Nolvadex and Clomid (estrogen receptor antagonists)

Estrogen receptor antagonists, more simply referred to as anti-estrogens (though this term is often loosely applied to all estrogen maintenance drugs), are drugs that block estrogens from exerting activity in the body. This is actualized by the ability of a particular substance to bind to a segment of the estrogen receptor, yet not activate it. This in turn prevents other estrogens from binding and activating the same receptor site. In a clinical setting an estrogen antagonist, most prominently the drug tamoxifen citrate (sold under the brand name Nolvadex) is typically used as the first line of defense during advanced breast cancer therapy. Its use can efficiently deprive estrogen responsive cancer cells of necessary hormone, allowing a high rate of response in patients with such forms of cancer.
Stronger agents such as aromatase inhibitors (discussed below) are usually a second choice, substituted when conventional antiestrogen therapy fails to elicit the desired response.
A drug like tamoxifen is preferred over other agents as the first course of breast cancer treatment for a number of reasons, most due to the fact that that it is both extremely effective yet does not inhibit the actual formation of estrogen in the body. Among other things, this may allow Nolvadex therapy to be somewhat more comfortable for the patient. Although many women (particularly pre-menopausal) seem to suffer menopausal-like side effects with virtually all estrogen maintenance drugs, estrogen antagonists are often somewhat more tolerable than agents that block the synthesis of estrogen. In fact the activity of tamoxifen is itself variable, such that in certain target tissues it may actually act as an agonist (activator) of the estrogen receptor. It therefore does not completely diminish the biological activity of estrogens, though it does considerably reduce it nonetheless.
It is also well understood in medicine today that estrogens play a supportive role in the cardiovascular system. For example, studies show that a rise in the estrogen level (as in post-menopausal estrogen replacement therapy) is typically linked with a reduction in LDL (bad) cholesterol, and a rise in HDL (good) cholesterol. The ability of tamoxifen to act as an estrogen agonist in the liver likewise gives it what may be its most welcome property, namely that it exhibits an estrogenic, rather than antiestrogenic, effect on blood lipid (cholesterol) values. As a 1998 study by the Department of Clinical Oncology in the Netherlands Cancer Institute shows, during long-term treatment with tamoxifen (6 months) a lowered LDL cholesterol level, and significantly elevated HDL cholesterol level and HDL-C/total-cholesterol ratio may result. This trend should reduce an important risk factor for heart disease, obviously a welcome effect during treatment.
For the steroid-using athlete already faced with negative alterations in lipid profiles, such an effect could obviously an important consideration.
Clomid (clomiphene citrate) is very similar in structure to Nolvadex, both drugs being classified as triphenylethylene compounds and used clinically for similar purposes (breast cancer as well as female infertility treatment). As well as we see with Nolvadex, Clomid is a partial agonist/antagonist of the estrogen receptor depending on the target tissue in question. Although athletes most commonly think of Clomid as a testosterone-stimulating drug only (another effect of antiestrogenic compounds), to be used at the conclusion of steroid treatment, its activity in the human body is not at all dissimilar to Nolvadex. It should likewise be thought of not as a drug with its own niche of use, but instead as another efficient remedy for gynecomastia similar to Nolvadex (with the related ability to support the release of testosterone). It could clearly replace Nolvadex as a preventative measure against gynecomastia during cycles with aromatizable steroids without noticeably altering the level of effect received, just as Nolvadex can be used effectively to increase the synthesis of testosterone in the body at the conclusion of steroid use.