Toremifene Citrate Overview & Features

Toremifene Citrate Overview and History

Toremifene (also known by the brand and trade name Fareston) belongs to the drug category, family, and class known as SERMs (Selective Estrogen Receptor Modulators).

SERMs belong to the broader drug category known as anti-estrogens, and the cousin family of SERMs (which also fall under anti-estrogens) are Aromatase Inhibitors, commonly abbreviated as AI.

SERMs include compounds such as Toremifene, Nolvadex (Tamoxifen), and Clomid (Clomiphene Citrate).

Aromatase Inhibitors (AIs) include compounds such as Arimidex (Anastrozole), Aromasin (Exemestane), and Letrozole (Femara).

While both fall under the category of anti-estrogens, SERMs and AIs are separate sub-categories in their own right because their mechanisms of action in the human body for modulating or blocking estrogen are vastly different.

There has been much misunderstanding and misconception regarding their respective actions over the decades, and this must always be clarified for the reader first before explaining Toremifene.

SERMs are true ‘estrogen blockers’, whereas AIs are not.

SERMs function by blocking the activity of estrogen at the target receptor sites in different tissues (primarily breast tissue), binding to the estrogen receptors in these tissues more strongly than estrogen itself, effectively taking estrogen’s place.

The SERM remains bound to the receptor site, inert (it does not activate the receptor or perform any action).

As a result, estrogen cannot bind to these receptors (because the SERM is already occupying them).

While SERMs block estrogen activity at specific receptor sites, they can and do act as estrogen at other receptor sites in other tissues of the body (e.g., the liver), which can be beneficial.

This is referred to as estrogen agonist and estrogen antagonist action.

In any case, SERMs do not function to lower the overall total circulating plasma concentration of estrogen in the body; they merely block its activity in specific tissues.

Aromatase Inhibitors (AIs) are compounds that bind to the enzyme responsible for converting (aromatizing) androgens into estrogen, thereby reducing the total circulating levels of estrogen in the body.

This enzyme is called aromatase.

AIs are more attractive as a substrate for the aromatase enzyme than the enzyme’s traditional substrate targets, the androgens (such as Testosterone).

As a result, the aromatase enzyme becomes occupied by the AI and cannot engage in a chemical reaction with androgens.

The result is that estrogen cannot be manufactured at its source, leading to an overall reduction in estrogen levels in the body.

Toremifene is a SERM with mixed agonist and antagonist actions on the estrogen receptor, classified as a triphenylethylene analog, bearing very close structural similarity to Nolvadex (Tamoxifen) and Clomid (Clomiphene Citrate).

Toremifene (Fareston) is so similar to Nolvadex that it can be considered a very close sister.

Toremifene is also a non-steroidal compound.

It is classified as a breast cancer drug, indicated for the treatment of breast cancer in postmenopausal women with estrogen receptor-positive (or unknown estrogen receptor) tumors.

This means it is a drug used to block and treat female breast cancer that is exacerbated by estrogen, where the cancer can be promoted by estrogen through its tissue growth-promoting actions within breast tissue.

Toremifene does this by binding to these receptor sites, as previously explained, thereby blocking the ability of estrogen itself to continue activating receptor sites within breast tissue, halting or stopping the progression of tumor growth that can be exacerbated by estrogen.

Toremifene has gained popularity among bodybuilders and athletes who use anabolic steroids for the same reasons as its sister, Nolvadex. (It is used to partially offset or block the effects of excess estrogen in the body resulting from the aromatization of various androgens like Testosterone or Dianabol).

Specifically, Toremifene is used to mitigate, alleviate, and/or prevent the estrogen-related side effect of gynecomastia (development of breast tissue in males).

Toremifene Citrate is a very new and recently developed compound, having received FDA approval as a prescription medication in 1997, and is most popularly sold under the brand and trade name Fareston in the US prescription drug market.

GTx, Inc. is the original and current pharmaceutical company that manufactured Toremifene under the brand name Fareston.

Toremifene, under the brand name Fareston, is also sold in various other nations overseas.

Like its close relative Nolvadex, it is a very popular and widespread product available almost anywhere worldwide.

A question that still remains (and is often asked) regarding Toremifene is whether it is as effective, more effective, or more favorable than its sister product, Nolvadex.

These questions will be answered later in this profile and in this article shortly.

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Toremifene Chemical Characteristics

Toremifene (Fareston) is a non-steroidal Selective Estrogen Receptor Modulator (SERM) that expresses both mixed agonist and antagonist actions in relation to estrogen in various tissues and cells in the human body.

Toremifene belongs to the family of compounds known as triphenylethylene compounds, to which Nolvadex (Tamoxifen) and Clomid (Clomiphene Citrate) also belong, and it is a compound very closely related to these two in particular.

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Toremifene Properties

It has already been covered that Toremifene is a SERM and functions by blocking estrogen at various receptor sites in specific tissues of the body, particularly breast tissue.

To put it simply, Toremifene acts as a ‘fake’ estrogen that occupies the estrogen receptors within breast tissue.

Once Toremifene occupies these receptors, real estrogen cannot perform its role there.

