Enclomiphene comes up in consultation more and more, usually because a man has read that it raises testosterone without the fertility hit that comes with TRT. That's broadly true, and it's only part of the story. The drug isn't licensed in the UK, two regulators have declined to approve it, and the trials behind it were short.
This is an explainer, not a recommendation.
What is enclomiphene?
Enclomiphene (also spelt enclomifene) is one half of an older drug called clomifene. Clomifene is a mixture of two mirror-image forms, or isomers: roughly 62% enclomifene, the trans isomer, and 38% zuclomifene, the cis isomer. Enclomiphene is the trans isomer on its own, and it belongs to a class called selective oestrogen receptor modulators, or SERMs.
To see what it does, you need the feedback loop that controls testosterone. Your pituitary sends luteinising hormone (LH) and follicle-stimulating hormone (FSH) to the testes, which respond by making testosterone and sperm. Oestrogen, some of it made from that testosterone, feeds back to the brain and tells it to ease off. We cover this loop in our guide to TRT and fertility and our article on what hCG is.
Enclomiphene blocks the oestrogen receptors in the pituitary. The brain reads that as low oestrogen and turns the signal up: LH and FSH rise, and the testes make more testosterone. Because the signal still runs from your own brain to your own testes, sperm production carries on. That's the fundamental difference from TRT, which supplies testosterone from outside and switches the signal off.
Enclomiphene vs clomifene
Clomifene is a licensed medicine in the UK, but not for men. The licence (you may know it as Clomid) covers ovulatory failure in women who want to become pregnant, and the product information doesn't mention male patients. When a UK doctor prescribes clomifene to a man with low testosterone, that's off-label use of a licensed medicine. It's been done for years in fertility and andrology clinics.
The case for isolating enclomiphene is that the useful part of clomifene is mostly the trans isomer. A 2019 review by Earl and Kim summarised the literature as suggesting most of the benefit comes from enclomiphene, with zuclomifene contributing little. A small 2024 retrospective study of 66 men who switched from clomifene to enclomiphene found a similar rise in testosterone on both, but oestradiol fell slightly on enclomiphene where it had risen on clomifene, and fewer men reported low libido, low energy or mood changes. One centre, looking backwards: a hint rather than proof.
Is enclomiphene licensed in the UK?
No. Enclomiphene has no UK marketing authorisation from the MHRA, so it's an unlicensed medicine here. It hasn't been approved anywhere else either. In the United States, the developer Repros Therapeutics filed for approval in February 2015 under the proposed name Androxal, for secondary hypogonadism in overweight men. On 1 December 2015 the FDA issued a complete response letter, saying the phase III design was no longer adequate to demonstrate clinical benefit and asking for further phase III trials. In Europe, the same drug was assessed as EnCyzix and refused in April 2018. The committee's reasoning is worth reading closely: the studies showed higher testosterone but didn't assess whether symptoms such as bone strength, weight, erections or libido improved, and there was a concern about venous blood clots. Development was discontinued in 2021. None of that means the drug doesn't raise testosterone. It clearly does. It means regulators wanted evidence that raising testosterone this way makes men better, and the trials weren't designed to show it.
How an unlicensed medicine can still be prescribed in the UK
UK law allows doctors to prescribe unlicensed medicines, within limits. Under Regulation 167 of the Human Medicines Regulations 2012, an unlicensed product (a "special") can be manufactured or imported to meet the special clinical need of an individual patient, on the order of a prescriber who takes responsibility for that patient. MHRA guidance is explicit that cost and convenience don't count, and that where a licensed medicine can meet the need it should be used instead. Imports have to be notified to the MHRA in advance, and the MHRA not objecting isn't the same as approval.
The GMC sets out the doctor's side: be satisfied there's sufficient evidence or experience to demonstrate safety and efficacy, take responsibility for monitoring and follow-up, tell the patient the medicine is unlicensed and why, and record the reasons. In early 2026 the British Society for Sexual Medicine published a position statement calling enclomiphene promising, but saying the Society does not recommend its routine use outside specialist settings and that any man prescribed it should be counselled about its unlicensed status.
One more legal point. UK law restricts the advertising of prescription-only medicines to the public. A clinic promoting enclomiphene to you as a product, rather than discussing it as one option after a proper assessment, has the order wrong.
What the evidence actually shows
The core trials were run by the developer and compared enclomiphene with testosterone gel in men with secondary hypogonadism. A randomised phase II trial (Wiehle and colleagues, Fertility and Sterility, 2014) found oral enclomiphene raised morning testosterone to levels similar to 1% testosterone gel, while LH and FSH went up rather than down and sperm counts were preserved.
