Also known by its brand name Androxal or clomiphene citrate, enclomiphene is an isomer derived from Clomid (clomiphene citrate), an FDA-approved drug for the treatment of female ovulatory dysfunction since 1967.
Clomid is made up of two isomers: enclomiphene and zuclomiphene.
Clomid works by having enclomiphene act as an antagonist – preventing estrogen from binding to estrogen receptors located at the hypothalamus and pituitary gland, while zuclomiphene functions as an agonist of the estrogen receptors – increasing long-term estrogen production.
So, what does this mean?
For men, enclomiphene is the “good” part of Clomid as it can safely increase testosterone levels whether you are suffering from hypogonadism or need a boost in your energy, libido, athletic performance, and overall health.
However since enclomiphene lacks the cis isomer zuclomiphene, this also reduces its half-life from 30 days to around 10 hours.
What are the common uses for Clomid?
The most common use for enclomiphene is in the bodybuilding space and some guys use it as a post-cycle therapy (PCT) after cycling anabolic steroids.
Another common use for Clomid is for treating fertility issues since it can boost follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, which we’ll talk about later in the article.
So, why not just use Clomid?
Aside from the fact that Clomid is normally used in women with ovulatory dysfunction, we highly recommend not using Clomid for your research solely because of zuclomiphene, which is an estrogen agonist associated with a number of side effects that stays in your system longer than enclomiphene while having little contribution.
As the enclomiphene in the Clomid stimulates your testosterone production, zuclomiphene does the opposite.
Since it’s an agonist that binds to the estrogen receptor, the body thinks that the estrogen levels in our body are higher than normal, so it will lower estrogen levels – the opposite of what we want.
What happens is that our hypothalamus reduces gonadotropin-releasing hormone (GnRH) levels, and then the pituitary gland gets the GnRH, which causes it to produce less LH and FSH levels. At the end of the HTPA axis, our Leydig cells (our primary source of testosterone) thus lower our testosterone levels.
According to a 2017 case report, an adult man treated with Clomid for his low sperm count (oligoteratospermia) experienced anxiety, decreased appetite, and mood swings within just five days of treatment.
So, a question that might be on your mind right now would be “Why do doctors still prescribe Clomid to increase testosterone levels even though zuclomiphene them?”
Good question. We believe that doctors are forced to follow the status quo of using Clomid to increase testosterone levels even though they have adverse side effects associated with zuclomiphene as the FDA hasn’t approved this compound (yet).
How Enclomiphene Works
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Enclomiphene belongs to a class of drugs called selective estrogen receptor modulators (SERMs) that regulate hormonal activity.
Enclomiphene’s role as a SERM is to impede the natural production of estrogen in your hypothalamic-pituitary-testicular axis (HPTA) by selectively binding to the estrogen receptors in your body.
So what does this mean? First, we’ll explain what agonists vs antagonists mean in simpler terms:
- Antagonist – antagonists are molecules that block the activity of specific peptide receptors, such as zuclomiphene. In this case, Enclomiphene binds to the estrogen receptor and blocks estrogen from binding instead. We’ll cover why this is important later in the article.
Let’s visualize an example: You pick up your friend’s phone, open it, and start texting their friends as if you are your friend. This is what zuclomiphene does when it binds to the estrogen receptor, pretending to be the estrogen in our body.
- Agonist – agonists are a molecule that binds to a receptor and activates it by mimicking the substances that bind to these receptors. In this case, zuclomiphene binds to estrogen receptors and activates them, similar to how estrogen would activate them.
Now, carrying the same example: You picked up your friend’s phone and hid it in your pocket, and now they can’t use it. This is what enclomiphene effectively does to estrogen by preventing it from attaching to the receptor.
Your body wants to maintain only a certain level of estrogen, and enclomiphene does that by binding to its receptor and blocking the estrogen from binding to it – tricking your body that estrogen levels are too low.
“So, what does this have to do with testosterone levels? I thought we were trying to increase it?” Good question. To understand this process, we first need to know how we create estrogen.
Men create estrogen by converting testosterone into estrogen through aromatase enzymes. When enclomiphene binds to estrogen receptors, the body thinks that estrogen levels are too low so the body follows the HPTA loop to get it to normal levels.