Toremifene does not lower total plasma estrogen levels.

In addition to its antagonistic action on estrogen receptors in breast tissue, it also acts as an antagonist to estrogen in the hypothalamus (this essentially ‘tricks’ the hypothalamus into thinking there is little to no circulating estrogen in the body, prompting it to increase Testosterone production to restore these levels, for which it can utilize aromatization).

Toremifene also acts on estrogen receptors located in other tissues of the body, particularly within the liver.

This means Toremifene acts as an anti-estrogen in breast tissue and the hypothalamus, but acts as an estrogen in the liver.

This can have beneficial effects, such as improving cholesterol profiles and shifting them into more favorable ranges, especially during anabolic steroid cycles.

Although Toremifene is closely related to Nolvadex, it differs quite significantly in other aspects discovered so far (some good, some bad).

The first issue to note when comparing it to Nolvadex is the concern many have regarding the carcinogenic effects of Nolvadex on liver tissue.

It must be understood that these effects were observed with extremely long-term use and are not an issue for bodybuilders and athletes using it short-term, but knowing that Toremifene exhibits less liver toxicity/carcinogenic effects than Nolvadex may be comforting to some.[1] [2] [3]

However, individuals should be aware that Toremifene, being an analog of Nolvadex, still exhibits many related toxic effects on the liver.

There is also clinical evidence that Toremifene may be more favorable than other SERMs like Nolvadex, not only in its ability to suppress breast tissue growth in breast cancer patients but also through its ability to induce apoptosis (or programmed cell death) in breast tissue and tumor cells[4].

While this is very promising evidence and information, it must be understood that breast cancer patients often respond very differently to drug therapy than healthy individuals.

However, it could be evidence that Toremifene can not only destroy and halt the growth of gynecomastia tissue but also prevent it.

Toremifene (Fareston) has also demonstrated the ability to reduce prolactin levels in the body at 300mg per day after 8 weeks[5].

This is very welcome news, as it means Toremifene could be utilized as an anti-prolactin drug if necessary.

However, this is likely only applicable to breast cancer patients.

Nevertheless, Toremifene does possess some negative aspects and properties.

The first and perhaps most important is the negative impact Toremifene has on SHBG (Sex Hormone Binding Globulin) levels in the body, where clinical studies have shown that while Toremifene can and does stimulate natural endogenous Testosterone production (which is good for Post Cycle Therapy – PCT), it actually increases SHBG levels in the body[6].

What this means for bodybuilders, athletes, and anabolic steroid users is that increased SHBG means less free, active Testosterone in the body.

SHBG is a protein that binds to sex hormones like Testosterone, rendering the Testosterone inactive while it is bound, effectively ‘handcuffing’ the Testosterone (or other androgens and sex hormones vulnerable to SHBG).

The result is that the bound hormone (Testosterone in this case) circulates the bloodstream unable to perform its duties (Free Testosterone vs. Bound Testosterone).

Therefore, an increase in SHBG is undesirable for post-cycle recovery or performance enhancement during a cycle, potentially diminishing Toremifene’s potential as a recovery compound in PCT (Post Cycle Therapy).

In comparison, Nolvadex, with over 50 years of use and research, has not demonstrated this effect on SHBG (compared to Toremifene’s research and use period of less than a year and a half).

Furthermore, regarding the restoration of HPTA (Hypothalamic Pituitary Testicular Axis) function during PCT, Toremifene has been proven to be less efficient than Nolvadex for this purpose[7].

In this study, 20mg of Tamoxifen (Nolvadex) per day for 8 weeks resulted in an over 70% increase in Luteinizing Hormone (LH) levels, leading to a 71% increase in Testosterone levels.

In contrast, Toremifene administered at 60mg per day for the same period resulted in only a 25% increase in LH and a 42% increase in Testosterone.

It should be noted, however, that 60mg of Toremifene per day is considered a low dose for this purpose, but it must be clearly emphasized that Nolvadex remains the most potent and effective SERM of the three for this purpose, requiring the lowest dose to elicit positive effects on HPTA function.

Proper dosing is discussed in the Toremifene Dosage section of this profile.

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Toremifene Side Effects

Toremifene is a well-tolerated compound by most individuals, especially males.

The most serious Toremifene side effects tend to be reported in females, particularly female breast cancer patients for whom the drug was originally intended and designated.

The reason Toremifene side effects are considered more severe or worse in females is due to the simple differences in endocrine dynamics between males and females, where the estrogenic agonist/antagonist properties of Toremifene affect females very differently than males.

Because females possess higher estrogen levels than males (and the female body is inherently more physiologically dependent on estrogen), the impact of Toremifene and its side effects is more extensive and pronounced in females than in males.

This is why Toremifene side effects can include abdominal or stomach pain, anxiety, change in vaginal discharge, confusion, dizziness or lightheadedness, hot flashes, vaginal bleeding, extreme fatigue, and other female-centric side effects.

Most of these Toremifene side effects are not experienced by males due to hormonal differences between the sexes.

