What are SARMs? Selective Androgen Receptor Modulators – SARMs are synthetic compounds that belong to the class of androgen receptor ligands and bind with high affinity to androgen receptors (AR). The main purpose and positive effects of SARMs are mainly their strong anabolic properties and the ability to cause a rapid increase in protein synthesis and hypertrophy in muscle tissue (hypertrophy is an increase in skeletal muscle cell volume) and have a positive effect on increasing bone density and their mineralization. >>YOU CAN BUY THE BEST SARMs HERE!<<
Due to these properties, the effectiveness of SARM in supporting the growth, development, and maintenance of muscle mass and bone density in this respect is comparable to the effectiveness of AAS (anabolic-androgenic steroids), which are generally considered to be one of the most effective for this purpose.
SARMs Vs. Steroids
However, a huge advantage of SARMs over anabolic steroids, testosterone, and its derivatives is the fact that SARMs represent significantly fewer possible and significantly less serious side effects and health problems or risks that the use of anabolic-androgenic steroids can and often causes. These advantages of SARM are provided by their high selectivity – their properties and ability to bind preferentially to androgen receptors, where desired – in muscles and bones and at the same time to act as little as possible on tissues and organs when it is unwanted and harmful (prostate, liver, kidneys, skin, etc.)
Thus, SARMs have many times the higher ratio of desired – anabolic effects compared to adverse – androgenic effects. All of these listed positive traits and benefits of SARMs make them hot candidates for research around the world and very promising substances for future use in the treatment of diseases associated with muscle loss or thinning bone density. Due to their excellent ability to maintain muscle mass growth and a much better safety profile compared to anabolic steroids, SARMs are also often sought after and experimentally used by bodybuilders to build muscle mass.
HISTORY OF SARM
Efforts to create new contraceptives have led scientists to discover and develop SERMs, selective modulators of estrogen receptors (ERs), synthetic compounds that act on estrogen receptors (as opposed to SARMs, which act on a completely different receptor, the androgen receptor). The discovery of SERM for many years preceded the discovery and development of the first SARM. The first SERM Clomifene was developed by chemist Frank Palopoli and his research team in the late 1950s, who later published the results of his first clinical trials. Mr. Palopoli also conducted successful research on the use of another SERM tamoxifen in the treatment of breast cancer and other tumors.
The 1987 discovery showed that SERMs tamoxifen and raloxifene, which are considered antiestrogens due to potent antagonistic effects in breast tissue, may be useful in preventing bone loss due to their estrogenic effects and have had a major impact on estrogen receptor understanding. and nuclear receptor function. The term SERM is coined to refer to those compounds that have a combination of estrogenic agonists, partial agonists, or tissue-dependent antagonistic activities. The successes in the development of SERM, the knowledge gained and the better understanding of their mechanisms of action, as well as the increasing use of tamoxifen in the treatment of breast cancer, have led other scientists to the idea and efforts to develop their analogs, the development of SARM began in the 1990s.
The modern era of nonsteroidal SARMs began on its own at Ligand Pharmaceuticals and the research work of Dwayne D. Miller and Jim Dalton, who were colleagues at the University of Tennessee Health Research Center. Researchers at Ligand Pharmaceuticals were the first to develop a series of cyclic quinolinones that had anabolic activity and some degree of tissue selectivity for skeletal muscle and became the basis for their SARM LG121071 (LGD-121071). Dalton and Miller’s discovery that aryl propionamides with structural similarity to bicalutamide and hydroxyflutamide can activate AR-dependent transcriptional activity provided the basis for the development of diaryl propionamide class SARM(Ostarin, Andarin, etc.). Over the last 20 years, the number of bioactive SARMs studied has been steadily increasing, as has the knowledge of scientists about the mechanisms of action of SARMs.
ANDROGEN RECEPTOR (AR)
The androgen receptor (AR or also known as NR3C4 (a subfamily of nuclear receptors 3, group C, gene 4)) belongs to the superfamily of nuclear steroid hormone receptors, and binding of testosterone and dihydrotestosterone, which are its natural endogenous ligands, modulates its function as a transcription factor. In humans, the androgen receptor (MW 110 kDa; 919-920 amino acids) is encoded by the AR gene located on the X chromosome of the long arm at the Xq11-Xq12 locus and is expressed in various tissues such as skeletal muscle, testis, prostate, breast, uterus. and others. The effects of the interaction between AR and androgens are complex and vary depending on gender, age, tissue type, and hormonal status. The androgen receptor has many other important effects, such as effects on bone density, strength, muscle mass, hematopoiesis, clotting or metabolism.
Androgen receptor function: Testosterone enters the cell and, if present in 5-alpha-reductase, is converted to dihydrotestosterone (DHT). After steroid binding, the androgen receptor (AR) undergoes a conformational change and releases heat shock proteins (hsps). Phosphorylation (P) occurs before or after steroid binding. The androgen receptor is translocated to the cell nucleus, where dimerization, DNA binding, and recruitment of coactivators occur. The target genes are transcribed (mRNA) and transformed into proteins.
HOW DOES SARMS WORK?
