RAD-140 / Testolone

The androgen receptor (AR) is a nuclear receptor transcription factor expressed in multiple tissues including muscle, bone, prostate, liver, skin, hair follicles, and the hypothalamus/pituitary. When androgens (testosterone, DHT) bind the AR, the receptor undergoes a conformational change and dimerizes; the ligand-receptor complex recruits specific coregulator proteins that modulate transcriptional activity. The key insight underlying SARM development: different tissues express different AR coregulators (coactivators and corepressors). The same compound can produce full agonist responses in tissues expressing specific coactivators while producing partial agonist, neutral, or antagonist responses in tissues with different coregulator profiles. By designing molecules that stabilize specific AR conformations preferentially, chemists attempted to engineer compounds that activate the muscle and bone AR coregulator suite while not activating (or antagonizing) the prostate AR coregulator suite. This is the theoretical basis for tissue selectivity — and it is pharmacologically sound in principle.

RAD-140 has been characterized as a full agonist at the AR in muscle tissue and a partial agonist or antagonist at the AR in prostate tissue in rodent and cell culture studies. The nandrolone equivalence ratio (NER) — the ratio of anabolic to androgenic effect — for RAD-140 in animal models is reported to be substantially higher than testosterone (ratios of 80:1 or higher have been cited in preclinical data, versus testosterone's 1:1). This preclinical selectivity data is the primary basis for the community's enthusiasm for RAD-140. The liver data complicates this picture: liver is also not a primary target for AR-mediated anabolism in RAD-140's design, yet the hepatotoxicity signal — both in the Phase 1 trial and in the DILI case reports — suggests off-target effects in liver that the selectivity architecture did not prevent.

RAD-140 binds the AR in hypothalamic and pituitary neurons that regulate GnRH pulsatility and LH/FSH secretion. This is the same negative feedback mechanism that testosterone uses to suppress the HPTA. The community belief that SARMs produce 'less HPTA suppression than testosterone' is based on preclinical data showing lower androgenicity in hypothalamic tissue. The human reality: virtually all community users of RAD-140 at doses above 5 mg/day report significant testosterone suppression during their cycle. Blood work from the community consistently shows LH/FSH falling to near-zero and testosterone declining to low-normal or hypogonadal range during RAD-140 use. The suppression severity correlates with dose and duration. This HPTA suppression is pharmacologically identical in mechanism to testosterone — AR-mediated negative feedback on the hypothalamus and pituitary.

LoRusso P, Hamilton E, Ma C, et al. (2022). A first-in-human Phase 1 study of a novel selective androgen receptor modulator (SARM), RAD140, in ER+/HER2- metastatic breast cancer. Clinical Breast Cancer. 22(1):67-77. doi:10.1016/j.clbc.2021.08.003. Design: Phase 1 dose-escalation; n=22 postmenopausal women with stage IV ER+/HER2- breast cancer; RAD-140 oral at escalating doses; primary endpoint: safety and tolerability. The hepatotoxicity findings: elevated AST = 59.1% of participants; elevated ALT = 45.5%; elevated total bilirubin = 27.3%. Additional adverse events included hypophosphatemia (22.7%), dehydration, vomiting, anorexia, and weight loss (27.3% each). This is the only controlled human clinical trial of RAD-140 published in peer-reviewed literature. The hepatotoxicity rate in 22 patients — more than half showing elevated liver transaminases — is the most important safety data available and directly contradicts the community narrative of a clean safety profile. Note: these were cancer patients taking therapeutic doses, not the lower community doses; however the hepatotoxicity signal is not dose-dependent in the DILI case reports (cases occurred at 10-20 mg/day community doses).

Beginning in 2020, case reports of RAD-140-associated drug-induced liver injury have been published in peer-reviewed gastroenterology and hepatology journals, with the case series now comprising 6+ published cases as of 2024. The clinical pattern across cases: predominantly cholestatic liver injury (elevated alkaline phosphatase and direct bilirubin with variable transaminase elevation); jaundice as the presenting symptom in most cases; onset 4-12 weeks after initiating RAD-140; resolution after discontinuation (typically 6-16 weeks for full normalization); liver biopsy findings: intracytoplasmic and canalicular cholestasis, prominent ductular reaction, minimal to moderate inflammation. Severity range: mild transaminase elevation (Grade 1-2 DILI) to severe cholestatic hepatitis requiring hospitalization; one Australian case with bilirubin of 708 μmol/L that was approaching liver transplant evaluation criteria. Drug-Induced Liver Injury Network (DILIN) causality scores: 'probable' to 'highly probable' in assessed cases. The cases span different geographic regions, different community vendors, and different lot numbers — suggesting the hepatotoxicity is pharmacological (from RAD-140 itself) rather than purely a contaminant issue.

