RAD140/Testolone

Note: RAD140 and other SARMs alike are considered research chemicals and are not approved for public consumption. Use of RAD140 and similar research chemicals should be restricted to a clinical setting.

 

RAD140/Testolone

 

RAD140, which is often termed testolone outside of clinical settings, is an emerging research chemical, classed as a selective androgen receptor modulator (SARM).

 

Thus far, RAD140 seems to be most promising for androgen-receptor positive cancers, such as breast cancer and a phase 1 clinical trial has commenced for this purpose. However, despite its potential influence on cancer progression and even lean body mass, almost no human data, or an established safety profile exists (1).

 

Until clinical trials provide conclusive evidence of RAD140’s safety and efficacy, use is not recommended.

 

RAD140 Is A SARM

 

RAD140 is a SARM, which means it selectively interacts with androgen receptors throughout the body and brain (2, 3).

 

As described with other SARMs like ostarine, SARMs are attractive because they are known to selectively activate receptors in tissues like muscle, while not influencing sex-specific tissues like the prostate (4).

 

This fact is the primary reason that SARMs are being considered in place of traditional hormones like testosterone and estrogen since the latter has been implicated in producing undesirable side effects, including prostate growth and can lead to poor quality of life (5, 6).

 

SARMs, on the other hand, seem to selectively target tissues, without generating many of the adverse side effects associated with hormone therapy on either side (4, 7).

 

Due to the recent emergence of SARMs as a potential treatment for many ailments, research regarding RAD140 is still in its infancy. Mostly, studies on this research chemical have been restricted to cell culture or rat models for potentially treating muscle wasting, neurodegenerative disorders like Alzheimer’s, and breast cancer.

 

Animal Studies Testing RAD140

 

Since the use of SARMs is still relatively new, scientists first use animals to understand the potency and safety of the drug. Thus far, the majority of studies have been conducted in rats.

 

 

 

RAD140 Castrated Rat Studies

 

One of the primary uses of SARMS is the ability to stimulate muscle growth without also encouraging the growth of sex-related tissues like the prostate. Imagine the ability to prevent muscle loss while experiencing cancer without potentially making things worse.

 

In one study, scientists observed the influence of RAD140 on muscle growth with castrated rats, compared to the administration of testosterone. By using castrated rats, researchers can understand how these drugs interact when endogenous hormones are removed, similar to hormone therapy for cancer.

 

What the researchers found was that RAD140 led to significant improvements in muscle weight. The same research did show some interaction between RAD140 and prostate growth; however, increases did not reach the same level as testosterone treatment (7).

 

As a result of RAD140 producing minimal effects in the prostate, the same scientists tested a combination of RAD140 and testosterone, under the pretense that RAD140 may inhibit testosterone’s influence on prostate growth.

 

What they found was that when co-administered, RAD140 and testosterone were synergistic, leading to further progression of the non-sex tissue. What they also determined was that RAD140 seemed to have a slight suppressive effect on testosterone’s influence on prostate weight, despite not reaching significance (7).

 

RAD140 Intact Rat Studies

 

Upon completion of testing in a castrated rat model, scientists then conducted a similar trial with intact rats, meaning they display normal levels of natural hormone production, which could represent a healthy population.

 

The findings were surprisingly similar to that of castrated rats. When administered RAD140, rats displayed increases in levator ani weight (non-sex tissue). Amazingly, however, only the highest dosage of RAD140 led to significant increases in prostate weight, differing from the findings of study one (7).

 

What this seems to suggest is that RAD140 may stimulate prostate growth, but only to a level generally associated with functioning hormones. Since the prostate will respond favorably to hormones like testosterone, removing the hormone could theoretically lead to a reduction of prostate weight.

 

It is, however, unknown if this would be consistent in a human model.

 

 

RAD140 Rat Studies Are Not Conclusive

 

Importantly, these rat studies are not conclusive and also show that RAD140 does have some small influence on prostate growth. Despite being less than that of testosterone, it’s important to consider that RAD140 could potentially stimulate further prostate growth and this reality should not be taken lightly.

 

Studies on SARMs like RAD140 are in their infancy, only just now reaching clinical trials. This means by and large, long-term and even short-term effects of using RAD140 are entirely unknown.

 

While many publications online will use the information in these studies as conclusive proof, these findings do indicate at least some interaction of RAD140 with sex-specific tissue, and this must be considered.

 

RAD140 & Cynomolgus Monkeys

 

Upon completion of rat studies, scientists turned towards young cynomolgus monkeys to more closely mimic the effect of RAD140 in humans.

