Table 1 Summary of clinical trials investigating NES/T, DMAU, and 11β-MNTDC

NES/T

Blithe and Myer 2023 [36, 37]

Ongoing phase II trial of 76–80 weeks daily topical NES/T for contraceptive efficacy; secondary outcomes include suppression of spermatogenesis, reversibility (recovery of spermatogenesis post-trial), hormone levels, mood symptoms, sexual side effects, and prostate function. N = 462 healthy couples. Primary endpoint completion estimated for September 2023 with full study completion by December 2024.

Anawalt et al. 2019 [38]

Double-blinded phase I RCT of 28 days daily application of NES/T 8.3 mg/62.5 mg gel demonstrated gonadotropin suppression in 84% of participants without serious adverse events. N = 44 healthy males.

Ilani et al. 2012 [39]

Double-blinded RCT of 6 months daily application of 10 g T with 0, 8, or 12 mg NES gel demonstrated sperm suppression in 23, 89, and 88% of men, respectively. T levels did not significantly change in any group, and adverse events were mild and minimal. N = 99 healthy males.

Mahabadi et al. 2009 [40]

RCT of 20 days daily application of NES, T, or combination (NES + T). 92% of participants who achieved gonadotropin suppression had suppressed spermatogenesis after 3–4 weeks. Three subjects withdrew, but no serious adverse events were reported. N = 119 healthy males.

DMAU

Wang and Page 2023 [41]

Ongoing placebo-controlled, double-blinded phase I RCT of single IM (80-800 mg) or SC (50-200 mg) injection of DMAU assessing safety, tolerability, mood symptoms, sexual function, and overall health parameters. Secondary outcomes include suppression of gonadotropins, T, E2, SHBG, and spermatogenesis. N = 84 healthy males. Completion estimated for December 2024.

Wang and Page 2020 [42]

Placebo-controlled, double-blinded phase II RCT of 12 weeks daily oral DMAU alone or with LNG after meal containing 25-30 g fat to assess suppression of spermatogenesis. Secondary outcomes include gonadotropin suppression, sperm counts, hormone changes, mood symptoms, sexual function, and overall health parameters. N = 100 health males. Publication of results is pending.

Thirumalai et al. 2019 [43]

Placebo-controlled, double-blinded phase I RCT of 28 days daily oral DMAU from 100-400 mg after meal containing 25-30 g fat assessing safety, tolerability, and adverse events. Secondary outcomes included pharmacokinetics, pharmacodynamics, hormone changes, and sperm counts. DMAU suppressed T at even the lowest dose and caused dose-dependent suppression of LH and FSH. No serious adverse events observed. N = 82 healthy males.

Ayoub et al. 2017 [44]

Placebo-controlled, double-blinded phase I RCT of single oral dose of 100-400 mg oral DMAU formulated in castor oil, self-emulsifying drug delivery system (SEDDS), or powder capsule fasted or following high-fat (50% calories as fat) meal assessing pharmacokinetics and pharmacodynamics, gonadotropin suppression, and hormone changes. High-fat meals increased absorption with all formulations, and DMAU exhibited dose-dependent suppression of gonadotropins, T, and E2 without serious adverse events. N = 44 healthy males.

Surampudi et al. 2014 [45]

Placebo-controlled, double-blinded phase I RCT of single oral dose of 25-800 mg DMAU in powder capsule fasted or following high-fat (50% calories as fat) meal assessing pharmacokinetics, safety, and dietary fat’s effect on absorption. High-fat meals increased absorption, and DMAU exhibited dose-dependent suppression of gonadotropins, T, and E2 without serious adverse events. N = 19 healthy males.

11β-MNTDC

Yuen et al. 2020 [46, 47]

Placebo-controlled, double-blinded phase II RCT of single oral dose of 200 or 400 mg 11β-MNTDC assessing pharmacokinetics and pharmacodynamics. Secondary outcomes included gonadotropin suppression, hormone changes, mood, and sexual function. 11β-MNTDC exhibited dose-dependent suppression of gonadotropins and T with only mild side effects. N = 42 healthy males.

Wu et al. 2019 [48]

Placebo-controlled, double-blinded phase I RCT of single oral dose of 100-800 mg 11β-MNTDC fasting or following high-fat (50% calories as fat) meal assessing receptor affinity. Secondary outcomes included safety, tolerability, pharmacokinetics, gonadotropin suppression, and hormone changes. 11β-MNTDC’s active metabolite demonstrated balanced affinity for androgen and progesterone receptors. 11β-MNTDC was well-tolerated and suppressed T without serious adverse events. N = 12 healthy males.