Enclomiphene: what the research shows
- By Reed Calder
- Last reviewed Nov 11, 2026
- 23 studies and official documents checked
In short
Enclomiphene is a pill, not a peptide. It is one half of the fertility drug clomiphene, and it raises testosterone by making the brain send stronger signals to the testes. In trials of up to 16 weeks in men with low testosterone, it raised testosterone about as much as a gel and kept sperm counts up, while the gel cut them. No trial measured symptoms with validated tools, and there are no long-term data. It isn’t FDA-approved, and Europe refused it in 2018, partly over a blood-clot risk.
EvidenceCellAnimalHuman
Enclomiphene is sold online by telehealth clinics and compounding pharmacies as an alternative to testosterone therapy. This page covers what it is, what the human trials found, how it compares with clomiphene and testosterone gel, the safety signals, and where it stands legally.
Names and forms you’ll see
| Name | What it is | Studied in men? |
|---|---|---|
| Enclomiphene, enclomifene, trans-clomiphene | One of the two mirror-image halves of clomiphene, and the half that blocks estrogen receptors in the brain (Rodriguez et al., 2016). A small-molecule pill | Yes |
| Enclomiphene citrate | The salt form used in trials and capsules. It has a mass of 598, against 406 for the base (PubChem) | Yes |
| Androxal, EnCyzix | Brand names from the drug’s developers: Androxal in the U.S. trials, EnCyzix in a European application that was refused (EMA) | Yes |
| Zuclomiphene | The other half of clomiphene. It stays in the body much longer: in men on clomiphene, blood levels were about 20 times those of enclomiphene (Helo et al., 2017) | Not used alone |
| Clomiphene (Clomid) | The mixture of both halves. FDA-approved since 1976 for ovulation in women, and used off-label in men (Rodriguez et al., 2016) | Yes, off-label |
CAS numbers
A CAS number is a substance’s chemical registry number. Some “research” vials list it in place of a name. A different number usually means a different form, such as a salt, or a different substance. Enclomiphene and zuclomiphene have different numbers, and so does each salt.
What enclomiphene is
A man’s testes make testosterone and sperm when the brain tells them to. The brain does this with two signals, LH and FSH, and estrogen acts as a brake on them. Enclomiphene blocks estrogen’s grip on its receptors in the brain. The brake eases, LH and FSH rise, and the testes make more testosterone and keep making sperm (Rodriguez et al., 2016; Wiehle et al., 2013).
Testosterone gel works the other way. The gel’s testosterone tells the brain to cut LH and FSH, and sperm output falls (Wiehle et al., 2013; Kim et al., 2016).
Enclomiphene was developed for secondary hypogonadism: low testosterone because the brain’s signal is weak, with low or normal LH, not because the testes have failed. Europe’s application was for overweight men with a BMI of at least 25 (EMA, 2018).
What has been studied
In men
- Three phase 2 trials. In 12 men, enclomiphene raised sperm counts in every man tested, while gel did not (Kaminetsky et al., 2013). In 48 men over 6 weeks, the strongest capsule strength gave an average morning testosterone of 604 ng/dL against 500 on gel, with no real difference, and LH rose on enclomiphene but fell on gel (Wiehle et al., 2013). A third, placebo-controlled trial found the same pattern, with testosterone and LH and FSH up and sperm conserved (Wiehle et al., 2014).
- Two phase 3 trials. In 265 overweight men over 16 weeks, enclomiphene brought testosterone to the normal range and kept sperm concentration in the normal range. In the gel groups it fell by about 57% and 33% (Kim et al., 2016; the sperm figures come from Rodriguez et al., 2016).
- Pooled results. A 2025 analysis of randomized trials of clomiphene and enclomiphene together found testosterone about 274 ng/dL higher than on placebo, and no clear difference from gel (Hohl et al., 2025). A 2023 analysis of 7 studies in 292 obese men found that clomiphene and enclomiphene both raised testosterone, enclomiphene by 7.5 nmol/L (Tienforti et al., 2023).