 

These monkeys were involved in this study for 70 days. For 21 days before dosing, body weights of the monkeys were assessed. From there, 28 days of dosing with RAD140 commenced, which was followed by an additional 21 days of post-testing.

 

The results indicated that RAD140 led to significant improvements in body weight, with non-significant increases in lean mass. Further, the data suggests that these improvements were retained at least 21 days after ending the final dose (7).

 

While prostate weights of monkeys were not tested, liver enzyme elevations were. These findings are important because oral hormones often lead to liver damage or elevations of liver enzymes. Testing these elevations with RAD140 is crucial because it tells us that taking by mouth might be both safe and effective (8).

 

Unsurprisingly, given the relative safety profile reported, even administering ten times the effective dose only elevated liver enzyme activity slightly. This suggests that a standard treatment may indeed be safe when administered orally (7).

 

Again, it is essential to understand that these findings are not conclusive, nor do they represent fully how a human body will interact with this SARM. Personal use at this time is not recommended.

 

RAD140 & Breast Cancer

 

Regardless of other potential benefits, arguably the most important is the potential for RAD140 to help treat breast cancers of many different types. Since RAD140 is a SARM and selective in the tissues it activates, it’s become an attractive area of research, even spurring the commencement of human clinical trials (1, 7).

 

Breast cancer is perhaps, as some would call, an epidemic.

 

According to some reports, breast cancer is the second leading cause of mortality for cancer-related deaths, which means finding a cure is of the utmost importance. What research shows is that around 75% of breast cancer tissues are hormone receptor-positive including estrogen receptors and in some cases, androgen receptors, such as those for testosterone. This means that these cancers rely on and respond favorably to these hormones in circulation (8-14).

 

For a female, this becomes a significant issue. Since estrogen is the primary female sex hormone, it's a vital hormone for development, sexual health, and even mental health. Despite this requirement, this same hormone then can stimulate further growth and proliferation of cancer cells, which presents significant issues (15, 16).

 

These findings have led to the use of many different therapies in an attempt to overcome this pervasive disease.

 

At first, scientists theorized that perhaps these diseases were due to hormonal imbalance, which of course led to the use of androgen therapy to restore balance. While in some specific tumor cases, androgen therapy does seem to benefit, but many times it does not and even leads to unfavorable changes, such as the development of masculine traits (17).

 

Further, these unfavorable changes are compounded by the fact that androgen administration, such as testosterone often aromatizes or metabolizes into estrogen. This aromatization is one of the reasons many bodybuilders using steroids develop gynecomastia, or the enlargement of breast tissue (18, 19).

 

For a breast cancer patient, however, this aromatization would ultimately defeat the purpose of the therapy in the first place, potentially leading to further progression of cancer through increasing estrogen production (17, 20).

 

Because of these conflicting results, many treatments are focused on the removal of reproductive organs and attempt to inhibit the action of estrogen. While removal of estrogenic tissue and activity of the hormone itself might help slow or abolish tumor progression, low estrogen or complete removal also comes with a host of potential side effects (6).

 

Fortunately, RAD140 has been implicated in selectively targeting breast cancer cells displaying androgen receptors. By targeting these receptors, research shows that RAD140 inhibited further tumor growth. Interestingly, RAD140 administration also led to the suppression of progesterone receptors in the same tissue, suggesting that it might also be useful for breast cancers that utilize the progesterone receptor (8).

 

RAD140 Protects Against Hormone Therapy

 

With RAD140 and other SARMs alike, these chemicals might provide therapeutic benefit outside of merely interacting with tumor cells.

 

Imagine a pre-menopausal woman diagnosed with metastatic breast cancer. As a first line treatment, since RAD140 hasn’t been approved, her oncologist prescribes a mastectomy and oophorectomy, which is the removal of breast tissue and ovaries, respectively. Since many breast cancers respond favorably to estrogen, the idea is to remove it from the body, thus killing cancer cells (13).

 

While this might work, we also need to consider the ramifications of completely removing the primary female sex hormone from the body. Undoubtedly, this leads to many complications, often associated with menopause such as changes to the menstrual cycle, poor metabolism leading to weight gain, changes in mental stability such as depression, reduced bone density, and muscle loss (14).

 

Because of this reality, finding alternatives to completely removing estrogen and other androgens is a good idea.

 

It's also worth pointing out that since RAD140 is considered non-steroidal and tissue-selective, use of this chemical might help limit or abolish muscle size and function loss often associated with cancer treatment and estrogen decline (6).

