RAD-140 (Testolone)

Potential Health Benefits of RAD-140

• Improves muscle mass and strength [1-3]
• Fights cancer [4-6]
• Improves brain health [7-12]
• Promotes weight loss [14]
• Improves sexual health [15-18]
• Treats benign prostatic hyperplasia (BPH) [19-20]
• Improves bone health [21-23]

What is RAD-140?

RAD-140, also known as Testolone, is a compound that belongs to the class of molecules called selective androgen receptor modulators (SARMs). Unlike anabolic androgenic steroids, this orally ingestible product is non-steroidal in nature, which means that it has anabolic effects (e.g. increased muscle mass and strength, and accelerated bone growth) with almost zero side effects. This is because RAD-140 interacts only with androgenic receptors of the muscles and bones, but it doesn’t activate these receptors in other body parts.

How RAD-140 Works

RAD-140 works by allowing its molecules to bind to androgen receptors in the body. This in turn sends signals to the body resulting in muscle build-up. This mechanism of action is similar to anabolic steroids. However, RAD-140 binds to androgen receptors only in bone and muscle tissue, thus decreasing the side effects.

Chemical Structure of RAD-140

Research on RAD-140

A. Improves Muscle Mass and Strength

Studies show that consumption of RAD-140 may lead to a considerable increase in muscle mass and strength:

1. In patients with severe diseases (cancer, AIDS, and multiple sclerosis) that cause muscle wasting, RAD-140 treatment led to weight gain and increases bone and muscle cell growth. [1]
2. In bodybuilders, RAD-140 administration increased muscle mass, decreased fat tissue, and improved stamina and endurance during high-intensity interval training. [2]
3. In animals, RAD-140 administration appears to increase lean muscle mass. [3]

B. Fights Cancer

RAD-140 is showing promising results in cancer treatment. According to studies, RAD-140 exerts its anti-cancer properties through the following important mechanisms:

1. In patients with breast cancer, RAD-140 treatment suppressed the growth of cancer cells by blocking the effects of estrogen on tissues. [4-5]
2. RAD-140 prevented the production of a protein called estrogen receptor 1 (ESR1), which is known to fuel cancer growth. [6]

C. Improves Brain Health

Evidence suggests that RAD-140 does have neuroprotective effects, which means that it has the ability to protect nerve cells (neurons) of the brain from injury or damage:

1. In rat models of Alzheimer’s disease (AD), RAD-140 administration protected the neurons and decreased the levels of amyloid beta, which are abnormal protein plaques and is considered a hallmark of AD. [7]
2. RAD-140 mimics the activation of beneficial androgen pathways in the brain which leads to the growth and development of brain tissues, enhanced neuron communication, memory formation, and cell survival. [8-11]
3. In rats, RAD-140 increased the survival of new neurons in the brain. [12]

D. Promotes Weight Loss

Supplementing with RAD-140 can lead to a dramatic fat loss over time. This is because RAD-140 can indirectly decrease fat tissue by increasing muscle mass. This effect also lowers circulating fat molecules known as low-density lipoprotein (LDL), which is implicated in obesity. [13] In addition, having higher levels of muscle mass increases the body’s metabolism, which ultimately leads to weight loss. [14]

E. Improves Sexual Health

SARMs such as RAD-140 may also boost one’s libido. Studies show that SARMs offer an improved safety profile for both sexes with fewer side effects:

1. In rats, SARMs enhanced the sexual preference of females for males but only if females had previous sexual experience. [15]
2. In women, SARMs enhanced and stimulated libido and other parameters of sexuality. [16]
3. In female rats that had undergone surgical removal of the ovaries, SARMs increased sexual motivation, with potency and efficacy comparable with testosterone propionate. [17]
4. In male rats, SARMs improved various sexual parameters such as mounts, intromissions, ejaculations, and copulation efficiency. [18]

F. Treats Benign Prostatic Hyperplasia (BPH)

BPH involves enlargement of the prostate gland and causes unpleasant urinary problems such as urinary frequency, difficulty urinating, weak urine stream, and urinary tract infection. Studies show that SARMs such as RAD-140 can effectively treat BPH:

1. SARMs at varying doses (5, 10, and 25 mg/kg) decreased prostate weight and were equal in efficacy to finasteride, a medication used mainly to treat BPH. [19]
2. Repeated treatment with SARMs decreased prostate weight just like flutamide, a medication for prostate cancer and BPH. [20]

G. Improves Bone Health

A novel approach to the treatment of osteoporosis and other bone disorders in men and women is the use of SARMs. Studies show that SARMs can stimulate the formation of new bone and prevent the age-related decline in bone density:

1. In androgen-deficient rats, SARMs administration prevented bone loss and maintained bone quality by stimulating bone formation while inhibiting bone breakdown. [21]
2. In men with late-onset hypogonadism (low levels of sex hormones), SARMs administration increased bone mineral density and strength just like testosterone replacement therapy. [22]
3. In castrated male rats, SARMs administration led to a significantly larger increase in total body bone mineral density. [23]

Associated Side Effects of RAD-140

RAD-140 side effects are very uncommon. There have been some side effects associated with the use of this drug wherein the patient had one of the issues listed below at some point while being on RAD-140. However, these side effects weren’t confirmed to be associated with the treatment and could have been a coincidence and not related to the use of RAD-140. Despite this, it was listed as a side effect associated with RAD-140 even though these associated side effects are very uncommon.

