Is enclomiphene FDA-approved?

No, and it never has been in the United States — not for hypogonadism, not for anything. A DailyMed query on 2026-09-20, against a database published 18 September 2026, returns zero Structured Product Labels for "enclomiphene" and zero for "enclomiphene citrate". Drugs@FDA holds no approved application. Repros Therapeutics filed a New Drug Application for enclomiphene — the compound its trials branded Androxal — and received a Complete Response Letter on 1 December 2015; the additional phase III work the FDA asked for was never carried out. Everything sold as enclomiphene in the United States today is compounded, and the FDA is explicit that compounded drugs are not FDA-approved and are not reviewed for safety, effectiveness or manufacturing quality before they are dispensed. This page checked the US registers only; it does not claim to have searched every national register, and it states no approval status outside the United States.

Does enclomiphene raise testosterone as much as TRT?

In the one study that measured both in the same men, at the highest arm, the difference was not statistically significant. Wiehle 2013 randomised 48 men with secondary hypogonadism to enclomiphene 6.25, 12.5 or 25 mg daily or transdermal testosterone; at day 42, mean total testosterone was 604 ± 160 ng/dL on 25 mg enclomiphene and 500 ± 278 ng/dL on transdermal testosterone, and the paper reports these as "not different from each other (p = 0.23, T-test)". Three caveats matter: it is a phase II study of 48 men, it was run by the drug's sponsor, and the comparator was a GEL. Nothing in it compares enclomiphene with injected testosterone cypionate, and no study does.

What dose of enclomiphene should I take?

This page will not tell you, and the reason is not caution for its own sake: no regulator has ever set a dose for enclomiphene, so there is no starting dose, no maintenance dose and no titration schedule to state. What can be reported is what named trials gave. Wiehle 2013 randomised three arms — 6.25 mg, 12.5 mg and 25 mg daily. Kim 2016 evaluated "two doses of enclomiphene citrate" over 16 weeks and its abstract does not name which two, so neither does this page. Those are trial arms, not a regimen, and anyone presenting them as a protocol is assembling something that does not exist.

Will TRT make me infertile?

The label does not use that word, but it describes the mechanism and names the effect. Depo-Testosterone's label states that "endogenous testosterone release is inhibited through feedback inhibition of pituitary luteinizing hormone (LH)" and that "at large doses of exogenous androgens, spermatogenesis may also be suppressed through feedback inhibition of pituitary follicle stimulating hormone (FSH)", and its precautions section adds: "Oligospermia may occur after prolonged administration or excessive dosage." Kim 2016 saw the same thing in a trial — "a marked reduction in spermatogenesis in the testosterone gel group" over 16 weeks. This is the single best reason to raise fertility with a prescriber before starting rather than afterwards, and the approved agent for addressing it in men is hCG.

Is enclomiphene the same as clomiphene?

It is one half of it. The CLOMID label states: "Clomiphene citrate is a mixture of two geometric isomers [cis (zuclomiphene) and trans (enclomiphene)] containing between 30% and 50% of the cis-isomer," and notes that "some data suggest that zuclomiphene has greater estrogenic activity than enclomiphene." Isolating the trans-isomer, to drop the more oestrogenic and longer-lingering half, is the entire premise of the drug. It is a reasonable premise and it is not an approval: clomiphene has one — for ovulation induction in women — and enclomiphene has none. Male use of clomiphene is itself off-label, and its label states that no adequate or well-controlled studies demonstrate effectiveness in male infertility.

What do the guidelines recommend?

Neither major guideline names enclomiphene, because both were written about approved drugs used off-label. The AUA guideline's statement 27 says clinicians "may use aromatase inhibitors, human chorionic gonadotropin, selective estrogen receptor modulators, or a combination thereof in men with testosterone deficiency desiring to maintain fertility" — a Conditional Recommendation at Evidence Level Grade C — and then adds the sentence that matters here: "Clinicians should understand that of these agents, only hCG has been approved by the FDA for use in males." The Endocrine Society's 2018 testosterone guideline carries one technical remark on the class, about clomiphene: "Clomiphene citrate has been used empirically in men with hypogonadotropic hypogonadism; however, neither its efficacy nor its safety has been demonstrated in randomized trials."

Head to head

TRT vs Enclomiphene

Testosterone is an approved medicine with a label. Enclomiphene has never been approved in the US for anything at all. That is the comparison — and it does not mean the trials found nothing.

Reviewed September 2026

The short answer

These are not two prescription options with different trade-offs, and any comparison that treats them as though they were has already gone wrong. Testosterone is an approved medicine. Enclomiphene has never been approved by the FDA for any indication. DailyMed returns no Structured Product Label for it. Drugs@FDA holds no approved application. Everything sold as enclomiphene in the United States is a compounded preparation, and the FDA states plainly that compounded drugs are not FDA-approved and are not reviewed for safety, effectiveness or manufacturing quality before they are dispensed.

