All three options try to raise testosterone by getting your own testes to make more of it, instead of replacing it from outside, which is what protects sperm production. hCG is the best established: it is FDA-approved, acts like LH directly on the testes, and is named in the American Urological Association guideline as a fertility-preserving option. Enclomiphene works one step higher, at the brain, but it isn't FDA-approved and an FDA advisory committee voted against adding it to the compounding list in 2022. Kisspeptin works at the top of the chain and raises LH and testosterone in human research studies, but it's a research compound with no approved use.
Why testosterone therapy and fertility collide
Testosterone made by your testes depends on a signal chain. The hypothalamus releases GnRH, the pituitary responds with LH and FSH, and LH tells Leydig cells in the testes to produce testosterone. Sperm production needs high testosterone levels inside the testes, along with FSH.
When you take testosterone from outside, the brain senses plenty and turns down LH and FSH. Blood levels look fine, but the testes get less signal, and sperm production can fall. That's why the AUA's testosterone guideline says exogenous testosterone should not be prescribed to men who are currently trying to conceive (a strong recommendation). The same guideline says clinicians may use aromatase inhibitors, hCG or selective estrogen receptor modulators (SERMs) to help maintain fertility, but that recommendation is conditional and rests on lower-grade evidence.
If you're still deciding between treatment routes, start with our TRT clinic vs peptide clinic guide.
The three options at a glance
| hCG | Enclomiphene | Kisspeptin | |
|---|---|---|---|
| Where it acts | Testes (mimics LH) | Hypothalamus and pituitary (blocks estrogen feedback) | Hypothalamus (triggers GnRH) |
| FDA status | Approved brand products (Novarel, Pregnyl) | Not FDA-approved | Not approved; research compound |
| Compounding | Treated as a biologic since 2020; FDA says biologics aren't eligible for compounding exemptions | PCAC voted 8–4 against adding it to the 503A bulks list (June 2022) | Not an approved-drug ingredient; research-use only |
| Human evidence in men | Long clinical use; named in the AUA guideline | Studied in men, but committee members cited a lack of clinical efficacy evidence | Short-term research studies showing LH and testosterone rises |
| WADA status | Prohibited at all times in males (S2) | Clomifene is listed as an anti-estrogenic substance (S4) | Prohibited at all times in males (S2) |
hCG: the established option
Human chorionic gonadotropin looks enough like LH to bind the same receptor on Leydig cells. That drives testosterone production inside the testes even when the brain's own LH signal is low. The FDA-approved products include Novarel and Pregnyl, and their approved uses include certain cases of hypogonadotropic hypogonadism in males.
The regulatory detail that matters most in 2026 is compounding. On March 23, 2020, chorionic gonadotropin moved from drug to biologic status. FDA's notice to compounders says products that transitioned "will not be eligible for the exemptions for compounded drugs." So if a clinic markets "compounded hCG", ask exactly what you'd be getting and from where.
Trade-offs: it's an injectable prescription drug, it needs monitoring like any hormone therapy, and access depends on brand-product supply and coverage.
Enclomiphene: the oral route with a regulatory problem
Enclomiphene is one of the two isomers that make up clomiphene citrate, a SERM long approved for ovulation problems in women and used off-label in men. By blocking estrogen's negative feedback at the hypothalamus and pituitary, it lets LH and FSH rise, and testosterone follows. Because the testes are being stimulated rather than bypassed, sperm production isn't suppressed the way it is with external testosterone.
The catch is status. Enclomiphene isn't an FDA-approved drug. At the June 8, 2022 meeting of FDA's Pharmacy Compounding Advisory Committee, FDA proposed that enclomiphene citrate not be included on the 503A bulks list. The committee voted 4 yes to 8 no, and several members who voted no cited a lack of clinical efficacy evidence. Our 503A vs 503B explainer covers why bulks-list status matters for anything a telehealth service compounds.
Trade-offs: it's a pill, which is convenient. But its compounding basis is contested, and quality depends on the pharmacy. Ask what the legal basis is before you start.
