Effective hormonal male contraceptive using testosterone undecanoate with oral or injectable norethisterone preparations

被引:91
作者
Kamischke, A
Heuermann, T
Krüger, K
Von Eckardstein, S
Schellschmidt, I
Rübig, A
Nieschlag, E
机构
[1] Univ Munster, Inst Reprod Med, D-48129 Munster, Germany
[2] Schering AG, D-13342 Berlin, Germany
关键词
D O I
10.1210/jc.87.2.530
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Suppression of spermatogenesis to azoospermia is the goal of hormonal male contraception based on T combined with gestagens. The combination of the long-acting T, ester testosterone undecanoate (TU), with norethisterone (NET) enanthate (E) showed high efficacy. In the present study, we tested the validity of this approach by varying the NET dose and mode of application. The aim of the study was to achieve high rates of suppression of spermatogenesis as reflected by sperm counts, monitor gonadotropins as well as other hormones, and evaluate any possible side effects. In a phase II clinical trial, groups of normal volunteers received: 1000 mg TU im at wk 2, 6,12, and 18 combined with 200 mg METE im at wk 0, 6, 12, and 18 (group I); 1000 mg TU im and 400 mg METE im at wk 0, 6, 12, and 18 (group II); and 1000 mg TU im at wk 0, 6, 12, and 18 with daily oral NET acetate (NETA) from wk 0 to 24 (group III). In all groups marked suppression of gonadotropins resulted in a significant decrease of spermatogenesis and azoospermia in 13/14,11/12, and 12/14 men in groups I to III, respectively. The remaining men all had less than 1 million sperm/ml. Reversible side effects included increase in body weight, erythrocytes, hemoglobin, and hematocrit and decrease in high-density lipoprotein cholesterol and alkaline phosphatase in all groups and increase in liver enzymes in the oral NETA group. This study documents the high efficacy of TU in combination with NET and confirms that this dose and mode of application (1000 mg TU im every 6 wk plus 400 mg METE im every 6 wk or plus 10 mg daily oral NETA) is as effective as the previously reported regimen containing 1000 mg TU + 200 mg METE im every 6 wk. The contraceptive efficacy of this combination of TU and METE should be evaluated in further clinical trials.
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页码:530 / 539
页数:10
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