Why Did the Last Hormonal Male Birth Control Trial Stop, and What Does New Research Say?

Published October 30, 2026 · Investigational · Not approved

The most-cited setback in male birth control is a trial that worked, and stopped anyway. In 2011, a multinational study of a hormonal injection for men was halted early after a safety review, mainly over mood-related side effects. In October 2026, researchers published a new look at that trial's blood samples in Human Reproduction Open. Here's what happened, what the new paper found, and why it matters for hormonal candidates still in development. Every product mentioned is investigational and not approved.

The trial: two hormone shots every eight weeks

The study was run by WHO's reproductive health research department and CONRAD, and its results were published in 2016 in the Journal of Clinical Endocrinology & Metabolism. It enrolled 320 healthy men aged 18 to 45, with their female partners, at 10 centers. Every 8 weeks the men got two injections: 200 mg of norethisterone enanthate (NET-EN), a progestin that suppresses sperm production, and 1,000 mg of testosterone undecanoate, to keep testosterone levels up.

By its own measures, the regimen performed well. The paper reports that 95.9 of every 100 continuing users suppressed their sperm count to 1 million/mL or less within 24 weeks. During the efficacy phase, 4 pregnancies occurred among the partners of 266 men, a rate of 1.57 per 100 continuing users. After 52 weeks of recovery, sperm production had returned in 94.8 of every 100 continuing users [1].

Why it stopped

The paper explains that the trial's own Data Safety and Monitoring Committee reviewed interim data in January 2011 and found the study met all criteria to continue. But in March 2011, WHO's Research Project Review Panel, an external peer-review committee, reviewed the same data and decided that, for safety reasons, recruitment should stop and men should stop getting injections. The adverse events that concerned the panel were mood changes, depression, injection-site pain and increased libido [1].

The most common adverse events overall were acne, injection-site pain, increased libido and mood disorders. Twenty men left the study because of product-related side effects, 6 of them for mood changes alone. The authors concluded the regimen gave "near-complete and reversible suppression" of sperm production but that "the frequencies of mild to moderate mood disorders were relatively high" [1].

The new analysis: does DHT explain who had side effects?

The new Human Reproduction Open paper is a secondary analysis of the same trial. Of the 320 men, 255 had serum samples available for central testing. Samples from the Jakarta, Indonesia center (65 men) were never sent to the central lab. The researchers measured testosterone, free testosterone, dihydrotestosterone (DHT, a hormone the body makes from testosterone), estradiol and norethisterone, then grouped the men by region [2].

They report "marked" differences between regions [2]:

Chile: higher testosterone and persistently higher DHT, with more reports of increased libido.
India: lower DHT and higher norethisterone levels, with no reported libido or mood changes.
Europe and Australia: comparatively lower DHT and the highest cumulative rate of mood disorders.

Across the analysis, declining DHT was associated with decreased libido and mood-related adverse events. The authors suggest that measuring DHT and other androgens could someday help identify men at higher risk of these side effects and support more individualized regimens [2].

What it doesn't show

The authors are clear about the limits. The analyses are exploratory and based on a trial that was already finished. Regional groups may reflect genetic, environmental, dietary, cultural, behavioral and reporting differences, and "causality cannot be inferred" [2]. In other words, the paper finds a pattern; it doesn't prove that low DHT causes mood problems, and it doesn't offer anyone a way to predict or prevent them yet.

Why this matters for NES/T

Mood side effects are the main open question for any hormonal male method, because those methods work by changing hormone levels in otherwise healthy men. The leading hormonal candidate today is NES/T, a daily gel combining segesterone acetate (Nestorone) with testosterone. According to NICHD, it was developed in a collaboration between the Population Council and NICHD's Contraceptive Development Program; Contraline now holds the rights, and its NES/T page describes it as investigational. NES/T uses a different progestin, a different route (skin, not injection) and a different testosterone product than the WHO/CONRAD shots, so the 2011 results can't simply be carried over.

The Phase 2 trial of NES/T is listed as completed on ClinicalTrials.gov, with a completion date of September 2024. Contraline says the Phase 2b trial enrolled 462 couples at 17 sites and that Phase 3 planning is underway [5]. Full Phase 2b results, including detailed mood and libido data, will be what to watch. If hormone measurements like those in the new paper prove useful, they could help future trials understand who tolerates these methods well. NES/T is investigational and not approved.

For the non-hormonal side of the field, see our YCT-529 update and our Alphatide explainer. For where every candidate stands, see the status tracker. Until something is approved, the male options remain condoms and vasectomy.

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This article is news and education, not medical advice. No male contraceptive described here is approved. Get notified of updates.