Enobosarm prevents loss of lean mass by 71% when using GLP-1 agonist for weight loss

– Study met primary endpoint: Enobosarm treatment resulted in statistically significant reduction in the loss of lean mass in subjects receiving WEGOVY (p=0.002) –

– Patients on Enobosarm on average lost 71% less lean mass than patients receiving WEGOVY alone –

– Patients on Enobosarm on average lost 27% more fat mass than patients receiving WEGOVY alone –

– Enobosarm improved body composition as mean total body weight loss was similar compared to subjects receiving WEGOVY alone –

– Enobosarm reduced the proportion of patients that lost clinically significant physical function versus subjects receiving WEGOVY alone –

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Very interesting! I’d be curious to see how this compares to just adding testosterone.

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Enobosarm, better known as Ostarine, has been around a while. Taking sarms like Ostarine and LGD 4033 tends to dramatically reduce a man’s natural testosterone production, so users tend to take sarms in addition to testosterone.

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Any idea if the data presented are from the 3mg vs the 6mg group (or both lumped together)?

These doses are significantly lower than what is typically taken recreationally (anywhere from 10mg to 30mg, from what I’ve read), so it’s exciting to see such impressive results from low doses, which should be markedly safer. I wonder how significant is the suppression of natural testosterone at a 3mg chronic dose of enobosarm? Does it still even need to be cycled?

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I wonder if taking spironolactone or bica to reduce androgen signalling [which I do b/c I detest testosterone] would accelerate muscle mass loss on glp1’s

Why would decreased androgen signaling inhibit muscle loss?

I’m not in the least bit surprised that it prevents muscle loss since Ostarine (that’s what people call it in the bodybuilding world) is anabolic, but I find it interesting that it is being studied under these conditions.

Generally, the only people who want to take SARMS (such as this one) are the “natural” guys who don’t want to shut down their natural testosterone production. I was under the impression the sides were not great but admittedly, I haven’t done too much of a deep dive into it yet. Some sarms have some nasty side effects that make them no safer than some anabolic steroids, but I think Ostarine is milder.

This is the drug that Ryan Garcia the boxer got suspended for taking after he knocked out Devin Haney last year.

Depends on the dosage of testosterone, but testosterone wins no contest at north of around 250mg per week when you get into supraphysiological and anabolic territory.

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Derek at moreplatesmoredates has a good write-up on it, including pros/cons:

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The trial was for 16 weeks, then you would stop, and have a suppressed test level and be worse off? Not to mention what it has done to estrogen or other health markers. It does not sound like a good idea to me.

They’re using some pretty low doses, so we’ll see what effect it has on those parameters once more data is released…

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Decreased Good Cholesterol (HDL)

The clinical data on this is inconsistent as there are some studies that show reductions in serum lipids (namely HDL and LDL) occurring in a dose dependent manner with Ostarine usage, as well as data showing only reductions in HDL levels (otherwise known as “good cholesterol”) [R, R].

We at least know for sure that Ostarine has a negative effect on HDL levels, which is notable as this is a common side effect of all traditional anabolic steroids, and other SARMs.

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On the other hand, so-called “good” cholesterol appears to worthless when it comes having any causal role in ameliorating CVD. I really only care about ApoB and Lp(a) these days, so hopefully ostarine will have minimal if any effect on the important lipids at low doses.

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Enobosarm (GTx-024) is an investigational drug that acts as a selective androgen receptor modulator (SARM). It is currently being studied as a potential treatment for muscle wasting conditions, such as cancer cachexia and age-related sarcopenia. [1, 2, 3, 4, 5]

Mechanism of Action: [6]

Enobosarm binds to androgen receptors in muscle tissue, mimicking the effects of testosterone. This leads to an increase in muscle protein synthesis and a decrease in muscle protein breakdown, resulting in muscle growth and strength. [7, 8, 9, 10]

Potential Benefits: [11]

  • Muscle wasting: Enobosarm has shown promising results in clinical trials for treating muscle wasting in patients with cancer and other conditions. It has been found to increase lean body mass and improve physical function. [2, 12]
  • Bone health: Studies suggest that enobosarm may also improve bone mineral density and reduce the risk of fractures. [13]
  • Body composition: Enobosarm may help reduce body fat while preserving muscle mass. [13]

Safety Concerns: [14]

While enobosarm appears to be generally well-tolerated, some potential side effects have been identified, including: [15]

Hot flashes, Increased cholesterol levels, Liver damage (rare), and Reproductive toxicity (in animals). [16, 17]

Current Status: [18]

Enobosarm is currently in Phase 3 clinical trials for the treatment of muscle wasting in cancer patients. It is not yet approved for any medical use. [4, 18, 19, 20]

Ostarine, also known as Enobosarm, GTx-024, and MK-2866, is a selective androgen receptor modulator (SARM) that has gained significant attention in both clinical research and the bodybuilding community. SARMs like Ostarine are designed to stimulate androgen receptors selectively, offering a higher anabolic activity (muscle and bone growth) relative to androgenic activity (development of male characteristics). This selectivity makes Ostarine a potential candidate for treating muscle and bone wasting diseases while minimizing the side effects associated with traditional anabolic steroids.

