Department of Obstetrics and Gynaecology, University of Botswana, Notwane Rd, Gaborone, Botswana.
Effective Care Research Unit, University of the Witwatersrand, Johannesburg, South Africa.
BMC Womens Health. 2024 Mar 8;24(1):167. doi: 10.1186/s12905-024-02990-8.
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.
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.
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).
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.
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.
了解激素避孕药对内源性雄激素的相对作用的可靠信息对于理解其有益和不良影响、方法选择和新方法的开发非常重要。
在东伦敦南非 ECHO 多中心随机试验的辅助研究中，我们比较了三种避孕方法对 18 至 35 岁避孕者血清雄激素水平的影响。参与者通过中央管理的随机分配接受开放标签的 depot 甲羟孕酮（DMPA-IM）、铜宫内节育器（IUD）或左炔诺孕酮植入物。主要结局是 6 个月时的游离睾酮。
我们分析了 615 名参与者中 398 名的基线和 6 个月时的血清样本（DMPA-IM 131/205、IUD 135/205 和植入物 132/205）。基线时睾酮中位数分别为 DMPA-IM 0.82、IUD 0.9 和植入物 0.87 nmol/L；6 个月时，DMPA 0.68（低于 IUD，平均百分比差异 28.35%，（p<0.001），IUD 0.86（不变）和植入物 0.66，低于 IUD，平均百分比差异-22.98%，p<0.001）。基线时 SHBG 中位数分别为 DMPA 52.4、IUD 50.5 和植入物 55.75 nmol/L；6 个月时，DMPA 40.65，低于 IUD（平均百分比差异 21.19%，p=0.005），IUD 49.1（不变），植入物 23.35 nmol/L，低于 IUD（平均百分比差异-50.04%，p<0.001 和 DMPA（平均百分比差异-39.45%，p<0.001）。基线时游离睾酮中位数分别为 DMPA 10、IUD 12 和植入物 11 pmol/L；6 个月时，DMPA 11，低于 IUD（平均百分比差异 13.53%，p=0.047），IUD 12 和植入物 14，高于 IUD（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）。
这是第一项随机试验，显示与 DMPA 相比，左炔诺孕酮植入物降低了 SHBG 并增加了游离睾酮，与报道的结合型雌二醇/左炔诺孕酮使用增加 SHBG 以及报道的 ETON 植入物降低雄激素（和受损的性功能）形成对比。与 ECHO 研究中记录的 DMPA 相比，LNG 植入物较高的游离睾酮可能会改善性功能、情绪和骨骼健康，并增加痤疮和多毛症等副作用，并且与植入物相比，与植入物相比，植入物与更多的性伴侣、新性伴侣和无保护性行为相关的更大的性行为一致。
ECHO 试验注册：ClinicalTrials.gov，编号 NCT02550067 15/09/2015。避孕，或计划生育，是妇女在社会中的核心作用。了解各种避孕选择的相对副作用的准确信息非常重要，以便赋予妇女权力，使她们能够根据自己的首选方法做出明智的选择。激素避孕药含有各种形式的女性性激素，雌激素和/或孕激素。这些激素直接作用于使用者，并且还可以调节使用者自身循环性激素的水平，包括“女性”和“男性”性激素（雄激素）。在这项研究中，要求避孕的同意参与者通过中央管理的随机分配接受 Depot 甲羟孕酮（DMPA-IM）每三个月注射一次孕激素、铜宫内节育器（IUD）、非激素避孕器插入子宫或左炔诺孕酮植入物，一种在皮下释放孕激素 5 年的装置。我们在 6 个月后测量了参与者的雄激素水平，首次发现与 DMPA-IM 相比，活性形式的睾酮（游离睾酮）高 29%。IUD 的水平居中，与其他两种方法有显著差异。这一发现与使用者的体验效果有关，因为游离睾酮对性功能、骨骼健康和情绪以及痤疮和毛发分布模式等疾病有影响。
