背景:关于激素避孕药对内源性雄激素的相对影响的可靠信息对于了解有益和不利影响很重要,方法选择和开发新方法。
方法:在东伦敦的这项辅助研究中,ECHO多中心随机试验的南非地点,我们比较了3种避孕方法对18~35岁避孕者血清雄激素水平的影响.参与者通过集中管理的随机化分配到开放标签仓库醋酸甲羟孕酮(DMPA-IM),铜宫内节育器(IUD)或左炔诺孕酮植入物。主要结果是6个月时的游离睾酮。
结果:我们分析了398/615参与者(DMPA-IM131/205,IUD135/205和植入物132/205)的储存基线和6个月血清样本。基线时的中位睾酮水平为DMPA-IM0.82,IUD0.9和植入物0.87nmol/L;在6个月时,DMPA0.68(低于宫内节育器,平均百分比差异28.35,(p<0.001),宫内节育器0.86(不变)和植入物0.66,低于宫内节育器,平均百分比差异-22.98,p<0.001)。基线时的中位数SHBG水平为DMPA52.4,IUD50.5和植入物55.75nmol/L;在6个月时,DMPA40.65,低于宫内节育器(平均百分比差异21.19,p=0.005),宫内节育器49.1(不变),植入物23.35nmol/L,低于IUD(平均百分比差异-50.04,p<0.001,低于DMPA(平均百分比差异-39.45,p<0.001)。基线时的游离睾酮水平为DMPA10,IUD12和植入物11pmol/L;在6个月时,DMPA11,小于宫内节育器(平均百分比差异13.53,p=0.047),宫内节育器12和植入物14,高于宫内节育器(平均百分比差异14.15,p=0.038)和DMPA,(平均百分比差异29.60,p<0.001)。
结论:这是第一个随机试验,显示左炔诺孕酮植入物的SHBG和游离睾酮水平低于DMPA,与口服乙炔雌二醇/左炔诺孕酮联合使用增加SHBG的报道相比,和减少的雄激素(和性功能受损)报告与依托诺孕酮植入物。使用液化天然气植入物的较高游离睾酮可能会改善性功能,情绪和骨骼健康以及增加的副作用,如痤疮和多毛症,并且与更大的性活动(关于多个性伴侣,与ECHO研究中记录的DMPA相比,植入了新的性伴侣和无保护的性行为)。
■ClinicalTrials.gov,编号NCT0255006715/09/2015。避孕,或者计划生育,是妇女在社会中的核心角色。最重要的是要获得有关各种避孕选择的相对副作用的准确信息,以便使妇女能够就其首选方法做出明智的选择。荷尔蒙避孕药含有各种形式的女性性激素,雌激素和/或孕激素。这些激素对使用者有直接影响,以及改变使用者自身循环性激素的水平,“女性”和“男性”性激素(雄激素)。在这项研究中,同意参与者要求避孕,被随机分配接受醋酸甲羟孕酮(DMPA-IM)的3个月孕激素注射,铜宫内节育器(IUD),插入子宫内的非激素避孕药,或者左炔诺孕酮植入物,放置在皮肤下的装置,可释放孕激素5年。我们测量了参与者6个月后的雄激素水平,并首次发现植入物的睾酮活性形式(游离睾酮)比DMPA-IM高29%。宫内节育器的水平处于中等水平,与其他两种方法有很大不同。这一发现与这些方法的用户所经历的效果有关,因为游离的睾酮对性功能有影响,骨骼健康和情绪,以及痤疮和头发分布模式等条件。
BACKGROUND: Robust information on relative effects of hormonal contraceptives on endogenous androgens is important for understanding beneficial and adverse effects, method choice and development of new methods.
METHODS: In this ancillary
study at the East London, South Africa site of the ECHO multicentre randomized
trial, we compared effects of three contraceptive methods on serum androgen levels among contraceptive users aged 18 to 35 years. Participants were allocated by centrally-managed randomization to open label depot medroxyprogesterone acetate (DMPA-IM), copper intrauterine device (IUD) or levonorgestrel implant. The primary outcome was free testosterone at 6 months.
RESULTS: We analysed stored baseline and 6-month serum samples in 398/615 participants (DMPA-IM 131/205, IUD 135/205 and implant 132/205). Median testosterone levels at baseline were DMPA-IM 0.82, IUD 0.9 and implant 0.87 nmol/L; at 6 months, DMPA 0.68 (lower than IUD, mean percentage difference 28.35, (p < 0.001), IUD 0.86 (unchanged) and implant 0.66, lower than IUD, mean percentage difference - 22.98, p < 0.001). Median SHBG levels at baseline were DMPA 52.4, IUD 50.5 and implant 55.75 nmol/L; at 6 months, DMPA 40.65, lower than IUD (mean percentage difference 21.19, p = 0.005), IUD 49.1 (unchanged), and implant 23.35 nmol/L, lower than IUD (mean percentage difference - 50.04, p < 0.001 and than DMPA (mean percentage difference - 39.45, p < 0.001). Free testosterone levels at baseline were DMPA 10, IUD 12 and implant 11 pmol/L; at 6 months, DMPA 11, less than IUD (mean percentage difference 13.53, p = 0.047), IUD 12 and implant 14, higher than IUD (mean percentage difference 14.15, p = 0.038) and than DMPA, (mean percentage difference 29.60, p < 0.001).
CONCLUSIONS: This is the first randomized
trial to show lower SHBG and higher free testosterone with the levonorgestrel implant than with DMPA, and contrasts with reports of increased SHBG with combined oral ethinyl estradiol/levonorgestrel use, and reduced androgens (and impaired sexual function) reported with the etonorgestrel implant. The higher free testosterone with the LNG implant might improve sexual function, mood and bone health as well as increasing side-effects such as acne and hirsutism, and is consistent with the greater sexual activity (with respect to multiple sex partners, new sex partner and unprotected sex) with the implant compared with DMPA documented in the ECHO
study.
UNASSIGNED: ClinicalTrials.gov , number NCT02550067 15/09/2015. Contraception, or family planning, is central to the role of women in societies. It is most important to have accurate information on the relative side-effects of various contraceptive options in order to empower women to make informed choices regarding their preferred method. Hormonal contraceptives contain various forms of the female sex hormones, estrogens and/or progestogens. These hormones have direct effects on the users, as well as modifying the levels of the users\' own circulating sex hormones, both the \'female\' and the \'male\' sex hormones (androgens). In this
study, consenting participants requesting contraception, were allocated randomly to receive either depot medroxyprogesterone acetate (DMPA-IM) a 3-monthly progestogen injection, the copper intrauterine device (IUD), a non-hormonal contraceptive inserted within the womb, or the levonorgestrel implant, a device placed under the skin which releases a progestogen for 5 years. We measured the participants\' androgen levels after 6 months, and found for the first time that the active form of testosterone (free testosterone) was 29% higher with the implant than with DMPA-IM. The level with the IUD was intermediate, and significantly different from the other two methods. This finding is relevant to the effects experienced by users of these methods, because free testosterone has effects on sexual function, bone health and mood, as well as on conditions such as acne and hair distribution patterns.