The phase III data came from two parallel randomised, double-blind, placebo-controlled trials (Kim, McCullough and Kaminetsky, BJU International, 2016). They enrolled overweight men aged 18 to 60 with a morning total testosterone of 300 ng/dL or less (roughly 10.4 nmol/L) and a low or normal LH, and compared enclomiphene with testosterone gel over 16 weeks. Enclomiphene restored testosterone to the normal range and raised LH and FSH; on the gel, LH and FSH fell. Sperm concentration stayed within the normal range on enclomiphene, while the gel group showed a marked reduction.
A 2025 meta-analysis pooled 10 randomised trials of clomifene and enclomiphene in 819 men. Against placebo, the SERMs raised total testosterone by about 274 ng/dL (roughly 9.5 nmol/L), with LH and FSH each up by around 4.6 IU/L. Against testosterone gel there was no significant difference in the testosterone achieved, but sperm concentration was about 70 million/mL higher and far fewer men fell below the 15 million/mL threshold for a low count.
Now the caveats. The trials were short: 16 weeks for the phase III studies, 24 weeks for the longest enclomiphene trial in the meta-analysis. They measured hormones and sperm, not how men felt, their bones or their hearts, which is exactly the gap the EMA pointed to. The participants were overweight men under 60 with secondary hypogonadism, so the results don't automatically transfer to older men or other causes. The BSSM's summary is blunt: small, short-term studies with limited safety and fertility data.
Who it tends to be discussed for, and who it isn't
Enclomiphene turns up the signal from the brain, which only works if the testes can respond. In secondary hypogonadism, testosterone is low because the signal is weak: LH and FSH are low or normal despite the low testosterone. That's the pattern the trials recruited and the group enclomiphene is usually discussed for, particularly men who want children now or later. The BSSM also mentions men who can't tolerate injections or gels. Our guide to how low testosterone is diagnosed explains why LH and FSH belong on a proper panel: they separate one type of hypogonadism from the other.
In primary hypogonadism, the testes themselves have failed. LH and FSH are already high because the brain is shouting and nothing is answering, and making it shout louder doesn't fix that. The BSSM notes limited success in certain types of primary and functional hypogonadism, and lists situations where enclomiphene shouldn't be used: a history of liver disease, uncontrolled adrenal or thyroid problems, certain pituitary conditions, and allergy to clomifene or enclomiphene.
So the starting point is the same whatever treatment ends up being discussed: a proper morning testosterone blood test that includes LH, FSH, SHBG, oestradiol and prolactin, read alongside your symptoms.
Side effects and what remains unknown
In the phase III trials, about 21% of men had an adverse event judged possibly or probably related to treatment, none severe or serious, and the rate wasn't significantly different from placebo. Two men on the higher dose stopped, one for a raised haematocrit and one for a raised PSA, and there was one death from a stroke in the enclomiphene group in a man with multiple risk factors. The BSSM statement lists headache (1.6%), hot flushes (1.1%), nausea (1.0%), muscle spasms (0.9%) and dizziness (0.7%). Beyond the trial data, three things I'd want any man to understand:
- Visual disturbance is a known SERM effect. The UK clomifene product information warns of blurring, spots or flashes, says these may be irreversible with higher doses or longer use, and advises stopping and seeing an eye specialist. The enclomiphene trials didn't report visual disturbances, but they were short, and the warning applies to the class.
- Blood clots. The EMA's committee cited a risk of venous thromboembolism as one reason for refusal. The trials weren't large or long enough to settle how big that risk is.
- Oestradiol and mood. Enclomiphene raises your own testosterone, so oestradiol tends to rise with it, and the phase II trial recorded exactly that. Mood changes are listed for clomifene with no reliable frequency; the 2024 study suggested they may be less common on enclomiphene. Either way, oestradiol belongs on the monitoring bloods.
The bigger unknown is time. There's no long-term safety data for enclomiphene on its own; its safety is inferred partly from decades of clomifene use, which is reassuring but not the same thing.