- Clinic records. In 66 men switched from clomiphene, enclomiphene gave a similar testosterone rise and fewer side effects, but this was a records review, not a randomized trial (Saffati et al., 2024). In another review of 78 men, LH, FSH and the number of moving sperm rose only on enclomiphene (Thomas et al., 2023).
- Symptoms were not measured properly. A 2016 review found that none of the enclomiphene studies measured symptoms or quality of life with validated tools (Rodriguez et al., 2016). Europe’s regulator made the same point in 2018 (EMA, 2018).
- Short trials. The trials ran 6 weeks to 6 months. A one-year open-label study is registered, with no results posted (ClinicalTrials.gov), and a 2026 position statement says long-term data are lacking (Foster et al., 2026).
- Company-linked data. A 2026 case series of 15 men on a compounded sublingual mix with boron, vitamin C and spermidine reported testosterone rising from 347 to 805 ng/dL in 60 days. It had no comparison group, and its lead author discloses personal fees and stock options from the product’s maker (Warren et al., 2026).
EvidenceCellAnimalHuman
The usual claims, checked
| Claim | What the studies found |
|---|---|
| Raises testosterone | Yes, in men with low testosterone and low or normal LH, about as much as a gel (Hohl et al., 2025; Wiehle et al., 2013) |
| Keeps your own production going, unlike TRT | LH and FSH rose on enclomiphene and fell on gel, and sperm counts held up in trials of 3 to 16 weeks (Kim et al., 2016; Wiehle et al., 2014) |
| Gets you to 1,000 ng/dL | Trial averages ran about 400 to 600 ng/dL, with 604 at the highest strength after 6 weeks (Wiehle et al., 2013). A company-linked 2026 case series reported 805 in 15 men (Warren et al., 2026) |
| Works as well as TRT for libido, energy and mood | Not measured with validated tools in the enclomiphene trials reviewed through 2018 (Rodriguez et al., 2016; EMA, 2018) |
| Has fewer side effects than clomiphene | Only in records reviews, which found fewer adverse events (Saffati et al., 2024). No randomized comparison |
| Is safe long term | No long-term data. Europe refused it over a risk of blood clots in veins (EMA, 2018; Foster et al., 2026) |
| Fixes ED, muscle or mood | Not measured in the trials we found |
| Is a peptide | No. It is a small molecule you swallow (PubChem) |
Enclomiphene, clomiphene and testosterone gel
| Enclomiphene | Clomiphene | Testosterone gel | |
|---|---|---|---|
| What it is | One half of clomiphene | A mixture of both halves | Testosterone applied to the skin |
| Approval | Not approved in the U.S. or Europe (Foster et al., 2026) | Approved for women; off-label in men (Rodriguez et al., 2016) | The standard treatment (Foster et al., 2026) |
| Testosterone | Raised | Raised | Raised; no clear difference from the pills (Hohl et al., 2025) |
| LH and FSH | Raised | Raised | Lowered (Kim et al., 2016) |
| Sperm counts | Held up in trials | Used to protect fertility | Fell in trials (Kim et al., 2016) |
| Long-lived zuclomiphene | No | Yes (Helo et al., 2017) | No |
What the studies used
| Study | Men | Compared with | Length |
|---|---|---|---|
| Kaminetsky 2013 | 12 with secondary hypogonadism | Testosterone gel, open-label | 6 months |
| Wiehle 2013 | 48 | Gel; three capsule strengths | 6 weeks |
| Wiehle 2014 | 124 enrolled, 73 completed | Gel and placebo; two strengths | 3 months |
| Kim 2016 | 265 overweight men, in two trials | Gel and placebo; two strengths | 16 weeks |
| Saffati 2024 | 66, records review | The same men’s earlier clomiphene | About 9 months |
| Thomas 2023 | 78, records review | Clomiphene vs enclomiphene | 3 months or more |
These are the studies’ methods, not a dose for anyone to use. Doses were set by trial protocols, and a prescriber sets any dose from lab results.
