SARMs
What is SARMs:
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Mechanisms of SARMs:
The androgen receptor (AR) is a member of nuclear receptors. Those receptors that bind mineralocorticoid, estrogen, glucocorticoid, and androgen [6]. The AR exists in male and female genitalia, liver, seminal vesicle, skin, and brain, sebaceous glands, prostate, cardiac, bone, skeletal muscle, smooth muscles. Those AR are activated mainly by testosterone along with a wide range of growth factors, peptides, and endogenous [6]. The idea of selective AR activators was originated from the development of selective estrogen receptor modulators (SERMs) in 1990s, where it is been used to treat cancer. In 1998, SARMs were initially released from a class of molecules called bicalutamides [7]. The term modulator was chosen to these substances because of their capability to range from full agonists in some tissues to partial agonists.
SARMs are taken orally and can have half-life of hours or even days. However, the affect of these substances may vary according to some factors such as sex, age, and hormonal status [8]. Several SARMs have been demonstrated to have anabolic/androgenic ratio of 20:1 in comparison to testosterone which just has ratio 1:1. However, the mechanisms of SARMs-action are still not clear and most of the facts about SERMs has been transferred to SARMs.
Benefits of SARMs:
In [1], the study showed that SARMs lead to increase gastrocnemius muscle weight and bone mineral density and bone biomechanical properties in ovariectomized female rates . In [2], the study showed significant improvements in lean body mass (LBM) in healthy men and sex drive.
Side Effects:
The side effect of SARMs is the same as in testosterone, but the degree is much less pronounced [3] [4] [5]. Several studies showed that a decrease in high-density lipoprotein, hepatotoxicity with increased liver enzymes. In addition, there are alterations in the plasma level of anabolic hormones involved in the hypothalamic-pituitary-gonadal axis.
References:
[1] Komrakova M, Furtwängler J, Hoffmann DB, Lehmann W, Schilling AF, Sehmisch S. The selective androgen receptor modulator ostarine improves bone healing in ovariectomized rats. Calcified Tissue International. 2020 Feb;106(2):147-57.
[2] Basaria S, Collins L, Dillon EL, Orwoll K, Storer TW, Miciek R, Ulloor J, Zhang A, Eder R, Zientek H, Gordon G. The safety, pharmacokinetics, and effects of LGD-4033, a novel nonsteroidal oral, selective androgen receptor modulator, in healthy young men. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences. 2013 Jan 1;68(1):87-95
[3] Dalton JT, Barnette KG, Bohl CE, Hancock ML, Rodriguez D, Dodson ST, Morton RA, Steiner MS. The selective androgen receptor modulator GTx-024 (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women: results of a double-blind, placebo-controlled phase II trial. Journal of cachexia, sarcopenia and muscle. 2011 Sep;2(3):153-61.
[4] Dobs AS, Boccia RV, Croot CC, Gabrail NY, Dalton JT, Hancock ML, Johnston MA, Steiner MS. Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial. The lancet oncology. 2013 Apr 1;14(4):335-45.
[5] Papanicolaou DA, Ather SN, Zhu H, Zhou Y, Lutkiewicz J, Scott BB, Chandler J. A phase IIA randomized, placebo-controlled clinical trial to study the efficacy and safety of the selective androgen receptor modulator (SARM), MK-0773 in female participants with sarcopenia. The journal of nutrition, health and aging. 2013 Jun;17(6):533-43.
[5] Gao W, Bohl CE, Dalton JT. Chemistry and structural biology of androgen receptor. Chemical reviews. 2005 Sep 14;105(9):3352-70.
[6] Dalton JT, Mukherjee A, Zhu Z, Kirkovsky L, Miller DD. Discovery of nonsteroidal androgens. Biochemical and biophysical research communications. 1998 Mar 6;244(1):1-4.
[7] Neil D, Clark RV, Magee M, Billiard J, Chan A, Xue Z, Russell A. GSK2881078, a SARM, produces dose-dependent increases in lean mass in healthy older men and women. The Journal of Clinical Endocrinology & Metabolism. 2018 Sep;103(9):3215-24.
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