INTRO

All across the world, modern men are dealing with "chemically castrated" levels of low testosterone.

Even young men at 20 years of age are facing an average testosterone level of just 481.5 ng/dl ¹... Which is less than the average testosterone levels of 45 - 71 year-old men back in the 1980's (501 ng/dl ²).

And it's not just younger guys. Many of our clients and subscribers are middle-aged and are noticing significant differences in their masculinity. I see this referenced both in the bedroom and in the weightroom.

And according to a recent poll by a popular YouTuber, most men are reluctant to resort to the unnatural route of testosterone replacement therapy. So, it makes sense to seek out natural methods to boost testosterone.

As someone who struggled with low testosterone in my mid-20s just a few years ago, I've explored every natural method out there – either by trying it myself or researching extensively. 

And being a health obsessed engineer (with OCD) and backdoor access to the most cutting-edge scientific literature in the world, I've delved deeper into these topics than most people ever could.

However, at the beginning of my journey, I have discovered that many people believe enclomiphene to be the most potent testosterone booster: afterall, it is used in practice to treat infertile men, even though its not FDA approved. 

However, I started seeing a lot of men report devastating side effects, such as blindness.

So when I looked into the actual SCIENCE behind enclomiphene and discovered all of the terrible side effects, not only was I shocked, I felt like I had to warn others.

That's why I'm sharing this scientifically backed article breaking down the DANGERS surrounding enclomiphene. I hope it helps you bypass one of the many landmines out there laid out by mainstream sources.

Now, more than ever, men need masculine vigor. It's my duty to share my knowledge and experiences to steer you away from pitfalls and help you evolve every day to conquer your limits.

How SERM's work

SERM's selectively either antagonize(block) or agonize(activate) estrogen receptors depending on the tissue.

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Because this effect is not ER subtype-selective but varies across tissues, predicting the effects across every tissue ³ becomes challenging. In the case of clomiphene, the stereoisomers zuclomiphene and enclomiphene are at play. The former exerts some estrogen receptor agonist effects in the hypothalamus, while the latter acts as a pure antagonist ⁴. This antagonist action blocks the hypothalamus from sensing negative feedback, essentially acting as a cheat code for the hypothalamus to continue releasing GNRH. This signals the pituitary to release LH/FSH, stimulating the Leydig cells in your testes to produce testosterone. Enclo is well-known as the strongest SERM with this effect.

The Dangers of Enclomiphene

Estrogen receptors have important physiological effects, and their modulation could have risks or undesirable effects. For example, inhibiting the hypothalamus ESR1 has been linked to a blocked melanocortin system and inhibition of ghrelin ⁵.

Melanocortins, particularly alpha-MSH and its derivatives, exhibit potent anti-inflammatory effects and immunomodulatory effects ⁶ ⁷. Therefore, blocking them could increase inflammation and reduce immune function. This, combined with enclo lowering DHEA levels ⁸, which we will get into later, may contribute to enclo reducing immune function, as it also plays a role ⁹.

This could be why we see a high incidence of respiratory infections in this trial ¹⁰.

The inhibition of ghrelin could also explain the reduced igf1 level seen in this trial ¹¹.

Reduced IGF1 impairs healing of connective tissue ¹².

Potential testicular toxicity

Enclomiphene causes a downregulation of LH receptors in the testes. Some may argue that HCG or anything that increases testosterone to the extent of enclomiphene would do the same, but that's not the mechanism here. Experiments on rats with their hypothalamus removed prove it's a direct hit, not an indirect effect from the hypothalamus boost ¹³. In fact, in this same study, it was found that enclomiphene decreased the responsiveness of HCG ¹⁴.

So, if enclo downregulates LH receptors in the testes, how does it increase testosterone so much?

It's twofold. While its effect on the hypothalamus and increased LH production overshadows its LH receptor downregulation, enclomiphene was shown to raise progesterone and pregnenolone in the same study ¹⁵, This increase is likely mediated through disrupting 17-alpha-hydroxylase activity, a key CYP enzyme that facilitates the conversion of pregnenolone and progesterone into 17-hydroxypregnenolone and 17-hydroxyprogesterone.

With less being converted, progesterone remains higher. Progesterone inhibits 5-alpha reductase (5AR), leading to less testosterone being converted into DHT, resulting in a higher testosterone:DHT ratio ¹⁶. This also makes enclomiphene less favorable for androgens and may lead to increased estrogen levels. Since DHT, which occupies androgen receptors, cannot undergo aromatization, and testosterone can, having little DHT and its metabolites to occupy androgen receptors means that more testosterone is available for aromatization.

17a hydroxylase interruption also prevents the hydroxylation of progesterone and pregnenolone into the 17-hydroxy versions of these hormones, which are necessary cofactors for cortisol synthesis and DHEA/Androstenedione, which are important steroids for improving mood and depression ¹⁷, immune health ¹⁸, and fatigue ¹⁹.

Disrupting 17a hydroxylase too much, as seen in genetic polymorphisms typically associated with male pseudo hermaphroditism, can end up causing adrenal cortex hyperplasia over time ²⁰.

When 17a hydroxylase is not present, pregnenolone and progesterone are forced to follow the pathway of being converted into corticosterone and then aldosterone. Through an increase in mineralocorticoids, you can experience increased sodium retention, reduced potassium retention, and the result is increased water retention and blood pressure ²¹.

The concerning thing about this is that a typical cortisol blood test is not enough to discover if you have a lack of cortisol from these conditions. This is because typical blood tests, like the 'Fluorometric assay,' test for both cortisol and corticosterone ²², giving a combined result. Your cortisol levels could be tanked, but your corticosterone could be high, and you would not know it through a typical cortisol blood test.

Concerning Anecdotes and Case Studies

There have been numerous case reports of testicular tumors in men treated with clomiphene ²³ ²⁴ ²⁵ and while there are no reports with enclo (yet), it's still worth noting.

Clomiphene is known to damage the retina ²⁶ and anecdotes of vision sides and blindness exist with enclo.

Conclusion

In my pursuit of excellence, I always shun methodologies that I find to be subpar, and due to the concerning mechanisms of actions and anecdotes I have seen, I hold reservations about the long-term safety of enclomiphene and its viability as a long-term testosterone booster.

Unleash Your Vigor and Conquer Your Limits,

-Brenden Henry