This disruption of estrogen also messes up your negative feedback loop to inhibit GnRH production and increase your GnRH secretion instead.
As a result, your pituitary gland secretes higher follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels to your which leads to an improved hormonal balance that can induce ovulation in women, but more importantly, boost testosterone levels in men.
In simpler terms, Enclomiphene stimulates your HPTA loop, increasing the testosterone levels in your Leydig cells (the primary source of testosterone or androgens in men).
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Here are some health benefits and positive effects associated with enclomiphene usage:
Boosts Testosterone Levels
As stated above, the primary benefit of enclomiphene is to boost testosterone levels in men by binding to estrogen receptors in your HPTA without reducing fertility.
According to a 2018 placebo-controlled trial to test the effects of clomiphene citrate on male obesity, 78 adult men received 50mg doses for 12 weeks.
After the weeks were up, the researchers found that the subjects had an increase in lean mass, fat-free mass, and muscle mass due to an improved hormonal profile and body composition when taking Clomid, which contains enclomiphene.
Researchers also use this medication alongside other compounds or therapies such as SARMS, but how effective is enclomiphene on its own?
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Good question, let’s use Paul’s inquiry for example – taking enclomiphene by itself would provide benefits without the nasty side effects Clomid would give, just don’t expect it to make a lot of difference for your research compared to other testosterone boosters out there.
Paul, If you have (relatively) low natural test levels, enclomiphene will raise it up to normal testosterone levels (around 1000 ng/dL) and gain some extra lean muscle mass. However, you’ll only really know the difference unless it comes up on the blood test.
Treats Male Infertility
Another benefit of enclomiphene is its efficiency in treating male infertility.
Several studies show that men with low sperm count, poor sperm motility, or abnormal sperm sizes and/or shape can greatly benefit from enclomiphene as it helps maintain sperm count and boosts testosterone production – a crucial component to producing healthy sperm and maintaining reproductive function.
Enclomiphene Side Effects
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As with any medication, there will always be some risk of side effects. Common side effects of using enclomiphene may include decreased libido due to increased estradiol levels, nausea, headaches, dizziness, joint pain, abdominal discomfort, and the common cold.
Additionally, some individuals should avoid taking enclomiphene. Avoid using this medication if you are:
- Pregnant or breastfeeding
- A woman who is experiencing uterine bleeding
- A woman with uterine cysts that are unrelated to polycystic ovarian syndrome (PCOS)
- An individual with a history of liver disease
- An individual with adrenal insufficiency or thyroid disorders
- An individual allergic to either clomiphene or enclomiphene
Verdict: Should You Use Enclomiphene
According to the studies mentioned above, enclomiphene as a research chemical can correct low testosterone counts without negatively affecting fertility by blocking out estrogen – significantly increasing testosterone production.
If you want a safe way to boost your testosterone without using injections, topical creams, or undergoing testosterone which is known to cause some serious problems. enclomiphene may be a vital component of your research.
However, before you use enclomiphene, we recommend discussing this with your doctor first to determine if it’s a suitable compound for your research.
FAQ
| Will enclomiphene build muscle? While there is still limited research on this benefit, enclomiphene boosts your testosterone levels which is a vital component in developing muscle tissue. |
| Why was enclomiphene discontinued?Enclomiphene itself is not FDA-approved, which is ironic since it’s derived from Clomid. Enclomiphene has been under review by the FDA since 2007 and was halted in 2015 when the FDA felt that its Phase III studies no longer demonstrated any notable clinical benefits. However, since it’s still a component of Clomid, enclomiphene was nominated for compounding under Section 503A of the FDA’s Federal Food, Drug, and Cosmetic Act, ultimately getting excluded from the list by June 2022. This means you are still allowed to buy enclomiphene liquid / capsules from a compounding pharmacy as long as you have a prescription. |
| Can enclomiphene cause gyno?Gyno, or gynecomastia, is an increase in the amount of one or both breast gland tissues in men due to a hormonal imbalance of estrogen and testosterone. According to several studies, selective estrogen receptor modulators (SERMs) such as enclomiphene are effective in reducing gyno. For example, in a study involving 12 adolescent boys aged 12 to 19, doses of 50 mg/day of Clomiphene citrate decreased mean breast size from 0% to 36%. |
