Evaluation of STS-557 as an oral contraceptive in male rat.
To examine the nature and site of post-testicular antifertility action of STS-557 (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4,9-dien-3-one), male rats were given the steroid orally daily for 60 days. In doses of 1 and 5 mg per animal per day it had no effect on fertility at the end of 3 weeks of treatment. When the treatment was extended for 60 days, spermatogenic arrest and loss of libido were evident in animals treated with 5 mg dose; animals receiving 1 mg dose of steroid showed no decrease of spermatogenesis or sexual activity and their fertility remained unaffected. In 35-day-old growing rats the steroid produced inconsistent effects on spermatogenesis after a 15-day treatment period at 1 and 5 mg doses. Both in adult and in growing rats the steroid caused a significant reduction in the weights and secretory function of the epididymis and other accessory sex organs; a dose-dependent response was seen in all the sex organs. Evaluation in castrated rat model revealed that STS-557 is a weak anti-androgen. Although this steroid is a potent inhibitor of spermatogenesis, its inhibitory effect on Leydig cell function is a contraindication for its use as a male oral contraceptive.
Division of Endocrinology, Central Drug Research Institute, Lucknow, India.
A
A
Srivastava
J P
JP
Maikhuri
B S
BS
Setty
D000818:Animals; D003272:Contraceptive Agents, Male; D004305:Dose-Response Relationship, Drug; D004822:Epididymis / Q000187:drug effects / Q000254:growth & development; D005837:Genitalia, Male / Q000187:drug effects; D008297:Male; D009277:Nandrolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013737:Testis / Q000033:anatomy & histology / Q000187:drug effects; D013739:Testosterone / Q000037:antagonists & inhibitors
D003272:Contraceptive Agents, Male; D013739:Testosterone; C023635:dienogest; D009277:Nandrolone