How do SARMs work

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SARMs have been receiving a lot of attention in the medical community over the past few years, as well as with bodybuilders, athletes, and fitness & supplement gurus, although in the U.S. their only official or sanctioned use is within medicine. The buzz and excitement comes from the ability of SARMs to dramatically build muscle and improve overall physiological function in muscle and bone without the array of adverse effects of anabolic-androgenic steroids (AAS), such as liver toxicity, enlargement of the prostate, heart, and other organs, and estrogen-related side-effects.

This article compares the effects of SARMs vs traditional steroids and explores the current state of use and acceptance of this new drug class since first discovered in the 1940’s. SARMs are not miracle drugs and are not without side-effects and risks. A growing body of evidence, however, shows sound scientific reasoning why these drugs are quickly gaining popularity.

less side effects?

Why All the Excitement with SARMs?

The role of steroids

To understand the new hype around SARMs and why pharmaceutical companies are investing small fortunes in their development it’s necessary to take a closer look at the role traditional steroids, such as testosterone, have played in the treatment of disease and overall health and human fitness over the past several decades.

Anabolic androgenic steroids (AAS) are steroidal androgens with anabolic (muscle-building) and androgenic (virilizing) effects. First synthesized in the 1930s, they are currently used in medicine to stimulate muscle growth and appetite, to induce male puberty, treat muscle wasting conditions such as cancer and AIDS, and for many other health uses.

In the decades following their inception steroids saw increased use in bodybuilding and general athletics as performance enhancers, and this trend continues to increase. Stigma around the personal and non-medical use of steroids continues to decrease, and more and more doctors, including those in sports medicine, are also legitimizing the daily use of steroids for low testosterone, injury recovery, and other preventative and remedial treatments.

Despite the numerous benefits of steroids and their increased acceptance, they have a problem: steroids are biologically dangerous — or, at best, unsafe. Long-term administration of exogenous Testosterone, even at mild doses cause, and even milder AAS such as Anavar, are associated with a host of health problems:

Some of the side effects of steroids..

- Enlargement of heart and other organs (causing early failure)

- Aromatization into estrogen and estrogen-related side-effects

- Known and unknown side-effects of prolonged SERM use; Selective Estrogen Receptor Modulators are used to counteract increased estrogen levels

- Enlargement of the prostate, causing urination problems, BHP, or worse

- Gynecomastia (“gyno”) and early balding in males

- Androgenic/virilizing side effects such as acne, hair thinning, excessive body hair, deepening voice, especially unwanted in females

- Suppression of natural Testosterone production

- Loss of sex drive

- Hypogonadism (shrinking of the testicles)Many other conditions related to endocrine system and hormonal imbalance

- Kidney and liver toxicity and damage (with orally-administered steroids)

- Cardiovascular problems, including heart attack

“There is a wild scenario of AAS side effects which affect, mainly, the cardiovascular system, the liver, the kidney, the musculoskeletal and the endocrine systems. It has become more and more evident anabolic steroids are very harmful to health. The mechanisms involved in the genesis of these toxic effects are not yet fully clarified,” conclude researchers in Side effects of AAS abuse: an overview.

Despite these risks, there is a clear and present need for steroidal drugs in medicine, and a growing desire for their personal use, albeit unsanctioned or even illegal in some countries, as performance enhancers. Clearly a safer alternative to AAS is needed, and early evidence suggests SARMs are filling that role.

SARMs work selectively

The difference

They activate only the AR pathways involved in skeletal muscle hypertrophy (growth), but not the prostate gland or other organs. Some Selective Androgen Receptor Modulators also work in bone tissue, increasing mineral density, strengthening and hardening the bones.

SARMs over Steroids

Thus, compared to the anabolic-androgenic ratio (desirable anabolic effects, compared to undesirable androgenic, virilizing effects), SARMs anabolic/androgenic ratio is, relatively, much higher, or favorable. For example, compared to a 1:1 baseline ratio with testosterone, RAD-140–a very powerful 2nd-gen SARM–is shown to present biologically at a ratio of 90:1 (source). This means that RAD-140 is at least as powerful as testosterone, but significantly less androgenic, showing almost no virilizing effects.

We know that dihydrotestosterone (DHT), an endogenous androgen sex steroid and hormone, into which AAS easily converts, is a critical mediator of prostate growth. This unwanted enlargement effect of AAS on the prostate may lead to a condition known as benign prostatic hyperplasia, commonly referred to as enlarged prostateUnlike AAS, SARMs do not easily convert to DHT, which eliminates this risk to the prostate, as well as other undesirable side effects associated with steroidal conversion to DHT, such as permanent hair loss.

Additionally, SARMS do not cause “gyno” or other estrogen-related side-effects the way testosterone and other AAS do. Prolonged use of exogenous steroids causes a biologial feedback loop: a surge in excess androgens that signals the elevation and action of the aromatase enzyme that, in turn, signals testosterone to morph into estradiol/estrogen.

Despite FDA warnings, growing evidence suggests that even the current more powerful generation of oral SARMs do not cause kidney or liver damage, since they do not mutate the way AAS do when passing through these organs on their way to their intended targets. On the other hand, most oral steroids are clearly associated with liver damage even at normal doses, and especially with prolonged usage. “We can only conclude that AAS can lead to peliosis hepatis and cholestatic jaundice when used in the normal therapeutic dosages” (Liver pathology associated with the use of anabolic-androgenic steroids).

Use of steroids, especially prolonged use at higher doses, can often cause high-blood pressure, high cholesterol levels and associated heart problems, as well as chemical addition. The degree to which SARMS may similarly cause these conditions is unknown, but the targeted nature and structural differences of SARMS compared to AAS almost certainly reduces their risks.

Then and now

SARMs Evolution

SARMs are getting better..

“At the doses that have been tested, the first generation SARMs induce modest gains in lean body mass… of 1.0 to 1.5 kg in fat-free mass… over 4–6 weeks… contrasted with 5–7 kg gains with testosterone enanthate. It is possible next generation of SARM molecules will have greater potency and selectivity than the first generation” (Selective Androgen Receptor Modulators (SARMs) as Function Promoting Therapies). This prediction came true, as first gen SARMs, such as Ostarine (MK-2866), are now considered fairly mild in their capacity to rapidly increase muscle volume compared to newer, more powerful, and more anabolic SARM compounds such as Ligandrol (LGD-4033) and Testalone (RAD-140).

SARMs win all day long

Like steroids, SARMs exhibit powerful and biologically-beneficial properties that excite researchers and practitioners in the medical community. Additionally, and despite FDA warnings and classification as “research chemicals”, bodybuilders and athletes looking to increase endurance or gain a competitive edge in sports have also adopted widespread use of SARMs.

The primary driver of the buzz and increased global usage of SARMs stems from their ability to perform the same or similar medical and performance-enhancing feats as traditional AAS (steroids), without the myriad negative physiological effects associated with prolonged steroid use.

The future of SARMs looks bright. They are in various stages of testing and production by manufacturers, and evaluation by the FDA and similar health agencies in other countries. The new ubiquity of Ostarine, Ligandrol, and other SARMs in the news has further increased awareness and driven higher usage of these powerful compounds.

Modern Science

There you go

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