Department of Medicine, University of Washington, Seattle, WA, USA.
Institute of Endocrinology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Andrology. 2019 Nov;7(6):878-887. doi: 10.1111/andr.12603. Epub 2019 Apr 10.
Novel male-based contraceptives are needed to broaden family planning choices. A progestin, Nestorone (Nes) gel, plus a testosterone (T) gel suppresses sperm concentrations to levels associated with effective contraception in normal men. However, administration of two gels on different parts of the body daily is impractical.
Compare the effectiveness of daily application of a single, combined 8.3 mg Nes-62.5 mg T gel (Nes-T) vs. 62.7 mg T gel to suppress serum FSH and LH concentrations to ≤1.0 IU/L (a threshold associated with suppression of sperm concentrations to ≤1 million and effective contraception) and to compare the pharmacokinetics of serum Nes and T concentrations between the gel groups.
We conducted a 28-day, double-blind, controlled trial of 44 healthy men randomized to daily Nes-T or T gel with measurement of hormones at baseline, treatment, and recovery and during 24-h pharmacokinetic studies on days 1 and 28 of treatment.
Of the subjects who met pre-defined inclusion criteria, 84% of the Nes-T group suppressed serum gonadotropin concentrations to ≤1.0 IU/L at days 21-28 vs. 16.7% in the T group (p < 0.001). On day 1, Nes concentrations rose significantly above baseline by 2 h and continued to rise up to 24 h after Nes-T gel application. Nes concentrations were not detectable in the T group. Serum total T concentrations rose and were significantly higher in the T gel group compared to the Nes-T group at 24 h on day 1 and days 11, 14, and 21 (p < 0.01). There were no serious adverse events in either group. About 80% of the subjects reported satisfaction with both gels.
Daily Nes-T gel effectively and safely suppresses serum gonadotropins and is acceptable to most men. It should be studied further in efficacy trials of hormonal male contraception.
需要新型男性避孕药具来拓宽计划生育选择。孕激素，Nestorone（Nes）凝胶加睾酮（T）凝胶可将精子浓度抑制至正常男性有效避孕相关水平。然而，每天在身体不同部位使用两种凝胶是不切实际的。
比较每日应用一种单一的，联合的 8.3mg Nes-62.5mg T 凝胶（Nes-T）与 62.7mg T 凝胶抑制血清 FSH 和 LH 浓度至≤1.0IU/L（与精子浓度抑制至≤100 万和有效避孕相关的阈值）的有效性，并比较两组凝胶中血清 Nes 和 T 浓度的药代动力学。
我们进行了一项为期 28 天，双盲，对照试验，共 44 名健康男性随机分为每日 Nes-T 或 T 凝胶组，在基线，治疗和恢复期以及在治疗第 1 天和第 28 天的 24 小时药代动力学研究中测量激素。
在符合预先定义的纳入标准的受试者中，84%的 Nes-T 组在第 21-28 天抑制血清促性腺激素浓度至≤1.0IU/L，而 T 组为 16.7%（p<0.001）。在第 1 天，Nes 浓度在 2 小时内显著高于基线，并持续升高至 Nes-T 凝胶应用后 24 小时。T 组中未检测到血清总 T 浓度升高，并在第 1 天和第 11、14、21 天的 24 小时时显著高于 Nes-T 组（p<0.01）。两组均无严重不良事件。约 80%的受试者对两种凝胶均表示满意。
每日 Nes-T 凝胶可有效，安全地抑制血清促性腺激素，且大多数男性均可接受。它应该在男性激素避孕的疗效试验中进一步研究。
