How Nolvadex Really Works

Tamoxifen citrate, or Nolvadex, is used to treat breast cancer, particularly in older women who have estrogen-sensitive breast cancer; 70 to 80 percent of all breast cancers are estrogen-sensitive. For years it’s also been used by male bodybuilders on anabolic steroids to help prevent gynecomastia, or the formation of male breast tissue.

Gyno is caused by an imbalance between estrogen and testosterone, favoring increased estrogen. The steroid drugs convert into estrogen through the actions of aromatase, an enzyme found throughout the body. The usual practice for preventing estrogen-related side effects, which include excess water and fat retention, is to take drugs that either interfere with aromatase activity, such as Arimidex, or block estrogen cell receptors, such as Nolvadex.

Nolvadex is the older of the two “estrogen solutions,” and most athletes looking to lower estrogen now rely on aromatase-inhibitors because of the notion that they’re more reliable in diminishing estrogen. Nolvadex is also thought to interfere with the activity of growth hormone and its anabolic product, insulinlike growth factor 1. On the other hand, lowering estrogen too much, which is possible with extended use of aromatase inhibitors, may interfere with the anabolic reactions involving androgen receptors and testosterone.

Nolvadex is structurally similar to estrogen and can bind to estrogen cell receptors, thereby blocking estrogen from binding to them. If estrogen cannot interact with its cellular receptors, it cannot exert biological activity and becomes inert. Nolvadex also interferes with the negative feedback signal sent by circulating estrogen in the blood to the pituitary gland. That results in blunting release of gonadatropins, including luteinizing hormone, which controls testosterone synthesis at the Leydig cells in the testes. The reduced estrogen-feedback signal induced by Nolvadex results in greater release of luteinizing hormone and higher blood testosterone. One author has noted that using 20 milligrams of Nolvadex daily—a standard bodybuilding dose—can raise blood testosterone by 150 percent. On the other hand, Nolvadex has both agonist and antagonist properties. That is, when used in high doses for extended times, it may act more like an estrogen agonist. Animal studies show that extended use of Nolvadex interferes with the activity of two testicular enzymes involved in testosterone synthesis, although that hasn’t been confirmed in human studies.

What’s interesting about Nolvadex is that recent research that directly compared it to the newer and supposedly more effective aromatase-inhibiting drugs found that Nolvadex appears to be more effective in preventing gynecomastia and other estrogen-related effects in men. How can that be?

A study presented at a scientific conference related to breast cancer research may provide the answer. Researchers from the famed Mayo Clinic explained that Nolvadex isn’t active but is rather like a pro-hormone. In the liver, enzymes convert Nolvadex into two metabolites that are the effective versions of the drug, endoxifen and 4-hydroxytamoxifen. The study sought to explain why using Nolvadex helps some women with breast cancer but not in others. The researchers found that an enzyme system in the liver called CYP2D6 must convert Nolvadex into its active metabolites in order for the drug to work. In some women that system isn’t as active, which means that they don’t convert the Nolvadex into its most active metabolite, endoxifen. For them Nolvadex doesn’t effectively treat breast cancer.

Most surprising, however, was the finding that endoxifen didn’t just block the estrogen cell receptor, as was previously supposed, but actually degraded it. No receptor means no estrogen cell activity. So drug researchers are now at work producing a direct endoxifen drug, since that’s the actual active form of Nolvadex. The direct form won’t depend on liver enzymes to become active.
While this study involved in vitro, or isolated-cell, protocols, there is no reason to believe that the results don’t apply to men. The findings explain why Nolvadex works better in preventing estrogen-related side effects in some men more than others. In addition, the fact that this active metabolite of Nolvadex actually degrades estrogen receptors explains why the head-to-head studies comparing Nolvadex to aromatase inhibitors showed Nolvadex to be superior in preventing estrogen-related side effects in men. A notable bonus: Nolvadex is far less expensive than most aromatase inhibitors.

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What a RUSHHHHHHHH!!!!!!!!