You might not have heard of enclomiphene, but chances are you’ve seen it advertised online or mentioned on social media without even realizing it. Despite having never been approved by the FDA, its global market size was valued at around $216 million USD in 2025 and is projected to hit $419 million by 2033. It’s the primary compound sold by a multitude of online “men’s health” websites as an oral treatment for low testosterone. But what actually is enclomiphene? Is it safe? Does it work? Why has it become so popular? There is a lot to unpack here, including the very gray world of compounded medications, beyond the FDA, where little exists to protect patients or prove efficacy.
Enclomiphene is one of the two compounds that make up clomiphene citrate, the fertility medication better known as Clomid ™. While clomiphene citrate is FDA-approved for the treatment of ovulatory dysfunction in women trying to get pregnant, it is also used off-label for male hypogonadism. Enclomiphene, on the other hand, has never been approved by the FDA for any indication.
Enclomiphene acts predominantly as an estrogen receptor antagonist at the hypothalamic-pituitary level. It blocks some of estrogen’s negative feedback, and the hypothalamus and pituitary respond by increasing gonadotropin signaling. LH rises, FSH rises, and — assuming the testes are capable of responding — the testes make more testosterone and continue producing sperm. This is an important distinction between enclomiphene and exogenous testosterone replacement therapy (TRT), and one of the driving forces behind its explosion in popularity in recent years.
TRT works by giving the body testosterone directly. This causes testosterone levels to rise, but as a result, LH and FSH typically fall. This can lead to intratesticular testosterone drops, which can substantially decrease spermatogenesis, and in turn lead to significant male infertility.
Contrast this to enclomiphene, which in theory can “restore” endogenous testosterone without affecting fertility. Now, in theory, this sounds great: a drug that can help “naturally” restore testosterone levels without affecting fertility. But there is one glaring catch: the evidence is very limited.
Evidence shows that enclomiphene does raise total testosterone (TT) levels. A 2013 trial compared the efficacy of enclomiphene as an alternative to topical testosterone gel in 12 men with known secondary hypogonadism who had previously been treated with TRT gel. The study found similar results in terms of TT level elevation between the two groups; however, only men in the enclomiphene group had significantly elevated LH and FSH levels, as well as increased sperm counts.
A 2015 phase III trial also found that enclomiphene both significantly raised TT levels and preserved sperm counts in obese hypogonadal men.
A systematic review published in July 2026 compared clomiphene citrate to TRT in male hypogonadism. The meta-analysis found a mean difference of +6.64 ng/dL favoring clomiphene, but it was not statistically significant, and the authors also noted potential bias in several studies.
This review also included studies that used both clomiphene citrate and enclomiphene, making it hard to draw meaningful conclusions. The analysis did not go into detail as to the actual increases in TT levels in the individual studies, which also greatly limits the takeaways from this review.
While there was some discussion about the potential preservation of fertility with clomiphene/enclomiphene, the authors emphasized that none of the studies directly assessed important fertility endpoints that would be critical to draw any conclusions. Basically, the authors felt that while clomiphene/enclomiphene can achieve TT levels comparable to TRT gel, the evidence quality is low, and any potential fertility advantages are presumptive at best.
Testosterone replacement therapy is classified as a schedule III controlled substance and is regulated by the DEA. This means prescribers must follow specific regulations, keep detailed records, adhere to refill limits, and face heightened scrutiny around telemedicine prescribing and maintaining an appropriate clinician-patient relationship.
For enclomiphene, the situation is completely opposite. Because enclomiphene theoretically works by boosting the body's natural testosterone production, it is not considered the same category as exogenous TRT in terms of qualifying as a controlled substance.
The FDA has previously denied its approval, citing unclear clinically meaningful benefits. It now exists as a compounded drug, due to looser and vague guidelines that govern compounded drugs under the FD&C Act. According to the FDA, compounded drugs themselves are not FDA-approved, and therefore are not investigated for safety, efficacy, or quality in the same manner as approved drugs.
In 2022, an FDA advisory committee voted 8-4 against recommending enclomiphene for inclusion on the final 503A bulk list of medications for use in traditional compounding, citing inadequate evidence of clinical benefit and the need for more studies. A final determination has yet to be made, which is why enclomiphene remains available today.
This is a hard question to answer. A pharmaceutical company trying to get FDA approval has strong financial reasons to fund RCTs. But a company that is already selling a compounded drug for cash doesn’t have the same financial incentive. They aren’t trying to get insurance companies to pay for their products; it’s a cash-only business. This doesn’t mean that the drug doesn’t work; it just means that once a commercially viable market exists that doesn’t require the FDA stamp of approval, what is the incentive to run lengthy and expensive studies, especially when you aren’t sure of what the data will show in the end.
Enclomiphene isn’t snake oil. In theory, its physiology makes sense: it raises testosterone, preserves fertility, and isn’t exogenous TRT.
It’s an interesting drug.
But interesting isn’t the same thing as proven. So when a patient you are seeing in clinic admits to taking compounded enclomiphene, take a tip from Ted Lasso: “be curious, not judgemental.” It’s our job to try and understand why they sought treatment, try to figure out the underlying cause, and make sure they understand what we know (and what we don't) about compounded drugs.
Because the question isn’t as simple as “Does enclomiphene raise testosterone?”
The most important question is, does raising a patient’s testosterone this way help our patients feel better, live healthier lives, and remain a safe treatment option in the long term?
And the honest answer right now is: We don’t know yet.
I try to write these blog posts about topics that align with our collective experiences as clinicians and the common issues we all face, regardless of clinical location. I welcome your feedback, stories, and suggestions. Shoot me an email at NP@hippoeducation.com; I would love to hear from you!
References
Coukell A. Risks of compounded drugs. JAMA Intern Med. 2014;174(4):613-614. doi:10.1001/jamainternmed.2013.12812
Kim ED, McCullough A, Kaminetsky J. Oral enclomiphene citrate raises testosterone and preserves sperm counts in obese hypogonadal men, unlike topical testosterone: restoration instead of replacement. BJU Int. 2016;117(4):677-685. doi:10.1111/bju.13337
Constantinou BT, Benedicto BC, Galligani L, et al. Clomiphene citrate versus testosterone replacement therapy in male hypogonadism: a systematic review of literature and meta-analysis. Eur J Clin Pharmacol. 2026;82(2):157-171. doi:10.1007/s00228-026-04134-3
Bickel L. Pharmacy Compounding Advisory Committee: IND drug development and expanded access (EA). Presentation at: FDA Pharmacy Compounding Advisory Committee meeting; June 8, 2022. Accessed October 27, 2026. https://www.fda.gov/media/159042/download
US Food and Drug Administration. FD&C Act provisions that apply to human drug compounding. Updated August 13, 2021. Accessed October 27, 2026. https://www.fda.gov/drugs/human-drug-compounding/fdc-act-provisions-apply-human-drug-compounding
US Food and Drug Administration, Center for Drug Evaluation and Research. Pharmacy Compounding Advisory Committee (PCAC) meeting: morning session [transcript]. June 8, 2022. Accessed October 27, 2026. https://www.fda.gov/media/161294/download