The 1990s established the proof of concept. Multicentre trials tested whether weekly testosterone injections could suppress spermatogenesis sufficiently to prevent pregnancy, and the answer was yes — in the men in whom suppression was achieved.
The systematic assessment of that body of work is the Cochrane review of steroid hormones for contraception in men,[1] and it remains the right place to see what the randomised evidence supports rather than what the field hoped.
What the trials demonstrated
Three things, and they are worth separating because they are usually collapsed together.
Suppression is achievable. Exogenous testosterone suppresses the hypothalamic-pituitary-gonadal axis, and suppressing that axis reduces spermatogenesis — the same mechanism that makes TRT a fertility problem.[2]
Suppression translates into contraceptive effect. Where azoospermia or severe oligozoospermia was achieved, contraceptive efficacy followed.
Suppression is not universal. Not every man reached the threshold, and the men who did not remained fertile. For a contraceptive, incomplete response in a minority is not a minor limitation — it is a product-defining one.
What stopped it becoming a product
Not efficacy. The obstacles were the ones that matter for a drug given to healthy people over decades:
Weekly intramuscular injection. An acceptable burden for treating a condition; a poor fit for contraception in healthy young men. The treatment-burden problem that shapes every testosterone formulation decision[3] applies with more force here.
Incomplete response rates. A contraceptive that fails in a definable minority requires monitoring to identify them — which means semen analyses, which means a clinical apparatus around what should be a simple product.
Time to onset and to recovery. Suppression is not immediate, and neither is reversal.
What it set up
Every subsequent programme has been an attempt to solve delivery rather than mechanism. An oral candidate is the subject of DMAU; a daily transdermal gel is the subject of the NES/T trial.
The pattern is identical to the therapeutic side of testosterone's history: the molecule was never the hard part. Getting it into the body acceptably was.
Frequently asked questions
Did the WHO-era trials work? They established that hormonal suppression could produce contraceptive efficacy. The systematic evidence is assessed in the Cochrane review.[1]
Why weren't they turned into a product? Delivery burden and incomplete response, not lack of effect.
Is suppression reversible? Generally, given sufficient time — though not in every man.[2]
Could I use testosterone as contraception now? No. TRT is not a contraceptive and must not be relied on as one.[2]
Next in this series
If weekly injection was the barrier, an oral candidate was the obvious next move.
Continue with DMAU, the almost-pill.
References
3 sources
- Grimes DA, Lopez LM, Gallo MF, et al. Steroid hormones for contraception in men. Cochrane Database Syst Rev. 2012;2012(3):CD004316. doi:10.1002/14651858.CD004316.pub4 · PMID 22419294
- McBride JA, Coward RM. Recovery of spermatogenesis following testosterone replacement therapy or anabolic-androgenic steroid use. Asian J Androl. 2016;18(3):373–380. doi:10.4103/1008-682X.173938 · PMID 26908067
- Bhasin S, Brito JP, Cunningham GR, et al. Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018;103(5):1715–1744. doi:10.1210/jc.2018-00229 · PMID 29562364
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