Metabolism of progestogens used for contraception and menopausal hormone therapy

Abstract

A variety of progestogens are widely used by women for contraception and menopausal hormone therapy. The progestogens undergo extensive metabolism by oral and parenteral routes of administration to form many metabolites. Although a small number of metabolites have been shown to be biologically active, most have not been tested for biologic activity. The present review shows that we know most about progesterone metabolism, followed by the metabolism of levonorgestrel and norethindrone. Very few studies have been carried out on metabolism of most of the progestogens. The clinical significance of this deficiency is that those progestogen metabolites that bind to the progesterone receptors may also bind to other steroid receptors and be responsible for some of the well-documented side effects of administered progestogens. We also discuss how obesity and genetic polymorphisms alter progestogen metabolism, and how development of oral progestogen formulations that are targeted to the colon, where the concentration of steroid-metabolizing enzymes is much lower than in the proximal gut, may have a beneficial effect on progestogen metabolism.