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.
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
Zhan-Jun
ZJ
Yang
Wei-San
WS
Ye
Guang-Hui
GH
Cui
Yan
Y
Guo
She-Pu
SP
Xue
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