Side effects and safety
- No long-term safety data. A review says side effects hadn’t been directly studied, and a 2026 position statement says safety and fertility data are limited (Rodriguez et al., 2016; Foster et al., 2026).
- What was reported. Raised estradiol, headache and abdominal discomfort in the trials (Rodriguez et al., 2016). The position statement lists headache (1.6%), hot flushes (1.1%), nausea (1.0%), muscle spasms (0.9%) and dizziness (0.7%) (Foster et al., 2026).
- Blood clots. Europe’s regulator cited a risk of venous thromboembolism, clots in the veins, when it refused the drug in 2018 (EMA, 2018).
- Heart rhythm. A 2026 case report describes atrial flutter in a man with heart-valve surgery after he took double his dose. The authors say cause can’t be established (Tariq et al., 2026). A thorough QT study of heart-rhythm effects in 54 healthy men is registered, with no results posted (ClinicalTrials.gov).
- The zuclomiphene problem. Men who take clomiphene instead get a long-lived second half: in one study its blood level was about 20 times that of enclomiphene (Helo et al., 2017).
- Liver. We found no published report of liver injury from enclomiphene. The position statement lists a history of liver disease as a reason not to use it (Foster et al., 2026).
- Product quality. Enclomiphene is sold as compounded capsules and mixtures. We found no independent test of them that we could verify.
- Unstudied. Long-term use, use in women, teens, and men with liver disease or heart rhythm problems.
Side effects people report from online products aren’t covered here; they come from users, not studies.
Legal and approval status
- Not FDA-approved. The developer sought approval, and an advisory meeting set for November 2015 was cancelled over concerns about the lab method used to measure the drug (Rodriguez et al., 2016). A drug reference says the company received a complete response letter in 2015 (RxList). A 2026 position statement says the maker discontinued development in 2021 (Foster et al., 2026).
- Europe refused it. The European Medicines Agency refused EnCyzix in 2018, saying the studies showed higher testosterone but did not look at symptoms, and noting a risk of blood clots in veins (EMA, 2018).
- Under FDA review for compounding. FDA lists enclomiphene citrate in Category 1, “under evaluation,” of the bulk substances nominated for compounding (FDA list, May 2026). That is a review status, not an approval. It isn’t on the FDA’s safety-risk page (FDA, 2026).
- Not in the October 2026 HHS policy. That temporary policy covers six peptides (Reuters, 2026).
- Banned in sport. The World Anti-Doping Agency’s 2026 list prohibits anti-estrogens and SERMs at all times and names clomifene, of which enclomiphene is one half (WADA, 2026). In one study, clomiphene’s other half was detectable in urine for 121 to over 261 days (Miller et al., 2019).
- “Research use only” products aren’t approved for use in people.
What to look for if you research it
We don’t name or link sellers. These checks come from the registries and the studies:
- Enclomiphene or clomiphene? They are different products. Enclomiphene is CAS 15690-57-0 as a base and 7599-79-3 as the citrate; zuclomiphene is 15690-55-8 (PubChem; PubChem).
- How much zuclomiphene. A pure enclomiphene report should show little or none. Zuclomiphene is the half that lingers (Helo et al., 2017).
- Mixtures. Some products add boron, vitamin C or other ingredients, or use a different route such as under the tongue. The trials tested capsules, so results don’t carry over (Warren et al., 2026).
- Who made it. With no approved product, enclomiphene sold in the U.S. is made by compounding pharmacies (Foster et al., 2026).
Our guide to what to look for explains what each test on a lab report proves and which routes are legal; how to read a peptide study explains how to judge the studies sellers cite. For other compounds in this group, see sexual health and hormones.
What’s still unknown
- Whether enclomiphene improves libido, energy, mood or erections, measured with validated tools.
- Long-term safety, including clots, heart rhythm and fertility.
- How it compares with clomiphene in a randomized trial.
- Whether compounded capsules and mixtures match the drug used in the trials.
- What the right candidate looks like outside overweight men with low LH.
