SARMs

Nonsteroidal SARMs: Alternative to Androgenic-Anabolic Steroids
Discovered in the late 1990s, SARMs are performance-enhancing agents that stimulate anabolism (i.e., increase muscle mass and strength) and facilitate recovery from exercise.SARMs are not anabolic steroids; rather, they are synthetic ligands that bind to androgen receptors (ARs).Depending on their chemical structure, they function as full agonists, partial agonists, or antagonists.Each SARM-AR complex possesses a different conformation, and various tissues (e.g., skeletal muscle, bone, prostate, brain, skin, liver) display a unique pattern of AR expression.It is, thus, in a tissue-selective manner that SARMs mediate coregulators and transcription factors or signaling cascade proteins to promote anabolic activity.Nonsteroidal SARMs serve as an attractive alternative to anabolic-androgenic steroids because they have fewer limitations.In contrast to steroidal androgen preparations, SARMs display high oral bioavailability. Nonsteroidal SARMs also exhibit diminished androgenic activity because they are not metabolized to dihydrotestosterone (DHT) by 5 alpha-reductase, an enzyme that is highly expressed in androgenic tissues.They are also not metabolized to estrogen by aromatase.For these features combined, nonsteroidal SARMs have been deemed to be advantageous over their steroidal counterparts.Indeed, SARMs have shown substantial therapeutic promise for male contraception and in the treatment of osteoporosis, prostate cancer, sexual dysfunction, benign prostatic hyperplasia, Alzheimer's disease, muscular dystrophy, breast cancer, and muscle wasting associated with cachexia and sarcopenia.Fueled, at least in part, by the perception that SARMs are safer than anabolic steroids, recreational users are now leveraging the various anabolic profiles of different SARMs to selectively achieve results in terms of “bulking” and “cutting.” Bulking refers to a muscle-gaining phase that combines a weight-gain diet with intense weight training, whereas cutting refers to a fat-losing phase that combines adherence to a strict weight-loss diet with aerobic exercise and less-intense weight training. Anecdotal evidence claims that different SARMs yield different results in terms of bulking versus cutting, which is why bodybuilders and other fitness enthusiasts commonly use them in combination (or stacked) with each other.

Ostarine/Enobosarm/GTx-024/MK-2866/S-22
Ostarine is an orally bioavailable, nonsteroidal SARM that was developed by Gtx, Inc. in the late 1990s primarily for the treatment of muscle wasting and osteoporosis. Ostarine is the best clinically characterized SARM. The few published clinical trials have examined its potential for treating skeletal muscle deficits seen with stress urinary incontinence, breast cancer, non–small-cell lung cancer, and cancer-related cachexia. In clinical trials conducted thus far, a significant increase in total lean body mass was consistently observed, including in cancer patients. In some studies, there was also an accompanying decrease in total fat mass with no difference in total body weight.Common low-grade side effects included headache, nausea, fatigue, and back pain.Other observed effects were transient elevation in the alanine transaminase (ALT), reductions in high density lipoprotein (HDL), blood glucose, insulin, and insulin resistance.These altered parameters all returned to normal upon cessation of treatment. Information provided on personal blogs and commercial websites advises fitness and bodybuilding enthusiasts to supplement with ostarine at dose ranges from 10 mg to 30 mg for at least 12 weeks.These doses are times those studied clinically. Anecdotal evidence suggests that taking ostarine at these high doses over this extended time period can adversely lead to lowered testosterone levels.The side effects of decreased testosterone include reduced sex drive, erectile dysfunction, infertility, muscle weakness, loss of bone density, weight gain accompanied by increased body fat, insomnia, and depression.Potential drug-drug interactions between ostarine (and its major metabolite) and itraconazole, probenecid, celecoxib, and rosuvastatin have been examined with little evidence of clinically relevant drug interactions.According to one website promoting SARMs, it is recommended that SARMs be “stacked” for enhanced and differential benefits.Whether taking higher doses of multiple SARMs chronically poses a risk for adverse drug-drug interactions remains unknown.

Ligandrol/LGD-4033/VK5211
Ligandrol is another orally bioavailable SARM. Developed by Ligand Pharmaceuticals, there has been only one clinical trial involving the drug.20 In the placebo-controlled study, 76 healthy men were randomized to placebo or 0.1 mg, 0.3 mg, or 1.0 mg LGD-4033 daily for 3 weeks. The drug was well tolerated, with no serious adverse drug-related events. Hemoglobin, prostate-specific antigen, aspartate aminotransferase (AST), ALT, and QT intervals were not altered at any dose. At the 1.0 mg dose, follicle-stimulating hormone and free testosterone were significantly suppressed; there was no change in luteinizing hormone. Hormone levels returned to normal when the treatment was discontinued. Lean body mass increased dose-dependently, but there were no statistically significant changes in fat or appendicular skeletal muscle mass. Strength and stair-climbing speed and power trended toward a dose-dependent improvement but were not statistically significant. Total and low density lipoprotein (LDL) cholesterol did not change significantly from baseline at any dose. Although HDL increased at the 0.3 and 1.0 mg doses, it returned to normal upon discontinuation. Triglyceride levels decreased from baseline at all doses. Headache and dry mouth were the most common side effects.

Testolone/RAD-140
Testolone is a SARM used primarily for the treatment of muscle wasting and breast cancer. Developed by Radius Health, Inc., Testolone is reportedly still in first-stage clinical trials, with results expected later this year. Thus, little is currently known about its safety. One recent case report, however, describes significant liver injury in a 49-year-old man who had taken the drug (dose not reported).21 Elevations in bilirubin, AST, ALT, and creatinine indicated mixed hepatocellular-cholestatic liver injury. Liver histology also revealed inflammation. However, all liver tests had completely normalized at 12 months following his initial presentation. For gaining lean muscle mass and strength in the gym, SARMs users anecdotally recommended that Testolone be taken at 5 mg to 30 mg daily for 8 to 16 weeks.23 There is additional anecdotal evidence of side effects including sleeplessness and lethargy.

Andarine/GTx-007/S-4
To date, there are no human clinical studies with Andarine. In the fitness community and on various online forums, it is touted as a muscle-boosting supplement that elicits weight loss and promotes muscle building and repair.However, it is regarded as being comparatively weaker than other popular SARMs, so it is commonly stacked with other SARMs.Using Andarine by itself at 25 mg per day purportedly improves mood and general wellness, whereas increasing the dose to 50 mg per day only modestly boosts strength, lean mass, and fat burning. For bulking, it is recommended that Andarine (50 mg) be stacked with Testolone (10 mg) daily for 8 to 12 weeks.For strength, it is suggested that Andarine (50 mg) be stacked with Ligandrol (10 mg) daily for 2 to 3 weeks.For cutting, it is advised that it (25 mg) be stacked with Cardarine (20 mg, a non-SARM, paroxisome proliferator-activated receptor-delta agonist) daily for 12 weeks.For body recomposition (i.e., simultaneously losing fat and gaining muscle), it is recommended that Andarine (50 mg) be stacked with both Ostarine (25 mg) and Cardarine (20 mg) daily for 9 to 12 weeks.25 The primary side effects reported with Andarine are altered vision (i.e., yellow-tinged) and suppression of testosterone.