Mechanisms of action of SARMs: The androgen receptor functions as a cellular nuclear receptor. SARM, which is its synthetic ligand, enters the cell, usually by diffusion, and encounters intact AR in the cytoplasm. After binding, AR dissociates from the cytosolic proteins in heat shock and migrates to the nucleus, where it binds to various co-regulatory proteins. The complex then interacts with specific DNA sequences and acts as a regulator of the transcription of androgen-reactive genes. A complex and tissue-specific process determines the transcriptional and thus cellular response. Although much scientific work has been done to determine how different SARM tissue specificity and partial agonism are achieved, the exact mechanisms remain unclear to this day.
Thus, the ability of SARMs to signal through AR appears to depend on how their unique conformations interact with functional AR domains and on how these domains interact with the cellular regulatory environment to direct DNA expression. While each SARM-AR complex has a different conformation and that tissues have unique AR expression patterns, levels of co-regulatory proteins, and transcriptional regulation, we can imagine the great variety and potential for tissue-specific and/or action-specific SARMs.
SARMs enter the cytoplasm, where they displace the androgen receptor from heat shock proteins. Once linked, they translocate into the cell nucleus and act as transcription factors by binding androgenic response elements (AREs). Depending on the tissue type and the regulatory environment of the cell, different co-regulatory proteins help to determine and modulate the transcriptional response. Legend: HSP = heat shock protein, AR = androgen receptor, ARE = androgen response elements.
SARMS AND MUSCLE GROWTH
The most valuable positive effects of SARMs include their strong anabolic properties and action on skeletal muscle in combination with the fact that their anabolic and androgenic effects can be preferentially and highly selectively targeted to these muscle tissues. By acting and binding to androgen receptors on muscle cells, SARMs are highly effective in stimulating increased protein synthesis and hypertrophy in skeletal muscle tissue (ie, they stimulate the growth and volume of their muscle cells).
SARMs are able to significantly support the growth and maintenance of lean muscle mass, similar to the endogenous ligands AR – the steroid hormones testosterone and DHT (dihydrotestosterone) or their synthetic derivatives – anabolic androgenic steroids (AAS), but they represent the least possible side effects, healthy and the risks posed by the use of testosterone or anabolic-androgenic steroids.
The most promising potential applications of Selective Androgen Receptor Modulators include conditions associated with loss of muscle mass (cachexia, muscular dystrophies). In healthy normal individuals, there is a balance between muscle breakdown and synthesis, and any change in the rate of breakdown or protein synthesis may favor atrophy (loss of muscle mass) or hypertrophy (growth of muscle cells). Many scientific and clinical studies have been conducted to demonstrate the strong ability of SARM to induce muscle hypertrophy – muscle cell growth. in skeletal muscle tissue, prevention of muscle atrophy (loss of muscle mass) and reverse iatrogenic and disease-induced catabolism, with minimal or beneficial antagonistic activity on androgenic tissues.
As SARMs have an excellent ability to effectively support muscle growth and at the same time a much better safety profile than testosterone and anabolic steroids, it is logical that they are also in the field of view of bodybuilders and strength athletes who experiment with their use for more -Massive growth of muscles and strength and increase productivity. In 2008, the World Anti-Doping Agency (WADA) banned SARMs in sport because of their potential for abuse in order to gain an undue advantage in physical competitions. Since then, the use of SARM in athletes has been considered doping and has been banned by most sports organizations.
SIDE EFFECTS AND HARMFUL EFFECTS OF ANABOLIC STEROIDS
It is well known that anabolic-androgenic steroids (AAS) are very effective in stimulating muscle growth (as well as strength and performance), and that their beneficial effects are often accompanied by a number of undesirable and serious possible side effects. And that when used, there is a high risk of permanent damage to health. Therefore, this is their main drawback and problem – high risk and likelihood of causing serious side effects and many health problems.
This is mainly because steroids have a strong effect on all androgen receptors in the body and in all tissues, not only in tissues where it is desired (anabolic effect on skeletal muscle and bone), but also on tissues where it is undesirable and harmful (causing androgenic harmful effects on the prostate, liver, skin, reproductive organs, brain, etc.).
Another serious problem with most steroids is that, like testosterone, they can also be widely converted to DHT (dihydrotestosterone) and estrogen in the body, which also contributes significantly to their possible unpleasant side effects. Among their less serious drawbacks may be the fact that many steroids require intramuscular injection (injection into a muscle) and will have no effect when used orally.
Studies show that some side effects of steroid use are reversible, while others are not – they can mean permanent damage. For example, reversible side effects may include testicular atrophy (contraction), severely suppressed or completely stopped sperm production in men, acne, cysts, oily hair, high blood pressure, “bad” cholesterol and/or increased aggression. Common irreversible injuries include, for example, androgenic alopecia (baldness in men), heart dysfunction, severe liver damage, or gynecomastia (breast growth in men).
