SARMs are under continuous development
SARMs display tissue-selective androgen activation, unlike AAS which bind with androgens throughout the body, adversely affecting untargeted tissues such as prostate, heart, or other organs (source). This tissue-selectivity makes SARMs ideal for improvement of musculoskeletal physical function, as well as bone health, and continues to drive clinical research and testing of these regenerative and restorative drugs.
See this page on alternative to anabolic–androgenic steroids (AAS) for more info.
MK-2866, typically referred to as Ostarine, is an investigational SARM currently developed by pharmaceutical company GTx Incorporated for the treatment of muscle wasting and osteoporosis. Ostarine can be bought online and is currently the most researched SARM in existence.
MK-2866 Clinical Trials
“Selective androgen receptor modulators (SARMs) differentially bind to androgen receptors depending on each SARM’s chemical structure. As a result, SARMs result in anabolic cellular activity while avoiding many of the side effects of currently available anabolic steroids. SARMs have been studied in the treatment of breast cancer and cachexia and have also been used as performance enhancing agents.” (source: Selective Androgen Receptor Modulators (SARMs) – Current Knowledge and Clinical Applications).
In a 2011 a 12-week double-blind, placebo-controlled phase II clinical trial was conducted to evaluate Ostarine in 120 healthy and women. 120 subjects were randomized to Ostarine 0.1, 0.3, 1.0 or 3.0 mg versus placebo over 3 months. At the end of the trial, a significant increase in total lean body mass and improvement in measures of physical function were measured in the 3-mg group (source: The selective androgen receptor modulator GTx-024 (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women).
Finally, in two separate Phase III trials of Ostarine, 325 patients with stage III or IV NSCLC and muscle wasting were randomized to Ostarine 3 mg versus placebo for 3 months, with primary endpoints including total lean body mass and improvement in physical function. Again, the researchers found a Significant increase in total lean body mass compared with placebo (GTx Announces Late Breaker Presentation on Results from the Two Phase 3 POWER Trials of Enobosarm).
LGD-4033, typically referred to as Ligandrol, is an investigational SARM discovered by Ligand Pharmaceuticals and currently under development by Viking Therapeutics for the treatment of conditions such as muscle wasting and osteoporosis.
LGD-4033 Clinical Trials
Researchers evaluated the safety of Ligandrol in a Phrase I trial that involved 76 healthy men (21–50 years). These men were randomized to placebo or 0.1, 0.3, or 1.0 mg LGD-4033 daily for 21 days. The researchers concluded by saying that Ligandrol was well tolerated (The Safety, Pharmacokinetics, and Effects of LGD-4033, a Novel Nonsteroidal Oral, Selective Androgen Receptor Modulator, in Healthy Young Men).
“LGD-4033 administration was associated with dose-dependent suppression of total testosterone, sex hormone–binding globulin, high-density lipoprotein cholesterol, and triglyceride levels. follicle-stimulating hormone and free testosterone showed significant suppression at 1.0-mg dose only. Lean body mass increased dose-dependently, but fat mass did not change significantly. Hormone levels and lipids returned to baseline after treatment discontinuation,” the researchers noted.
In 2017, Viking Therapeutics completed enrollment in Phase II trial of Ligandrol in patients recovering from hip fracture. Viking Therapeutics plans to administer once-daily doses of 0.5 mg, 1.0 mg, 2.0 mg, or placebo for 12 weeks to 108 patients to study the effects of Ligandrol on lean body mass, functional performance, and quality-of-life, among other things (source).
MK-677, typically referred to as Ibutamoren, a potent non-peptide agonist of the ghrelin receptor and a growth hormone secretagogue. Ibutamoren mimics the growth hormone (GH)-stimulating action of the endogenous hormone ghrelin, which regulates appetite and plays a significant role in regulating the distribution and rate of use of energy.
MK-677 Clinical Trials
The effects of MK-677 on the growth hormone (GH)-insulin-like growth factor I axis were studied during a phase I and II trial involving 32 healthy subjects. The subjects received placebo or 2, 10, or 25 mg MK-677, orally, once daily for 2 separate study periods of 14 and 28 days. Once daily treatment of older people with oral MK-677 for up to 4 weeks at a dose of 25 mg/day restored serum IGF-I concentrations to those of young adults (Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretogogue (MK-677) in healthy elderly subjects).
During a 1999 trial whose purpose was to determine the effect of chronic administration MK-677 on serum IGF-I and markers of bone turnover in 187 elderly adults, 30 subjects received either placebo for 4 weeks or 25 mg of MK-677 daily for 2 weeks followed by 50 mg daily for 2 weeks. The researchers noted the ability of MK-677 to significantly increase serum IGF-I levels stimulates bone turnover in elderly subjects (Oral administration of the growth hormone secretagogue MK-677 increases markers of bone turnover in healthy and functionally impaired elderly adults).
RAD-140, typically referred to as Testalone, is an a potent, orally highly-bioavailable, nonsteroidal SARM currently under development by Radius Health for the treatment of conditions such as muscle wasting and breast cancer.
RAD-140 Clinical Trials
Several studies have been conducted showing impressive and muscle-selective anabolic activity. A 2010 study with monkeys produced lean muscle mass weight gain of greater than 10% in just 28 days at a dose of just 0.1 mg/kg, as well as significant reduction in fat tissue. More recently, RAD-140’s inhibiting effect on the growth of the androgen/estrogen receptor has found it to be a very promising drug in the fight against breast cancer. An exciting study in 2014 showed RAD-140 may provide neuroprotective actions and resilience to neurodegenerative diseases, which may indicate an ability to assist in prevention and mitigation of Alzheimer’s and related diseases.
