Enclomiphene vs clomiphene (clomifene): what the trials report

Searches for "enclomiphene vs clomiphene" usually ask one thing: is enclomiphene a different compound, or clomifene under a new name? The short answer is that it is one of clomifene's two components. Clomifene, spelt clomiphene in the United States, is a mixture of two geometric isomers of the same molecule, and enclomiphene is one of them, isolated on its own. That single change affects how long the compound persists, which receptor effects dominate, and how regulators treated each. This guide covers the chemistry, the mechanism, the controlled trials and their adverse findings, the position in the UK, EU and US, the WADA status, and the questions people search most. It contains no guidance on use. Enclomiphene is sold on this site for laboratory research only.

What are enclomiphene and clomifene?

Clomifene is a non-steroidal selective oestrogen receptor modulator (SERM) from the triphenylethylene family. It has been a prescription medicine for ovulation induction in women for decades, and it exists as two geometric isomers that share one formula and one molecular weight but differ in how their groups are arranged around a carbon-carbon double bond:

• Enclomiphene, the (E) or trans isomer, international non-proprietary name enclomifene, also listed as trans-clomiphene and RMI 16,289.
• Zuclomiphene, the (Z) or cis isomer.

Enclomiphene's identifiers are CAS 15690-57-0, formula C26H28ClNO, molecular weight 406.0 g/mol and InChIKey GKIRPKYJQBWNGO-OCEACIFDSA-N, the last of which encodes the (E) geometry. Repros Therapeutics developed the isolated isomer as enclomiphene citrate for men with secondary hypogonadism, and a capsule product called EnCyzix was later submitted to the European Medicines Agency.

How they act on the hormone axis

In men, oestradiol made from testosterone feeds back on the hypothalamus and pituitary and restrains the release of luteinising hormone (LH) and follicle-stimulating hormone (FSH). A SERM that blocks oestrogen receptors at that level removes part of the brake. More LH reaches the Leydig cells of the testes, which make testosterone, and more FSH supports sperm production. Testosterone given from outside works the other way: the axis reads a high level and turns LH and FSH down.

The two isomers do not pull in the same direction. The 2026 British Society for Sexual Medicine (BSSM) position statement describes enclomiphene as the more anti-oestrogenic isomer and zuclomiphene as the more oestrogenic one, with a tendency to suppress gonadotrophins (Foster 2026). Their persistence also differs. In 15 men on long-term clomifene for secondary hypogonadism, the median serum concentration was 2.2 ng/mL for enclomiphene and 44.0 ng/mL for zuclomiphene, a ratio of 20 to 1, because the slowly cleared zuclomiphene builds up (Helo 2017). Three of that paper's authors were affiliated with Repros, then developing the single isomer.

The mechanism also sets a limit. A signal from the pituitary only helps if the testes can answer it, which is why the trials enrolled men with secondary hypogonadism, where the fault lies above the testes. The BSSM notes limited success in some types of primary or functional hypogonadism (Foster 2026).

What the trials report

Enclomiphene: the phase III programme

The largest controlled data come from two parallel phase III trials, coded ZA-304 and ZA-305, published together (Kim 2016). They were randomised, double-blind, double-dummy, placebo-controlled and multicentre. The participants were overweight men aged 18 to 60 whose early morning total testosterone was at or below 300 ng/dL (10.4 nmol/L) and whose LH was low or normal, each confirmed on two occasions. Two strengths of enclomiphene citrate were compared with a testosterone gel and with placebo over 16 weeks. The authors reported that:

• total testosterone rose from baseline in all the active groups;
• LH and FSH rose with enclomiphene and fell with the gel;
• sperm concentration stayed within the normal range with enclomiphene, while the gel group showed a marked reduction in sperm production.

The limits matter as much. Sixteen weeks is short, the outcomes were blood hormones and semen counts rather than how men felt or functioned, and the population was narrow. The EMA made the same point in refusing authorisation, as described below.

