一种男性注射用复方激素避孕药的疗效与安全性

Efficacy and Safety of an Injectable Combination Hormonal Contraceptive for Men.

作者信息

Behre Hermann M, Zitzmann Michael, Anderson Richard A, Handelsman David J, Lestari Silvia W, McLachlan Robert I, Meriggiola M Cristina, Misro Man Mohan, Noe Gabriela, Wu Frederick C W, Festin Mario Philip R, Habib Ndema A, Vogelsong Kirsten M, Callahan Marianne M, Linton Kim A, Colvard Doug S

机构信息

Center for Reproductive Medicine and Andrology (H.M.B.), Martin Luther University, Halle-Wittenberg, D-06120 Halle, Germany; Center of Reproductive Medicine and Andrology (M.Z.), University of Münster, Münster, Germany; Medical Research Council Centre for Reproductive Health (R.A.A.), Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, United Kingdom; Anzac Research Institute (D.J.H.), University of Sydney, and Andrology Department, Concord Hospital, Sydney, Australia; Department of Medical Biology (S.W.L.), Faculty of Medicine, University of Indonesia, Jakarta, Indonesia; Hudson Institute of Medical Research (R.I.M.), Monash Medical Centre, Melbourne, Australia; Clinic of Gynecology and Physiopathology of Reproduction (M.C.M.), University of Bologna, Bologna, Italy; National Institute of Health and Family Welfare (M.M.M.), New Delhi, India; Instituto Chileno de Medicina Reproductiva (G.N.), Santiago, Chile; Department of Endocrinology (F.C.W.W.), Manchester Royal Infirmary, Manchester, United Kingdom; Department of Reproductive Health and Research (M.R.P.F., N.A.H., K.M.V.), World Health Organization, Geneva 1211, Switzerland; and CONRAD (M.M.C., K.A.L., D.S.C.), Arlington, Virginia 22209.

出版信息

J Clin Endocrinol Metab. 2016 Dec;101(12):4779-4788. doi: 10.1210/jc.2016-2141. Epub 2016 Oct 27.

DOI:10.1210/jc.2016-2141

PMID:27788052

Abstract

CONTEXT

The development of a safe and effective reversible method of male contraception is still an unmet need.

OBJECTIVE

Evaluation of suppression of spermatogenesis and contraceptive protection by coadministered im injections of progestogen and testosterone.

DESIGN

Prospective multicentre study.

SETTING

Ten study centers.

PARTICIPANTS

Healthy men, aged 18-45 years, and their 18- to 38-year-old female partners, both without known fertility problems.

INTERVENTION

Intramuscular injections of 200-mg norethisterone enanthate combined with 1000-mg testosterone undecanoate, administered every 8 weeks.

MAIN OUTCOMES MEASURES

Suppression of spermatogenesis by ejaculate analysis, contraceptive protection by pregnancy rate.

RESULTS

Of the 320 participants, 95.9 of 100 continuing users (95% confidence interval [CI], 92.8-97.9) suppressed to a sperm concentration less than or equal to 1 million/mL within 24 weeks (Kaplan-Meier method). During the efficacy phase of up to 56 weeks, 4 pregnancies occurred among the partners of the 266 male participants, with the rate of 1.57 per 100 continuing users (95% CI, 0.59-4.14). The cumulative reversibility of suppression of spermatogenesis after 52 weeks of recovery was 94.8 per 100 continuing users (95% CI, 91.5-97.1). The most common adverse events were acne, injection site pain, increased libido, and mood disorders. Following the recommendation of an external safety review committee the recruitment and hormone injections were terminated early.

CONCLUSIONS

The study regimen led to near-complete and reversible suppression of spermatogenesis. The contraceptive efficacy was relatively good compared with other reversible methods available for men. The frequencies of mild to moderate mood disorders were relatively high.

摘要

背景

开发一种安全有效的男性可逆避孕方法仍是未满足的需求。

目的

评估联合肌内注射孕激素和睾酮对精子发生的抑制作用及避孕效果。

设计

前瞻性多中心研究。

地点

10个研究中心。

参与者

年龄在18至45岁的健康男性及其18至38岁的女性伴侣，双方均无已知生育问题。

干预措施

每8周肌内注射200毫克庚酸炔诺酮与1000毫克十一酸睾酮。

主要观察指标

通过精液分析评估精子发生的抑制情况，通过妊娠率评估避孕效果。

结果

在320名参与者中，100名持续使用者中的95.9名（95%置信区间[CI]，92.8 - 97.9）在24周内精子浓度抑制至小于或等于100万/毫升（Kaplan-Meier法）。在长达56周的疗效期内，266名男性参与者的伴侣中有4例怀孕，每100名持续使用者的妊娠率为1.57（95%CI，0.59 - 4.14）。恢复52周后精子发生抑制的累积可逆率为每100名持续使用者中的94.8名（95%CI，91.5 - 97.1）。最常见的不良事件是痤疮、注射部位疼痛、性欲增强和情绪障碍。根据外部安全审查委员会的建议，提前终止了招募和激素注射。