YK-11 is a myostatin inhibitor, in the form of a synthetic SARM, with significant anabolic activity demonstrated during an in vitro study (Selective androgen receptor modulator, YK11, regulates myogenic differentiation of C2C12 myoblasts by follistatin expression).
YK-11 Clinical Trials
Animal and human trials are lacking for YK-11.
It is reported however, that accompanied by follistatin, YK11 causes increased production of myogenin, myogenic factor 5 (Myf5) and myogenic differentiation factor (MyoD). These myogenins cause increases in differentiated muscle cells at a higher rate than DHT or Testosterone alone.
Because in vitro studies are performed with microorganisms, cells, or biological molecules outside their normal biological context, they may not fully or accurately predict the effects on a whole organism.
GW-501516, typically referred to as Cardarine, is a PPARδ receptor agonist. It was invented in a collaboration between Ligand Pharmaceuticals and GlaxoSmithKline in the 1990s as a drug candidate for metabolic diseases and cardiovascular diseases.
GW-501516 Clinical Trials
A 2012 study showed this SARM capable of assisting with repairing liver damage. During animal testing Cardarine was found to cause cancer cells to develop when given to rats at daily ultra-doses of 3 mg per kg of body weight (source). A few clinical trials have also been performed on cardarine and its effects on fat metabolism. Despite pressimistic findings in rodents, “no significant adverse effects were reported in any of the human studies, which may reflect the considerably lower doses administered (up to 10 mg/day) for much shorter periods of time (up to 12 weeks)” (source).
S-4, typically referred to as Andarine, is an investigational SARM developed by GTx Incorporated for treatment of conditions such as muscle wasting, osteoporosis, and benign prostatic hypertrophy. Although Andarine is known to have a similar chemical structure to Ostarine (the chemical structure of Ostarine has never been publicly disclosed), the two drugs are not exactly the same.
S-4 Clinical Trials
In various trials, S-4 treatment was shown to decrease body fat and increase body strength. GTx completed phase I studies on both Andarine and Ostarine and found both drugs equally safe. According to Nonsteroidal Selective Androgen Receptor Modulators (SARMs): Dissociating the Anabolic and Androgenic Activities of the Androgen Receptor for Therapeutic Benefit, “Ostarine was selected for advanced clinical development based on corporate strategy,” while all testing of Andarine was ceased.
Stenabolic was developed to help better understand the circadian rhythm, your body’s internal 24-hour clock.
Rev-erbs help stabilize the internal clock by turning off BMAL1. SR9009 reportedly improves the effect of our body’s rev-erbs, which leads to a whole host of interesting benefits that have to due with energy output and red blood cell modulation.
SR-9009 Clinical Trials
While there haven’t been any tests on humans, animals have seen many exceptional benefits from this process, and for that reason, we’ve seen a growth in SR9009 becoming a popular research material.
So we know that the Rev-erb proteins impact the circadian behavior of mice which impacts their sleeping patterns, but how does that affect humans? We don't know yet if we look at clinical trials.
It’s important to understand that circadian rhythm and energy go hand in hand. If you have a regulated sleeping pattern, you generally have more energy throughout the day to accomplish things. One significant reported benefit of SR9009 is it attempts to take a natural approach to increase your strength by trying to optimize sleep.
Here are some of the ways the Rev-erb works:
1. In mice, it shut down genes that create glucose without altering insulin sensitivity. It also reversed the process by turning off genes that create fat cells, which can reduce weight gain and help eliminate fat.
2. Since Rev-erb encourages fat burning, it increases the mitochondria activity and promotes the new generation while eliminating the old. This will help burn fat faster and produce newer, more healthy cells in the body.
3. Rev-erb turns fat-storing genes off, which reduces triglyceride production.
S23 is a non-steroidal Selective Androgen Receptor Modulator (SARM) from GTx Inc. Despite being a relatively new SARM, S23 is quite popular in the bodybuilding world. This popularity is mostly thanks to its ability to help you bulk, get stronger while at the same time reducing fat.
S-23 Clinical Trials
Anecdotal evidence suggest S-23 can be effective for treating issues like muscle wasting and osteoporosis. However, the clinical research on these drugs is lacking and no human trials have been conducted to date.
Aside from its weightlifting benefits, another reason for the interest in S23 is its potential use as a male contraceptive.
This substance caused infertility in rats while they were taking S23, though their reproductive abilities returned to normal once they stopped taking it. In humans, it could lower sperm count enough to be an effective contraception.
Note: the effective birth control dosage of S23 is pretty narrow, meaning too high an S23 dosage could have the opposite effect and support sperm production - but further studies are needed to confirm this
There was a small trial conducted analysing the effects of female libido in rats.
It is not uncommon following the menopause for women to experience a fall in sexual desire and arousal (due to natural decreases in sex hormones).
Normally, this lack of sexual motivation (HSDD) is treated with testosterone; however, this can lead to further problems such as an increased risk of heart disease and breast cancer.
S23 could potentially create a positive boost in sexual desire with none of the risks commonly associated with testosterone. When given to postmenopausal rats, S23 helped to increase their sexual motivation, whilst maintaining the size and lining of their uterus.