Enclomiphene vs Clomiphene
Research Comparison

Research Overview

Enclomiphene vs clomiphene compares one isomer with the mixture that contains it. Clomiphene citrate, a nonsteroidal triphenylethylene estrogen receptor ligand, combines trans enclomiphene with cis zuclomiphene, and its FDA label specifies 30% to 50% of the cis isomer. In the immature rat uterus, enclomiphene was partially estrogenic with antiestrogenic properties, like tamoxifen, while zuclomiphene was predominantly estrogenic (Jordan et al., 1981).

The two isomers also clear at very different speeds (Mikkelson et al., 1986). Disguised Alpha supplies enclomiphene only, as Enclomiphene Citrate capsules (12.5MG) and Liquid Enclomiphene (12.5MG/ML, 30ML bottle), for laboratory research use only.

Structure and Composition

Both isomers are 2-[4-(2-chloro-1,2-diphenylethenyl)phenoxy]-N,N-diethylethanamine and differ only in geometry at the central double bond: enclomiphene is the (E) form (PubChem CID 1548953), zuclomiphene the (Z) form (CID 1548955). They share one formula and mass, C32H36ClNO8 and 598.1 g/mol as citrates (the figures on the Enclomiphene Citrate product page), so mass alone cannot tell enclomiphene from clomiphene.

Under the label specification, enclomiphene is 50% to 70% of clomiphene citrate; the developer's phase 2 paper gives 62% enclomiphene and 38% zuclomiphene (Wiehle et al., 2013). PubChem's enclomiphene record lists both trans-clomiphene and cisclomiphene as synonyms, so match isomer names to E or Z structure, not to cis or trans labels.

Side by Side

Research Context: Enclomiphene

Enclomiphene's profile depends on species. In sheep pituitary cells at 1 µM it blocked estradiol's augmentation of the LH response to LHRH, while earlier rat pituitary cultures had shown it acting as an estrogen; the authors cautioned against predicting the mixture's action in any species without direct testing (Huang and Miller, 1983). Models: sheep and rat pituitary cells.

In a chronic study in male mice from the developer, Repros Therapeutics, zuclomiphene alone altered Leydig cells, epididymis, seminal vesicles, kidneys and serum testosterone, FSH and LH, while isolated enclomiphene raised testosterone production and left testicular histology unchanged (Fontenot et al., 2016). Model: male mice.

The human trials also came from the developer. In a randomized phase 2 study of 48 men with secondary hypogonadism, three daily amounts of enclomiphene citrate raised serum total testosterone, LH and FSH, while a testosterone gel raised testosterone and suppressed LH; drug peaks did not line up with LH or testosterone peaks, and the LH and testosterone changes persisted at least a week after exposure stopped (Wiehle et al., 2013).

In two parallel randomized, placebo-controlled phase 3 trials (NCT01993212, NCT01993225) in overweight men with secondary hypogonadism, enclomiphene raised total testosterone, LH and FSH over 16 weeks while LH and FSH fell with the gel, and sperm concentration held in the normal range with enclomiphene but was not maintained with the gel (Kim et al., 2016). Model: randomized trials in men.

The FDA advisory committee meeting on the new drug application, set for 3 November 2015, was canceled over concerns about bioanalytical method validation that arose late in the review (Rodriguez et al., 2016). In 2018 an enclomiphene citrate capsule product was refused EU marketing authorization; the European Medicines Agency committee noted that the studies did not examine symptoms and cited a risk of venous thromboembolism. Enclomiphene is approved by neither the FDA nor the EMA, and its manufacturer discontinued development in 2021 (Foster et al., 2026).

Research Context: Clomiphene

Clomiphene adds zuclomiphene, which was predominantly estrogenic in the rat uterus (Jordan et al., 1981) and an estradiol agonist on the LH response in sheep pituitary cells, where the mixture blocked estradiol as enclomiphene did; zuclomiphene also opposed estradiol's suppression of FSH (Huang and Miller, 1983). In ovariectomized rats, zuclomiphene was a potent estrogen agonist on every tissue measured, enclomiphene reduced its uterotrophic effect, and the pair together had larger effects on bone volume and architecture than either alone (Turner et al., 1998).