Beyond hepatotoxicity, the case report literature documents: acute myopericarditis (inflammation of the heart muscle and pericardium) in a 16-year-old male following his first RAD-140 dose (Padappayil et al., Cureus 2022). This cardiovascular adverse event in a teenager after a single dose represents the most alarming safety signal in the RAD-140 literature — particularly given the widespread marketing of RAD-140 to young men for muscle building. The mechanism for myopericarditis from a single dose is not established but may involve immune-mediated or direct cardiotoxic effects.

THE HEPATOTOXICITY SIGNAL IS NOT A COMMUNITY RUMOR — IT IS PUBLISHED MEDICAL LITERATURE

At the time of this writing (mid-2026), there are: 6+ peer-reviewed published case reports of RAD-140-associated DILI in major gastroenterology/hepatology journals; 1 published case of myopericarditis after a single RAD-140 dose; Phase 1 trial data showing elevated liver enzymes in 59% of 22 participants. The FDA has issued multiple public warnings about SARMs specifically citing liver toxicity. The Australian Prescriber journal published a case report titled 'Severe liver injury following use of RAD-140 for body building' — in a case where discontinuation only happened a week before liver presentation and the injury continued to progress for six weeks afterward, nearly necessitating liver transplantation. Anyone using RAD-140 without baseline liver enzyme testing and periodic monitoring during use is taking a documented risk without the minimum harm reduction information.

During RAD-140 use, exogenous AR stimulation signals the hypothalamus to reduce GnRH pulsatility and signals the pituitary to reduce LH and FSH secretion. LH and FSH fall to near-zero within weeks. Testicular LH stimulation drops → Leydig cell testosterone production falls → intratesticular testosterone drops → spermatogenesis is partially suppressed. The clinical result: serum total testosterone typically falls to 150-400 ng/dL during RAD-140 cycles at 10-20 mg/day in most users — the hypogonadal to low-normal range. Users in this state have: reduced libido; reduced energy and mood; potentially reduced spermatogenesis. Testicular atrophy is less pronounced than with exogenous testosterone (because RAD-140 does not suppress LH/FSH as completely as exogenous testosterone at typical doses) but still occurs with longer cycles.

Post-Cycle Therapy (PCT) for RAD-140 typically uses a SERM (Selective Estrogen Receptor Modulator) to block estrogen's negative feedback on the pituitary and stimulate LH/FSH recovery: Nolvadex (tamoxifen) 20-40 mg/day for 4-6 weeks; or Clomid (clomiphene) 25-50 mg/day for 4-6 weeks; or both in combination. HCG (500-1,000 IU every other day for 2-4 weeks) before SERM PCT may accelerate testicular recovery in longer or more suppressive cycles. Recovery of natural testosterone to pre-cycle levels typically takes 6-12 weeks with PCT; without PCT, recovery may take months longer. In rare cases of prolonged or high-dose SARM use, full hormonal recovery may require more extended time or specialist intervention.

Suppression Level

LH/FSH

Testosterone

Recovery (with PCT)

Mild (5 mg/day, <6 wks)

Reduced but detectable

200-400 ng/dL

4-8 weeks

Moderate (10-15 mg/day, 6-8 wks)

Near-zero

100-250 ng/dL

6-12 weeks

Significant (20+ mg/day, >8 wks)

Zero

<100 ng/dL (hypogonadal)

8-16+ weeks; specialist referral if persistent

Community protocols for RAD-140 have converged on the following ranges, noting that these are not validated by clinical trials and all efficacy claims are derived from community reports: Men: 10-20 mg/day oral; 6-8 week cycles; 8-12 weeks off between cycles; PCT after each cycle. Women: 5-10 mg/day; 6 week maximum; lower doses due to virilization risk even from SARMs at higher doses. Starting dose recommendation: begin at 5-10 mg/day to assess tolerance before escalating. The body composition effects reported in the community (lean mass gain 2-5 kg over 6-8 weeks; strength improvements; fat reduction) are anecdotal — no placebo-controlled body composition trial has been published in healthy young adults.

