据报道,使用炔诺酮(NET)庚酸酯(NET-EN)的HIV感染风险低于肌内醋酸甲羟孕酮(DMPA-IM)。我们研究了这些仅孕激素的可注射避孕药对血清睾酮和性激素结合球蛋白(SHBG)水平的影响,因为这些可能在性行为和HIV感染中起作用。开放标签的临床试验,从2018-2019年在南非的两个地点进行,将18-40岁的HIV阴性女性随机分配至150mgDMPA-IM,每周12次(n=262)或200mgNET-EN8次(n=259).我们通过UHPLC-MS/MS和SHBG通过免疫测定在基线(D0)和开始后25周(25W)的峰值血清孕激素水平(n=214-218对)收集的配对血清样品中测量了睾酮。两种避孕药都大幅减少,从D0到25W,总睾酮[DMPA-IMD00.560,25W0.423nmol/L,-24.3%(p<0.0001);NET-END00.551,25W0.253nmol/L,-54.1%,(p<0.0001)],SHBG[DMPA-IMD045.0,25W32.7nmol/L,-29.8%(p<0.0001);NET-END050.2,25W17.6nmol/L,-65.1%(p<0.0001)],并计算游离睾酮水平[DMPA-IMD06.87,25W5.38pmol/L,-17.2%(p=0.0371);净END06.00,25W3.70,-40.0%(p<0.0001)]。从D0调整后,总睾酮,DMPA-IM的SHBG和计算的游离睾酮水平明显高于NET-EN(64.9%,p<0.0001;101.2%,p<0.0001;和38.0%,分别为p=0.0120)。睾酮和SHBG水平的实质性和差异性降低并不能解释我们先前的发现,即从D0到25W,DMPA-IM或NET-EN使用者的危险性行为或性功能没有降低。甲羟孕酮(MPA)和NET是雄激素性的,并且在25W时均以超过睾酮和SHBG浓度的摩尔过量存在。避孕组内部或之间对大脑行为的任何雄激素作用都可能由MPA和NET的雄激素活性主导,而不是由内源性睾丸激素水平降低主导。该临床试验已在泛非临床试验注册中心(PACTR202009758229976)注册。
HIV acquisition risk with norethisterone (NET) enanthate (NET-EN) is reportedly less than for depo-medroxyprogesterone acetate intramuscular (DMPA-IM). We investigated the effects of these progestin-only injectable contraceptives on serum testosterone and sex hormone binding globulin (SHBG) levels, since these may play a role in sexual behavior and HIV acquisition. The open-label WHICH clinical
trial, conducted at two sites in South Africa from 2018-2019, randomized HIV-negative women aged 18-40 years to 150 mg DMPA-IM 12-weekly (n = 262) or 200 mg NET-EN 8-weekly (n = 259). We measured testosterone by UHPLC-MS/MS and SHBG by immunoassay in matched pairs of serum samples collected at baseline (D0) and at peak serum progestin levels at 25 weeks post initiation (25W) (n = 214-218 pairs). Both contraceptives substantially decreased, from D0 to 25W, the total testosterone [DMPA-IM D0 0.560, 25W 0.423 nmol/L, -24.3% (p < 0.0001); NET-EN D0 0.551, 25W 0.253 nmol/L, -54.1%, (p < 0.0001)], SHBG [DMPA-IM D0 45.0, 25W 32.7 nmol/L, -29.8% (p < 0.0001); NET-EN D0 50.2, 25W 17.6 nmol/L, -65.1% (p < 0.0001)], and calculated free testosterone levels [DMPA-IM D0 6.87, 25W 5.38 pmol/L, -17.2% (p = 0.0371); NET-EN D0 6.00, 25W 3.70, -40.0% (p < 0.0001)]. After adjusting for change from D0, the total testosterone, SHBG and calculated free testosterone levels were significantly higher for DMPA-IM than NET-EN (64.9%, p < 0.0001; 101.2%, p < 0.0001; and 38.0%, p = 0.0120, respectively). The substantial and differential decrease in testosterone and SHBG levels does not explain our previous finding of no detected decrease in risky sexual behavior or sexual function for DMPA-IM or NET-EN users from D0 to 25W. Medroxyprogesterone (MPA) and NET are androgenic and are both present in molar excess over testosterone and SHBG concentrations at 25W. Any within or between contraceptive group androgenic effects on behavior in the brain are likely dominated by the androgenic activities of MPA and NET and not by the decreased endogenous testosterone levels. The clinical
trial was registered with the Pan African Clinical Trials Registry (PACTR 202009758229976).