Enclomiphene and Fertility: Understanding the Connection

If you have low testosterone and you’re hoping to have kids anytime soon, your healthcare provider may be hesitant to prescribe testosterone replacement therapy (TRT). This is because TRT affects your body’s ability to produce sperm, a fact that has led some researchers to claim that “testosterone is a contraceptive.” 

Although testosterone replacement therapy can reduce sperm production, this effect is typically reversible after you stop treatment. However, it can take several months for sperm counts to return to normal.

Largely for this reason, a medication called enclomiphene citrate has gained attention as a potential alternative to TRT for men who want to preserve their fertility.

Although it is not FDA-approved, enclomiphene may be used by certain specialists based on compounding arrangements that meet federal requirements, or in research settings for men with secondary hypogonadism (low testosterone caused by faulty signaling between the brain and the testes). 

Below, we’ll dig into the research around enclomiphene and fertility, how enclomiphene compares to TRT, and what else you should know about this treatment.

Understanding how sperm are made is essential for understanding the relationship between enclomiphene and fertility.

To maintain spermatogenesis, your body relies on a hormonal feedback loop that starts in the brain. The hypothalamus releases gonadotropin-releasing hormone (GnRH), signaling the pituitary gland to secrete luteinizing hormone (LH) and follicle-stimulating hormone (FSH).

LH then stimulates Leydig cells in the testes to produce testosterone, and FSH activates Sertoli cells, which are essential for maturing sperm.

What does enclomiphene have to do with all this? Well, enclomiphene is a selective estrogen receptor modulator (SERM). Unlike testosterone therapy, which supplies the body with synthetic testosterone and over time shuts down LH and FSH production, enclomiphene stimulates the release of LH and FSH by blocking estrogen’s negative feedback on the brain. In other words, SERM drugs “unblock” your brain’s message to release the hormones that tell your testes to get back to work. This mechanism of action helps your body produce more of its own testosterone and sperm. 

It’s possible that enclomiphene can boost sperm production by boosting LH and FSH levels, but more research is needed.

One very small study compared enclomiphene citrate to testosterone gel in 12 hypogonadal men previously treated with topical testosterone. While both treatments restored total testosterone levels to the normal range over six months, men taking enclomiphene showed significantly elevated sperm counts, with sperm concentrations ranging from 75 to 334 million/mL (a sperm concentration below 15 million/mL is considered low).

At three months, none of the men on testosterone gel had sperm counts above 20 million/mL, and at six months, only 2 out of 5 had any measurable improvement.

These preliminary findings show that enclomiphene may maintain and enhance spermatogenesis by stimulating the body’s hormonal signaling, which is suppressed by exogenous testosterone therapy. However, this was just one small study, and more research needs to be done to confirm its findings.

Enclomiphene is one of two isomers found in Clomid^® (clomiphene citrate), a medication approved by the FDA for female infertility but sometimes prescribed off-label to men with low testosterone levels. As mentioned earlier, enclomiphene blocks estrogen receptors in the brain, which nudges the body to produce more testosterone.

The other isomer in Clomid, zuclomiphene, behaves quite differently — it acts like estrogen, potentially lowering some of the testosterone-stimulating effects of enclomiphene and contributing to estrogen-related side effects like breast growth and mood swings.

Despite this biochemical tug-of-war, Clomid is still considered a fertility-friendly testosterone booster for men with low T. A systematic review of clinical studies found that men treated with clomiphene saw notable increases in sperm concentration and motility, with the authors noting that it may potentially be a safe option for enhancing sperm parameters in men facing infertility.

Another study reinforced the potential of SERMs like clomiphene and enclomiphene as fertility-preserving alternatives to TRT. The study noted that enclomiphene is primarily responsible for clomiphene’s benefits in treating male hypogonadism, while zuclomiphene appears to contribute little to the medication’s intended effects.

In a clinical trial comparing enclomiphene to topical TRT, both treatments were found to be effective in increasing serum testosterone, but they had opposite effects on sperm parameters. Men on topical TRT were much more likely to develop low sperm counts, while those on enclomiphene generally kept normal sperm counts. 

The study also found that TRT users had reduced sperm motility. Meanwhile, enclomiphene users maintained healthy motility levels, comparable to placebo.

Infertility may not be on the list, but the research done so far has uncovered certain enclomiphene side effects. Consider these before asking your provider about this medication:

• Headaches

• Muscle spasms

• Nausea

• Hot flushes

• Blurred vision

• Aggression

• Increase in estradiol

That said, there’s still a lot we don’t know about enclomiphene for men and its side effects since it hasn’t been FDA-approved and extensively studied, so it’s important to discuss it closely with a healthcare provider.

If you’re looking for ways to boost low testosterone levels without sacrificing your fertility, enclomiphene may be an attractive option.

For men who qualify, Hims offers access to a few different testosterone treatments, including enclomiphene and a 2-in-1 combination therapy combining enclomiphene and tadalafil (Cialis^®) for men who want to improve their testosterone levels and sexual performance at the same time. 

Here’s what we know about enclomiphene for low T:

• Enclomiphene has been shown to promote natural testosterone production in men with low T by stimulating the release of LH and FSH. This is different from testosterone replacement therapy, which tends to impact your body’s natural production of testosterone 

• Enclomiphene may help preserve fertility in men with low testosterone. Unlike testosterone therapy, enclomiphene preserves sperm count and motility. Research so far shows it supports both hormone balance and reproductive health in men with low T.

• Enclomiphene may be especially useful for men who want to improve testosterone levels without compromising their ability to conceive. Men hoping to avoid the fertility-suppressing effects of TRT may want to discuss SERM drugs like clomiphene or enclomiphene with their provider.

• Enclomiphene isn’t FDA-approved. Enclomiphene isn’t FDA-approved on its own, but it’s a key ingredient in clomiphene, an FDA-approved fertility drug. 

To find out if you qualify, schedule a telehealth consultation with a healthcare provider today and ask about at-home testosterone testing.