List of possible harmful side effects of anabolic-androgenic steroids:
hepatotoxicity / high hepatic toxicity (oral steroids), possible severe hepatic impairment, liver tumors and cysts
enlarged prostate, increased risk of prostate cancer
kidney problems or failure
high blood pressure, multiple cardiovascular complications, increased risk of heart attack
high density cholesterol (LDL) (“bad” cholesterol)
low-density lipoprotein (HDL) cholesterol (“good” cholesterol)
suppressed or completely stopped sperm production in men, infertility, erectile dysfunction
severe inhibition of endogenous testosterone production
testicular atrophy, testicular cancer
gynecomastia (breast growth in men)
a sharp rise in cortisol and estrogen levels
massive fluid retention
severe acne and cysts, oily hair
androgenic alopecia (male pattern baldness)
increased climate and a deeper voice in women
excessive growth of body hair in women
menstrual disorders in women
increased aggression, mood swings, delusions, depression
anxiety and/or sleep problems
dullness, brain degradation, dementia
ADVANTAGES OF SARM OVER ANABOLIC STEROIDS
The goal in the development of SARMs was and is to create synthetic androgen receptor ligands (androgen receptor modulators) that will respond to the tissues being treated (skeletal muscle, bone) in the same way as testosterone; but they will not respond to other tissues where testosterone and androgens produce unwanted side effects (as little as possible or ideally not at all). Thus, to create substances that will have the strongest possible anabolic effect where desired, but at the same time possible minimum androgenic effects when it is undesirable.
Thus, a key feature underlying the potential of SARMs is their tissue specificity and high selectivity . While steroid hormone replacement therapy may be associated with a high rate of side effects, in part due to widespread and nonspecific AR activation in many different tissues, SARMs seek to circumvent these adverse effects as much as possible and to act selectively and beneficially only in tissues. where appropriate and desirable.
Therefore, most SARMs have a significantly higher (better) ratio of anabolic and androgenic effects than testosterone and steroids: While testosterone has a 1: 1 ratio of anabolic and androgenic effects, for example SARM RAD140 has an incomparably better and safer ratio – up to 90 times stronger anabolic effects than its possible androgenic effects (therefore its possible androgenic side effects are essentially almost completely ruled out).
Another great advantage of most SARMs over steroids is that SARMs are highly effective even when administered orally., and at the same time without serious harmful effects on the liver. (This is true for most SARMs, but there are exceptions such as SARM MK-3984, which is excluded from studies and does not continue to develop due to an increase in liver enzymes to more than three times the upper limit of normal established for its use.) Because SARMs, unlike oral steroids, are not methylated and therefore not toxic and dangerous to the liver in this way. While most anabolic steroids are either not active and effective when administered orally (must be injected intramuscularly), or anabolic steroids that are active and effective when administered orally tend to cause dose-dependent stress and liver adverse effects. which can damage the liver very seriously if used excessively.
In addition, SARMs do not metabolize to dihydrotestosterone (DHT), do not aromatize to estrogens, nor do they cause significantly increased water retention in the body. SARMs also do not have such a strong and rapid effect on reducing and suppressing the body’s own testosterone production. At the same time, if such a decrease in endogenous testosterone production occurs with the use of SARM, its recovery after use and cessation of SARM is significantly easier, faster and more likely than when suppressing endogenous testosterone production by anabolic steroids. Therefore, research on SARMs certainly represents another significant step towards a safer class of androgenic drugs.
List of benefits and advantages of SARM over anabolic-androgenic steroids:
The effectiveness of SARM in supporting the growth, development and maintenance of muscle mass and bone density in this respect is comparable to the effectiveness of anabolic-androgenic steroids, but SARMs represent significantly fewer possible and significantly less serious side effects and health problems or risks that the use of anabolic-androgenic steroids can and often does cause
SARMs can be highly selective and targeted to specific tissues, meaning that they can have a positive effect when desired (strong anabolic effect on skeletal muscle and bone) and as little as possible when it is undesirable or harmful (prostate, liver, skin, etc.)
Most SARMs have a significantly higher (better) ratio of anabolic and androgenic effects than testosterone and steroids, for example, while testosterone has a 1: 1 ratio of anabolic and androgenic effects, SARM RAD140 has an incomparably better and safer 90: 1 ratio. (up to 90 times stronger anabolic effects than possible androgenic effects)
SARMs do not have such a strong and rapid effect on the reduction and suppression of endogenous testosterone production in the body and if the use of SARM reduces endogenous testosterone production, its recovery after use and cessation of SARM is significantly easier, more quickly, and more likely against anabolic steroids
SARMs are highly effective even when administered orally (no muscle injections are required) and at the same time without serious adverse effects on the liver, as SARMs are not methylated and therefore not toxic to the liver in this way.
SARM can help build higher quality, more stable, and longer-lasting muscle gains from steroids
SARMs are not metabolized to dihydrotestosterone (DHT) and are not flavored with estrogens
SARMs do not cause significantly increased water retention in the body
SARMs do not cause acne, cysts or oily hair and skin
SARMs do not cause kidney problems or failure
SARMS VERSUS ANABOLIC STEROIDS
The biggest difference and advantage of SARMs over anabolic steroids is that SARMs have significantly fewer possible and less serious side effects, health problems, and risks. These advantages of SARM are due to the fact that SARMs are highly selective – they act preferentially on androgen receptors where desired – ie. in muscles and bones and at the same time have minimal or no effect on tissues and organs where it would be undesirable and harmful (prostate, liver, kidneys, skin, genitals, etc.)
