Raloxifene Overview and History
Raloxifene hydrochloride (brand name Evista) is a fairly new anti-estrogen drug on the prescription market.
It belongs to the category of drugs known as Selective Estrogen Receptor Modulators (SERMs), which is actually a subcategory of the broader category of drugs known as anti-estrogens.
The other subcategory of anti-estrogens is Aromatase Inhibitors (AIs), which include the most common three: Aromasin (Exemestane), Arimidex (Anastrozole), and Letrozole (Femara), although there are many other aromatase inhibitors.
SERMs and AIs constitute the broad class of anti-estrogens.
SERMs and AIs differ greatly in their mechanisms of action and how they operate physiologically.
As with all profiles dealing with SERMs and AIs, the differences between these two classes of anti-estrogen drugs must be made clear and explained before discussing Raloxifene specifically.
It is common in the anabolic steroid and bodybuilding community to confuse the two and assign the wrong (or even opposite) anti-estrogen properties to them.
SERMs work by acting on estrogen receptors in various tissues in the body, specifically by blocking the activity of estrogen at the receptor sites in breast tissue (also known as estrogen antagonism).
They effectively occupy the estrogen receptor while simultaneously ‘booting out’ any estrogen occupying the receptor, preventing estrogen from accessing the receptor site.
Furthermore, SERMs can and do act as estrogen agonists in other tissues in the body (e.g., the liver).
As an estrogen agonist, the drug performs the opposite action described previously, and instead binds to the receptor to initiate estrogenic effects in that tissue.
As a result, SERMs only serve to antagonize (or block) the effects of estrogen in specific tissues, and do not reduce the total circulating plasma concentration of estrogen in the body, which is why some estrogenic side effects such as water retention and bloating cannot be treated with SERMs.
Aromatase Inhibitors (AIs), on the other hand, work by binding to the aromatase enzyme, which is the enzyme responsible for the conversion (aromatization) of androgens into estrogen, thereby disabling the very root cause of estrogen production in the body.
With the aromatase enzyme inhibited and disabled, it cannot perform its action of creating estrogen in the body, thus effectively reducing total circulating plasma estrogen levels in the body.
Aromatase Inhibitors can and do eliminate estrogenic side effects that SERMs cannot treat, such as abdominal bloating or water retention.
Raloxifene, specifically, is a non-steroidal SERM that belongs to the benzothiophene class.
Raloxifene operates very similarly to Nolvadex (Tamoxifen), in that it exhibits both estrogenic agonist and estrogenic antagonist effects in various tissues throughout the body.
Specifically, Raloxifene acts as an estrogen antagonist in breast tissue and uterine tissue, while simultaneously acting as an estrogen agonist in bone tissue.
In fact, because Raloxifene exerts estrogenic action in bone, it is utilized in medicine for the prevention of osteoporosis in post-menopausal women.
Nolvadex, in contrast, is known to act as an estrogen antagonist in bone, which can understandably be problematic for female breast cancer patients prescribed Nolvadex.
Given these properties, it is easy to see how Raloxifene has proven to possess a distinct advantage over Nolvadex and has proven itself as a novel drug for the treatment of various post-menopausal conditions in female patients.
Raloxifene was developed by Eli Lilly and Company, and Raloxifene (brand name Evista) hit the prescription market following FDA approval in 1997.
It was initially used for the treatment of osteoporosis (due to its estrogenic effect in bone tissue, increasing bone density in patients).
A decade later in 2007, Raloxifene’s approved uses were expanded to include breast cancer treatment.
It has since become a very popular drug, used in over 50 countries worldwide.
Research into Raloxifene’s application for other diseases, such as prostate cancer, hyperplasia, uterine cancer, cardiovascular disease, and breast cancer, continues due to the great differences in its selectivity for estrogenic action and antagonism in various tissues in the body.
Bodybuilders and anabolic steroid users are generally attracted to the use of Raloxifene for its properties as an anti-estrogen to combat estrogen-related side effects resulting from the use of aromatizing androgens, which increase the plasma concentration of estrogen in the body.
A common estrogenic side effect resulting from this is the development of gynecomastia.
In the area of gynecomastia specifically, Raloxifene has actually demonstrated more promising effects than Nolvadex (Tamoxifen).
Like all SERMs and anti-estrogens, Raloxifene also holds significant benefit for the stimulation of endogenous natural Testosterone production in males, with studies demonstrating that Raloxifene administration at 120mg per day resulted in a 20% increase in serum Testosterone levels.
Chemical Characteristics of Raloxifene
Raloxifene (Evista) is a non-steroidal Selective Estrogen Receptor Modulator (SERM) that exhibits both mixed agonist and antagonist actions in relation to estrogen in various areas of the body.
Raloxifene belongs to a family of compounds known as benzothiophene compounds.
Other SERMs, such as Clomid (Clomiphene Citrate) and Nolvadex, are also SERMs but instead belong to the family of compounds known as triphenylethylene compounds.
Although Raloxifene is not from the same family of compounds, it is in fact a very closely related compound to Nolvadex and Clomid.
Properties of Raloxifene
As explained earlier, Raloxifene is an anti-estrogen component, but it does not lower the total plasma concentration of estrogen in the body.
Instead, it works by blocking the effects of estrogen at the estrogen receptors in specific tissues in the body (breast tissue), while promoting estrogenic effects in other tissues (bone and uterine tissue).
Therefore, it is effective for the prevention and/or treatment of gynecomastia.
Furthermore, Raloxifene acts as an estrogen antagonist in the hypothalamus, stimulating the production of gonadotropins (LH and FSH) from the pituitary gland, ultimately leading to increased endogenous Testosterone levels.
Raloxifene Hydrochloride (aka Evista)
| Chemical Name | [6-hydroxy-2-(4-hydroxyphenyl)- benzothiophen-3-yl]- [4-[2-(1-piperidyl)ethoxy]phenyl] -methanone |
| Molecular Weight | 473.584 g/mol or |
| Formula | C28H27NO4S |
| Manufacturer | Eli Lilly and Co. |
| Half-Life | 27.7 hours |
| Detection Time | Currently unknown. |
| Anabolic Rating | None |
| Androgenic Rating | None |