Clinical trials involving female breast cancer patients revealed Toremifene side effects (listed in order of most frequently occurring) such as dizziness, hot flashes, sweating, elevated liver enzymes, nausea, vaginal discharge, edema, vomiting, and vaginal bleeding.

Much rarer Toremifene side effects found in clinical trials involving female breast cancer patients include muscle stiffness, jaundice, dyspnea (shortness of breath), constipation, itching, loss of appetite, loss of strength, depression, tremors, and visual disturbances.

Again, these Toremifene side effects occur almost exclusively in females and are rarely experienced by males.

Among bodybuilders and athletes (who are overwhelmingly male) using anabolic steroids, very few side effects or adverse effects have been reported.

Toremifene has gained high value and popularity among anabolic steroid users due to many users reporting an almost non-existent occurrence of side effects.

Some users may report mood swings (due to its estrogenic agonist/antagonist actions in the body) and a positive impact on libido (due to its positive impact on Testosterone production).

Some users have reported a decrease in libido after Toremifene use, which could be due to its SHBG-increasing property, resulting in less active free Testosterone circulating in the body.

Anecdotally, many users report that mood swings only last for the first few days of use before subsiding back to normal.

There is a notable lack of clinical data concerning Toremifene side effects specifically in males and anabolic steroid users.

This is because Toremifene has only been available for about 16 years, and most of its use has been solely in clinical settings for female breast cancer treatment.

Therefore, the only current data on Toremifene side effects in male anabolic steroid users is anecdotal and based on various user experiences.

Toremifene Administration and Dosage

For breast cancer treatment, Toremifene is used at a dosage of 60mg per day.

Both women and men may be prescribed Fareston (Toremifene) to prevent the proliferation of cancer cells in breast tissue.

Toremifene is typically administered for one year but can be extended to 2-3 years if remission is not seen or if cancerous duct and glandular tissue is reducing.

Steroid users and bodybuilders may use Toremifene to prevent gynecomastia because it blocks estrogen receptors (ER) in breast tissue.

Administering Testosterone-based anabolic steroids can increase circulating estrogen levels, leading to estrogen-related side effects.

Toremifene is recommended at 30-60mg per day, although Nolvadex (Tamoxifen Citrate) is often chosen as a cheaper and more effective alternative.

Steroid users primarily use Aromatase Inhibitors (AIs) to manage high estrogen levels, rather than blocking estrogen.

Estrogen blockade is considered a last resort when AI therapy alone is insufficient.

When using multiple androgens like Testosterone Enanthate, Dianabol, and Deca-Durabolin, both an AI and a SERM like Toremifene may be necessary.

Toremifene is an effective Post Cycle Therapy (PCT) agent, but comparative studies show it is not as potent as Tamoxifen (Nolvadex).

However, Toremifene is considered a second-generation SERM and a safer alternative to Nolvadex with fewer side effects.

For Toremifene, it is recommended to take 120mg for the first week, followed by 60mg per day for 5 weeks as post-therapy for low Testosterone symptoms.

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Toremifene References

[1] Genotoxicity assessment of tamoxifen in the liver and kidney of F344 gpt delta transgenic rats in 3-week and 13-week repeated dose studies. Kawamura Y, Hayashi H, Kurata Y, Hirazuka K, Masumura K, Nohmi T. Toxicology. 2013 Jul 30: S0300-483X(13)00193-5. doi: 10.1016/j.tox.2013.07.014.

[2] DNA adducts caused by tamoxifen and toremifene in human microsomal system and lymphocytes in vitro. Hemminki,K., Widlak,P. and Hou,S.-M.. (1995). Carcinogenesis, 16, 1661-1664.

[3] Major difference in the hepatocarcinogenicity and DNA adduct forming ability between toremifene and tamoxifen in female Crl:CD(BR) rats. GC Hard, MJ Iatropoulos, K Jordan, L Radi, OP Kaltenberg, AR Imondi, GM Williams. 1993 Oct 1;53(19):4534-41.

[4] Apoptosis in toremifene-induced growth inhibition of human breast cancer cells in vivo and in vitro. Wärri AM, Huovinen RL, Laine AM, Martikainen PM, Härkönen PL. 1993 Sep 1;85(17):1412-8.

[5] Hormonal effects of toremifene in breast cancer patients. Számel I, Vincze B, Hindy I, Kerpel-Fronius S, Eckhardt S, Mäenpää J, Grönroos M, Kangas L, Sundquist H, Hajba A. J Steroid Biochem. 1990 Jun 22;36(3):243-7.

[6] The effect of toremifene on endocrine regulation in breast cancer patients. Számel I, Hindy I, Vincze B, Eckhardt S, Kangas L, Hajba A. Eur J Cancer. 1994;30A(2):154-8.

[7] The effect of selective estrogen receptor modulator administration on the hypothalamic-pituitary-testicular axis in men with idiopathic oligozoospermia. Tsourdi E, Kourtis A, Farmakiotis D, Katsikis I, Salmas M, Panidis D. Fertil Steril. 2009 Apr;91(4 Suppl):1427-30. doi: 10.1016/j.fertnstert.2008.06.002. Epub 2008 Aug 9.

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Toremifene Citrate (aka Fareston, Acapodene)