TABLE OF SARMS AGAINST STEROIDS – COMPARISON OF HARMFUL AND ADVERSE EFFECTS:
Possible harmful/adverse effects or likelihood of health risks with >>>SARMs:Steroids: Overall risk of serious damage to health NO High liver toxicity – possible severe liver damage, tumors and cysts.
Enlarged prostate, increased risk of prostate cancer!
Kidney problems or failure
High blood pressure
Cardiovascular complications, increased risk of heart attack with High Density (LDL) (“Bad” Cholesterol)
Reduced high-density lipoprotein (HDL) cholesterol (“good” cholesterol)
Extremely suppressed or completely stopped sperm production in men
Infertility and impotence
Strong suppression of endogenous testosterone production
Testicular atrophy, testicular cancer
Sharp rise in cortisol and estrogen levels
Gynecomastia (breast growth in men)
Massive fluid retention
Severe acne and cysts
Oily skin, oily hair, very severe deterioration of skin quality
Lost hair and androgenic alopecia (male pattern baldness)
Androgenic mutations, deepening of the voice
Increased climate and a deeper voice in women
Excessive body hair growth in women
Menstrual irregularities in women
Increased aggression, mood swings, delusions, depression
Mental disorders, Anxiety and/or sleep problems, Excessive sweating, Dullness, brain degradation, and dementia
SARMS AND BONE DENSITY
Bone is living tissue that is constantly decomposing (bone resorption) and at the same time regenerating (bone formation) from osteoclasts and osteoblasts. Androgenic ligands affect bone mineral density (BMD, the number of bone minerals in bone tissue) by altering the total osteoblastic activity and osteoclastic activity that result from changes in the total number of each cell type and the individual functional capacity of the cell. These actions are mediated directly by the androgen receptor and by the paracrine and autocrine actions.
Androgens have been shown to have the ability to slow the bone remodeling cycle and to tilt the focal balance of the cycle toward the bone formation. Androgen deprivation is thought to increase the rate of bone remodeling by removing the limiting effects on osteoblastogenesis and osteoclastogenesis. Androgens also have dual effects on the viability of mature bone cells, with antiapoptotic effects on osteoblasts and osteoclasts and proapoptotic effects on osteoclasts. Dihydrotestosterone also stimulates osteoblast proliferation and has a suppressive effect on osteoclast differentiation. The ability of SARMs to increase bone density in animal models suggests that they may provide a unique dual approach to the treatment of osteoporosis.
SCIENCE, RESEARCH AND THERAPEUTIC POTENTIAL OF SARM
SARMs offer many opportunities for clinical applications and possible uses in the future with the promise of safe use in the treatment of serious diseases and conditions such as cachexia, benign prostatic hyperplasia, hypogonadism, breast and prostate cancer, and more. Depending on their chemical structure, SARMs can act as agonists, antagonists, partial agonists or partial antagonists of androgen receptors in various tissues, which represents their huge advantages over conventional androgens. In addition, to date, SARMs have been shown to be well-tolerated, easily administered orally, and generally have no significant side effects, which are often a problem with many drugs, which can only further increase the future usefulness of SARM. It is therefore logical that SARMs have been the subject of research by many scientists and extensive research around the world. Therefore, their development has advanced significantly in recent years and a number of scientific and clinical studies on SARMs have been conducted, and further development continues.
MUSCLE LOSS DISORDERS
In healthy individuals, muscles are in balance between their breakdown and synthesis, and any change in the rate of breakdown or protein synthesis may favor muscle atrophy (loss of muscle mass, catabolism) or hypertrophy (growth of muscle cells). Statistics show that adults over the age of 40 lose about 1% of their muscle mass each year. Age-related muscle loss or sarcopenia (sarcopenia is progressive, generalized loss of muscle mass, muscle strength, and muscle function) and loss of muscle mass as a result of cancer (cancer cachexia) are two serious disorders of muscle loss. Patients with advanced cancer lose muscle mass quickly, and studies show that muscle mass is directly correlated with survival in cancer patients.
Androgens are highly effective in building and maintaining skeletal muscle and, due to their anabolic effects on muscle, are often used to treat cancer cachexia and sarcopenia. Androgens increase the cross-sectional area of type I and type II muscle fibers in a dose-dependent manner, but do not alter the absolute number or ratio of type I and type II fibers. The androgen-induced increase in muscle fiber cross-section correlates with an increase in the number of myonuclear cells and the number of satellite cells. This means that androgen increases the number of satellite cells, which leads to hypertrophy of muscle fibers and increases the number of myonuclear cells.
However, a serious problem with androgens is their current androgenic side effects on other tissues. Therefore, SARMs are particularly interesting, promising and important in this regard due to their high tissue selectivity and potential to provide comparable positive therapeutic effects and muscle gains, but at the same time with significantly reduced possible harmful effects on other tissues. SARMs have been shown to be effective in eliminating and reversing several preclinical patterns of muscle loss, including glucocorticoid-mediated muscle atrophy. Numerous scientific studies have clearly shown that SARM stimulates tissue anabolism and muscle protein synthesis. SARMs have the ability to reverse and prevent iatrogenic and disease-induced catabolism with minimal or beneficial antagonistic effects on other androgenic tissues.
