title: Contraceptive steroids influence the hemostatic activation state in healthy men.
abstract: Hormonal contraception for men requires administration of testosterone and gestagens. The effects of a long-acting testosterone ester and 2 different progestins on hemostatic activation parameters were studied in relation to cardiovascular risk. In phase 1, 7 healthy men aged 28-38 years received a single intramuscular injection of 200 mg norethisterone-enanthate (NET-EN) on Day 0. Plasma samples were obtained on Days 0, 14, 41, and 84. In phase 2, 3 groups of 14 healthy men aged 18-45 years received four injections (every 6 weeks) of 1000 mg testosterone undecanoate (TU), plus daily oral placebo or daily oral levonorgestrel (LNG, 250 microg); or four injections (every 6 weeks) of NET-EN. Treatment lasted 24 weeks. Plasma samples were obtained at weeks 0, 16, 24, and 52. All samples were assayed for levels of coagulation factors VIIc, VIIa, XIIc, and XIIa; prothrombin fragment F1+2 (F1+2); antithrombin; plasmin-alpha(2)-antiplasmin-complex (PAP); and fibrinogen. NET-EN alone led to a depletion of sexual hormones and a marked shift in hemostatic parameters with increasing levels of FXIIc, fibrinogen, antithrombin, and F1+2, whereas FVIIc and FVIIa levels decreased. PAP levels increased significantly. Opposite effects were seen in the TU/placebo group, with a significant down-regulation of fibrinolysis and the hemostatic turnover rate. Testosterone effects were attenuated by additional administration of gestagens. The effect of hormonal male contraception using long-acting testosterone esters with or without gestagens was significantly measurable within the hemostatic system. Down-regulation of the hemostatic system with testosterone alone may indicate an antithrombotic effect, whereas clinical consequences of an additional gestagen compound cannot be derived.
authors.affiliation: Institute of Reproductive Medicine of the University, Münster, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Zitzmann
authors.forename: Ralf
authors.initials: R
authors.lastname: Junker
authors.forename: Axel
authors.initials: A
authors.lastname: Kamischke
authors.forename: Eberhard
authors.initials: E
authors.lastname: Nieschlag
mesh_terms: D000328:Adult; D003272:Contraceptive Agents, Male / Q000494:pharmacology; D004347:Drug Interactions; D005342:Fibrinolysis; D006487:Hemostasis / Q000187:drug effects*; D006537:Heptanoates / Q000494:pharmacology*; D006801:Humans; D016912:Levonorgestrel / Q000494:pharmacology; D008297:Male; D009640:Norethindrone / Q000494:pharmacology*; D013739:Testosterone / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology*
chemical_list: D003272:Contraceptive Agents, Male; D006537:Heptanoates; D013739:Testosterone; D016912:Levonorgestrel; C010792:testosterone undecanoate; D009640:Norethindrone