Treatment of severe hirsutism resulting from hyperandrogenism with the reverse sequential cyproterone acetate regimen

Women with severe hirsutism resulting from hyperandrogenism often respond poorly to suppressive therapy aimed at decreasing adrenal or ovarian androgen production. Antiandrogens, such as cyproterone acetate, prevent androgens from expressing their activity at target sites by inhibiting the formation of the androgen/cytosol binding protein complex. Seven severely hirsute hyperandrogenic women were treated for six months with the reverse sequential cyproterone acetate regimen. Pretreatment plasma testosterone (T) levels were elevated in all subjects, and sex hormone binding globulin (SHBG) binding capacity was depressed. A free testosterone index, as assessed by the T/SHBG ratio, was markedly elevated. A marked and significant decrease in T levels and the T/SHBG ratio occurred during the first two cycles of treatment (p less than 0.01). Hirsutism grading assessed by the semiquantitative method of Ferriman and Gallwey did not change significantly until four months after the beginning of therapy but improved by six months of treatment. There was a marked antigonadotropic effect in terms of suppression of LH and FSH. The reverse sequential cyproterone acetate regimen produces rapid normalization of the plasma T, SHBG and free testosterone index, but resolution of the hirsutism is slower and requires several months of therapy.