Enclomiphene vs TRT vs hCG
These three get lumped together because they all raise testosterone, but they do it differently and sit in different places legally.
| Item | Enclomiphene | TRT | hCG |
|---|---|---|---|
| Mechanism | Blocks oestrogen feedback at the pituitary; your own LH and FSH rise | Supplies testosterone from outside; LH and FSH switch off | Acts like LH directly on the testes |
| Form | Daily tablet (12.5 mg and 25 mg in trials) | Injection, gel or other licensed preparation | Subcutaneous injection, a few times a week |
| Own production and fertility | Preserved; sperm counts stayed normal in trials | Suppressed; sperm production falls, often markedly | Maintained, with or without TRT; not guaranteed |
| UK licensing | Unlicensed; no MHRA, FDA or EMA approval | Licensed prescription-only medicines; Class C controlled drug | Licensed prescription-only medicine (mainly fertility); Class C; use with TRT is off-label |
| Monitoring | Testosterone, LH, FSH, oestradiol; semen analysis if fertility matters; any eye symptoms | Testosterone, haematocrit, oestradiol, PSA, blood pressure | Testosterone, oestradiol; semen analysis where fertility is the aim |
| On stopping | Effect ends; your axis was never suppressed, but the underlying low output is still there | Natural production takes months to over a year to recover; a structured protocol helps | Stimulation stops; sometimes used in a restart protocol after TRT |
Notice what the table doesn't say: that one is better. TRT has the licensing, the long-term safety data and the symptom evidence. Enclomiphene has the fertility advantage and a tablet, and far less data. Which fits depends on your LH and FSH, your plans for children, and how you weigh an unlicensed drug against a licensed one. There's more on hCG in our article on TRT and fertility.
Questions to ask your doctor
If enclomiphene comes up in a consultation, these are the questions I'd want a patient to put to me.
- Do my LH and FSH results point to secondary hypogonadism, or is something else going on?
- Is there a reversible cause (weight, sleep apnoea, medication, thyroid) we should deal with first?
- Why an unlicensed medicine rather than a licensed one, and what evidence are you relying on?
- Where would it come from, and has the MHRA been notified of the import?
- What will you monitor, how often, and what result would make you stop?
- If fertility is the reason, will we check a semen analysis rather than assume it's protected?
A doctor who has thought this through will have clear answers. A doctor who hasn't will change the subject.
Where this leaves you
Enclomiphene is a real drug with a real mechanism and a genuine advantage for men who want to keep their fertility. It's also unlicensed, backed by short trials that measured hormones rather than how men feel, and recommended by the UK's own sexual medicine society only within specialist settings. Both halves are true at once. Whatever you end up discussing, the sequence is the same: confirm your testosterone is actually low on two separate samples, find out whether the problem is the signal or the testes, then weigh the options with someone who will monitor you properly.
Thinking about TRT?
Arc TRT is a UK doctor-led testosterone clinic that has helped over 3,000 men investigate their symptoms and, where appropriate, begin properly monitored treatment. Start with a simple at-home blood test.
This article is for general information and does not replace personalised medical advice. Speak to a qualified clinician about your individual circumstances.
Sources: 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;117:677-685. Wiehle RD et al. Enclomiphene citrate stimulates testosterone production while preventing oligospermia: a randomized phase II clinical trial comparing topical testosterone. Fertil Steril 2014;102:720-727. Hohl A et al. Clomiphene or enclomiphene citrate for the treatment of male hypogonadism: a systematic review and meta-analysis. Arch Endocrinol Metab 2025;69(5). Earl JA, Kim ED. Enclomiphene citrate: a treatment that maintains fertility in men with secondary hypogonadism. Expert Rev Endocrinol Metab 2019;14:157-165. Saffati G et al. Safety and efficacy of enclomiphene and clomiphene for hypogonadal men. Transl Androl Urol 2024;13:1984-1990. Foster J et al. British Society of Sexual Medicine: position statement for the potential use of enclomiphene in the treatment of male hypogonadism. World J Mens Health 2026;44:480-483. European Medicines Agency, EnCyzix (enclomifene): refusal of marketing authorisation, CHMP opinion 25 January 2018, refused 6 April 2018. Repros Therapeutics, announcement of FDA complete response letter for enclomiphene, 1 December 2015. MHRA Guidance Note 14, The supply of unlicensed medicinal products ("specials"); Human Medicines Regulations 2012, Regulation 167. General Medical Council, Good practice in prescribing and managing medicines and devices: prescribing unlicensed medicines (paragraphs 103-108). Specialist Pharmacy Service, Understanding unlicensed medicines. Clomifene 50mg Tablets, Summary of Product Characteristics, electronic medicines compendium (sections 4.1, 4.4, 4.8).
Keep reading
For the complete picture, see our full guide to TRT in the UK, covering eligibility, blood test thresholds, NHS and private routes, costs and monitoring. If you are still working out whether any of this applies to you, start with the symptoms of low testosterone.
