Effective Care Research Unit, Eastern Cape Department of Health/Universities of the Witwatersrand and Fort Hare, East London, South Africa.
Wits MRU (MatCH Research Unit), Department of Obstetrics and Gynecology, Faculty of Health Sciences, University of the Witwatersrand, Durban, South Africa.
PLoS One. 2024 Mar 26;19(3):e0295764. doi: 10.1371/journal.pone.0295764. eCollection 2024.
Observational data suggest lower HIV risk with norethisterone enanthate (NET-EN) than with depo-medroxyprogesterone acetate intramuscular (DMPA-IM) injectable contraceptives. If confirmed, a switch between these similar injectable methods would be programmatically feasible and could impact the trajectory of the HIV epidemic. We aimed in this paper to investigate the effects of DMPA-IM and NET-EN on estradiol levels, measures of depression and sexual activity and menstrual effects, relevant to HIV risk; and to ascertain whether these measures are associated with estradiol levels.
This open-label trial conducted at two sites in South Africa from 5 November 2018 to 30 November 2019, randomized HIV-negative women aged 18-40 to DMPA-IM 150 mg intramuscular 12-weekly (n = 262) or NET-EN 200 mg intramuscular 8-weekly (n = 259). Data were collected on hormonal, behavioral and menstrual effects at baseline and at 25 weeks (25W).
At 25W, median 17β estradiol levels were substantially lower than at baseline (p<0.001) for both methods: 76.5 pmol/L (interquartile range (IQR) 54.1 to 104.2) in the DMPA-IM group (n = 222), and 69.8 pmol/L (IQR: 55.1 to 89.3) in the NET-EN group (n = 225), with no statistical difference between the two methods (p = 0.450). Compared with DMPA-IM, NET-EN users reported significantly less amenorrhoea, fewer sexual acts, fewer users reporting at least one act of unprotected sex, more condom use with steady partner, more days with urge for sexual intercourse, more days feeling partner does not love her, and more days feeling sad for no reason. We did not find a clear association between estradiol levels and sexual behavior, depression and menstrual effects. Behavioral outcomes suggest less sexual exposure with NET-EN than DMPA-IM. The strength of this evidence is high due to the randomized study design and the consistency of results across the outcomes measured.
Estradiol levels were reduced to postmenopausal levels by both methods. Secondary outcomes suggesting less sexual exposure with NET-EN are consistent with reported observational evidence of less HIV risk with NET-EN. A randomized trial powered for HIV acquisition is feasible and needed to answer this important question.
PACTR 202009758229976.
观察性数据表明，使用庚酸炔诺酮（NET-EN）比使用醋酸甲羟孕酮肌内注射（DMPA-IM）避孕药的 HIV 风险更低。如果这一结果得到证实，那么在这两种类似的注射方法之间进行转换在方案上是可行的，并且可能会影响 HIV 流行的轨迹。我们旨在本文中调查 DMPA-IM 和 NET-EN 对雌二醇水平、抑郁和性行为以及月经影响的影响，这些因素与 HIV 风险相关；并确定这些措施是否与雌二醇水平相关。
本项于 2018 年 11 月 5 日至 2019 年 11 月 30 日在南非的两个地点进行的开放性标签试验，将年龄在 18-40 岁之间的 HIV 阴性女性随机分配至 DMPA-IM（150mg 肌内注射，每 12 周 1 次）或 NET-EN（200mg 肌内注射，每 8 周 1 次）组（n=262）或 NET-EN 组（n=259）。在基线和 25 周（25W）时收集激素、行为和月经影响的数据。
在 25W 时，两种方法的中位 17β雌二醇水平均明显低于基线（p<0.001）：DMPA-IM 组为 76.5pmol/L（四分位距（IQR）54.1 至 104.2）（n=222），NET-EN 组为 69.8pmol/L（IQR：55.1 至 89.3）（n=225），两种方法之间无统计学差异（p=0.450）。与 DMPA-IM 相比，NET-EN 使用者报告的闭经更少，性行为次数更少，报告至少一次性行为无保护措施的使用者更少，与稳定伴侣使用避孕套的更多，有性交冲动的天数更多，感觉伴侣不爱她的天数更多，以及无缘无故感到悲伤的天数更多。我们没有发现雌二醇水平与性行为、抑郁和月经影响之间存在明确的关联。行为结果表明 NET-EN 比 DMPA-IM 具有更少的性暴露。由于采用了随机研究设计和所测量的结果的一致性，因此该证据的强度很高。
两种方法均将雌二醇水平降低至绝经后水平。NET-EN 报告的次要结果表明性行为的性暴露较少，这与观察性研究报告的 NET-EN 与 HIV 风险较低的结果一致。对于 HIV 获得的随机试验具有可行性，并且需要回答这个重要的问题。
PACTOR 202009758229976。
