Short answer: Testosterone from outside the body tells the brain to stop sending the signals (LH and FSH) the testes need to make sperm. The AUA guideline says TRT should not be prescribed to men trying to conceive. In contraception studies most men recovered sperm within a year of stopping. Of the add-ons used to protect fertility, only hCG is FDA approved for use in males.
| Compound | Best evidence | What it shows |
|---|---|---|
| hCG (Novarel, Pregnyl) | Approved for a different use | Approved in males for some pituitary causes of low testosterone, not for fertility on TRT. In a review of 26 men on TRT plus low-dose hCG, semen did not change during follow-up and none lost all sperm. |
| Enclomiphene | Human trials | In a phase 2 trial it raised testosterone, LH and FSH while sperm counts were conserved, unlike testosterone gel. Not FDA approved. |
| Clomiphene (Clomid) | Approved for a different use | Approved only for ovulation problems in women. The label says no adequate studies show it works for male infertility. |
| Anastrozole | Approved for a different use | Approved only for breast cancer. The AUA guideline lists aromatase inhibitors among options clinicians may use, with low-grade evidence. |
| Kisspeptin-10 | Small or early human studies | Raised LH and FSH in a handful of healthy men given it into a vein. No trial in men on TRT. FDA lists it in 503A Category 2 (significant safety risks). |
"Animal or lab studies only" means no published human trial for this goal that we could find. Results in rats or cells often do not carry over to people. Compounds that are not FDA-approved have no tested label for dose, purity or safety.
Sperm production needs a high level of testosterone inside the testes, which the testes make when the pituitary sends LH. When testosterone comes from injections or gel, the brain senses enough testosterone and turns LH and FSH down. Blood testosterone can look normal while testosterone inside the testes falls. The AUA guideline describes this directly: exogenous testosterone (testosterone from outside the body) inhibits testosterone production inside the testes, which normal sperm production depends on.
The labels agree. The Depo-Testosterone and testosterone enanthate labels say large doses can suppress sperm production, and the enanthate label says this happens through feedback on FSH. The AUA guideline adds that a review of 33 randomized trials found higher doses more likely to cause azoospermia (no sperm), but the dose effect was not consistent.
The best data come from male contraception studies, where healthy men took testosterone on purpose to stop sperm production. An analysis of 1,549 men across 30 studies found the typical chance of sperm count recovering to 20 million per mL was 67% within 6 months, 90% within 12 months, 96% within 16 months and 100% within 24 months. Shorter treatment and shorter-acting testosterone recovered faster.
Those men were healthy and had normal testosterone before starting. The AUA guideline warns that recovery is "not well-established" in men who already had fertility problems, and says to discuss this before starting TRT.
AUA Statement 27 says clinicians may use aromatase inhibitors, hCG, SERMs (selective estrogen receptor modulators, like clomiphene and enclomiphene) or a mix in men with low testosterone who want to keep fertility. It is a conditional recommendation with grade C evidence, and the guideline notes only hCG is FDA approved for use in males.
| Option | FDA status for men | Main human evidence |
|---|---|---|
| hCG | Approved for selected hypogonadotropic hypogonadism and prepubertal cryptorchidism; not specifically for fertility on TRT | Retrospective review of 26 men on TRT plus low-dose hCG: semen unchanged, none became azoospermic, 9 contributed to a pregnancy |
| Enclomiphene | Not approved; FDA advisers voted 4 to 8 against adding it to the compounding list in 2022; Category 1 (under evaluation) on the May 2026 list | Phase 2 trial vs testosterone gel: testosterone, LH and FSH rose and sperm counts were conserved |
| Clomiphene | Approved only for women; label says effectiveness in male infertility is not shown | Endocrine Society: used empirically in men, but efficacy and safety not shown in randomized trials |
The hCG data come from one clinic, with no control group, and a mean follow-up of about 6 months. That is useful but weak evidence. hCG works by standing in for LH, so the testes keep making testosterone. Enclomiphene raised the body's own LH, FSH and testosterone in its phase 2 trial, rather than replacing testosterone.
No large randomized trial has tested any add-on for keeping fertility in men who stay on TRT. Pregnancy rates, the best measure, are rarely reported. Clomiphene's label also reports testicular tumors and gynecomastia (breast tissue growth) in men who took it, though it says a cause was not proven, and it warns about visual symptoms.
Kisspeptin is a hormone that signals the brain to release GnRH, the trigger for LH and FSH. In a small study, kisspeptin-10 given into a vein raised LH and FSH in healthy men. That is a research finding, not a treatment. FDA lists kisspeptin-10 in Category 2 of its 503A bulk substances list, meaning it raised significant safety risks for compounding.
Diagnosis and prescribing decisions belong with a licensed clinician who can examine you and order labs. A fertility specialist (reproductive urologist) can order a semen analysis and advise on timing.
Terms on this page: Washout period · Compounding pharmacy · 503A vs 503B