Another group of diseases in which SARMs can be very useful in treatment are muscular dystrophies. Duchenne muscular dystrophy (DMD) is a genetic disease that occurs due to mutations in the cytoskeletal protein dystrophin. Boys with DMD suffer from progressive muscle loss and weakness, and before reaching puberty, this insidious disease and loss of muscle function often lead them to wheelchairs. In addition, they suffer from heart and respiratory defects due to weakness of the heart and lungs, leading to premature death.
Studies using oxandrolone in boys with DMD have shown muscle growth and increased protein synthesis, but the hepatotoxicity of this steroid and genital side effects are serious barriers to such treatment.
One of the very promising strategies proposed to combat DMD is the use of SARMs, alone or in combination with other exon-skipping drugs, or with other strategies such as myostatin inhibitors (e.g., Follistatin-344 or ACE-031). SARMs administered to patients with DMD have the potential to cause an increase in muscle mass and protein synthesis comparable to those seen with oxandrolone but without the side effects. Each SARM should show broad tissue selectivity and a perfect safety profile in children with DMD.
Osteoporosis (thinning of the bone) is a disease of bone metabolism, which manifests itself by a decrease in the amount of bone mass and disorders of bone microarchitecture, which leads to a weakening of the overall strength of bone and thus to their increased fragility and fragility. SARMs not only have strong abilities to increase protein synthesis and stimulate the growth and maintenance of muscle mass, but they can also have a positive effect on mineralization and increase bone density and strength, as clearly demonstrated by several studies on animal models.
In preclinical models, SARMs have been shown not only to prevent bone loss in castrated male rats and ovariectomized female rats, but also to increase bone strength (meaning increased bone density). Under these experimental conditions, they also increased cortical mineral density. and trabecular bones above baseline. Or SARM BA321, which binds to both androgen receptors (AR) and estrogen receptors (ER) without androgenic effects, is able to completely restore bone loss in mice with orchidectomy.
Currently, osteoporosis in humans is treated primarily with anti-resorptive agents that prevent further breakdown of bones in the body. Antiresorptive agents potentially prevent further bone metabolism, but will not be able to increase bone mass. However, SARMs have the unique potential to provide a complete dual approach to the treatment of osteoporosis, i. they not only effectively prevent further thinning of the bones, but can also effectively renew and increase bone mass.
BENIGN PROSTATIC HYPERPLASIA (BPH)
In the prostate, testosterone is rapidly converted to dihydrotestosterone (DHT) by the action of 5α-reductase type 2. This conversion to DHT improves the action of testosterone 3-5 times due to the significantly higher binding affinity of DHT (compared to testosterone) to androgen receptor. DHT plays a crucial role in determining prostate size before and during adulthood and is considered essential for the development of benign prostatic hyperplasia (BPH), which occurs in 50% of men over the age of 50 and up to 90% of men. over this age of 80. The main problem associated with BPH is lower urinary tract symptoms (LUTS).
Much evidence suggests the importance of DHT for the development of BPP (eg, BPH does not develop in men with 5α-reductase type 2 mutations or in men with very low androgen levels due to hypogonadism associated with hypopituitarism). Clinical treatment with BPH with a type 2α-reductase inhibitor (eg finasteride or dutasteride) induces epithelial cell apoptosis, which in turn significantly reduces prostate volume. Therefore, the addition of testosterone in older men raises concerns about the acceleration of BPH. The role of age-related changes in the intraprostatic hormonal environment in the development of BPH was recently investigated. Despite the decrease in testosterone and the intraprostatic production of DHT associated with aging, an increased estradiol-DHT ratio has been found in the transitional aging zone of the human prostate. Therefore, this relatively estrogen-dominant state is also considered important for the development of BPH. In addition, research has found that estradiol is able to induce precancerous lesions and prostate cancer in adult dogs.
SARMs can be very attractive for the treatment of BPH because they have exceptional abilities to act as agonists, antagonists, partial agonists or partial antagonists of androgen receptors in various tissues. For example, a scientific study compared the use of flutamide with SARM S-40542 in a rat PPH model: Both substances similarly reduced prostate weight in a dose-dependent manner, but S-40542 had a weaker effect on the avatar muscle than flutamide. . [In addition, S-40542 showed no effect on testosterone or luteinizing hormone (LH) levels, both of which were elevated by flutamide.
In another study, researchers compared SARM S-1 and S-4 with finasteride and hydroxyflutamide in the treatment of BPH in a rat model. Both finasteride and SARM S-1 selectively reduced prostate weight to a similar extent without altering muscle or plasma levels of testosterone, follicle-stimulating hormone (FSH) or LH, all of which were altered by hydroxyflutamide treatment. SARMs S-1 and S-4 slightly reduce 5-alpha-reductase levels, suggesting that they reduce prostate size by a mechanism other than finasteride. These results increase the possibility of using SARM as monotherapy for the treatment of BPH with minimal side effects.