Retracted and flagged studies
A retracted study has been pulled by its journal, usually for serious errors or misconduct, and its results shouldn’t be relied on. A withdrawn paper was pulled, often before final publication. An expression of concern means the journal has flagged a problem it is still looking into.
We check every study this page cites against PubMed and the Retraction Watch database, and search both for flagged studies that mention Enclomiphene. We recheck every month. Last checked Nov 11, 2026.
We found no retracted, withdrawn or flagged studies that mention Enclomiphene.
Studies this page relies on
| Study | Published in | Status |
|---|---|---|
| Kaminetsky et al., 2013 | J Sex Med | No retraction or concern |
| Wiehle et al., 2013 | BJU Int | No retraction or concern |
| Wiehle et al., 2014 | Fertil Steril | No retraction or concern |
| Kim et al., 2016 | BJU Int | No retraction or concern |
| Rodriguez et al., 2016 | Expert Opin Pharmacother | No retraction or concern |
| Helo et al., 2017 | BJU Int | No retraction or concern |
| Miller et al., 2019 | J Clin Endocrinol Metab | No retraction or concern |
| Tienforti et al., 2023 | Andrology | No retraction or concern |
| Thomas et al., 2023 | Cureus | No retraction or concern |
| Saffati et al., 2024 | Transl Androl Urol | No retraction or concern |
| Hohl et al., 2025 | Arch Endocrinol Metab | No retraction or concern |
| Foster et al., 2026 | World J Mens Health | No retraction or concern |
| Warren, 2026 | Cureus | No retraction or concern |
| Tariq et al., 2026 | Cureus | No retraction or concern |
Bring your questions to other researchers
Our forum opens once 100 researchers join the waitlist. Members post studies, ask what they actually found, and answer with sources.
Questions
What is enclomiphene?
One half of the fertility drug clomiphene, taken as a pill to raise testosterone in men with low testosterone and a weak brain signal (Rodriguez et al., 2016). It isn’t approved in the U.S. or Europe.
Is enclomiphene a peptide?
No. It is a small molecule, a pill, with no chain of amino acids (PubChem).
How does enclomiphene work?
It blocks estrogen receptors in the brain. Estrogen normally slows the LH and FSH signals to the testes, so blocking it raises LH, FSH and testosterone (Wiehle et al., 2013).
Does enclomiphene work?
It raises testosterone in men with low testosterone, about as much as a gel in trials up to 16 weeks (Hohl et al., 2025; Kim et al., 2016). Whether it improves symptoms hasn’t been measured with validated tools (Rodriguez et al., 2016).
Is enclomiphene a testosterone booster?
In the sense that it raises the body’s own testosterone, yes, in men with low testosterone. It isn’t a supplement; it is an unapproved drug (Foster et al., 2026).
Can enclomiphene get you to 1,000 testosterone?
Trial averages ran about 400 to 600 ng/dL (Wiehle et al., 2013). One company-linked case series of 15 men reported a mean of 805 (Warren et al., 2026).
Can enclomiphene affect sperm count?
In trials it kept sperm counts in the normal range, while gel reduced them (Kim et al., 2016). Trials were 16 weeks or shorter.
Is enclomiphene safe?
We don’t know long term. Europe refused it over a clot risk (EMA, 2018), and a 2026 statement says long-term data are lacking (Foster et al., 2026).
What are the side effects of enclomiphene?
Trials and reviews list raised estradiol, headache, abdominal discomfort, hot flushes and nausea (Rodriguez et al., 2016; Foster et al., 2026).
Is enclomiphene safe for your liver?
We found no published report of liver injury. A 2026 position statement lists liver disease as a reason not to use it (Foster et al., 2026).
Enclomiphene vs clomiphene: what is the difference?
Clomiphene is a mixture of two halves; enclomiphene is one of them. The other half, zuclomiphene, stays in the body longer (Helo et al., 2017). Records reviews found fewer side effects on enclomiphene (Saffati et al., 2024).
Enclomiphene vs TRT: which is better?
No trial compared symptoms. Enclomiphene raised testosterone about as much as gel while keeping sperm counts up, but TRT is the approved standard (Foster et al., 2026; Hohl et al., 2025).
