Enclomiphene for Men: Testosterone, Fertility and Side Effects

Enclomiphene in three numbers

Three figures from randomized trials sum up why this drug draws so much interest.

Study figures come from PubMed papers. What users do in practice is not studied; where we describe it, we say so.

What this enclomiphene guide covers

What is enclomiphene?

Enclomiphene is one half of clomiphene. Clomiphene, sold as Clomid, is a mix of two mirror image molecules: enclomiphene and zuclomiphene (PMID 23530575).

Clomiphene is approved for ovulation problems in women. Doctors have used it off label for years in men with low testosterone, especially when fertility matters (PMID 27337642).

Reviews suggest most of clomiphene's benefit in men comes from this half, while zuclomiphene adds little to the intended effect (PMID 31063005).

As a stand alone drug, it has struggled to win FDA approval as a new drug, a 2019 review notes (PMID 31063005).

How enclomiphene works

Estradiol tells the brain to slow down testosterone production. This drug blocks that estrogen signal at the hypothalamus (PMID 41066380).

The brain reads that as low estrogen and releases more LH and FSH. LH drives the testes to make testosterone; FSH supports sperm production (PMID 27337642).

That is the key difference from TRT. Testosterone from outside lowers LH and FSH, and sperm production falls. In a WHO trial, 200 mg a week stopped sperm production in 157 of 271 men (PMID 1977002).

Does enclomiphene work? The testosterone numbers

The pooled answer. Across randomized trials, clomiphene or enclomiphene raised total testosterone by 274 ng/dL more than placebo. It was not significantly different from testosterone gel (PMID 41066380).

A head to head. 12 men came off testosterone gel with a morning level of 165. After 6 months, the pill gave 525 and gel gave 545, close to the same (PMID 23530575).

A month after stopping, testosterone fell back to where it started (PMID 23530575).

Obese men. In two phase III trials of overweight men over 16 weeks, the drug raised testosterone, LH and FSH. Gel raised testosterone but lowered LH and FSH (PMID 26496621).

A meta analysis of obese men found enclomiphene raised testosterone by 7.5 nmol/L, about 216 ng/dL (PMID 36604313).

Enclomiphene and fertility

This is where it stands apart. In the small trial, it raised sperm counts in 7 of 7 men at 3 months and 6 of 6 at 6 months. Counts reached 75 to 334 million per mL (PMID 23530575).

Testosterone gel did not raise any of 5 men above 20 million per mL at 3 months (PMID 23530575).

A phase II trial against gel found the same pattern: testosterone, LH and FSH up, sperm counts conserved (PMID 25044085).

In the phase III trials, the drug kept sperm in the normal range, while gel caused a marked drop in sperm production (PMID 26496621).

Pooled, SERM therapy gave 70.4 million per mL more sperm than gel. The risk of falling below 15 million per mL was 90 percent lower (PMID 41066380).

Enclomiphene vs TRT

Blood thickening is a known cost of TRT. In 363 men, polycythemia hit 11.2 percent on testosterone and 1.7 percent on clomiphene, with similar testosterone gains (PMID 27984109).

Enclomiphene vs clomiphene

Clomiphene is half zuclomiphene, and zuclomiphene lingers. In 15 men on clomiphene, zuclomiphene levels were 20 times higher than enclomiphene (PMID 27511863).

In 66 men who switched from clomiphene to the pure isomer, testosterone rose a median 166 vs 98 ng/dL. The difference was not significant (PMID 39434750).

Estradiol behaved better: −5.9 pg/mL after the switch vs +17.5 on clomiphene. Low libido, low energy and mood changes were less frequent, odds ratio 0.18 (PMID 39434750).

In 78 men treated for infertility or low testosterone, both raised testosterone, but only the pure isomer significantly raised LH and FSH (PMID 37546076).

Enclomiphene side effects

Trials report few side effects, but they were short and small.

Longer data come from clomiphene. In 120 men on it for more than 3 years, 88 percent reached normal testosterone. 8 percent reported side effects, mostly mood, blurred vision and breast tenderness (PMID 31216250).

Another long term series saw testosterone of 612, 562 and 582 ng/dL at 1, 2 and 3 years, with no adverse events reported (PMID 22458540).

Enclomiphene dosage and PCT use

Trials used 12.5 and 25 mg a day by mouth, for 12 to 16 weeks (PMID 41066380, 26496621). In obese men, it was given at 12.5 to 25 mg a day for 1.5 to 4 months (PMID 36604313).

After steroid cycles, men who used post cycle therapy normalized hormones in a median 13 weeks vs 26 without. The authors call PCT unproven and not recommended (PMID 38102386).

Users commonly describe it for 4 to 8 weeks as PCT, or longer as a TRT alternative. That is practice, not a studied protocol.

For tested athletes: 30 days of clomiphene raised testosterone 146 percent in healthy men. Zuclomiphene stayed detectable in urine for 4 months or more (PMID 30295816).

Bloodwork to track on this drug

7 proven facts about enclomiphene

1. It is half of Clomid. The trans isomer of clomiphene (PMID 23530575).

2. It raises your own testosterone. +274 ng/dL vs placebo, pooled (PMID 41066380).

3. As much as gel. No significant difference in total testosterone (PMID 41066380).

4. It keeps sperm. +70.4 million/mL vs gel (PMID 41066380).

5. Less thick blood. Polycythemia 1.7% vs 11.2% (clomiphene vs TRT, PMID 27984109).

6. Fewer complaints than clomiphene. Odds of side effects 0.18 (PMID 39434750).

7. The effect ends when you stop. Back to baseline in a month (PMID 23530575).