Description:
Reversible Hormonal Male Contraception with a Selective Androgen Receptor Modulator
Amanda Jones1, Dong Jin Hwang2, Duane D. Miller2, and James T. Dalton2
1 Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH 43210 and 2 Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee, Memphis, TN 38163.
Purpose To examine the reversibility of a selective androgen receptor modulator (SARM) for hormonal male contraception. Methods We previously showed that C-31, an aryl propionamide SARM discovered in our laboratories, induced azoospermia in rats with a 100% infertility rate when administered at a dose of 0.1 mg/day with estrogen benzoate (EB, 5 ug/day). C-31 maintained muscle weight while selectively decreasing weights of prostate, seminal vesicles, testis, and epididymis. In the current study, pharmacologic activity and reproductive activity of C-31 (doses ranging from 0.05 to 0.75 mg/day) combined with EB (necessary to support libido in the rat) was investigated. Male rats were treated for 70 days and a mating trial was conducted at the end of this period to assess fertility. The animals were then maintained for an additional 70 days without treatment, after which a second mating trial was performed. Endpoint markers included fertility, spermatogenesis, androgen-dependent organ weights and hormonal biomarkers. Results An 83% fertility rate was achieved 70 days after termination of treatment. However, infertility was fully reversible after 100 days, with a 100% pregnancy rate. Mean sperm counts, as well as testicular, epididymal and seminal vesicle weights were restored to that of control. Muscle weights were maintained, however, prostate weights remained below that of control. Conclusion C-31 is a tissue selective SARM with the ability to effectively and reversibly influence spermatogenesis. Supported by NIH grant #1 R01 DK 59800-07.
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