Selective oestrogen receptor modulators

Abstract

The relevance of hormone-replacement therapy (HRT) in the treatment of the short- and long-term complications of the menopause has become clearly evident. This treatment, however, has been associated with the emergence of complications, namely breast cancer and endometrial neoplasia.These side effects have led to research in the direction of tissue-specific effects leading to the evolution of selective oestrogen receptor modulators (SERMs). Tamoxifen was the first SERM employed in the prevention of breast cancer recurrence. Although anti-oestrogenic to the breast tissue, tamoxifen was found to maintain bone mass and preserve a favourable lipoprotein profile. Tamoxifen, however, led to endometrial stimulation with consequent polyp formation and hyperplasia.Raloxifene, a more recent SERM appears to have similar effects as tamoxifen on breast tissue, bone density and the lipoprotein profile. However, unlike tamoxifen, raloxifene does not appear to stimulate the endometrium – on the contrary it appears to be anti-oestrogenic to the endometrial epithelium. A more recent SERM, droloxifene appears to have a more anti-oestrogenic effect to the endometrium with bone sparing effects.Raloxifene has not been shown to improve on the short-term effects of the menopause, such as hot flushes and sweats. Similar to HRT, there appears to be a slight risk for deep vein thrombosis with raloxifene treatment.Tibolone is a SERM-like compound with beneficial effects on both the short- and the long-term complications of the menopause. Tibolone appears to have a beneficial influence of hot flushes, bone density and the lipoprotein profile. Conversely, tibolone does not appear to stimulate significantly either breast or endometrial tissue.SERMS and SERM-like compounds appear to have a promising future for the treatment and prevention of menopausal complications. Clinical proof for the affectiveness is still required. Possibly with further pharmacological manipulation more modern SERMS may be able to reduce both the short- and long-term complications of the menopause and simultaneously reduce the incidence of neoplasia such as breast and uterine carcinoma.