Effects of cyproterone acetate and ethinylestradiol on endometrial histology

The influence of cyproterone acetate (CPA) containing drugs on the endometrium has not yet been investigated. Therefore, endometrial biopsies were obtained in 22 hirsute patients between day 14 and 28 of the cycle after 7-18 months of oral antiandrogen therapy. The effects of various regimens consisting of different doses of CPA in combination with ethinylestradiol (EE) were evaluated. The low-dose standard regimen (50 micrograms of EE plus 2 mg of CPA daily from day 5 to 25) caused regressive changes in the endometrium, i.e., sparse atrophic glands, relatively compact stroma, islands of stromal edema. These alterations correspond to those induced by conventional balanced low-dose combined oral contraceptives. High-dose reversed sequential regimen (40 micrograms of EE daily from day 5 to 25 plus 100 mg of CPA daily from day 5 to 14) resulted in pseudodeciduation and massive stromal edema. Pseudodeciduation during the early secretory phase is taken as a sign of the progestational depot effect of CPA, while the stromal edema is regarded as a result of the relatively unopposed estrogen intake during the second half of the treatment cycle. Thus, the effects of CPA containing drug on the endometrium depend essentially on their type, dosage and mode of administration.