Clomifene in men: long-term clinic data

Clomifene has no comparable licensing trials in men, but it has more years of use. A retrospective review at two US institutions covered 400 men with baseline testosterone below 300 ng/dL treated off-label between 2010 and 2018, for a mean of 25.5 months (Krzastek 2019). Of the 120 treated for more than three years, 88 per cent reached a testosterone level in the normal range, 77 per cent reported improved symptoms and 8 per cent reported side effects. Oestradiol rose significantly. A retrospective series only includes men who stayed on treatment long enough to be reviewed, so it cannot show how many stopped early, and it has no control group.

Head to head: enclomiphene after clomifene

The only direct comparison we can cite is a retrospective review of 66 men at one academic centre who took clomifene first and enclomiphene later (Saffati 2024). The median testosterone rise was 166 ng/dL on enclomiphene and 98 ng/dL on clomifene, a difference that was not statistically significant (P=0.20). Oestradiol changed by -5.92 pg/mL on enclomiphene against +17.50 pg/mL on clomifene (P=0.001), and documented adverse effects, including reduced libido, reduced energy and mood changes, were less frequent on enclomiphene (odds ratio 0.18). Every man took the two in the same order, the clomifene values served as the new baseline, and the BSSM notes the paper gave no dose information (Foster 2026). It is a signal to test, not a settled result.

Side effects and adverse findings

• Venous thromboembolism. The EMA's refusal notice cites a risk of blood clots in the veins, a recognised concern across the SERM class.
• Reported undesirable effects of enclomiphene. The BSSM lists headache (1.6 per cent), hot flushes (1.1 per cent), nausea (1.0 per cent), muscle spasms (0.9 per cent) and dizziness (0.7 per cent), and describes the evidence as small and short-term, with limited data on harms and fertility (Foster 2026).
• Clomifene and oestradiol. In the Helo series, median oestradiol doubled, from 17.0 to 34.0 pg/mL, on long-term clomifene (Helo 2017).
• Clomifene symptoms over years. Among men treated for more than three years, the side effects most often recorded were mood changes (5 men), blurred vision (3) and breast tenderness (2) (Krzastek 2019).

All of these figures come from diagnosed men under medical supervision with blood monitoring, using prescribed material. They say nothing about unsupervised use or about products of unverified content. None of this is a claim about any product sold on this site.

Regulatory status: UK, EU and US

United Kingdom

Enclomiphene holds no UK marketing authorisation. The BSSM statement calls it unlicensed in the UK and does not recommend routine use outside specialist or research settings (Foster 2026). Clomifene is a licensed prescription-only medicine whose licence covers female infertility, so its use for low testosterone in men is off-label. Neither is an authorised food supplement or a controlled drug under the Misuse of Drugs Act 1971. Free Muscle supplies enclomiphene as a research chemical to adults aged 18 or over, for laboratory use only.

European Union

On 25 January 2018 the EMA's Committee for Medicinal Products for Human Use adopted a negative opinion on EnCyzix, recommending refusal, and marketing authorisation was refused later that year. The EMA's published reasons were that the studies showed rising testosterone but did not look at symptoms such as bone strength, weight gain, impotence and libido, and that there was a risk of venous thromboembolism, so the benefits did not outweigh the risks. The manufacturer discontinued development in 2021 (Foster 2026).

United States

Enclomiphene is not approved by the FDA (Foster 2026). Clomifene is FDA-approved for ovulation induction in women, and its use for low testosterone in men is off-label (Krzastek 2019).

WADA and sport

Section S4 of the WADA Prohibited List, hormone and metabolic modulators, covers anti-oestrogenic substances including SERMs and names clomifene. Enclomiphene and clomifene are both prohibited at all times, in and out of competition, and UK Anti-Doping applies strict liability. The controlled detection data concern clomifene. In an open-label study run by an anti-doping laboratory, 12 healthy men took clomifene for a short period; testosterone, LH and FSH rose during treatment, and zuclomiphene stayed detectable in urine for between 121 and more than 261 days (Miller 2019). Isolated enclomiphene should contain little or no zuclomiphene, the long-lasting marker in that study, and no verified window exists for it, so the accurate statement is: detectable, window not established.

Common questions

Is enclomiphene legal in the UK, and can it be bought there?

Adults aged 18 or over can buy and hold it as a research chemical. It cannot lawfully be sold for human consumption, it is not a licensed medicine, and it is banned in sport. Our UK orders go by free tracked delivery in plain packaging.

