The role of antiandrogens in hormone replacement therapy

The most widely used antiandrogens in clinical practice are cyproterone acetate, a derivative of 17-hydroxyprogesterone, and dienogest, a 19-norprogestin. An established sequential preparation for hormone replacement therapy (HRT) consists of 11 days of 2 mg estradiol valerate, 10 days of 2 mg estradiol valerate with 1 mg cyproterone acetate, followed by a 7-day drug-free interval (Climen, Schering AG, Berlin, Germany). Cyproterone acetate is highly progestogenic, has no androgenic properties, and is antiandrogenic above a certain dose. Cyproterone acetate does not counteract the estrogenic effects of estradiol valerate in Climen. This therapy, therefore, has optimal effects on lipid metabolism and coronary heart disease risk, protects the endometrium and reduces menopausal symptoms, preserves bone and reduces osteoporotic fracture risk, and has antiandrogenic effects on the skin and other androgen-sensitive epidermal structures. Dienogest, on the other hand, will soon be introduced in a continuous combined HRT. Dienogest has a 17 alpha-cyanomethyl group instead of the 17 alpha-ethinyl group typical of the common 19-nortestosterone derivatives. It is also referred to as a hybrid progestogen because it has pharmacodynamic properties (e.g. antiandrogenicity) in common with progesterone derivatives. A fixed formulation containing 2 mg estradiol valerate and 2 mg dienogest (Climodien) for continuous combined HRT has been developed. This formulation had excellent effects on vasomotor and neurovegetative symptoms. The bleeding pattern was generally highly satisfactory and similar to that with Kliogest, as were the results of endometrial biopsies after 12 cycles of treatment. Lipid metabolic changes may be interpreted as beneficial. Dienogest had no adverse effects on the vasorelaxant effect of estradiol valerate in postmenopausal women, as shown by markers of vascular function. Neuropsychological studies utilizing evoked potentials showed shortening effects on sleep latency and an improvement in cognitive information processing. Continuous combined HRT with dienogest, therefore, may come to be regarded as the HRT of choice in postmenopausal patients with mood defects. In summary, HRT with antiandrogenic progestogens has its specific indications with respect to preserving metabolic estrogenicity, specific antiandrogenic effects and specific effects on vigilance and mood disorders.