Clinical significance of the androgenicity of progestins in hormonal therapy in women

Optimal efficacy has been achieved in both oral contraception and postmenopausal replacement therapy. The current challenge is to minimize the side effects and metabolic impact of the administered hormones in both oral contraceptives and hormone replacement agents. When the dose of estrogen in oral contraceptives was reduced the risk of thromboembolism decreased, but the androgenic side effects of the progestin became increasingly apparent. The addition of progestins to hormone replacement therapy reduces the risk of endometrial cancer associated with unopposed estrogen, but their androgenicity offsets the favorable effects of estrogen on lipid metabolism. Androgens not only cause troublesome clinical side effects but also induce changes in blood levels of lipoproteins that have been associated with an increased risk of atherogenesis and coronary heart disease, as well as alterations in glucose and insulin levels. Both the side effects and the adverse effects on lipoprotein and glucose metabolism can be reduced by the use of less androgenic progestins.