Clomiphene citrate, which also goes by the name Clomid, is commonly used off-label to treat low testosterone in men. It consists of two isomers: enclomiphene and zuclomiphene.
While enclomiphene blocks estrogen from binding to estrogen receptors at the hypothalamus and pituitary gland in the brain, zuclomiphene increases estrogen and accumulates over time.
Both enclomiphene and Clomid are superior to TRT, but enclomiphene is superior to Clomid because it has fewer side effects and stays in the body for a shorter amount of time.
Enclomiphene can be safely used to boost testosterone, whether you have low levels or simply want to have an edge when it comes to your energy, confidence, sexual function, and athletic performance.
As men age, testosterone levels tend to go down, leading to symptoms like increased body fat, low libido, and decreased energy. Clomiphene citrate, which also goes by the name Clomid, is commonly used off-label to treat low testosterone in men, though it is one of the most popular fertility drugs for women. It works by binding to estrogen receptors in the brain to influence hormone production.Clomid contains a mixture of two isomers: enclomiphene and zuclomiphene, and they couldn’t be more different.
Enclomiphene, on the other hand, contains just that one isomer. It’s often prescribed for men with secondary hypogonadism and is shown to boost testosterone levels with limited side effects.
Find out more about how Clomid compares to enclomiphene, the side effects associated with each, and how to decide which is right for you.
What is Clomid?
Clomid is a fertility medication that has been approved by the FDA since 1967 to stimulate ovulation in women who cannot produce or release eggs on their own. It is commonly prescribed as a first-line treatment by primary care physicians or OB-GYNs before referring a couple to a fertility specialist. Though it is not approved by the FDA to treat low testosterone or infertility in men, it is often used off-label for these reasons.
Clomid consists of two isomers: 62% enclomiphene and 38% zuclomiphene. As an estrogen receptor antagonist, enclomiphene blocks estrogen from binding to estrogen receptors at the hypothalamus and pituitary gland in the brain. Conversely, zuclomiphene is an estrogen receptor agonist, meaning it increases estrogen and accumulates over time.
How Clomid works
Clomid is a selective estrogen receptor modulator (SERM), which is a class of drugs that impact estrogen production. By blocking estrogen production, Clomid tricks the body into thinking that it’s not getting enough estrogen, thus stimulating the production of luteinizing hormone (LH) and follicle stimulating hormone (FSH). In women, this helps to stimulate ovulation. In men, boosting LH and FSH helps to stimulate testosterone production and spermatogenesis.
Despite its popularity in treating low testosterone, some research shows that there may be downsides to using Clomid, mostly due to its inclusion of zuclomiphene. A 2017 study found that long-term use of clomiphene citrate resulted in a significant alteration of enclomiphene and zuclomiphene concentrations, with the latter staying in the system a lot longer than the former.
Zuclomiphene is also known to have side effects lasting beyond the therapeutic effects of the drug. For these reasons, researchers have concluded that because the two isomers have vastly different biochemical and toxicological properties, there is a “need for the development of a pure selective estrogen receptor antagonist” for the treatment of men with low testosterone.
Which is where enclomiphene comes in.
What is enclomiphene?
Enclomiphene citrate is the purified isomer of Clomid. Studies show that it successfully raises LH and FSH levels without negatively impacting semen parameters. And it works quickly, too. This study found that taking enclomiphene was able to restore normal testosterone levels in hypogonadal men in as little as 14 days.
How enclomiphene works
As an estrogen receptor antagonist, enclomiphene blocks estrogen, making the body amp up its LH and FSH levels. This stimulates the testes to produce more testosterone and more sperm. And unlike testosterone replacement therapy (TRT), which replaces your body’s natural production of testosterone with a synthetic version, enclomiphene helps your body produce more of its own natural testosterone. This helps you maintain fertility and avoid the side effects tied to synthetic testosterone like testicular shrinkage, enlarged prostate, cardiovascular issues and more.
Can enclomiphene work without zuclomiphene?
Signs point to yes on this one. Remember—clomiphene citrate contains the two isomers enclomiphene and zuclomiphene. But with enclomiphene, you don’t have that zuclomiphene isomer, which may offer some interesting benefits.
When looking into clomiphene citrate’s positive effects on testosterone levels and fertility, researchers have suggested that zuclomiphene contributes little to the medication’s intended outcomes, indicating the powerful role of enclomiphene.
And in a study comparing enclomiphene to TRT, enclomiphene was found to be just as effective as testosterone therapy while maintaining sperm concentration.
Meanwhile, we also know that enclomiphene increases LH and FSH levels and helps maintain fertility. Even more, testosterone levels in those taking enclomiphene remain elevated even after the cessation of treatment.
How enclomiphene compares to Clomid
Research shows that both enclomiphene and Clomid are superior to TRT in terms of maintaining fertility and generally carrying fewer side effects. But with fewer side effects and more benefits, enclomiphene is the preferred choice for safely boosting testosterone.
Side effects of Clomid and enclomiphene
In a study comparing zuclomiphene and enclomiphene (remember, these are the two isomers in Clomid), zuclomiphene was shown to harm the male reproductive tract. Along with causing a significant reduction in the size of testes with testicular degeneration, zuclomiphene also caused Leydig cell loss, an absence of sperm in the seminiferous tubules, and a reduction in size of the epididymis, seminal vesicles, and kidneys.
Due to its mixed estrogenic and antiestrogenic effects, Clomid can also cause emotional dysregulation, such as mood swings and depression. This is thought to occur because of the estrogenic imbalance caused by zuclomiphene staying in the system longer than enclomiphene.
Other reported side effects of Clomid include irritability, anxiety, and enlarged breasts.
Enclomiphene is generally well tolerated with minimal side effects occurring rarely, such as headache (in less than 4% of patients), nausea (less than 3%), and joint pain (less than 2%). The medication may also increase testicular size, unlike TRT which is associated with testicular shrinkage.
In a head-to-head comparison by Dr. Khera at Baylor College of Medicine, a study involving 66 patients revealed that enclomiphene is as effective as clomiphene in increasing testosterone levels, with the median rise recorded at 166 ng/dl. However, enclomiphene has the advantage of causing less fluctuation in estradiol levels, with a decrease of 5.92 pg/ml compared to clomiphene's increase of 17.50 pg/ml. Additionally, the study showed enclomiphene has significantly fewer side effects, including decreased libido, reduced energy, and mood changes. Statistical analysis further confirmed a lower likelihood of overall adverse events with enclomiphene use.
How long enclomiphene and Clomid stay in your system
Zuclomiphene has been shown to have a longer half-life, which means it stays in the system longer than enclomiphene. Not only does this contribute to the emotional dysregulation seen in those who take Clomid, but it can also have detrimental effects throughout the body based on how the tissues absorb the isomers. In a study that tracked the pathways of zuclomiphene and enclomiphene in the body, enclomiphene left the system and was found only in low amounts after 24 hours, but zuclomiphene was distributed to more organs and remained associated with discrete tissues for longer periods of time.
Some signs you have low testosterone and could benefit from enclomiphene include
Low libido
Fatigue
Reduced lean muscle mass
Irritability
Erectile dysfunction
Depression
Hair loss
Bone loss
Poor memory
Low sperm count
But you don’t have to have low testosterone levels to benefit from enclomiphene. Boosting your testosterone levels can also result in enhanced athletic performance, more energy, more lean mass, and even greater confidence.
And if you enroll in the Maximus Testosterone Protocol, you’ll reap the benefits of more testosterone while also having access to consultations with licensed doctors, live coaching and community, and lab tests to ensure the protocol is working for you.
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