SARMs also have the potential to be useful in the treatment of prostate cancer. A scientific study in mice showed that SARM FL442 achieved high tissue concentrations in the prostate and acted as an androgen receptor antagonist in prostate cancer cell models (PCa) with efficacy comparable to that of enzalutamide, an antiandrogen used to treat castration resistance. of PCa. In particular, SARM FL442 maintains the ability to prevent cell proliferation, even in cell lines with AR mutations that confer resistance to enzalutamide.
Another study focused on SARM MK-4541, which induces Caspase-3 activity and apoptosis in androgen-independent AR-positive prostate cancer cell lines, while comparing AR- and AR + non-prostate cancer cells. Administration of SARM MK-4541 has been shown to reduce plasma testosterone levels, possibly via AR-mediated negative feedback fed through the hypothalamic-pituitary-gonadal axis.
These results suggest significant potential for SARM in the treatment of hormone-resistant diseases by activating AR-induced expression profiles that are toxic to cancer cells, while avoiding the negative effects of traditional antiandrogen therapies.
Although androgens are considered a risk factor for prostate cancer, they are recommended for the treatment of breast cancer. Prior to the discovery of SERM and aromatase inhibitors, steroid androgens such as medroxyprogesterone and fluoxymesterone were used to treat breast cancer. AR expression in breast cancer consistently correlates with better disease-free survival and overall survival. In addition, the combined expression of AR with steroidogenic enzymes, leading to increased androgen synthesis, has been shown to be extremely useful in breast cancer. However, these steroid androgens, as mentioned above, have caused virilization, which is a very serious problem.
SARMs are another option for the safe and effective treatment of women with breast cancer. Although the mechanism underlying the role of AR in breast cancer has not been fully elucidated, experimental evidence suggests that AR inhibits ER function to inhibit the growth of ER-positive breast cancer. Up to 85% of ER-positive breast cancers and 95% of ER-negative breast cancers express AR. Androgen receptors in breast cancer are likely to provide a survival advantage by modulating ER signaling, which may reduce the risk of metastasis and aggressive disease.
Men with hypogonadism suffering from testosterone deficiency show a decline in various cognitive processes, including episodic memory, working memory, processing speed, visual-spatial processing and powerful functions. These functions are partially regulated by areas of the brain that are modulated by AR. The researchers subanalyze the Baltimore Longitudinal Aging Study, which included 407 men without dementia who were followed for an average of 9.7 years. The subjects underwent medical, physiological and neuropsychological assessments, as well as laboratory tests for total testosterone and steroid hormone-binding globulin. The free testosterone index is calculated based on the total levels of testosterone and steroid hormone-binding globulin. The results showed
Testosterone depletion and deficiency are considered important risk factors for Alzheimer’s disease, and circulating testosterone levels are inversely related to amyloid β (Aβ) levels in the brain of older men. Androgens inhibit the accumulation of Aβ by regulating the expression of neprilysin, which degrades amyloid. Given the important positive effects of testosterone on cognition, we can assume that SARMs may also be useful in the treatment of cognitive disorders such as Alzheimer’s disease. For example, Akita Kazumasa et al. demonstrated that SARM NEP28 increases the activity of neprilysin in addition to systemic anabolic effects with reduced androgenic effects. Therefore, further progress and research in the field of SARM also give new hope to patients with Alzheimer’s disease,
BENEFITS, EFFECTS AND RESULTS OF SARM
SARMs can be highly selective and target specific tissues, meaning that they can have a positive effect when desired (strong anabolic effect on skeletal muscle and bone) and as little as possible when it is unwanted or harmful (prostate, liver, skin, etc.)
SARM have strong anabolic properties and the ability to cause a rapid increase in protein synthesis and hypertrophy in muscle tissue (growth and increase in the volume of skeletal muscle cells), they allow to achieve rapid and massive growth of muscle mass
SARMs are also very effective in maintaining muscle mass and can prevent muscle breakdown as they have strong anti-catabolic effects.
SARMs can be a great and many times safer alternative to androgens and anabolic steroids
SARMs have the least possible side effects compared to anabolic steroids and a much better safety profile
SARM can have a significantly higher (better) ratio of anabolic and androgenic effects than testosterone and steroids
SARMs are not metabolized to dihydrotestosterone (DHT) and are not flavored to estrogens
SARM can help build higher quality, more stable and longer lasting muscle gains from steroids
SARMs have a positive effect on increasing bone density and their mineralization
SARMs are highly effective, even when administered orally (no intramuscular injection required)
SARMs based on current scientific knowledge do not have serious adverse effects on the liver, kidneys and prostate
SARMs do not cause significantly increased water retention in the body or do not cause acne, cysts or oily hair and skin
SARMs offer many opportunities for clinical applications and possible future uses with the promise of safe use in the treatment of serious diseases and conditions.
SARMs can act as agonists, antagonists, partial agonists or partial antagonists of androgen receptors in various tissues, which is their huge advantage over conventional androgens.