Side effects associated with RAD-140 may include the following:

• Acne
• Aggression
• Hair loss
• Headache
• Hormonal disorder
• Nausea

References

1. Bhasin S, Jasuja R. Selective Androgen Receptor Modulators (SARMs) as Function Promoting Therapies. Current opinion in clinical nutrition and metabolic care. 2009;12(3):232-240. doi:10.1097/MCO.0b013e32832a3d79. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2907129/.
2. Geyer H, Schänzer W, Thevis M. Anabolic agents: recent strategies for their detection and protection from inadvertent doping. British Journal of Sports Medicine. 2014;48(10):820-826. doi:10.1136/bjsports-2014-093526. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4033149/.
3. Miller CP, Shomali M, Lyttle CR, et al. Design, Synthesis, and Preclinical Characterization of the Selective Androgen Receptor Modulator (SARM) RAD140. ACS Medicinal Chemistry Letters. 2011;2(2):124-129. doi:10.1021/ml1002508. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018048/.
4. Yu Z, He S, Wang D. Selective Androgen Receptor Modulator RAD140 Inhibits the Growth of Androgen/Estrogen Receptor-Positive Breast Cancer Models with a Distinct Mechanism of Action. Clinical cancer research : an official journal of the American Association for Cancer Research. 2017; 23(24):7608-7620. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/28974548.
5. Ziyang Yu, Suqin He, Jeffrey Brown, Chris Miller, Jamal Saeh, Gary Hattersley. RAD140, an orally available selective androgen receptor modulator, inhibits the growth of AR/ER positive breast cancer cell line- and patient-derived xenograft models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3608. doi:10.1158/1538-7445.AM2017-3608. Retrieved from http://cancerres.aacrjournals.org/content/77/13_Supplement/3608.
6. Yu Z, He S, Wang D. Selective Androgen Receptor Modulator RAD140 Inhibits the Growth of Androgen/Estrogen Receptor-Positive Breast Cancer Models with a Distinct Mechanism of Action. Clinical cancer research : an official journal of the American Association for Cancer Research. 2017; 23(24):7608-7620. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/28974548.
7. Jayaraman A, Christensen A, Moser VA, et al. Selective Androgen Receptor Modulator RAD140 Is Neuroprotective in Cultured Neurons and Kainate-Lesioned Male Rats. Endocrinology. 2014;155(4):1398-1406. doi:10.1210/en.2013-1725. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3959610/.
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9. Qui MS, Green SH. PC12 cell neuronal differentiation is associated with prolonged p21ras activity and consequent prolonged ERK activity. Neuron. 1992;9:705–717. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/1382473.
10. Krapivinsky G, Krapivinsky L, Manasian Y, et al. The NMDA receptor is coupled to the ERK pathway by a direct interaction between NR2B and RasGRF1. Neuron. 2003;40:775–784. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/14622581.
11. Alonso M, Viola H, Izquierdo I, Medina JH. Aversive experiences are associated with a rapid and transient activation of ERKs in the rat hippocampus. Neurobiol Learn Mem. 2002;77:119–124. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/11749089.
12. Hamson DK, Wainwright SR, Taylor JR, Jones BA, Watson NV, Galea LA. Androgens increase survival of adult-born neurons in the dentate gyrus by an androgen receptor-dependent mechanism in male rats. Endocrinology. 2013; 154(9):3294-304. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/23782943.
13. Kesaniemi YA, Grundy SM. Increased low density lipoprotein production associated with obesity. Arteriosclerosis (Dallas, Tex.). ; 3(2):170-7. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/6838434.
14. McPherron AC, Guo T, Bond ND, Gavrilova O. Increasing muscle mass to improve metabolism. Adipocyte. 2013;2(2):92-98. doi:10.4161/adip.22500. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3661116/.
15. Kudwa AE, López FJ, McGivern RF, Handa RJ. A selective androgen receptor modulator enhances male-directed sexual preference, proceptive behavior, and lordosis behavior in sexually experienced, but not sexually naive, female rats. Endocrinology. 2010; 151(6):2659-68. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/20392832.
16. Negro-Vilar A. Selective androgen receptor modulators (SARMs): a novel approach to androgen therapy for the new millennium. The Journal of clinical endocrinology and metabolism. 1999; 84(10):3459-62. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/10522980.
17. Jones A, Hwang DJ, Duke CB. Nonsteroidal selective androgen receptor modulators enhance female sexual motivation. The Journal of pharmacology and experimental therapeutics. 2010; 334(2):439-48. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/20444881.
18. Miner JN, Chang W, Chapman MS. An orally active selective androgen receptor modulator is efficacious on bone, muscle, and sex function with reduced impact on prostate. Endocrinology. 2007; 148(1):363-73. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/17023534.
19. Omwancha J, Brown TR. Selective androgen receptor modulators: in pursuit of tissue-selective androgens. Current opinion in investigational drugs (London, England : 2000). 2006; 7(10):873-81. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/17086931.
20. Nejishima H, Yamamoto N, Suzuki M, Furuya K, Nagata N, Yamada S. Anti-androgenic effects of S-40542, a novel non-steroidal selective androgen receptor modulator (SARM) for the treatment of benign prostatic hyperplasia. The Prostate. 2012; 72(14):1580-7. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/22430536.
21. Rosen J, Negro-Vilar A. Novel, non-steroidal, selective androgen receptor modulators (SARMs) with anabolic activity in bone and muscle and improved safety profile. Journal of musculoskeletal & neuronal interactions. 2002; 2(3):222-4. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/15758439.
22. Coss CC, Jones A, Hancock ML, Steiner MS, Dalton JT. Selective androgen receptor modulators for the treatment of late onset male hypogonadism. Asian Journal of Andrology. 2014;16(2):256-261. doi:10.4103/1008-682X.122339. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955335/.
23. Gao W, Reiser PJ, Coss CC, et al. Selective Androgen Receptor Modulator Treatment Improves Muscle Strength and Body Composition and Prevents Bone Loss in Orchidectomized Rats. Endocrinology. 2005;146(11):4887-4897. doi:10.1210/en.2005-0572. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2039881/.