In a randomized crossover study in 24 healthy women, the Z isomer peaked later than the E isomer and was eliminated much more slowly, with significant plasma levels up to a month after one exposure (Mikkelson et al., 1986). In 15 men with secondary hypogonadism on long-term clomiphene citrate, median serum zuclomiphene was 44.0 ng/mL against 2.2 ng/mL for enclomiphene, a 20:1 ratio; three authors were from Repros Therapeutics, enclomiphene's developer (Helo et al., 2017).

In an open-label study of 12 healthy men exposed daily for 30 days, zuclomiphene stayed detectable in urine 121 to more than 261 days from the first exposure (Miller et al., 2019). Reported enclomiphene half-lives are about 7 hours (Wiehle et al., 2013) and 10 hours, against 30 days for zuclomiphene (Rodriguez et al., 2016).

Metabolites matter too. Of nine metabolites formed by human liver microsomes, the strongest estrogen receptor inhibitors were (E)-4-hydroxyclomiphene and (E)-4-hydroxy-N-desethylclomiphene (IC50 2.5 and 1.4 nM), formed mainly by CYP2D6; healthy women with non-functional CYP2D6 alleles had 8 and 12 times lower peak levels of them (Mürdter et al., 2012).

Drugs@FDA lists the original clomiphene citrate tablet application, approved in February 1967, as discontinued, with a Federal Register determination that this was not for safety or effectiveness reasons; clomiphene citrate tablets remain listed under abbreviated applications. The label's indication is ovulatory dysfunction in women. The 2026 WADA Prohibited List names clomifene under S4.2, anti-estrogenic substances, prohibited at all times.

Choosing Between Them for a Research Question

Choose by whether the question concerns one isomer or the mixture. Enclomiphene isolates the E isomer; clomiphene suits questions about the mixture, such as the rat findings where enclomiphene opposed zuclomiphene in the uterus but the pair acted together on bone (Turner et al., 1998). A clean isomer comparison needs zuclomiphene as its own arm.

Time courses differ by about two orders of magnitude, and zuclomiphene predominated 20:1 in men on long-term clomiphene (Helo et al., 2017), so studies that include clomiphene should measure each isomer separately.

In cell or animal studies, work in moles of each isomer: either citrate is about 1.67 µmol per milligram, and only 50% to 70% of clomiphene citrate is enclomiphene. For targets further up the axis, see the kisspeptin research guide and the gonadorelin research guide.

Handling and Storage

The Enclomiphene Citrate product page lists 15 to 25°C for sealed capsules in the original container, away from moisture and direct light. The Liquid Enclomiphene page lists 15 to 25°C unopened and 2 to 8°C once the seal is broken, protected from light and never frozen.

For quantitative work, use each lot's certificate in the COA portal: the September 2026 certificate for capsule lot 543D reports 13.15 mg against the 12.5MG label, and liquid lot EC01 12.28 mg/mL against 12.5MG/ML. Because zuclomiphene shares the formula and mass, confirm identity with a method that resolves the E and Z forms.

Questions Researchers Ask

Enclomiphene vs clomiphene: what is the difference?

Enclomiphene is the trans (E) isomer of clomiphene citrate; the mixture adds 30% to 50% of the cis (Z) isomer, zuclomiphene (FDA label), which was the more estrogenic of the two in the rat uterus (Jordan et al., 1981) and clears far more slowly (Mikkelson et al., 1986).

Enclomiphene vs Clomid: is that a different comparison?

No. That brand name refers to clomiphene citrate tablets, so it is the same comparison: one E isomer against the E and Z mixture, whose zuclomiphene reached 20 times the serum level of enclomiphene with long-term exposure (Helo et al., 2017).

Which clomiphene isomer lingers, and why?

Zuclomiphene, still detectable in urine 121 to more than 261 days after the start of a 30-day exposure (Miller et al., 2019). The FDA label says its persistence may suggest stereospecific enterohepatic recycling or sequestering.

Are enclomiphene and clomiphene approved or prohibited in sport?

Clomiphene citrate tablets are FDA-approved for ovulatory dysfunction in women; enclomiphene is approved by neither the FDA nor the EMA (Foster et al., 2026). The 2026 WADA Prohibited List names clomifene under S4.2, prohibited at all times; that class covers SERMs including, but not limited to, those named.

Does Disguised Alpha sell clomiphene?

Not currently. Disguised Alpha supplies enclomiphene only, for laboratory research: Enclomiphene Citrate capsules (12.5MG) and Liquid Enclomiphene (12.5MG/ML, 30ML bottle).