 

Considering that most cell and animal models have shown promise in terms of selectively building mass and its ability to inhibit breast tumor growth, the use of RAD140 may prove useful for breast cancer patients should clinical trials find the same (7, 8).

 

RAD140 Protects The Brain

 

Animal research on RAD140 has shown that the substance can selectively target androgen receptors in the body and brain, without significantly influencing healthy reproductive tissue such as the prostate (7).

 

In addition to potentially treating cancer, these findings have led scientists to believe that RAD140 may be useful in the prevention of Alzheimer’s and other neurodegenerative disorder-related cell death.

 

A primary theory behind the progression of Alzheimer's is the accumulation of amyloid beta plaques and tau protein tangles, which interfere with cellular transmission and result in brain cell death. Amyloid beta plaque, however, is likely the term you've most often associated with Alzheimer's disease and it's one of the primary theories behind the progression of the disease (21, 22).

 

Scientists seem to agree that an amyloid precursor protein is somewhat responsible for the progression of the disease. Paradoxically, this precursor protein seems to support cell growth and repair in healthy individuals, but in some cases, metabolism of this protein results in the formation of deadly plaques (23).

 

When this amyloid protein interacts with specific enzymes, it's chopped up into smaller pieces; some of which begin to accumulate outside of the brain cell. When this accumulation progresses, the chopped up parts of this protein form what are known as amyloid beta plaques. These plaques disrupt signaling between neurons and can result in reduced cognitive ability and cell death (21, 24).

 

Another common attribute of Alzheimer’s is the accumulation of tau protein tangles, within brain cells.

 

In a healthy brain, neurons (brain cells) send nutrients and signals through structures known as microtubules. Essentially, this creates a network like a subway system to communicate information and nutrients. In healthy brains, the tau protein helps to support this network (25, 26).

 

During (or before) the progression of Alzheimer’s, this protein malfunctions and accumulates within this network of microtubules. As a result, this impedes transmission of nutrients and information, leading to cellular death. A good way to imagine this is almost like a blood clot, where tau proteins accumulate and inhibit nutrients and information from traveling through this neural network (25, 26).

 

Alzheimer's disease currently has no cure, which means that the progression of the disease is inevitable. This also means that neuronal death is also inevitable, creating a vicious cycle of proteins and plaques killing brain cells, encouraging scientists to find a solution. Fortunately, RAD140 might provide the protection the brain needs.

 

RAD140 Prevents Neuronal Death

 

Research suggests that androgens might play a role in the progression of Alzheimer's disease, which means that targeting receptors early might help treat or prevent the disease. Studies indicate that low testosterone in the brain and in circulation have been present both during and before clinical diagnosis of Alzheimer's, which strongly suggests a role (27).

 

Importantly, however, it seems that testosterone's influence on brain health is dependent on androgen receptor activation, rather than the hormone itself. Considering that hormone-based therapies have been indicated in adverse effects, consideration of other androgen receptor activators, such as SARMs have been considered (3).

 

Since RAD140 is a non-steroidal SARM, with a high affinity for the androgen receptor in the body and brain, the use of this chemical is considered for at least protecting existing brain cells. While RAD140 won't prevent the potential causes of Alzheimer's, it does show promise for at least protecting neurons from further damage or at the very least, slowing the process.

 

Thus far, three tests have been run, using RAD140 in the presence of neurons.

 

First, researchers tested RAD140 in cell cultures that were exposed to amyloid peptides, which are considered to be responsible for Alzheimer's related cell death. These cells were incubated with RAD140, testosterone or another SARM called RAD192 for 24 hours.

 

After, levels of cell survival were compared to cells incubated only with the amyloid beta peptide to understand the protective effects of each substance (3).

 

Trial two consisted of a similar practice, exposing cells to a substance known as apoptosis activator II, which has the purpose of stimulating cell-induced death or apoptosis. These cells were then exposed to RAD140 and testosterone, to understand the protective effect of these substances (3).

 

The results of these tests were clear. When using these RAD140 and even testosterone, the cellular survival rate was drastically higher than control, suggesting a protective effect of all substances tested with a non-significant difference between. Suggesting that RAD140 is as effective as testosterone therapy for protecting neurons (3).

 

From there, researchers continued their quest, using gonadectomized (removal of sex organs) rats by exposing them to a substance known as kainate, which is known to stimulate excitotoxicity of neurons and seizure (3, 28).

 

While this might seem cruel, seizures result in the over-excitation of brain cells, which ultimately produces their death. Similar to Alzheimer's testing, observing the protective effect of RAD140 on a direct and immediate threat to cellular integrity could provide us with information regarding its effectiveness at protecting against a disease that results in progressive brain damage.

