Toremifene Citrate (AKA Fareston, Acapodene)

Overview and History of Toremifene Citrate

Toremifene (also known by the brand and trade name Fareston) belongs to a category, family, and class of drugs known as selective estrogen receptor modulators (SERMs).

SERMs belong to a broader category of drugs known as anti-estrogens, and a cousin family of SERMs (which are also anti-estrogens) are aromatase inhibitors, commonly abbreviated as AIs.

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 they both fall under the category of anti-estrogens, they are subcategories that are separated into their own families because SERMs and AIs differ significantly in their mechanisms of action in the body to regulate or block estrogen.

There have been many misconceptions and misunderstandings about their respective actions over the past few decades, and this should always be made clear to the reader before describing toremifene.

SERMs are true “estrogen blockers,” while AIs are not.

SERMs work by blocking the activity of estrogen at targeted receptor sites in other tissues (primarily breast tissue), and they bind to estrogen receptors in these tissues more strongly than estrogen itself, effectively taking estrogen's place where it belongs.

SERMs remain inactive (do not activate the receptor or perform any action) while bound to the receptor site, resulting in estrogen being unable to bind to these receptors (because they are already occupied by the SERM).

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

This is called estrogen agonist and estrogen antagonist action.

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

Aromatase inhibitors (AIs) are compounds that reduce total circulating levels of estrogen in the body by binding to the enzyme that converts (aromatizes) androgens into estrogen.

This enzyme is called aromatase. AIs are more attractive as substrates for aromatase enzymes than androgens (such as testosterone), which are the traditional substrate targets of aromatase enzymes.

As a result, the aromatase enzyme becomes occupied by AI and is unable to chemically react with androgens.

As a result, estrogen is not produced at its source, resulting in an overall decrease in estrogen levels in the body.

Toremifene is a SERM that is a mixture of agonist and antagonist to the estrogen receptor, and is classified as a triphenylethylene analog, very similar in structure 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 because it is used to treat breast cancer in postmenopausal women who test positive for estrogen receptors (or estrogen receptor unknown).

This means that it is a drug used to block and treat female breast cancer that is aggravated by estrogen, which can promote the growth of cancer through estrogen's activity at receptors in breast tissue, which can promote tissue growth in the breast.

Toremifene works by binding to these receptor sites, as described earlier, and blocking the ability of estrogen itself to continue to activate the receptor sites within breast tissue, thereby blocking or halting the progression of tumor growth that may be exacerbated by estrogen.

Toremifene has become popular among bodybuilders and athletes who use anabolic steroids for the same reason as Nolvadex (it is used to offset or block some of the effects of too much estrogen in the body due to the aromatization of various androgens such as testosterone and Dianabol).

In particular, toremifene is used to alleviate, mitigate, and/or prevent the estrogen-related side effects of gynecomastia (the development of breast tissue in men).

Toremifene citrate is a fairly new and recently developed compound that was approved as a prescription drug by the FDA in 1997, and is most popularly sold in the U.S. prescription drug market under the brand and trade name Fareston.

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

Toremifene is also sold under the brand name Fareston in many countries abroad:

Like its close relative, Nolvadex, it is extremely popular and widespread, and can be found almost anywhere in the world.

A lingering (and often asked) question about Toremifene is whether it is as effective, more effective, or more beneficial than its sister product, Nolvadex.

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

Chemical Properties of Toremifene

Toremifene (Fareston) is a non-steroidal selective estrogen receptor modulator (SERM) that exerts both mixed agonistic and antagonistic effects with respect to estrogen in several tissues and cells in the human body.

Toremifene belongs to a family of compounds known as triphenylethylene compounds; Nolvadex (tamoxifen) and Clomid (clomiphene citrate) also belong to this family, and the two compounds in particular are very closely related to each other.

Properties of Toremifene

We've already covered the fact that Toremifene is a SERM, and that it works by blocking estrogen at various receptor sites in certain tissues in the body (particularly breast tissue).

In layman's terms, Toremifene pretends to be a “fake” estrogen that occupies estrogen receptors within breast tissue.

Once Toremifene occupies these receptors, real estrogen is unable to do its job.

Toremifene does not lower total plasma estrogen levels.

Not only does it antagonize the estrogen receptors in breast tissue, but it also antagonizes estrogen in the hypothalamus (which essentially 'tricks' the hypothalamus into thinking that there is little or no circulating estrogen in the body, allowing it to increase production of testosterone and utilize aromatization to restore those levels.

Toremifene also acts on estrogen receptors in other tissues in the body (especially in the liver).

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

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

Toremifene is closely related to Nolvadex, but is quite different in other ways (some good, some bad) that have been discovered so far.

The first issue to observe when comparing it to Nolvadex is that many people are concerned about the carcinogenic effects of Nolvadex on liver tissue.

While it should be understood that these effects have been observed with extremely long term use and are not an issue for short term use by bodybuilders and athletes, it may be comforting for some to know that Toremifene has less liver toxicity/carcinogenic effects than Nolvadex[1][2][3].

However, individuals should be aware that toremifene is still an analog of Nolvadex and therefore still exhibits many of the associated toxic effects on the liver.

There is also clinical evidence that toremifene may have an advantage over other SERMs such as Nolvadex in breast cancer patients through its ability to inhibit breast tissue growth as well as inhibit apoptosis (or programmed cell death) of breast tissue and tumor cells [4].