There was an application. Repros Therapeutics filed a New Drug Application for enclomiphene — the study drug its trials called Androxal — and received a Complete Response Letter on 1 December 2015: the FDA said the phase III study design was "no longer adequate to demonstrate clinical benefit" and asked for additional phase III work, and also raised concerns about study entry criteria, titration and bioanalytical method validation. Those studies were never run. That is not a technicality being held against a good drug — it is the reason there is no dose, no monitoring schedule and no labelled anything.

The trials that do exist are head-to-head, and they found real things. Wiehle 2013 randomised 48 men to three enclomiphene doses or transdermal testosterone; after 6 weeks, total testosterone on the 25 mg arm was 604 ± 160 ng/dL against 500 ± 278 on transdermal testosterone, "not different from each other (p = 0.23)". Kim 2016, two phase III studies over 16 weeks, found enclomiphene "maintained sperm concentration in the normal range" while "there was a marked reduction in spermatogenesis in the testosterone gel group".

So the honest position is neither "enclomiphene is unproven nonsense" nor "enclomiphene is TRT without the downsides". It is a compound with a coherent mechanism and two head-to-head trials against testosterone GEL — not against injected cypionate — whose sponsor was told to run more studies and did not. If your priority is preserving fertility, that is the one question the trials actually addressed, and it is worth taking to a prescriber alongside the approved option for it, which is hCG.

1 of 14 dimensions are materially the same. They are marked below rather than dressed up as differences.

Testosterone replacement therapy

Depo-Testosterone · Xyosted · AndroGel

Exogenous testosterone. An approved medicine with a labelled dose range, a required diagnostic work-up and a DEA schedule.

Dosing protocol →

Enclomiphene

Androxal (never approved)

The trans-isomer of clomiphene, taken to raise your own testosterone. No US approval for any indication; every US capsule is compounded.

Dosing protocol →

Side by side

Every row carries how well supported it is. A claim that only reflects common practice is labelled as such rather than presented as fact.

