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SARMs Affect On Thyroid Markers

Do SARMs like GW-501516, MK-2866 or S-4 affect thyroid markers?

Unfortunately, there is not much literature that directly addresses the effect of GW-501516, MK-2866, or Andarine S-4 on various thyroid markers (eg.Thyroid-stimulating hormone [TSH], Free T3, Total T3 or Free T4). Let’s break this down by each compound:

GW501516: An activator of PPARδ

In normal, primary thyroid cells (i.e. cells biopsied from a human), GW-501516 increased thyroid cell proliferation (similar to the known actions of TSH [1], [2]), but GW501516 did not change the expression levels of PPARδ itself, and the authors did not examine thyroid hormone levels [3]. However, there are instances in which GW501516 can act mimic the action of T3 hormone due to “crosstalk” between PPAR signaling and thyroid hormone signaling, as illustrated below:

Nuclear receptors crosstalk targeting metabolic pathways

Fig. 1.  Nuclear receptors crosstalk targeting metabolic pathways. Thyroid hormone signaling involves thyroid hormone receptor crosstalk with other nuclear hormone receptor including PPAR, for the transcriptional control of metabolic gene expression. Although nuclear receptor interaction is an intricate mechanism that needs further investigations, it could be explained at least by the competition to bind similar DNA response elements (RE) on common metabolism-related target genes and to form binding partners with RXR that exists in limiting amounts. Also, another interaction could be a reciprocal effect on their expression levels. Dashed line: direct or indirect crosstalk between signaling pathways. Adapted from [4]

 MK-2866 (GTx-024, Enobosarm): 

Although there is no direct data on the ability of MK-2866 to modulate thyroid hormone levels, there is some indirect evidence to consider. In one study, MK2866 dosing did not change levels of luteinizing hormone (LH) in men [5]. This is interesting to note since LH is a potent binding partner of the thyroid stimulating hormone (TSH) receptor [6]. In another recent Phase II clinical study, MK2866 dosing was associated with hyperthyroidism in 6% of patients, but this type of study cannot provide sufficient evidence to demonstrate causality [7].

Andarine S-4 (GTx-007):

Unfortunately there is no preclinical or clinical data which reports the effect of Andarine on any thyroid hormone levels.

Affect On Thyroid Markers Conclusion

Overall, there does not appear to be strong evidence that GW-501516, MK-2866 or Andarine S-4 modulates thyroid hormone levels.

*The information herein is for educational and informational purposes only. THE PRODUCTS DESCRIBED HEREIN ARE FOR RESEARCH USE ONLY. For use in animal studies, all research must be conducted with oversight from the appropriate Institutional Animal Care and Use Committee (IACUC) following the guidelines of the Animal Welfare Act (AWA).

  • [1] T. Kimura, A. Van Keymeulen, J. Golstein, A. Fusco, J. E. Dumont, and P. P. Roger, “Regulation of thyroid cell proliferation by tsh and other factors: A critical evaluation of in vitro models,” Endocrine Reviews. 2001.
  • [2] C. Maenhaut, D. Christophe, G. Vassart, J. Dumont, P. . Roger, and R. Opitz, Ontogeny, Anatomy, Metabolism and Physiology of the Thyroid. 2000.
  • [3] L. Zeng, Y. Geng, M. Tretiakova, X. Yu, P. Sicinski, and T. G. Kroll, “Peroxisome proliferator-activated receptor-δ induces cell proliferation by a cyclin E1-dependent mechanism and is up-regulated in thyroid tumors,” Cancer Res., 2008.
  • [4] S. Kouidhi and M. S. Clerget-Froidevaux, “Integrating thyroid hormone signaling in hypothalamic control of metabolism: Crosstalk between nuclear receptors,” International Journal of Molecular Sciences. 2018.
  • [5] J. T. Dalton et al., “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,” J. Cachexia. Sarcopenia Muscle, vol. 2, no. 3, pp. 153–161, 2011.
  • [6] M. Yoshimura, J. M. Hershman, X. P. Pang, L. Berg, and A. E. Pekary, “Activation of the thyrotropin (TSH) receptor by human chorionic gonadotropin and luteinizing hormone in Chinese hamster ovary cells expressing functional human TSH receptors,” J. Clin. Endocrinol. Metab., 1993.
  • [7] J. S. Lee-Bitar et al., “A phase II clinical trial of pembrolizumab and selective androgen receptor modulator GTx-024 in patients with advanced androgen receptor-positive triple-negative breast cancer.,” J. Clin. Oncol., vol. 37, no. 15_suppl, pp. 1069–1069, May 2019.

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