–16 .…”