Comparison of the Effects of Cyproterone, Cyproterone Acetate and Oestradiol on Testicular Function, Accessory Sexual Glands and Fertility in a Long-Term Study on Rats

Abstract

Treatment of adult male rats with oestradiol, cyproterone acetate or cyproterone affected spermatogenesis, accessory sexual glands and fertility in different ways. Suppression of Leydig cells, spermatogenesis, accessory sexual glands and fertility ran parallel in oestradiol-treated animals. High doses of cyproterone acetate caused severe suppression of the accessory sexual glands and fertility but had only a slight inhibitory influence on spermatogenesis, Leydig cells were only temporarily affected. With high doses of cyproterone, Leydig cells were over-stimulated initially but returned to normal appearance during treatment. There was almost no effect on spermatogenesis but the accessory sexual gland weights and fertility were markedly reduced. Recovery from any changes was rapid after cessation of cyproterone acetate and cyproterone treatment but not after oestradiol. Lower doses of cyproterone acetate and cyproterone did not affect testicular morphology but significantly depressed the accessory sexual gland weights. Different mechanisms of action for the three steroids are discussed. Objections are raised against the use of cyproterone acetate for the control of male fertility.

Further Regression of Seminal Vesicles of Castrated Guinea Pig by Administration of Cyproterone Acetate

“…Cyproterone acetate is also known to inhibit the formation of the nuclear androgen receptor complex and the retention of DHT in the male accessory sex glands of rodents [Geller et al, 1968;Liao, 1969, 1971;Walsh and Korenman, 1970;Belham and Neal, 1971;Stern and Eisenfeld, 1969], It also abolishes the effect of testosterone proprionate, androstenedione. DHEA, ACTH and prolactin on the rat prostate [Neumann et al, 1970], Other effects of cyp roterone acetate include the displacement of androgen from their specific cytosol receptor and the inhibition of steroid synthesis by the Leydig cells [Neumann et al, 1966;Hoffmann and Brener, 1968;Steinbeck, et al, 1971;Grant and Stitch, 1973;Neumann and Steinbeck, 1974]. Little is known about the fate of the cytosol receptor-antiandrogen complex.…”

Action of Cyproterone Acetate on Male Reproductive Functions

“…Steinbeck et al [26] have expressed strong reservations against the use of cyproterone acetate as a contraceptive agent for men. These observations are based primarily on studies of W h a len and Lu t t g e [33], Steinbeck et al [26] and of other earlier studies by N eu m a n n et al [16] who used very high doses of cyproterone acetate.…”

“…These observations are based primarily on studies of W h a len and Lu t t g e [33], Steinbeck et al [26] and of other earlier studies by N eu m a n n et al [16] who used very high doses of cyproterone acetate. It is clear that such antifertility effects reported by W halen and L u t t g e [33] in which the accessory glands were atrophic and spermatogenesis was partially impaired, would be unacceptable for use in men.…”

“…16 for review of literature). Cyproterone acetate inhibits spermatogenesis in the presence of normal interstitial tissue by antiandrogenic action of the steroid at the level of the germinal epithelium [26]. Since the seminiferous tubules are exposed to a higher concentration of androgen than that present in the peripheral blood [14], much lower amounts of antiandrogen are needed to suppress the function of the accessory organs than for the inhibition of spermiogenesis [16]; even among the accessory glands, the response to cyproterone acetate appears to be variable and dose-dependent [20].…”

Some effects of cyproterone and cyproterone acetate on the reproductive physiology of the male rat

“…The precise mechanism whereby antiandrogens such as cyproterone and cyproterone acetate inhibit androgen activity both peripherally and centrally and the overall effects produced in vivo by the drugs have evoked numerous studies (Stern & Eisenfeld, 1969; Singh & Rajalakshmi, 1970;Steinbeck, Mehring & Neumann, 1971;Walsh, Swerdloff & Odell, 1972;Hasan, Neumann & Schenck, 1973;Neumann & Steinbeck, 1975; Schenck, Elger, Schopflin & Neumann, 1975).…”