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Old 05-01-2019, 10:53 PM   #1
Sabaki
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Why enclomiphene is better than clomid.

Why enclomiphene is better than clomid.

Clomiphene is a SERM. It binds to the estrogen receptors and acts as both an agonist and antagonist. This means that it can both activate the estrogen receptors and also block or prevent the receptor from activating, because of this it has both estrogenic and anti-estrogenic effects. I will try to give a simplified explanation of why clomid can have contradictory effects and why understanding this is important. First let me briefly review what most of you may already know about how clomid and other SERMS work to increase natural testosterone production, as well as increase fertility by promoting spermatogenesis, while at the same time preventing gynecomastia. As we know, one of the drawbacks of exogenous testosterone is that it can cause infertility as well as lead to gyno. Taking an AI may help prevent gyno, but does nothing to promote spermatogenesis or improve testicular function.

Although only FDA approved for treating ovulation disorders in women, clomid has been successfully used for many years off-label to restore testicular function, increase fertility, as well as treat gynecomastia. It is very important to emphasize that all of these beneficial effects of clomid use in men result from its anti-estrogenic effects, not its pro-estrogenic effects. In fact the pro-estrogenic effects of clomid have the exact opposite effects, just the opposite of what we want to achieve. The net effects of clomid tend to be positive only because the anti-estrogenic effects dominate the pro-estrogenic effects. What if it were possible to achieve the beneficial anti-estrogenic effects without any of the adverse pro-estrogenic effects?

Clomid promotes testicular function by blocking estrogen receptors in the hypothalamus region of the brain. This blocks the negative feedback loop of the HPT axis increasing LH and FSH which in turn stimulate the testes to produce both sperm and testosterone. Testosterone plays a crucial role in spermatogenesis, but unfortunately exogenous testosterone only increases systemic test levels, not intratesticular levels which need to be much higher than systemic levels for spermatogenesis to occur. Similarly, clomid prevents gyno by blocking estrogen receptors in breast tissue; but it doesn’t do this as well as other SERMS such as tamoxifen. Without getting into all of the details about different types of estrogen receptors (alpha and beta) etc. a major problem with clomid is that the positive benefits of its antagonistic effects are completely offset by agonistic effects in the very same tissue types. If we had a version of clomid that had purely antagonistic effects, it should in theory do everything we want much better. In fact, just such a form of clomid exists and is available for us to use. It is called enclomiphene.

How is it possible for a single compound to have opposite effects in the very same tissue type? Actually, clomiphene is a mixture of two different versions, which are called “isomers”. They have the same chemical formula, but slightly different molecular structures. The antagonistic isomer is called “enclomiphene” and the agonistic one is called “zuclomiphene”. Zuclomiphene binds to and activates the estrogen receptors having opposite effects of enclomiphene. It is anti-gonadotropic lowering LH and FSH and it promotes breast tissue proliferation rather than inhibit it. Fortunately, regular clomid is composed of 70% enclomiphen and only 30% zuclomiphene, which explains why in most tissue types clomid is more anti-estrogenic than it is pro-estrogenic.

Enclomiphen has been very thoroughly studied for many years for use in males to treat hypogonadism. It has been shown to be safe and to be effective at restoring testosterone and sperm levels in men who had previously taken exogenous testosterone.(ref) It appears to have the benefits of test without the adverse effects; but unfortunately it still hasn’t been FDA approved. The FDA has been quibbling about technical details of the experimental design in phase III clinical trials. Theoretically, it should work better than regular clomid for PCT, and might even be good to use on cycle to maintain function and fertility while also preventing gyno. I would be very interested to hear from anyone here who has used enclomiphene whether or not it worked any better than regular clomid.

Last edited by Sabaki; 05-02-2019 at 10:23 PM..
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