While this is very promising evidence and information, it is important to understand that breast cancer patients often respond very differently to different medications than healthy individuals.

However, it does provide evidence that toremifene can not only destroy gynecomastia tissue and stop it from growing, but can also prevent it.

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

This is very welcome information as it means that toremifene can be utilized as an antiprolactin drug if needed.

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

However, there are some negative aspects and properties of toremifene.

The first, and perhaps most important, is the negative effect it has on SHBG (sex hormone binding globulin) levels in the body, as clinical studies have proven that while it can and does stimulate the natural endogenous production of testosterone (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 testosterone in the body.

SHBG is a protein that binds to sex hormones such as testosterone and renders them inactive while it is bound, in effect “handcuffing” testosterone (or other androgens and sex hormones that are vulnerable to SHBG).

As a result, the bound hormone (in this case testosterone) is left floating around in the circulation (free testosterone and bound testosterone), unable to do its job.

Therefore, elevated SHBG is not good for post cycle recovery or performance during a cycle, and this can reduce the potential of Toremifene as a recovery compound during post cycle therapy (PCT).

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

Furthermore, in terms of restoring 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, taking 20 mg of tamoxifen (Nolvadex) per day for 8 weeks resulted in a more than 70% increase in luteinizing hormone (LH) levels and a 71% increase in testosterone levels.

In comparison, taking 60 mg of toremifene per day for the same period of time resulted in only a 25% increase in LH levels and a 42% increase in testosterone levels.

However, it is important to note that while 60mg per day of toremifene is considered a low dose for this purpose, Nolvadex is still the most potent and effective of the three SERMs for this purpose, and it should be clearly emphasized that the lowest dose is required to elicit positive effects on HPTA function.

More information on appropriate doses is discussed in the Toremifene Dosage section of this profile.

Toremifene side effects

Toremifene is a compound that is well tolerated by most individuals, especially men.

The most severe toremifene side effects tend to be reported in women, especially female breast cancer patients, which is the original intended and designated use of this medication.

The reason why toremifene side effects are considered more severe or worse in women is that the estrogen agonist/antagonist properties of toremifene affect women in a very different way than men due to simple differences in endocrine system dynamics between men and women.

Because women have higher levels of estrogen than men (and because women's bodies are inherently more physiologically dependent on estrogen), the effects of toremifene and its side effects will be more widespread and have a greater impact on women than on men.

That's why toremifene side effects can include stomach or abdominal pain, anxiety, changes 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 men due to hormonal differences between the sexes.

Clinical trials in female breast cancer patients have shown the following toremifene side effects (listed in order of most frequent occurrence): dizziness, hot flashes, sweating, elevated liver enzymes, nausea, vaginal discharge, edema, vomiting, and vaginal bleeding.

Much rarer toremifene side effects found in clinical trials in women with breast cancer include muscle stiffness, jaundice, dyspnea (shortness of breath), constipation, itching, loss of appetite, loss of muscle strength, depression, tremor, and visual disturbances.

Again, these toremifene side effects are almost exclusively seen in women and rarely in men.

When anabolic steroids are used by bodybuilders and athletes (almost all of whom are male), few side effects or adverse reactions have been reported.

Because many users report very few side effects, Toremifene is highly valued and popular among anabolic steroid users.

Some users may report mood swings (due to its estrogen agonist/antagonist action in the body) and a positive effect on libido (due to its positive effect on testosterone production).

Some users have reported a decrease in libido after taking toremifene, which may be due to less free testosterone circulating in the body due to the SHBG-raising properties of toremifene.

Many users have anecdotally reported that mood swings only last for the first few days of use and then return to normal.

Clinical data regarding the side effects of Toremifene, especially in men and anabolic steroid users, tends to be fairly scarce.

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

Therefore, the only current data regarding toremifene side effects in male anabolic steroid users is anecdotal data and varying experiences of users.

Toremifene Administration and Dosage

For the treatment of breast cancer, toremifene is used at a dose of 60 mg per day.

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

Toremifene is usually given for 1 year, but may be extended to 2-3 years if remission is not seen or if cancerous ductal and adenocarcinoma tissue decreases.

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

Administration of testosterone-based anabolic steroids can increase circulating estrogen levels, which can lead to estrogen-related side effects.

Toremifene is recommended at a dose of 30-60 mg per day, but Nolvadex (tamoxifen citrate) is often chosen as a cheaper and more effective alternative.

For steroid users, the priority is to control high estrogen levels with an aromatase inhibitor (AI), not to block estrogen.

Estrogen blockade is considered a last resort for AI treatment and is not sufficient.

If you are using multiple androgens such as Testosterone Enanthate, Dianabol, or Deca Durabolin, you may need an AI and a SERM such as Toremifene.

Toremifene is an effective post cycle therapy (PCT) agent, but it is not as potent as tamoxifen (Nolvadex) in comparative studies.

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

The recommended dose of Toremifene is 120 mg for the first week, followed by 60 mg per day for five weeks as a post-treatment for low testosterone symptoms.

References for Toremifene

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

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

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

[4] Apoptosis in the growth inhibition of human breast cancer cells in vivo and in vitro by toremifene. 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] Effects of toremifene on endocrine regulation in breast cancer patients. Számel I, Hindi I, Vince B, Eckhardt S, Cangas L, Hajba A. Eur J Cancer. 1994;30A(2):154-8.

[7] 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.