What is Enclomiphene? How It Increases Testosterone Without Shutting Down Natural Production
If you've been researching Testosterone Therapy (TRT), you've probably come across enclomiphene. It's a medication that's generating a lot of interest because it offers something traditional testosterone replacement can't: the ability to raise testosterone levels while keeping your body's natural production running. Enclomiphene has several advantages and is an effective alternative to Testosterone Therapy for some men. While TRT increases testosterone levels for (almost) all men, enclomiphene is effective for most men.
For men who want to feel better but aren't ready to commit to Testosterone Therapy (TRT), or for those who want to preserve their fertility, enclomiphene represents a different path forward.
What Is Enclomiphene?
Enclomiphene is a selective estrogen receptor modulator, or SERM—a medication that blocks estrogen in some tissues while activating it in others. It's one of two components found in clomiphene citrate (namebrand Clomid), a medication that's been used for decades to treat female infertility and, more recently, used off-label to help men with low testosterone.
Here's what makes enclomiphene unique: it's the purified, more active isomer of clomiphene. While clomiphene is a mixture of two isomers (enclomiphene and zuclomiphene), enclomiphene isolates just the part that has anti-estrogen effects. Zuclomiphene, by contrast, actually has some estrogenic activity and can work against testosterone production.
By removing the zuclomiphene component, enclomiphene provides a simpler, more targeted approach to raising testosterone naturally.
How Enclomiphene Works
To understand how enclomiphene works, it helps to know how your body regulates testosterone production in the first place.
The Hypothalamic-Pituitary-Gonadal Axis
In a healthy male hormonal system, your brain and testes work together in a feedback loop. The hypothalamus (a part of your brain) releases gonadotropin-releasing hormone (GnRH). This signals your pituitary gland to release two important hormones: luteinizing hormone (LH) and follicle-stimulating hormone (FSH).
LH tells your testes to produce testosterone. FSH supports sperm production. When testosterone levels rise, some of that testosterone converts to estrogen through a process called aromatization. The estrogen then signals back to your brain to slow down LH and FSH production. This feedback loop keeps your hormones balanced.
Where Enclomiphene Comes In
In some men, this signaling system gets disrupted. Often, there's too much negative feedback from estrogen, which keeps LH and FSH levels inappropriately low, leading to low testosterone production.
Enclomiphene works by blocking estrogen receptors in the hypothalamus and pituitary gland. When these receptors are blocked, your brain can't sense the negative feedback from estrogen. Without that brake pedal, your body naturally increases the release of LH and FSH. These hormones then travel to your testes and stimulate natural testosterone production, while preserving sperm counts.
Research from clinical trials has shown this mechanism works remarkably well. In a 2013 clinical trial published in BJU International, men taking enclomiphene daily saw their average testosterone levels rise significantly after six weeks, comparable to men using topical testosterone gel. The key difference? The enclomiphene group maintained elevated LH and FSH levels, while the testosterone gel group saw those signals suppressed.
Why This Matters: Natural Production vs. Replacement
This is the fundamental difference between enclomiphene and Testosterone Therapy (TRT).
When you take exogenous testosterone (injections, gels, or pellets), you're giving your body testosterone from an outside source. Your brain senses this elevated testosterone and shuts down its signals to produce more. Over time, your testes stop making their own testosterone. This leads to testicular shrinkage and decreased sperm production. This is why most men on TRT programs through Affinity also are prescribed enclomiphene for their testicular health.
Instead of replacing your testosterone, enclomiphene stimulates your body to make more of its own. Your testes remain active, your natural hormone production pathways stay intact, and fertility is preserved.
A phase IIb clinical trial comparing enclomiphene to topical testosterone found that both treatments increased testosterone levels effectively. However, only men taking enclomiphene saw preservation of their sperm counts over the three-month study period. The testosterone gel group experienced significant decreases in sperm production, which is a common side effect of conventional testosterone replacement.
Who Might Benefit From Enclomiphene?
Enclomiphene isn't for everyone, but it can be a good fit for certain situations. At Affinity Whole Health, we offer enclomiphene monotherapy along with Testosterone Therapy (TRT) because we understand that different men have different needs and goals.
Men Who Want to Preserve Fertility: If you're planning to have children soon, enclomiphene allows you to raise testosterone without sacrificing sperm production.
Younger Men With Secondary Hypogonadism: Men whose low testosterone is caused by a signaling problem (not a testicular problem) often respond well to enclomiphene.
Men Who Prefer Oral Medication: Unlike testosterone injections or daily gel applications, enclomiphene is taken as an oral capsule.
Men Who Want to Avoid Long-Term Commitment: Because enclomiphene works with your body's natural systems rather than replacing them, it may be easier to stop if needed. Research shows that enclomiphene's effects on LH and testosterone can persist for at least one week after discontinuing treatment, suggesting the drug supports rather than replaces natural function.
Your medical provider can help determine if you're a good candidate based on your hormone labs, underlying cause of low testosterone, and personal goals.
How Quickly Does It Work?
One of the encouraging aspects of enclomiphene is how quickly it can produce results. A study examining the pharmacodynamics of enclomiphene found that after just 14 days of treatment, men experienced significant, dose-dependent increases in testosterone levels. This is similar to the timeline you'd see with Testosterone Therapy (TRT).
That said, raising testosterone levels on a lab test and feeling relief of testosterone deficiency symptoms are two different things. Most men report noticing symptom improvements within several weeks, but full effects on energy, mood, libido, and body composition may take longer, typically around three months.