SARMs can be very useful in the treatment of diseases associated with loss and loss of muscle mass (age-related muscle loss, sarcopenia, cachexia, Duchenne muscular dystrophy)
SARMs have the unique potential to provide a complete dual approach to the treatment of osteoporosis (effectively prevent further thinning of the bones and at the same time effectively renew and increase bone mass)
Possibility to use SARMs as monotherapy for the treatment of benign prostatic hyperplasia (BPH) with minimal side effects
SARMs also have great potential to be useful in the treatment of prostate cancer
SARMs are another option for the safe and effective treatment of women with breast cancer
SARMs may also be useful for patients with Alzheimer’s disease in the future
SARMS POSSIBLE SIDE EFFECTS, WORRIES
SARMs can suppress the body’s natural production of testosterone (but much softer and weaker than anabolic androgenic steroids). The likelihood and rate of reduction in testosterone production often depends directly on the dose and duration of SARM use, as well as the specific type of SARM.
The large number of counterfeits on the market (which do not actually contain SARM at all), more than half of the alleged SARMs offered on the Internet are counterfeit by fraudsters
Possible increased risk of heart attack or stroke in SARM, which lowers high-density lipoprotein (HDL) cholesterol levels
For some SARMs there are considerations or assumptions that they could be harmful to the liver (these are mainly SARMs RAD140 and YK11). To date, however, there are no clinical trials to provide reliable and relevant evidence
The long-term effects of SARM use have not yet been well tested
Please note that all our products, weapons and peptides are sold exclusively for scientific purposes. They are not food or food supplements and should not be used for purposes other than those for which they are intended. Any use outside of research is at your own risk.
ARE SARMS HARMFUL TO THE LIVER? SCIENCE VS. RUMORS
Opinions differ as to whether non-steroidal SARMs are harmful to the liver (or whether their use poses a risk to the liver). While one group of people will claim that SARMs do not pose any risk or burden to the liver at all, another group of people will claim that all SARMs are certainly or may be harmful to the liver. Many websites and people without knowledge on this issue will blindly or purposefully prefer the opinion of the first group (for example, especially fraudsters – fake sellers who always write only in their favor), on the contrary, enemies of SARMs, steroids and doping in general will be at all costs defends the opinion of the second group.
We always try to give people serious, as relevant, reliable and accurate information as possible from all available knowledge and resources (whether they suit us more or less). So let’s try to find the truth based on an objective view and existing scientific knowledge about SARM, or at least get as close as possible to it:
they would be very highly degraded and inactivated during the first passage through the hepatic metabolism and would not cause essentially any anabolic effects in the body. 17-alkylation involves the addition of an alkyl group (methyl or ethyl) to the alpha position of the carbon steroid of the steroid. Alkylation in this position prevents the main pathway of androgen inactivation – oxidation to 17-ketosteroid. This allows much of the steroid to avoid metabolic degradation of the liver for the first time. While 17-alpha alkylation is a very effective way to achieve steroid efficacy even when administered orally, a serious problem is that it places a heavy burden on the liver and can cause very serious liver damage.
However, non-steroidal SARMs are not methylated , so it is absolutely foolish to suspect that they damage the liver in a similar way to oral steroids (oxymetholone, methandrostenolone, androstanazole and others). Or, in the end, many critics of SARM will limit themselves to the fact that they have read somewhere that a coach or organization has said that SARM seriously damages the liver, so it must be applied and the issue is resolved and clear.
Some other people refer to a study in which (also) SARM Ostarine(MK-2866) has been used, during which an increase in liver enzymes, which usually signal liver damage, to more than three times the upper limit has been noted. The simplification and misinterpretation of the results of this study are probably behind the birth of information and claims that have spread on the Internet and suggest that SARM Ostarine is harmful to the liver. Again, however, this is manipulated and incorrect information, although it also applies to scientific sources and the research actually carried out, but its results are distorted, cut out and misinterpreted. Let’s take a closer look at the aforementioned scientific study, which found excessive stress or possible liver damage:
June 21, 2010 GTx, Inc. reports the results of clinical trials in which SARM Ostarine (GTx-024, MK-2866) and SARM MK-3984 have been used and tested. The 12-week randomized clinical trial evaluated Ostarin 3 mg and two doses of MK-3984 compared with placebo in 88 postmenopausal women. Total body weight was measured with DEXA at baseline and after 12 weeks, and physical performance was assessed at the same interval with a bilateral leg press. SARM Ostarine increased lean body mass and leg pressure in a self-conducted study evaluating Ostarine and another selective androgen receptor modulator, SARM MK-3984, in postmenopausal women.
After 12 weeks of treatment, Ostarine and MK-3984 significantly increased total net body weight. Compared with placebo, mean differences from baseline in lean body mass were observed with an increase of 1.54 kg (p value <0.001) for both Ostarin 3 mg and 50 mg MK-3984 SARMs and an increase of 1.74 kg ( p value <0.001) for 125 mg MK-3984. Increases in thigh muscle volume, as measured by MRI for Ostarine and MK-3984, were noted as early as week 4, with an effect that lasted until the end of the study. Treatment with Ostarine and MK-3984 resulted in increased leg muscle strength. The mean leg muscle strength after 12 weeks in patients treated with SARM Ostarine increased by 22 pounds from baseline. Ostarine and MK-3984 are tissue selective. Treatment in these women did not cause virilization, as there was no change in sebaceous gland volume, sebum secretion rate, or hair follicle gene expression. In addition, Ostarine and MK-3984 did not stimulate endometrial proliferation as measured by endometrial thickness.
