Effects of SERMs on gonadotropin secretion

Garas A, Kallitsaris A, Messsinis IE

Department of Obstetrics and Gynecology, University of Thessaly, Larissa, Greece.

Correspondence: Garas Antonis, Department of Obstetrics and Gynecology, University of Thessaly, University hospital of Larissa, GR-41110, Larissa, Greece 

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Abstract

Estrogens are predominant regulators of gonadotrophin secretion during the reproductive years. However, the descriptions of a gene encoding a second type of estrogen receptor, termed ER-β, has prompted a reexamination of the estrogen signaling system and hence of the mechanisms that regulate the gonadotrophin secretion. Recent studies have shown that estrogens may also exert biological effects through nongenomic pathways. SERMs are an interesting and clinically useful class of compounds that exert mixed estrogen agonistic and antagonistic properties, depending on the specific target-tissue. They exert their action through estrogen receptors and they appear to have different effect on gonadotrophin secretion. Clomiphene, which has been extensively investigated for its effect on the gonadotrophin secretion seems to exert an anti-estrogenic activity in women of reproductive age. In postmenopausal women clomiphene demonstrates estrogenic activity on the hypothalamic-pituitary axis. Tamoxifen demonstrates a similar to clomiphene activity on gonadotrophin secretion. Raloxifene, seems to have anti-estrogenic activity in women of reproductive age. In postmenopausal women, following raloxifene administration, the levels of gonadotrophins remain unchanged or decline slightly, action indicative of an estrogenic activity. Additionally, recent findings suggest that SERMs may act on the hypothalamic-pituitary axis through mechanisms that they do not involve the nuclear receptors (non-genomic action). More studies are needed in order to obtain further insights into the role of oestrogenic mechanisms in hypothalamic-pituitary interaction.

Key words: estrogen receptors; raloxifene; clomiphene; gonadotrophins; SERMs