Dimension	Testosterone replacement therapy	Enclomiphene	Basis
FDA approval	Approved — multiple products and dosage forms	No US approval, for any indication	labelDepo-Testosterone is approved under ANDA 085635; the class also has approved gels, pellets and an auto-injector. For enclomiphene, a DailyMed query on 2026-09-20 returns zero Structured Product Labels and Drugs@FDA holds no approved application. Non-US registers were not searched and no claim is made about them.
Is there a label at all	Yes — indication, dose, route, warnings, monitoring	No. None exists to read	labelThe word "enclomiphene" appears in FDA labelling only inside clomiphene labels, describing one of the two isomers clomiphene is made of: "Clomiphene citrate is a mixture of two geometric isomers [cis (zuclomiphene) and trans (enclomiphene)]". There is no document to check your capsule against.
Labelled dose	50–400 mg every two to four weeks (cypionate)	None — no regulator has ever set one	labelDepo-Testosterone, verbatim: "For replacement in the hypogonadal male, 50 - 400 mg should be administered every two to four weeks." The only enclomiphene figures that can be cited at all are trial arms — Wiehle 2013 randomised 6.25, 12.5 and 25 mg daily — and a trial arm is not a starting dose, a maintenance dose or a schedule.
Route and dosage form	Intramuscular for cypionate; gels, pellets and an auto-injector also approved	Oral capsule, compounded — no approved dosage form	labelDepo-Testosterone, verbatim: "DEPO-Testosterone Injection is for intramuscular use only." Every approved testosterone product has a labelled route. Enclomiphene has no approved vehicle, strength or dosage form — the strength on a compounded capsule is a figure a prescriber chose and a pharmacy prepared.
Product oversight	Manufactured under an FDA-approved application	Compounded — not FDA-reviewed before dispensing	labelThe FDA states that compounded drugs are not FDA-approved: the agency does not verify their safety, effectiveness or quality before they are marketed. Product bought from an online seller without a prescription is outside even that, with identity, strength and purity unverified by anyone.
Controlled substance status	Schedule III	Not scheduled — because it is not an approved drug	labelNot an advantage. Being unscheduled is a consequence of never having been approved, not a statement that a regulator looked at enclomiphene and found it benign.
Diagnosis required before starting	Two low morning testosterone measurements	Nothing is required, because nothing is labelled	labelDepo-Testosterone, verbatim: "confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning on at least two separate days and that these... are below the normal range." Both enclomiphene trials used a similar entry criterion, but a trial protocol is not a labelled requirement.
Labelled monitoring	Haemoglobin and haematocrit, periodically	None exists — whatever your prescriber decides	labelDepo-Testosterone, verbatim: "Hemoglobin and hematocrit levels (to detect polycythemia) should be checked periodically in patients receiving long-term androgen administration." Enclomiphene has no labelled baseline, interval or stopping rule — any monitoring on it is your prescriber’s protocol, not a label’s.
Effect on LH and FSH	Suppressed — this is in the label's own mechanism section	Raised above the normal range in the trials	labelDepo-Testosterone, verbatim: "endogenous testosterone release is inhibited through feedback inhibition of pituitary luteinizing hormone (LH)." Wiehle 2013, verbatim: enclomiphene "consistently increased serum TT into the normal range and increased LH and FSH above the normal range." Opposite directions — the whole argument for the class.
Effect on fertility	"Oligospermia may occur after prolonged administration or excessive dosage"	Sperm concentration maintained in the normal range	literatureThe testosterone half is a verbatim label warning. The enclomiphene half is Kim 2016 (PMID 26496621), 16 weeks: sperm concentration "maintained... in the normal range" against "a marked reduction in spermatogenesis in the testosterone gel group." The comparator was a gel, not an injection.
Head-to-head testosterone levels	500 ± 278 ng/dL on transdermal testosterone	604 ± 160 ng/dL on 25 mg enclomiphene	literatureWiehle 2013 (PMID 23875626), 48 men, randomised single-blind, at day 42: the two "were higher than Day 1 values but not different from each other (p = 0.23, T-test)". A sponsor-run phase II against a GEL is not a basis for choosing between enclomiphene and an injection — but it is a real comparison rather than two trials subtracted.
What happened to the application	Approved; marketed since the 1950s	Complete Response Letter, 1 December 2015	literatureRepros Therapeutics' own announcement: "the FDA stated that... the design of enclomiphene Phase 3 studies is no longer adequate to demonstrate clinical benefit and recommended that Repros conduct an additional Phase 3 study or studies", and also "noted concerns regarding study entry criteria, titration and bioanalytical method validation". Those studies were never run.
What the guidelines say	Recommended, with monitoring, in confirmed hypogonadism	Not addressed — the guidelines predate and exclude it	guidelineThe AUA guideline permits SERMs, aromatase inhibitors and hCG for men wanting to preserve fertility, then adds: "Clinicians should understand that of these agents, only hCG has been approved by the FDA for use in males." Neither the AUA nor the Endocrine Society names enclomiphene — both were written about approved drugs used off-label.
The approved option for fertilitysame	hCG — approved in men, and can be given alongside	hCG — the same approved alternative	labelIf fertility is the reason you are reading this page, one drug here has an FDA approval in men for it. PREGNYL and NOVAREL both list "Selected cases of hypogonadotropic hypogonadism (hypogonadism secondary to a pituitary deficiency) in males". That is the conversation to have before an unapproved compound.

label: Stated on the FDA label
guideline: Clinical practice guideline
literature: Published literature
practice: Common practice, not documented

Which one

Choose Testosterone replacement therapy if

You have confirmed hypogonadism — two low morning measurements — and want the treatment a regulator has reviewed, with a labelled dose, labelled monitoring and a manufactured product behind it.
Your own pituitary signal is the problem. Testosterone works regardless of whether the hypothalamic–pituitary axis can respond; a SERM depends on it being able to.
You are past wanting children, or you are prepared to use hCG alongside — the one agent in this space that is FDA-approved for use in men.
You want something your insurer, your pharmacist and your next doctor will all recognise and be able to check against a document.

Choose Enclomiphene if

Preserving your own sperm production is the reason you are asking. That is the only question the trials actually tested, and enclomiphene maintained sperm concentration where testosterone gel did not — but ask first why hCG, which is approved in men for exactly this, is not the answer.
You have a prescriber who will write down a dose, a monitoring schedule and a stopping rule before you start, and who can tell you what each of those is based on — because no label supplies any of them.
You understand you are taking a compounded preparation that the FDA has not reviewed for safety, effectiveness or manufacturing quality, and that the strength on the capsule is a figure someone chose rather than a figure someone approved.
You would rather your LH and FSH go up than down, and you accept that the evidence for that preference is two sponsor-run trials against a gel and a Complete Response Letter.

The framing that sells enclomiphene — "restoration instead of replacement" — is the subtitle of one of its own trial papers, and it is doing a lot of work. What is true is that the two drugs move LH and FSH in opposite directions and that one trial showed sperm counts holding on enclomiphene and falling on testosterone gel. What is also true is that ten years after those phase III studies read out, no regulator anywhere has approved the drug, and the sponsor never ran the studies the FDA asked for. If the reason you are considering it is fertility, hCG has an approved male indication and belongs in the conversation first. If the reason is that you would rather take a pill than inject, that is a real preference, and it is worth knowing that you are paying for it with a compounded product that has no label at all.