“This is Ostarine’s third clinical trial to measure endpoints of lean body weight and physical performance, and SARM Ostarine is constantly demonstrating its ability to increase muscle mass and strength. We also continue to enjoy Ostarine’s safety profile, “said Mitchell Steiner, CEO.
In terms of safety, 7 patients treated with SARM MK-3984 were excluded from the study due to an increase in liver enzymes more than three times the upper limit of normal, while patients treated with SARM Ostarine showed no clinically significant increase in liver enzymes . Thus, the study concluded, in summary, 12-week treatment with Ostarin (3 mg) and MK-3984 had comparable efficacy on overall lean body mass, muscle strength, and tissue selectivity in postmenopausal women. And while SARM MK-3984 shows an increase in liver enzymes and therefore its further development is stopped, Ostarin is well tolerated without a clinically significant increase in liver enzymes .
The second case known to us, and also the first published report dealing exclusively with significant liver damage due to the “alleged” use of SARM, is the case report “Drug-related liver injury Alpha Bolic (RAD-140) and Alpha Elite (RAD-140 and LGD-4033) ”, published in June 2020. This report mentions the case of a 52-year-old man who stated that he was taking two preparations containing SARM , one of which is declared as RAD140 and the other is a combination of RAD140 and LGD-4033. This man asked the hepatology clinic to evaluate his elevated liver enzymes and jaundice. According to his statement, about 4 months before that he started taking 20 mg of RAD-140 (which was to be contained in the first preparation) daily for 4 weeks, and after stopping RAD140, he started taking 7.5 mg of RAD-140 and 5 mg of LGD-4033 (which should be included in the second preparation) daily for 3 weeks to build muscle. The total duration of use is 7 weeks. Shortly afterwards, he developed jaundice, upper right quadrant pain, itching and diarrhea. He also said he drinks bourbon and beer every day and uses marijuana.
The report evaluates and presents the results of the liver biopsy (liver biopsy is a medical examination that is performed to help diagnose liver disease, to assess the severity of liver damage). In summary, the results reported diffuse centrifugal canalicular cholestasis, marked ductular response, and mild lobular inflammation with rare necrotizing epithelioid granuloma suggesting liver damage due to the use of said SARMs. At the same time, liver enzymes were reported to return to normal approximately 3 months after the patient discontinued both drugs.
However. The veracity and significance of the allegation or unequivocal conviction that the liver damage found in that person was in fact caused by the use of SARM (or simply SARM) is challenged by several significant doubts. It is not possible to draw an appropriate and reliable conclusion based on a number of unverified important inputs , where their only source is the data reported by this patient and which have not been scientifically reviewed, verified and monitored at all (as should be the case). case in clinical trials). And just rely on the fact that this information and facts provided to patients hoped to be true, accurate and accurate.
What if, for example, this person covers up the fact that he is taking anabolic steroids with SARM? What bodybuilders who experiment with using SARM to increase muscle mass in bodybuilding forums often report that they do – that they combine SARM and steroids, expecting that this will lead to even greater muscle gain or that SARM have the ability to eliminate the negative effects of steroids to some extent if taken concomitantly. Or what if this person uses counterfeit fraudsters who instead of SARM contain mostly anabolic steroids or even no SARM at all? No one has studied and analyzed the substances (preparations) that the man used – what was actually their composition and content, which may not coincide at all with what is stated on their packaging that it really is in the content. SARMs are significantly more expensive compounds than anabolic steroids, which are cheap, which can be abused by suspicious people and unscrupulous fraudsters: To have minimal costs, they can include cheap anabolic steroids in the content instead of real SARM, which reduces their costs. to a minimum, but also ensures that the inexperienced client will see some of the effects to which he is directed and expected – ie. anabolic effects.
In both cases, this would completely change the true origin and main source of the detected liver damage, which may be caused by anabolic steroids rather than non-steroidal SARMs. In addition, regular alcohol consumption may have predisposed the patient to liver damage.
Concerns about steroid SARM YK11: Some scientists have suggested that the use of YK-11 may have potentially toxic effects on the liver. The reason is its chemical structure, which is derived from 5-α-dihydrotestosterone (DHT) and also similar to steroids, which are considered toxic to the liver. Due to the 4 methylated groups present in the structure of steroid SARM YK11, partial liver damage can indeed be expected. To date, no human clinical trials with SARM YK11 have been performed, so the answers to these questions about the safety of SARM YK11 have not yet been reliably given (the only source of information so far is only the experience of experimental users published and shared with various users). bodybuilding forums).
To date, we do not have reliable, relevant and reliably proven information that non-steroidal SARMs exist, which continue or are in our proposal, show a significant