A Daily Gel You Rub on Your Shoulders — and an International Efficacy Trial

NES/T is a self-administered daily transdermal gel containing testosterone and segesterone acetate (Nestorone), and it is the subject of an international male contraceptive efficacy trial.[1] That last phrase is what distinguishes it: an efficacy trial, designed to measure whether pregnancies are prevented — not a pharmacokinetic study of whether the drug is absorbed.

Reaching that stage is the field's furthest progress in three decades.

Why the combination

Two agents, two jobs.

The progestin (segesterone acetate) drives suppression of the hypothalamic-pituitary-gonadal axis, and therefore of spermatogenesis.

The testosterone replaces the endogenous androgen that suppression removes — preventing the hypogonadism that would otherwise be the price.

That division of labour is more efficient than asking one molecule to do both, and it is the architecture that separates NES/T from the single-agent approaches.

Why a gel

Because delivery is what killed the injectable programmes. The 1990s trials showed hormonal suppression works;[2] a weekly intramuscular injection is not a contraceptive healthy young men will adopt.

A self-administered daily transdermal gel[1] changes that calculation entirely. It bypasses the liver — the constraint that has shaped testosterone products since 1935[3] — and it is applied at home in seconds. Transdermal delivery is why gels dominate testosterone replacement in the first place, for their patient acceptability and non-occlusive nature.[4]

What "almost worked" means here

The slug's framing deserves care. Reaching an international efficacy trial is not a failure — it is further than any hormonal male contraceptive had previously gone.

What remains true is that no product has been marketed. The Cochrane review of steroid hormones for contraception in men assesses the class systematically,[2] and the gap between demonstrated mechanism and available product has now persisted for thirty years.

The obstacles were never mechanistic. They are delivery, tolerability in healthy users, completeness of response, and reversibility — the same list every candidate has faced.

Frequently asked questions

Is NES/T available? No. The cited work describes the design of an international efficacy trial.[1]

How would it be used? As a self-administered daily transdermal gel.[1]

Would it be reversible? Testosterone-induced suppression is generally reversible given sufficient time, though not in every man.[6] Reversibility in this specific regimen is a trial question.

Can men use testosterone gel as contraception now? No. TRT does not reliably suppress spermatogenesis enough for contraception and must never be relied on.[6]

Next in this series

Thirty years, a demonstrated mechanism, two credible candidates — and still nothing on a shelf.

Continue with why male contraception still doesn't exist.

References

6 sources

1. Amory JK, Blithe DL, Sitruk-Ware R, et al. Design of an international male contraceptive efficacy trial using a self-administered daily transdermal gel containing testosterone and segesterone acetate (Nestorone). Contraception. 2023;124:110064. doi:10.1016/j.contraception.2023.110064 · PMID 37210024
2. 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
3. Nieschlag E, Nieschlag S. ENDOCRINE HISTORY: The history of discovery, synthesis and development of testosterone for clinical use. Eur J Endocrinol. 2019;180(6):R201–R212. doi:10.1530/EJE-19-0071 · PMID 30959485
4. Hadgraft J, Lane ME. Transdermal delivery of testosterone. Eur J Pharm Biopharm. 2015;92:42–48. doi:10.1016/j.ejpb.2015.02.015 · PMID 25709060
5. U.S. Food and Drug Administration. AndroGel (testosterone gel) 1% — prescribing information, including BOXED WARNING: secondary exposure to testosterone. Reference ID 021015s044. 2019. accessdata.fda.gov
6. 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