Last updated 25 August 2026.
Enclomiphene is not an FDA-approved drug. It is available as a compounded medication, prepared by a licensed pharmacy for an individual patient on the prescription of a licensed clinician. Compounded medications are not reviewed by FDA for safety, effectiveness or quality before being dispensed. This page is educational. It is not medical advice, and whether any treatment is appropriate for a particular person is a decision for a state-licensed clinician.
The honest summary is that the side effect profile of enclomiphene is less well characterised than most sites imply. This page separates what was actually measured in trials from what is inferred from the wider drug class, because those are different things and the difference matters.
What the trials reported
In the two Phase III trials, covering roughly 256 men across all arms over 16 weeks:
- 53 men, about 21%, had adverse events that investigators judged possibly, probably or definitely related to the study drug.
- None of those were severe and none were serious, in the trial-reporting sense of those words.
- Three people discontinued across all arms. Two for raised haematocrit or haemoglobin, one for a raised PSA.
- The investigators reported that no adverse event occurred more frequently in the enclomiphene group than in the placebo group.
One death from stroke occurred in an enclomiphene arm. Investigators attributed it to pre-existing risk factors and judged a drug relationship highly unlikely. We mention it because leaving it out would be selective.
The number nobody publishes
There are no per-symptom frequencies for enclomiphene. No published trial breaks its adverse events down by term, so there is no sourced figure for how often enclomiphene causes headache, mood change, visual disturbance or altered libido.
If you find a site giving specific percentages for individual enclomiphene side effects, ask where the number came from. It is not in the trial literature. We are not going to invent one to fill the gap.
What is inferred from the wider drug class
Enclomiphene is one isomer of clomiphene, and clomiphene has an approved product with a label. Some of what is known about the class comes from there. This is inference, not measurement, and we are labelling it as such.
Visual disturbances
The approved labelling for clomiphene notes that blurring or other visual symptoms such as spots or flashes may occasionally occur during therapy. It states these are usually reversible, but that cases of prolonged visual disturbance have been reported, and that effects may be irreversible, particularly with increased dose or duration.
Worth knowing: when enclomiphene was in development, the sponsor built visual acuity testing and slit lamp eye examinations into its six-month safety study. That tells you the people running the programme treated ocular safety as a live question rather than a settled one.
Blood count and PSA
The two discontinuations for raised haematocrit or haemoglobin, and one for raised PSA, suggest both are worth monitoring. A clinician should be checking these rather than assuming they are only a concern with testosterone replacement.
Mood
Mood instability appears in reviews of clomiphene side effects. No frequency is given, and no enclomiphene trial measured it as an endpoint.
Bone density
Genuinely unresolved. One early enclomiphene study found no significant effect on bone markers over six weeks. Reviews of the wider class cite one study observing a decline in bone density and another showing improvement over three years. That is not a conclusion, it is a contradiction.
Gynecomastia and testicular findings
The approved clomiphene labelling notes that testicular tumours and gynecomastia have been reported in males using clomiphene. The mechanistic argument is that enclomiphene, being the purely antiestrogenic isomer, should carry less gynecomastia risk than the mixture. That argument is plausible and is made in the literature. It has not been demonstrated by a trial.
What is unknown, and should be said plainly
- Anything past six months. The longest adequately powered randomised trial ran 16 weeks. The longest documented exposure in any controlled study is around six months, and those results appear to be unpublished.
- Cardiovascular outcomes. No data of any kind.
- Prostate safety over time. No data.
- Ocular safety with chronic use. No data.
- What happens after stopping, beyond about a week in one study.
- Safety in men over 60. Trial enrolment was capped at 60.
The 2025 meta-analysis of this drug class stated its own limitation directly: it remains underpowered with regard to safety endpoints. That is the most current systematic assessment available, and that is what it concluded.
Contraindications
There is no enclomiphene label, so there is no approved contraindication list. Anything published on this is extrapolation from the clomiphene label, most of which concerns use in women and does not transfer.
The considerations that do carry across are hypersensitivity to the ingredient, liver impairment, uncontrolled thyroid or adrenal dysfunction, and an organic intracranial lesion. That last one matters for a specific reason: a pituitary lesion can cause secondary hypogonadism, and it needs finding rather than working around.
Two more that are clinically obvious rather than label-derived. Men actively trying to conceive should have a proper reproductive evaluation first. And enclomiphene will not work in primary hypogonadism, because the mechanism depends on the testes being able to respond.
What this means practically
The reasonable position is that enclomiphene has a short-term safety record that looks unremarkable in the trials that exist, and essentially no long-term record at all. A clinician should be monitoring bloodwork rather than treating it as a set-and-forget medication, and anything unusual with vision is worth reporting rather than waiting out.
More on what the drug does and does not do on our main enclomiphene page, and on how it compares with clomiphene here.
References
- Kim ED, McCullough A, Kaminetsky J. Oral enclomiphene citrate raises testosterone and preserves sperm counts in obese hypogonadal men, unlike topical testosterone. BJU Int. 2016;117(4):677-685. PMID 26496621
- Wiehle RD, Fontenot GK, Wike J, et al. Enclomiphene citrate stimulates testosterone production while preventing oligospermia: a randomized phase II clinical trial comparing topical testosterone. Fertil Steril. 2014;102(3):720-727.
- Wiehle R, Cunningham GR, Pitteloud N, et al. Testosterone restoration using enclomiphene citrate in men with secondary hypogonadism. BJU Int. 2013;112(8):1188-1200. PMID 23875626
- Kaminetsky J, Werner M, Fontenot G, Wiehle RD. Oral enclomiphene citrate stimulates the endogenous production of testosterone and sperm counts in men with low testosterone. J Sex Med. 2013;10(6):1628-1635. PMID 23530575
- Hohl A, Chavez MP, Pasqualotto E, et al. Clomiphene or enclomiphene citrate for the treatment of male hypogonadism: a systematic review and meta-analysis of randomized controlled trials. Arch Endocrinol Metab. 2025;69(5):e250093. PMC12510335
- Repros Therapeutics. Receipt of Complete Response Letter from FDA for enclomiphene, 1 December 2015.
- FDA. Bulk drug substances nominated for use in compounding under section 503A, updated 14 May 2026.
The product page for what we dispense is Enclomiphene, where the price is shown before any intake form.
General educational information about a medication. Not medical advice, not a recommendation to take anything, and not a claim about effectiveness or safety. Prescription decisions are made by state-licensed clinicians. Report any side effect to your clinician.
