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.