Long-term effects of dimethandrolone 17β-undecanoate and 11β-Methyl-19-Nortestosterone 17β-dodecylcarbonate on body composition, bone mineral density, serum gonadotropins, and androgenic/anabolic activity in castrated male rats

Abstract

The potent androgens dimethandrolone 17β-undecanoate (DMAU) and 11β-methyl-19-nortestosterone 17β-dodecylcarbonate (11β-MNTDC) are in development for androgen replacement therapy and hormonal contraception in men. They can be delivered either orally or as long-acting injectables. In the current study, their long-term effects on body composition (percentage lean and fat mass); bone mineral density (BMD); serum gonadotropin levels; and weights of the prostate, seminal vesicles, and levator ani muscle were assessed. Four-week-old male rats were shamoperated (intact) or castrated (Cx) and treated subcutaneously for 16 weeks postsurgery with vehicle (Cx, intact), DMAU, or 11β-MNTDC every 4 weeks; testosterone enanthate (TE) every 2 weeks; or a testosterone (T) implant. There were significant differences in body weights over time with a general trend of intact = Cx + T = Cx + TE > Cx + 11β-MNTDC > Cx > Cx + DMAU. At week 18, rats were evaluated by dual-energy x-ray absorptiometry using the whole-body function of the Hologic software. The percentage lean body mass and BMD were lower (P < .05) in Cx rats than intact rats but equivalent in all groups of androgen-treated Cx rats and intact rats (P > .05). The highest percentage body fat was observed in Cx rats. Only DMAU- and 11β-MNTDC-treated rats had lower percentage body fat compared with Cx rats (P < .05). Prostate, seminal vesicles, and levator ani muscle weights, corrected for final body weight, were decreased (P < .05) in Cx compared with intact rats and increased to varying extents in androgen-treated Cx rats compared with Cx rats (P .05). Collectively, our data indicate that androgen replacement with DMAU or 11β-MNTDC in Cx rats resulted in favorable changes in body composition and maintenance of BMD comparable to those of T.