Combined administration of low-dose gossypol acetic acid with desogestrel/mini-dose ethinylestradiol/testosterone undecanoate as an oral contraceptive for men.
To evaluate the efficacy and feasibility of a new regimen of low-dose gossypol acetic acid (GA) combined with desogestrel/ethinylestradiol and testosterone undecanoate (DSG/E/TU) as a male contraceptive, adult male rats were fed orally with GA (12.5 mg/kg/day) and DSG (0.125 mg/kg)/E (0.025 mg/kg)/TU (100 mg/kg) daily for 8 weeks as loading dose until infertility, and a similar low dose of GA alone for infertility maintenance. Control animals were administered a single low dose of GA (12.5 mg/kg/day) or DSG (0.125 mg/kg)/E (0.025 mg/kg)/TU (100 mg/kg), and vehicle, respectively. Results demonstrated that the combined dosage regimen could damage epididymal sperm motility and density, and induce infertility within 8 weeks in rats; the infertility could be consistently sustained by giving single GA (12.5 mg/kg/day), and was reversible in about 8 weeks following withdrawal of gossypol. The regimen rendered treated male rats with spermiation failure within a period of 6-20 weeks of treatment. Also, the serum luteinizing hormone, follicle-stimulating hormone and testicular interstitial fluid testosterone levels showed a transient decrease at the end of 6 or 8 weeks, which returned to control levels after 8 weeks of recovery phase. No hypokalemia or other adverse effects in viscera were observed. These results provide a promising approach to using the new regimen for the development of an effective and reversible oral male contraceptive.
Yang
Zhan-Jun
ZJ
Department of Anatomy, Histology and Embryology, Institute of Basic Medical Science, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China. zhanjunyang@hotmail.com
Ye
Wei-San
WS
Cui
Guang-Hui
GH
Guo
Yan
Y
Xue
She-Pu
SP
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003272:Contraceptive Agents, Male / Q000008:administration & dosage* / Q000592:standards; D003280:Contraceptives, Oral, Synthetic / Q000008:administration & dosage* / Q000592:standards; D017135:Desogestrel / Q000008:administration & dosage* / Q000592:standards; D004997:Ethinyl Estradiol / Q000008:administration & dosage* / Q000592:standards; D005298:Fertility / Q000187:drug effects; D006072:Gossypol / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000592:standards; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012726:Sexual Behavior, Animal / Q000187:drug effects; D013081:Sperm Motility / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects; D013737:Testis / Q000187:drug effects / Q000254:growth & development; D013739:Testosterone / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000592:standards
D003272:Contraceptive Agents, Male; D003280:Contraceptives, Oral, Synthetic; D013739:Testosterone; D004997:Ethinyl Estradiol; D017135:Desogestrel; C010792:testosterone undecanoate; D006072:Gossypol; C028178:gossypol acetic acid