Enclomiphene vs clomiphene

Clomiphene and enclomiphene are closely related: clomiphene is a mix of two mirror-image forms (isomers), and enclomiphene is one of those forms on its own. Both are pills that prompt the pituitary gland to send more LH and FSH, so the testes make more of their own testosterone and keep making sperm. The differences are in the other isomer, the evidence and the legal status. Clomiphene is an FDA-approved generic, approved only for women and prescribed to men off-label. Enclomiphene has no FDA-approved product, so what you get online is compounded.

Here is how they compare, what the studies in men show, and what each costs as of October 2026.

At a glance

How they work

Both drugs block estrogen’s feedback at the hypothalamus and pituitary. With that brake off, the pituitary releases more luteinizing hormone (LH) and follicle-stimulating hormone (FSH). LH tells the testes to make testosterone and FSH supports sperm production. That is the opposite of testosterone therapy, which supplies the hormone directly and can shut that signal down.

Because they work through LH, both are used for secondary hypogonadism, where the testes still respond. The AUA guideline says men with low testosterone and low or low-normal LH can be considered for this kind of drug (a selective estrogen receptor modulator, or SERM), particularly if they want to preserve fertility. It also notes that, among these alternatives to testosterone, only hCG is FDA-approved for use in men.

The isomer difference

The Clomid label says clomiphene citrate contains between 30% and 50% of the cis isomer, zuclomiphene, with the trans isomer, enclomiphene, making up the rest. It adds two points that matter for men taking it every day:

• Zuclomiphene has more estrogen-like activity. The label says some data suggest zuclomiphene is more estrogenic than enclomiphene.
• Zuclomiphene lingers. In single-dose studies it had a longer half-life than enclomiphene and stayed detectable for more than a month. A 1986 study of 24 volunteers given one 50 mg dose found significant zuclomiphene levels up to a month later (Mikkelson et al.).

Daily dosing makes the gap wider. In 15 men who had taken clomiphene 25 mg a day for a median of about 26 months, the median ratio of zuclomiphene to enclomiphene in the blood was 20 to 1 (Helo et al., 2017). Their median testosterone had risen from 205 to 488 ng/dL, so the drug worked, but the authors argued that zuclomiphene’s build-up supports using a pure isomer instead. Enclomiphene is that pure isomer.

What the studies in men show

Enclomiphene

Enclomiphene was studied as a drug candidate called Androxal, which was never approved:

• Phase II: in 44 men with secondary hypogonadism, enclomiphene 25 mg a day brought morning testosterone to 604 ng/dL after six weeks, against 500 ng/dL on testosterone gel, a difference that wasn’t statistically significant. LH and FSH went up on enclomiphene, while LH was suppressed on the gel (Wiehle et al.).
• Phase III: two 16-week trials in overweight men aged 18 to 60 compared two enclomiphene doses with AndroGel 1.62%. Both raised testosterone, but enclomiphene kept sperm concentration in the normal range while the gel sharply reduced sperm production (Kim et al.).

Clomiphene

Clomiphene has no FDA-reviewed trials in men, and the Clomid label says there are no adequate or well-controlled studies showing it treats male infertility. It also notes that testicular tumors and breast enlargement have been reported in men taking it, without a known cause-and-effect link. In a small open-label study of 12 healthy men aged 25 to 38 taking 50 mg a day for 30 days, mean testosterone rose 146%, LH 177% and FSH 170% (Miller et al., 2019).

Head to head

No randomized trial has compared the two. The closest is a retrospective study from one academic center of 66 men who took clomiphene and later switched to enclomiphene (Saffati et al., 2024):

Because each man took clomiphene first and enclomiphene second, and nobody was randomized or blinded, the study can’t show cause and effect. Treat it as a reason to discuss enclomiphene if clomiphene gave you side effects, not as proof that it works better.

Side effects and warnings

Clomiphene’s label lists visual symptoms (blurring, spots or flashes) that become more common with higher doses and longer use. They usually go away, but the label says they may be prolonged or irreversible, and anyone with visual symptoms should stop and have a complete eye exam. It is also contraindicated in liver disease. Most of the label’s other warnings, such as ovarian hyperstimulation, apply only to women.

Enclomiphene has no FDA label, so there are no FDA-reviewed warnings or doses for it, and its long-term safety in men hasn’t been established. Ask for a testosterone blood test before you start either drug and while you take it.

Legal status

Clomiphene is FDA-approved and sold as a generic, so clinics prescribe the commercial tablet. Its use to raise testosterone in men is off-label.

Enclomiphene has no approved product. It is on the FDA’s 503A Category 1 list of bulk substances under evaluation (updated May 14, 2026), which means the FDA doesn’t intend to act against state-licensed pharmacies that compound it for an individual prescription while it is evaluated. It is not on the final 503A bulks list, and that status can change. Compounded enclomiphene is not FDA-approved, and the FDA hasn’t reviewed it for safety, effectiveness or quality.

Neither drug is a controlled substance, so the DEA telemedicine rule that governs testosterone doesn’t apply to them.

Athletes should know that clomiphene is misused to raise testosterone in sport. In the 2019 study above, zuclomiphene stayed detectable in urine for 121 to more than 261 days after 30 days of use.

What each costs online

Prices as of October 2026, from each provider’s own pages, medication included:

Scroll sideways to see the full table

PeterMD sells enclomiphene for $278 on a 2-month plan (regularly $345). For clomiphene, the clinic’s fee is most of the cost: at Hone Health the $155 membership is four times the $38 medication price. Compare enclomiphene prices at enclomiphene cost, and see the clomiphene and enclomiphene pages for doses and providers.

Which to ask your clinician about

Both are options for men with secondary hypogonadism who want to raise their own testosterone and keep sperm production. Clomiphene may suit you if you want an FDA-approved generic with a longer track record, accept that its use in men is off-label, and don’t mind the zuclomiphene. Enclomiphene may suit you if you had side effects on clomiphene or want to avoid zuclomiphene’s build-up, and you accept a compounded drug that isn’t FDA-approved. The AUA’s advice on these drugs covers men with low or low-normal LH. A high LH points to the testes themselves, where pushing LH higher may not help, and testosterone therapy is the labeled treatment.

Either way, the diagnosis comes first: symptoms plus two morning tests below the normal range. See low testosterone symptoms and TRT and fertility.

The bottom line

Enclomiphene is the trans isomer of clomiphene, without the slower-clearing, more estrogenic zuclomiphene. Clomiphene is an FDA-approved generic used off-label in men; enclomiphene is compounded, not FDA-approved, and sold under the FDA’s interim 503A policy. No randomized trial has compared them. As of October 2026, enclomiphene starts at $79 to $197 a month online, and clomiphene’s price mostly depends on the clinic’s membership. Compare clinics on our testosterone hub.