What is the enclomiphene dosage?
The trials gave daily capsules at three strengths for 6 weeks to 6 months (Wiehle et al., 2013). No study has set a dose for symptoms or long-term use. A prescriber sets any dose from lab results.
Is enclomiphene legal?
It isn’t FDA-approved. It is on FDA’s “under evaluation” compounding list (FDA list, May 2026), and it is banned in sport (WADA, 2026). Our guide to what to look for covers the routes people use.
Sources
- Rodriguez KM, et al. Enclomiphene citrate for the treatment of secondary male hypogonadism. Expert Opin Pharmacother. 2016. PubMed 27337642
- Kaminetsky J, et al. Oral enclomiphene citrate stimulates the endogenous production of testosterone and sperm counts in men with low testosterone: comparison with testosterone gel. J Sex Med. 2013;10(6):1628-35. PubMed 23530575
- Wiehle R, et al. Testosterone restoration by enclomiphene citrate in men with secondary hypogonadism: pharmacodynamics and pharmacokinetics. BJU Int. 2013;112(8):1188-200. PubMed 23875626
- 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(3):720-7. PubMed 25044085
- 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. PubMed 26496621
- 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):171-6. PubMed 27511863
- Tienforti D, et al. Selective modulation of estrogen receptor in obese men with androgen deficiency: a systematic review and meta-analysis. Andrology. 2023;11(6):1067-76. PubMed 36604313
- Hohl A, 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). PubMed 41066380
- Saffati G, et al. Safety and efficacy of enclomiphene and clomiphene for hypogonadal men. Transl Androl Urol. 2024;13(9):1984-90. PubMed 39434750
- Thomas J, et al. Efficacy of clomiphene citrate versus enclomiphene citrate for male infertility treatment: a retrospective study. Cureus. 2023;15(7):e41476. PubMed 37546076
- 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):480-3. PubMed 41714894
- Tariq MN, et al. Newly detected atrial flutter after enclomiphene dose escalation in a patient with prior mitral valve repair and immune thrombocytopenia. Cureus. 2026;18:e114562. PubMed 42741668
- Warren S, et al. Changes in serum testosterone after sublingual enclomiphene citrate combined with a mineral oxide delivery system. Cureus. 2026;18:e109299. PubMed 42170362
- Miller GD, et al. Hypothalamic-pituitary-testicular axis effects and urinary detection following clomiphene administration in males. J Clin Endocrinol Metab. 2019;104(3):906-14. PubMed 30295816
- European Medicines Agency. EnCyzix (enclomifene): refusal of the marketing authorisation. Opinion adopted January 25, 2018. EMA page
- RxList. Enclomiphene: side effects, uses, dosage, interactions, warnings. RxList page
- U.S. Food and Drug Administration. Bulk drug substances nominated for use in compounding under section 503A. Updated May 14, 2026. FDA document
- U.S. Food and Drug Administration. Safety risks associated with certain bulk drug substances nominated for use in compounding. Content current as of April 22, 2026. FDA page
- ClinicalTrials.gov. NCT01386567 (one-year open-label study of Androxal) and NCT02117830 (heart-rhythm study of Androxal in healthy men). NCT01386567; NCT02117830
- World Anti-Doping Agency. 2026 Prohibited List (S4.2, anti-estrogenic substances). WADA document
- Reuters. U.S. health department to allow temporary sale of some unapproved peptides. October 28, 2026. Article
- National Library of Medicine. PubChem compound record: Enclomiphene (free base) (CID 1548953). PubChem
- National Library of Medicine. PubChem compound record: Enclomiphene citrate (CID 6420009). PubChem
- National Library of Medicine. PubChem compound record: Zuclomiphene (the other half of clomiphene) (CID 1548955). PubChem
Last reviewed Nov 11, 2026. Approval and compounding status change often; we recheck this page when they do. Nothing here is medical advice; see our medical disclaimer. Found a mistake? Email editors@peptideresearchstudy.com.