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.
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 sham-operated (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). The most marked increases were observed in the DMAU-treated rats in which prostate and seminal vesicle weights/kg body weight were 2.4 to 2.7 times those of intact rats, and levator ani muscle weights were increased approximately 1.5-fold. Blood was collected from the tail vein at weeks 4, 8, 12, and 16 for measurement of serum levels of androgens and at necropsy at week 18 for measurement of serum gonadotropins. Serum levels of luteinizing hormone and follicle-stimulating hormone were greatly elevated in Cx rats at week 18 and suppressed to levels comparable to those in intact rats by DMAU, 11β-MNTDC, and T implants (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.
Attardi
Barbara J
BJ
Molecular Endocrinology Laboratory, Division of Reproductive Endocrinology and Toxicology, BIOQUAL Inc, 9600 Medical Center Drive, Rockville, MD 20850, USA. bjattardi@bioqual.com
Marck
Brett T
BT
Matsumoto
Alvin M
AM
Koduri
Sailaja
S
Hild
Sheri A
SA
D015502:Absorptiometry, Photon; D045930:Anabolic Agents / Q000494:pharmacology; D000728:Androgens / Q000502:physiology; D000818:Animals; D001823:Body Composition / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D005640:Follicle Stimulating Hormone / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009277:Nandrolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000033:anatomy & histology / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012669:Seminal Vesicles / Q000033:anatomy & histology / Q000187:drug effects
C555235:11-methyl-19-nortestosterone-17-dodecylcarbonate; D045930:Anabolic Agents; D000728:Androgens; C555234:dimethandrolone-undecanoate; D009277:Nandrolone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone