Novel Progestogenic Androgens for Male Contraception: Design, Synthesis, and Activity of C7 Alpha-Substituted Testosterone

The document discusses the development of novel progestogenic androgens (PAs) for male contraception, focusing on two testosterone (T) analogs: 7α-Methyltestosterone (7α-MT) and 7α-Ethyltestosterone (7α-ET). These compounds were designed to have improved androgenic and progestogenic activities compared to testosterone. The study found that both analogs showed favorable activities in androgen receptor and progesterone receptor binding and transcriptional activation assays. They were also active substrates for aromatase, which could help maintain bone mineral density, and had reduced metabolism by 5α-reductase, potentially minimizing the risk of prostatic growth. In vivo rat and rabbit bioassays demonstrated that 7α-MT and 7α-ET had superior androgenic, anabolic, and progestogenic activities compared to T. These findings suggest that 7α-MT and 7α-ET are promising candidates for further development as male contraceptive agents.