The need for tissue selective menopausal agents

Abstract

For decades, hormone therapy (HT) has been the mainstay for managing menopausal symptoms. However, fear of breast cancer, as well as side-effects such as breast pain and return of vaginal bleeding, have made many women stop HT or refuse to take it. There is therefore a clear need for alternative treatments. Recent years have seen the development of hormonal agents with selective effects, such as tibolone. Tibolone has a unique mode of action and is described as a STEAR (Selective Tissue Estrogenic Activity Regulator). The main action of tibolone is mediated through two 3-hydroxy metabolites; small amounts of a third metabolite are also found in the circulation. In the brain, the effect is estrogenic and perhaps androgenic and, as such, tibolone relieves hot flushes and improves energy and sexual well-being. The uterus converts tibolone and its hydroxy metabolites into a Δ4 metabolite that has a progestogenic effect. In the breast, the metabolites of tibolone inhibit key enzymes that result in estrogen depletion within the breast itself. Clinically, tibolone does not stimulate the breast and it does not increase mammographic density. There are several key large, placebo-controlled international trials of tibolone currently underway, one of which (LIBERATE) aims to test the safety of tibolone (vs placebo) in women with a history of breast cancer who are suffering from climacteric symptoms.