S4, also known as Andarine, was developed by GTX, inc for the treatment of muscle wasting, osteoporosis, and benign prostatic hypertrophy . In a rat model, 1.6mg/kg bodyweight has been shown to significantly increase bone mineral density, lean mass and body composition. 3mg/kg/day demonstrated significant increases in muscle mass [1, 2]. In the ovariectomized rat model for osteoporosis, 3 and 10mg/kg/day were administered for 8 weeks and both groups showed improvements in whole body and trabecular bone mineral density, cortical content, and decreased body fat . Primary culture of bone marrow osteoprogenitor cells showed that S4 was more anabolic than DHT for promoting osteoblast formation, further confirming its anabolic potential in bone tissue [1, 3].
Partial agonists like S4, in the presence of full agonists like Testosterone or DHT can behave as competitive antagonists depending on the tissue . S4 has been shown to decrease prostate weight with similar efficacy to 5mg/kg finasteride without affecting levator ani muscles. This suggests that SARMS may be an ideal candidate for reducing prostate size much like SERMs are used to decrease breast tissue . S4 was ultimately abandoned in clinical trials because subjects administered higher doses experienced some blurred vision at night accompanied by a yellowish tint.
S4 Investigational Benefits Summary:
1. Increases muscles mass and bone mineral density
2. Decreases body fat
3. Potential to protect the prostate gland from hypertrophy
1. Hott JL, Borkman RF (November 1989). “The non-fluorescence of 4-fluorotryptophan”. The Biochemical Journal. 264 (1): 297–9. doi:10.1124/jpet.102.040840. PMC 1133577. PMID 2604714
2. Gao W, Reiser PJ, Coss CC, Phelps MA, Kearbey JD, Miller DD, Dalton JT. Selective androgen receptor modulator treatment improves muscle strength and body composition and prevents bone loss in orchidectomized rats. Endocrinology. 2005;146:4887–4897.
3. Kearbey JD, Gao W, Miller DD, Dalton JT. Selective androgen receptor modulators inhibit bone resorption in rats. AAPS PharmSci. 2003;5
4. Gao W, Kearbey JD, Nair VA, Chung K, Parlow AF, Miller DD, Dalton JT. Comparison of the pharmacological effects of a novel selective androgen receptor modulator, the 5alpha-reductase inhibitor finasteride, and the antiandrogen hydroxyflutamide in intact rats: new approach for benign prostate hyperplasia. Endocrinology. 2004;145:5420–5428