The FDA Status Question
You might be wondering about enclomiphene's FDA approval status. The short answer is that enclomiphene itself is not FDA-approved.
A drug called Androxal went through extensive clinical trials and was submitted for FDA approval in 2015. However, the FDA issued a Complete Response Letter stating that the study design was no longer adequate to demonstrate clinical benefit. The FDA requested additional Phase 3 studies, which were never completed. In 2021, development of enclomiphene was discontinued for all indications.
Despite not having FDA approval, enclomiphene is legally available through compounding pharmacies when prescribed by a physician. It's derived from clomiphene citrate (Clomid), which is FDA-approved for female infertility and commonly used off-label in men.
What About Side Effects?
Enclomiphene has been studied in over 1,400 people across phase 2 and phase 3 clinical trials. The medication appears to be generally well-tolerated, with side effects that are typically mild.
Reported side effects have included:
Headaches
Changes in mood
Elevated estradiol levels in some cases
Hot flashes
Visual disturbances (though less common than with clomiphene)
Because enclomiphene is a SERM, it carries a theoretical increased risk of thromboembolic events (blood clots), similar to other medications in this class. This is something to discuss with your healthcare provider, especially if you have other risk factors.
Dosing and Administration
The medication is taken as an oral capsule, which many men find more convenient than daily gel applications. Most patients achieve results with 12.5mg taken daily, although some may need a higher dose based on recheck of labs and symptoms.
Dosing should always be individualized based on your lab results, symptoms, and response to treatment. Regular monitoring of testosterone levels, as well as LH, FSH, estradiol, and other markers, helps ensure the medication is working effectively and safely.
Enclomiphene vs. Testosterone Therapy (TRT): Making the Choice
This is one of the most common questions we hear: which option is better? The honest answer is that neither is universally superior. The right choice depends entirely on your individual situation, goals, and medical history.
At Affinity Whole Health, we offer both enclomiphene and Testosterone Therapy (TRT) because we understand that different men need different approaches. Our medical providers don't push one treatment over another. Instead, they work with you to understand your specific needs and help determine which path makes the most sense for your body and your life.
Enclomiphene may be the better fit if:
You have secondary hypogonadism (low testosterone due to inadequate brain signaling, not testicular failure)
Fertility preservation is important to you now or soon in the future
You prefer an oral medication over injections
Your hormone labs show you're a good candidate for stimulating natural production
Testosterone Therapy (TRT) may be the better choice if:
You have primary hypogonadism (your testes aren't functioning properly)
You've tried enclomiphene or similar medications without adequate response
Fertility is not a concern for you now or soon in the future
You prefer the longer track record of safety data with testosterone
You want the most direct route to stable testosterone levels
There's also a third option (combining TRT & enclomiphene):
Many men benefit from combination approaches that use both enclomiphene and Testosterone Therapy (TRT) together. This can help maintain testicular function and fertility while still providing the benefits of supplemental testosterone. Your provider can discuss whether this makes sense based on your lab results and goals.
The key is that this decision should be made with comprehensive lab work, a thorough understanding of your symptoms, and guidance from an experienced medical provider. That's exactly what we provide at Affinity Whole Health.
The Bottom Line
Enclomiphene represents an important alternative for men dealing with low testosterone. By working with your body's natural hormone production pathways rather than replacing them, it offers a way to raise testosterone levels while preserving fertility and testicular function.
The research is solid. Multiple clinical trials have demonstrated that enclomiphene effectively increases testosterone, LH, and FSH levels in men with secondary hypogonadism. The effects are comparable to topical testosterone in terms of raising testosterone, but with the added benefit of maintaining natural production and sperm counts.
That said, enclomiphene isn't the right answer for every man with low testosterone. It works best for men whose issue stems from inadequate signaling from the brain to the testes, not from testicular failure. And like any medical treatment, it requires proper diagnosis, monitoring, and medical supervision.
The good news? You don't have to figure this out on your own. With access to both enclomiphene and Testosterone Therapy (TRT) options, along with experienced medical providers who can interpret your labs and understand your goals, and dedicated Patient Care Coordinators, you can find the approach that actually works for your situation. It's not about choosing between "good" and "bad" options. It's about finding what's right for you.
Getting Started
If you're interested in exploring whether enclomiphene, Testosterone Therapy (TRT), or a combination approach might be right for you, the first step is comprehensive lab work to confirm low testosterone and understand the underlying cause.
At Affinity Whole Health, we offer both enclomiphene and Testosterone Therapy (TRT) because we know there's no one-size-fits-all solution. Our experienced medical providers, led by Dr. Michael Koehler, MD, take the time to understand your individual situation, review your complete hormone panel, and discuss your goals before recommending any treatment approach.
We're not trying to push you toward one option or another. We're here to help you make an informed decision based on what's actually happening in your body and what matters most to you. Whether that's preserving fertility, finding the most convenient treatment option, or simply getting your testosterone levels optimized as effectively as possible, we'll work with you to create a plan that fits.
Our Patient Care Coordinators are available to answer questions and guide you through the entire process, from your initial consultation through ongoing monitoring and adjustments. You're never navigating this alone.
The goal isn't just to raise a number on a lab report. It's about helping you feel like yourself again, with the energy, focus, and vitality you deserve. And with the right medical guidance, we can find the path that works best for your body.