Kisspeptin: the interesting research option
Kisspeptin sits at the very top of the chain. It's the signal that tells GnRH neurons to fire. In a set of studies from the University of Edinburgh group, intravenous kisspeptin-10 given to men in a research unit raised LH in a dose-dependent way. In a longer high-dose infusion in four healthy men, mean LH rose from 5.5 to 20.9 IU/L and testosterone from 16.6 to 24.0 nmol/L. LH also rose in a small group of men with type 2 diabetes and low testosterone.
Those are meaningful physiology findings. They're also short-term infusions in a handful of men under supervision, measuring hormones, not sperm counts or long-term outcomes. Kisspeptin isn't approved for any use, and research-grade kisspeptin isn't sold for human use. See our kisspeptin-10 profile for the wider literature and our male fertility overview for how it fits with other fertility-related compounds.
hCG: approved drug, decades of use, guideline-named. Enclomiphene: it has been studied in men, but it isn't approved and FDA's advisory committee wasn't persuaded. Kisspeptin: human physiology studies only, with no approved product.
How to choose, with a clinician
- Confirm the diagnosis first. Two early-morning testosterone tests and an LH level, per the AUA guideline. Our bloodwork guide explains the markers. LH tells your clinician whether the problem starts in the brain or the testes, which changes which option makes sense.
- Get a semen analysis if conception is a near-term goal. Hormone numbers don't tell you sperm numbers.
- Ask about approved options first. An FDA-approved product with a label gives you a known manufacturing standard.
- If something compounded is proposed, ask for the pharmacy name, whether it's 503A or 503B, and the legal basis for compounding that ingredient.
- If you're already on TRT, don't stop or switch on your own. Coming off testosterone changes how you feel and how your hormones read for a while, so plan it with the prescriber.
Questions to bring to the appointment
- Is my low testosterone primary (testicular) or secondary (pituitary or hypothalamic)?
- Which of these options fits that cause, and why?
- Is the drug FDA-approved? If compounded, on what basis?
- Which labs, and a semen analysis, will we repeat, and when?
- What happens if it doesn't work after a reasonable trial?
If you're starting from scratch, this is the TRT telehealth service we link to. Bring the questions above and say up front that fertility matters:
Dosing for any of these is set by the prescribing clinician. Research-use-only peptides are not sold for human use and have no approved human dose. See our medical disclaimer.
If you and your partner have been trying to conceive for a year without success (six months if your partner is 35 or older), or you have a known testicular problem, see a urologist or reproductive specialist for a full evaluation rather than starting a hormone on your own.
Sources
- American Urological Association, Evaluation and Management of Testosterone Deficiency (2018, validity confirmed 2024).
- FDA, Final summary minutes, Pharmacy Compounding Advisory Committee, June 8, 2022 (enclomiphene citrate).
- FDA, Notice to compounders on the March 23, 2020 biologics transition and the list of NDAs deemed to be BLAs (Novarel, Pregnyl).
- George JT et al., J Clin Endocrinol Metab 2011;96(8):E1228–E1236, and George JT, PhD thesis 2012 (University of Edinburgh record).
- World Anti-Doping Agency, 2026 Prohibited List.
Frequently Asked
hCG has the stronger standing: it is FDA-approved, has long clinical use, and is named in the AUA guideline as a fertility-preserving option. Enclomiphene is not FDA-approved, and an FDA advisory committee voted 8 to 4 against adding it to the 503A bulks list in 2022. The right choice depends on the cause of your low testosterone, so decide with a clinician.
Chorionic gonadotropin was transitioned to a biologic on March 23, 2020, and FDA's notice to compounders says transitioned biologics are not eligible for the exemptions for compounded drugs. FDA-approved brand products include Novarel and Pregnyl.
In short-term research studies, intravenous kisspeptin-10 raised LH and testosterone in healthy men and raised LH in men with type 2 diabetes and low testosterone. Those were small supervised infusions measuring hormones, not fertility outcomes, and kisspeptin is not approved for any use.
External testosterone signals the brain to reduce LH and FSH. The testes then get less stimulation, so testosterone inside the testes and sperm production can fall even while blood testosterone looks normal.
Yes for male athletes. The 2026 WADA Prohibited List names chorionic gonadotrophin, luteinizing hormone, and kisspeptin and its agonist analogues as testosterone-stimulating peptides in males, prohibited at all times.