Frequently asked questions

Is enclomiphene FDA-approved?: No, and it never has been in the United States — not for hypogonadism, not for anything. A DailyMed query on 2026-09-20, against a database published 18 September 2026, returns zero Structured Product Labels for "enclomiphene" and zero for "enclomiphene citrate". Drugs@FDA holds no approved application. Repros Therapeutics filed a New Drug Application for enclomiphene — the compound its trials branded Androxal — and received a Complete Response Letter on 1 December 2015; the additional phase III work the FDA asked for was never carried out. Everything sold as enclomiphene in the United States today is compounded, and the FDA is explicit that compounded drugs are not FDA-approved and are not reviewed for safety, effectiveness or manufacturing quality before they are dispensed. This page checked the US registers only; it does not claim to have searched every national register, and it states no approval status outside the United States.
Does enclomiphene raise testosterone as much as TRT?: In the one study that measured both in the same men, at the highest arm, the difference was not statistically significant. Wiehle 2013 randomised 48 men with secondary hypogonadism to enclomiphene 6.25, 12.5 or 25 mg daily or transdermal testosterone; at day 42, mean total testosterone was 604 ± 160 ng/dL on 25 mg enclomiphene and 500 ± 278 ng/dL on transdermal testosterone, and the paper reports these as "not different from each other (p = 0.23, T-test)". Three caveats matter: it is a phase II study of 48 men, it was run by the drug's sponsor, and the comparator was a GEL. Nothing in it compares enclomiphene with injected testosterone cypionate, and no study does.
What dose of enclomiphene should I take?: This page will not tell you, and the reason is not caution for its own sake: no regulator has ever set a dose for enclomiphene, so there is no starting dose, no maintenance dose and no titration schedule to state. What can be reported is what named trials gave. Wiehle 2013 randomised three arms — 6.25 mg, 12.5 mg and 25 mg daily. Kim 2016 evaluated "two doses of enclomiphene citrate" over 16 weeks and its abstract does not name which two, so neither does this page. Those are trial arms, not a regimen, and anyone presenting them as a protocol is assembling something that does not exist.
Will TRT make me infertile?: The label does not use that word, but it describes the mechanism and names the effect. Depo-Testosterone's label states that "endogenous testosterone release is inhibited through feedback inhibition of pituitary luteinizing hormone (LH)" and that "at large doses of exogenous androgens, spermatogenesis may also be suppressed through feedback inhibition of pituitary follicle stimulating hormone (FSH)", and its precautions section adds: "Oligospermia may occur after prolonged administration or excessive dosage." Kim 2016 saw the same thing in a trial — "a marked reduction in spermatogenesis in the testosterone gel group" over 16 weeks. This is the single best reason to raise fertility with a prescriber before starting rather than afterwards, and the approved agent for addressing it in men is hCG.
Is enclomiphene the same as clomiphene?: It is one half of it. The CLOMID label states: "Clomiphene citrate is a mixture of two geometric isomers [cis (zuclomiphene) and trans (enclomiphene)] containing between 30% and 50% of the cis-isomer," and notes that "some data suggest that zuclomiphene has greater estrogenic activity than enclomiphene." Isolating the trans-isomer, to drop the more oestrogenic and longer-lingering half, is the entire premise of the drug. It is a reasonable premise and it is not an approval: clomiphene has one — for ovulation induction in women — and enclomiphene has none. Male use of clomiphene is itself off-label, and its label states that no adequate or well-controlled studies demonstrate effectiveness in male infertility.
What do the guidelines recommend?: Neither major guideline names enclomiphene, because both were written about approved drugs used off-label. The AUA guideline's statement 27 says clinicians "may use aromatase inhibitors, human chorionic gonadotropin, selective estrogen receptor modulators, or a combination thereof in men with testosterone deficiency desiring to maintain fertility" — a Conditional Recommendation at Evidence Level Grade C — and then adds the sentence that matters here: "Clinicians should understand that of these agents, only hCG has been approved by the FDA for use in males." The Endocrine Society's 2018 testosterone guideline carries one technical remark on the class, about clomiphene: "Clomiphene citrate has been used empirically in men with hypogonadotropic hypogonadism; however, neither its efficacy nor its safety has been demonstrated in randomized trials."

Sources

Next steps

Compare online TRT providersWhich platforms prescribe testosterone, which push compounded enclomiphene, and what monitoring is included.TRT — how it works and what it costsDiagnosis, the full panel, fertility, and what to expect in the first six months.

Other comparisons

Educational reference, not medical advice. Which medication suits you is a decision for your prescriber.