 

What the results showed was a significant protective effect of RAD140 against seizure-induced cell death. Rats treated with RAD140 displayed similar protection as testosterone, with a slight tendency to be even more effective (3).

 

Importantly, during this study, the researchers also tested prostate, seminal vesicle and levator ani weight, pre and post administration of treatments. Results indicated a non-significant increase in prostate and seminal vesicle weight with a significant increase in levator ani weight, (non-reproductive tissue). These findings further strengthen the notion that RAD140 specifically targets tissues, with little secondary influence on reproductive tissue (3).

 

RAD140 Human Clinical Trials

 

Currently, RAD140 is being tested in a clinical trial using postmenopausal women that display metastatic hormone receptor-positive breast cancer. The point of this study is to understand the relative dosing and safety profile of the drug in the target population before commencing further in the clinical setting (1).

 

The fact that RAD140 has commenced to human clinical trials is impressive and alludes to the fact that this SARM may be advantageous for treating breast cancer.

 

Again, however, it's important to understand that these studies are in their infancy. For example, Ostarine, which is another popular SARM progressed as far as Phase 3 clinical testing but was abandoned due to not reaching established criteria (29).

 

This means that RAD140, while promising, has not been approved for human consumption. Until clinical trials indicate a strong safety profile, use of RAD140 is not recommended.

 

Safety Considerations Of RAD140

 

Despite the relatively unknown effects of RAD140, many people consider SARMs to not be harmful, undoubtedly due to information such as SARMs being selective and not displaying side effects similar to steroids. But with no human research, the safety of RAD140 is unknown.

 

No Human Data

 

While cell cultures using human cells and animal studies may indicate some level of safety when using RAD140, what happens in cell cultures and rats is often not indicative of what happens in the body.

 

Quite simply, apart from the current clinical trial in progress testing RAD140 with metastatic breast cancer patients, human data regarding safety and effectiveness does not exist.

 

Above all else, this lack of human data should discourage personal use.

 

Few Side Effects Reported

 

Fortunately, few side effects of using RAD140 have been reported. However, since the majority of data is in animal models, it's difficult to know if the same will hold for humans.

 

Additionally, if other SARMs like ostarine are to be used as an example, illicit users of SARMs often use dosages that far exceed those used during research studies. This means that higher dosages for any amount of time may produce unknown and undesirable side effects, which must be considered.

 

Orally Available

 

Being orally available with little risk of damaging the liver is a significant benefit of RAD140. Hormones like testosterone can damage the liver when taken by mouth, but RAD140 doesn't seem to do this (7, 8).

 

This makes use of the drug easy, especially for those with an aversion to using needles and injections.

 

Potential For Prostate Growth

 

The reason SARMs are attractive is that they are considered to be tissue-selective and do not exert influence on sex-specific tissue such as the prostate (3, 7).

 

However, one study did note significant increases in prostate weight as a result of using RAD140. While this only occurred in castrated rats, (which could suggest prostate wasting), it is still a detail of concern since many people might use RAD140 under the pretense that it won’t promote prostate enlargement (7).

 

This research suggests that RAD140 might induce prostate growth and must be considered.

 

Final Verdict On RAD140

 

RAD140/Testolone is an emerging research chemical, which is classed as a SARM. Currently, no human data regarding RAD140 exists apart from a current clinical trial testing the substance in postmenopausal breast cancer patients.

 

Otherwise, few studies have been conducted in rats and even monkeys, which suggest an influence on muscle growth and a potential anti-cancer effect. Thus far, RAD140 does appear to be a promising agent, in particular, for combating female-centric breast cancer.

 

However, this research is still very young with almost no human data on record. Considering this reality, use of RAD140 is not recommended until further safety in humans is established. Even then, use should be restricted to a clinical setting.

 

References

 

  1. Phase 1, First-in-Human Study of RAD140 in Postmenopausal Women With Breast Cancer – Full Text View. (n.d.). Retrieved from https://clinicaltrials.gov/ct2/show/NCT03088527
  2. NCI Drug Dictionary. (n.d.). Retrieved from https://www.cancer.gov/publications/dictionaries/cancer-drug/def/selective-androgen-receptor-modulator-rad140
  3. Jayaraman, A., Christensen, A., Moser, V. A., Vest, R. S., Miller, C. P., Hattersley, G., & Pike, C. J. (2014). Selective androgen receptor modulator RAD140 is neuroprotective in cultured neurons and kainate-lesioned male rats. Endocrinology155(4), 1398-1406.
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