Enclomiphene vs TRT: Differences, Benefits, Side Effects, and When to Use Each

This article explores the use of enclomiphene as an alternative or companion therapy to testosterone replacement therapy. 

TRT has become increasingly common, with millions of men in the United States using various forms of testosterone supplementation. 

Enclomiphene, a derivative of clomiphene citrate and first studied in the 1960s, has recently gained more attention as a treatment option for men with low testosterone.

As interest in enclomiphene grows, it is important for clinicians to provide accurate and balanced information about its effectiveness, risks, and side effects compared with established testosterone therapies.

Key differences include:

TRT is an exogenous form of testosterone therapy. Enclomiphene is a selective estrogen receptor modulator.

TRT adds testosterone to the body. Enclomiphene stimulates the body to produce its own testosterone.

TRT is widely used. Enclomiphene is newer in mainstream men’s health practice.

Both treatments address hypogonadism, defined as low functioning of the testes.

This article outlines how these therapies work, their side effects, their potential benefits, and the reasons some clinicians avoid using enclomiphene as a standalone treatment for low testosterone.

What Is Enclomiphene?

Enclomiphene is the trans-isomer of clomiphene citrate. It works by increasing the release of hormones from the brain (FSH and LH) that stimulate the testes. This helps maintain natural, pulsatile hormone production.

How enclomiphene works:

It blocks estrogen receptors in the brain, causing the hypothalamus to sense low estrogen levels. This stimulates the release of GnRH, which increases LH and FSH. LH and FSH are signals from the brain telling the testicles to increase testosterone and sperm production.

Enclomiphene is not FDA-approved for hypogonadism but is used off-label in various specialties, including urology, fertility medicine, endocrinology, and men’s health clinics.

Side Effects of Enclomiphene

Common effects:

Acne or oily skin

Mood swings or irritability

Headaches

Less common effects:

Blurred vision

Gynecomastia

Changes in liver enzymes

Rare clotting events such as DVT or PE

Side effects tend to increase with higher dosages. Unlike TRT, enclomiphene does not reduce sperm count. Instead, it often increases sperm production. Patients using enclomiphene should be monitored for changes in estradiol, hematocrit, and liver enzymes.

What Is TRT?

Testosterone replacement therapy involves administering testosterone from an external source to raise blood testosterone levels. Methods include injections, gels, creams, and newer oral formulations. TRT is generally recommended for men with confirmed low testosterone based on appropriate blood testing and clinical evaluation. Many speciality clinics offer subscription TRT plans since insurance often does not cover therapy.

Side Effects of TRT

TRT can lower sperm count because external testosterone reduces LH and FSH production. This can be offset with the use of HCG when fertility preservation is important.

Other effects include acne or oily skin, testicular atrophy, mild mood changes during initiation, and occasional redness at injection sites.

Patients on TRT should maintain regular follow-up and monitoring. Abruptly discontinuing therapy is generally discouraged unless medically required; tapering is usually recommended.

Efficacy and Benefits of Enclomiphene vs TRT

Both treatments raise testosterone levels and may improve symptoms of low testosterone. These include increases in muscle mass, improved energy, libido, mood, bone density, erectile function, and cognitive clarity.

Key differences:

Enclomiphene typically has a slower onset, often taking 4 to 12 weeks.

TRT effects are often noticeable within 1 to 6 weeks.

TRT is generally more effective for severe hypogonadism.

TRT suppresses sperm production. Enclomiphene does not.

TRT often requires injections. Enclomiphene is taken orally.

Why Enclomiphene Should Not Be Used as Monotherapy for Low Testosterone

Many clinicians in men’s health avoid using enclomiphene alone to treat hypogonadism. Enclomiphene increases testosterone by altering hormone signaling at the level of the brain. Relying solely on this mechanism can lead to fluctuating estrogen levels, variable testosterone responses, and potential testicular desensitization over time. Some “natural testosterone boosters” marketed by compound pharmacies rely mainly on enclomiphene, which may create short-term increases followed by diminished responsiveness.

Because hormone regulation involves multiple interconnected systems, stimulating the central nervous system alone may not produce consistent or sustainable long-term results for men with true hypogonadism.

Using Enclomiphene with TRT

Using enclomiphene alongside testosterone can be a viable strategy for men who want to preserve fertility, maintain testicular size, or benefit from additional central hormonal stimulation.

When combined with TRT:

Bioidentical testosterone provides stable testosterone levels.

Enclomiphene supports LH and FSH release.

This reduces the burden on the testes to produce supraphysiologic testosterone and helps balance estrogen and testosterone levels.

Although HCG remains the gold standard for maintaining testicular function during TRT, enclomiphene is an alternative option for men who prefer oral therapy. A small percentage of men experience erectile dysfunction or changes in orgasm quality after starting TRT. For those individuals, the LH and FSH stimulation from enclomiphene may improve symptoms.

For men focused on fertility, enclomiphene can support sperm production. In more advanced fertility cases, clinicians may combine enclomiphene with HCG or even injectable FSH.

How to Get Started

Starting testosterone replacement therapy, with or without enclomiphene, requires baseline laboratory testing. Recommended labs include testosterone, LH, FSH, CBC, Estradiol (Estrogen), and PSA.

Testing can be completed at Lucidity Health clinics, at LabCorp, or through a home blood-spot collection kit.

Individuals interested in TRT should reach out to Lucidity Health to discuss next steps and receive care under experienced clinical supervision.

If you are experiencing symptoms of low testosterone or want expert guidance on whether enclomiphene, TRT, or a combined approach is right for you, Lucidity Health’s performance medicine clinic can help. We provide hormone optimization and TRT services in Oregon and in multiple other states and regions.