Is enclomiphene a SARM or a peptide?

Neither. It is a small synthetic molecule that acts on oestrogen receptors, not on the androgen receptor, so it is not a SARM, and it is not a chain of amino acids, so it is not a peptide. It is often listed beside SARMs because both act on the same hormone axis, in different ways. We do not give cycle or post-cycle advice. See What Are SARMs? and Why Post-Cycle Therapy Matters.

What does "enclomiphene citrate" mean?

It is the molecule paired with citric acid as a salt, the form used in the trials and in EnCyzix. The identifiers above describe the free base. The citrate weighs more, so a milligram figure means little unless the label says which form it refers to.

Enclomiphene tablets or capsules?

Clomifene is sold as tablets; EnCyzix was to be capsules. For research material the form matters mainly for verification: a capsule's powder fill can be emptied and assayed against the label. The two enclomiphene products linked on this page, both in our enclomiphene collection, are capsules.

Enclomiphene vs TRT

The phase III trials above used testosterone gel as the comparator, but that is not a basis for choosing a treatment. Low testosterone is diagnosed with blood tests and managed by a doctor, and a research chemical is not an alternative to prescribed therapy.

Does enclomiphene affect muscle?

We know of no published controlled trial reporting muscle or strength outcomes for enclomiphene, and we make no such claims.

Do you publish enclomiphene dosage or results information?

We do not publish dosing, cycle or outcome guidance, and we make no claims about effects in people. On a listing, a milligram figure is the stated content per capsule, to be checked against the certificate. Forum reports cannot confirm what was in the bottle.

How to verify a batch

For enclomiphene, identity means the right isomer as well as the right molecule. Enclomiphene and zuclomiphene share a molecular weight, so HPLC retention time against an (E)-isomer reference standard is what tells them apart. A useful certificate shows:

1. Identity: named as enclomiphene, not just clomifene, with the method stated.
2. Purity: the main peak as a percentage, where zuclomiphene is the impurity of most interest.
3. Content: milligrams measured per capsule against the label, stating citrate or free base.
4. Batch number and test date matching the pack, and the laboratory's name.

Every batch of Free Muscle enclomiphene is assayed by Janoshik Analytical, an independent laboratory, and the certificate for your batch is sent by email on request. For Yakka Strength enclomiphene, a certificate is shown only where the manufacturer supplies one for the batch we hold. A brand-wide PDF with no batch number is not a batch certificate. See How to Read a Certificate of Analysis, our lab tests page and the UK supplier checklist.

Related reading

• Enclomiphene collection: every brand stocked, with pack size and certificate status.
• PCT blends: multi-ingredient products compared by stated contents and batch certificate.
• Why Post-Cycle Therapy Matters: background on hormonal recovery compounds.
• How to choose a SARMs or peptide supplier in the UK.

Enclomiphene is sold for laboratory research use only. It is not a licensed medicine, no product sold here has been evaluated by the MHRA, EMA or FDA, it is not a food supplement and it is not for human consumption. Products are supplied to adults aged 18 and over. It is prohibited in sport under the WADA Code. Nothing on this page is medical advice or dosing, cycle or usage guidance. Summaries of published studies describe what researchers reported in their study populations and are not claims about any product.

References

1. Kim ED, et al. 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):677-85. PMID: 26496621.
2. Helo S, et al. Serum levels of enclomiphene and zuclomiphene in men with hypogonadism on long-term clomiphene citrate treatment. BJU Int. 2017;119(1):171-176. PMID: 27511863.
3. Krzastek SC, et al. Long-Term Safety and Efficacy of Clomiphene Citrate for the Treatment of Hypogonadism. J Urol. 2019;202(5):1029-1035. PMID: 31216250.
4. Saffati G, et al. Safety and efficacy of enclomiphene and clomiphene for hypogonadal men. Transl Androl Urol. 2024;13(9):1984-1990. PMID: 39434750.
5. Miller GD, et al. Hypothalamic-Pituitary-Testicular Axis Effects and Urinary Detection Following Clomiphene Administration in Males. J Clin Endocrinol Metab. 2019;104(3):906-914. PMID: 30295816.
6. 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(3):480-483. PMID: 41714894.