Mechanism of Action
Ostarine works by selectively binding to androgen receptors, primarily in muscle and bone tissues. This selective binding allows for significant anabolic effects with reduced androgenic side effects compared to testosterone and other steroids. The ideal anabolic agent should be selective for muscle and bone, orally bioavailable, and avoid converting to DHT or estrogen, which are associated with side effects like prostate issues and gynecomastia. Ostarine aims to meet these criteria, making it a promising alternative to traditional anabolic steroids.

Clinical Trials and Findings
Ostarine has been extensively studied in clinical trials, with over 1500 subjects treated in 27 completed or ongoing trials. Dosages in these trials have ranged from 0.1 mg to 100 mg per day. Notably, Ostarine was the first drug to be placed on the FDA’s fast-track development program for the prevention and treatment of muscle wasting in cancer patients.

In a significant Phase III trial, 325 lung cancer patients were given either 3 mg of Ostarine per day or a placebo. While the trial did not meet its primary endpoints for preventing muscle loss in the overall population, it did show that Ostarine significantly increased or maintained lean body mass (LBM) compared to the placebo. This finding highlighted Ostarine’s potential anabolic effects, even at low doses.

Another Phase II trial focused on Ostarine as a treatment for stress urinary incontinence in women, but the results did not achieve statistical significance. However, a different Phase II trial evaluated Ostarine as a form of hormonal therapy for women with estrogen receptor-positive (ER+) and androgen receptor-positive (AR+) breast cancer. This trial, using dosages of 9 mg and 18 mg daily, met its primary efficacy endpoint, demonstrating clinical benefit response (CBR).

Dosage and Usage
In clinical trials, dosages ranged from 0.1 mg to 100 mg per day. In the bodybuilding community, dosages typically range from 10 to 25 mg per day. Anecdotal reports suggest gains of 5-10 pounds of lean mass are common with these dosages.

Side Effects
Decreased HDL Cholesterol:
Ostarine has been shown to reduce HDL cholesterol levels, a common side effect with anabolic steroids and other SARMs.

Testosterone Suppression:
Ostarine suppresses LH and FSH, leading to decreased testosterone levels in a dose-dependent manner. It also lowers SHBG levels. While suppression is less than that of traditional steroids, it is still significant.

Estrogen Imbalance:
Ostarine does not aromatize into estrogen but can create an imbalance by suppressing natural testosterone and occupying androgen receptors, potentially leading to elevated or decreased estrogen levels. Symptoms of high estrogen include acne, erectile dysfunction, low libido, lethargy, and gynecomastia. Symptoms of low estrogen include dull orgasms, dry skin, dehydration, and mood swings.

Androgenic Activity:
Ostarine exhibits a dose-dependent increase in androgen activity, although to a lesser extent than traditional steroids. This can still lead to androgen-related side effects, albeit reduced.

Hair Loss:
While Ostarine generally does not cause significant androgenic alopecia at common dosages, hormonal fluctuations can lead to temporary shedding.

Liver Toxicity:
Clinical trials showed short-lived increases in ALT levels in some subjects, but these resolved while continuing the dosage. At higher recreational dosages, some liver enzyme elevation is possible but likely resolves after discontinuation.

Lack of Aromatization and 5-Alpha Reduction:
Ostarine does not aromatize or undergo 5-alpha reduction, which contributes to its muscle-selective profile and lack of water retention, reducing cardiovascular stress compared to steroids like Anadrol.

Half-Life and PCT
Ostarine has a half-life of 23.8 hours, allowing for once-daily dosing. Post-cycle therapy (PCT) is recommended after an Ostarine cycle to restore natural testosterone levels. PCT should start the day after the last Ostarine dose due to its half-life.

Conclusion
Ostarine is a promising SARM with significant potential for treating muscle and bone wasting diseases due to its selective anabolic activity and reduced androgenic side effects. While it has shown positive results in increasing lean body mass in clinical trials, more research is needed to determine its long-term safety and efficacy. In the bodybuilding community, Ostarine is valued for its ability to enhance muscle growth and strength with fewer side effects than traditional steroids. However, users should be aware of potential side effects such as HDL cholesterol reduction, testosterone suppression, and estrogen imbalance. Proper PCT is crucial to mitigate these effects and maintain health.

Enobosarm has minimal bone marrow stimulating effects compared to testosterone, which is a positive if you’re suffering from polycythemia.

https://www.researchgate.net/figure/Changes-in-hematocrit-following-testosterone-or-enobosarm-treatment-Mean-changes-from_fig3_259651871

Which begs the question….how much of an issue is decreased HDL if LDL is also low?

Do we know if there are independent risks associated with low HDL in the absence of high LDL?

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