Given the documented hepatotoxicity signal, liver enzyme monitoring is the minimum responsible harm reduction measure for any RAD-140 user. Protocol: baseline ALT, AST, total bilirubin, alkaline phosphatase before starting any cycle; repeat at 4 weeks into cycle; repeat at cycle end; and 4 weeks post-PCT. Action thresholds: any elevation above 2x upper limit of normal (ULN) = reduce dose by 50%; any elevation above 3x ULN = stop RAD-140 immediately; jaundice, dark urine, pruritus (itching), or RUQ pain = emergency evaluation — do not wait for lab work. The cases in the DILI literature that progressed to severe injury often involved users who noticed early symptoms (mild jaundice, fatigue) but continued use or delayed medical evaluation. Prompt discontinuation at first signs of liver involvement is critical.

Multiple of the published RAD-140 DILI cases and the myopericarditis case involved users under 25 years of age. Exogenous androgen receptor stimulation in men whose hypothalamic-pituitary-gonadal axis is still maturing (typically through mid-20s) carries specific risks beyond the adult population: premature epiphyseal closure (bone growth plates may still be active in younger users); HPTA disruption during a critical developmental period; increased susceptibility to androgenic side effects in some tissues. RAD-140 is not appropriate for men under 21 — this is not a regulatory statement but a harm reduction recommendation based on developmental biology.

Grade A (Negative safety signal): 59% AST elevation in Phase 1 trial; 6+ DILI case reports in peer-reviewed literature; mechanism unclear (cholestatic pattern suggests bile duct transport inhibition or bile acid metabolism disruption); may be idiosyncratic (some users have no liver signal while others develop severe injury). Mandatory monitoring: baseline liver enzymes; 4-week monitoring during cycle. Discontinue immediately if symptomatic or enzymes elevated >3x ULN.

Real and predictable. LH/FSH suppression leading to testosterone decline occurs at virtually all community doses. PCT required. Recovery variable but generally complete within 8-16 weeks with appropriate PCT. Persistent hypogonadism requiring endocrinology consultation reported in some users after prolonged or multiple cycles.

One published case of myopericarditis after a single RAD-140 dose in a 16-year-old. Mechanism unknown. No systematic cardiovascular safety data from controlled trials. Community reports of elevated blood pressure in some users.

Despite the selectivity claim: acne reported by community users (suggests some androgenic activity in skin); hair shedding reported at higher doses or in genetically susceptible individuals; virilization risk in women (voice changes, clitoral enlargement) at doses above 5-10 mg/day. These androgenic effects suggest the claimed tissue selectivity is incomplete.

Active malignancy: hard stop. RAD-140 was developed partly as a potential breast cancer treatment — in ER+/AR+ breast cancer, AR agonism may have anti-proliferative effects. In AR+ prostate cancer, RAD-140 theoretically antagonizes the AR. However: the net cancer biology of SARM use in active malignancy is complex, tissue-specific, and not established. Additionally, the 2021 case report associating RAD-140 with cholangiocarcinoma (bile duct cancer) — while a single report requiring cautious interpretation — adds further uncertainty. Active malignancy of any type requires physician consultation before any SARM use.

'Fewer side effects than testosterone' is not the same as 'safe.' RAD-140 has documented hepatotoxicity across multiple independent case reports and the only human clinical trial. Traditional anabolic steroids have a well-characterized safety profile developed over 60+ years; RAD-140 has minimal human safety data. The comparison to steroids may be accurate for some steroid-specific side effects (no aromatization to estrogen; no DHT conversion); it is not accurate for hepatotoxicity (where RAD-140's signal is arguably more concerning in the available data than many oral anabolic steroids at equivalent doses).

This myth is contradicted by the pharmacological mechanism (AR-mediated HPTA negative feedback), the community blood work documentation, and the clinical trial data. SARMs suppress LH and FSH in humans. RAD-140 at 10-20 mg/day produces testosterone values in the 100-400 ng/dL range in most users. The community belief that SARMs 'don't need PCT' or 'barely suppress' is demonstrably incorrect for RAD-140 at community doses.

RAD-140 is not FDA-approved for human use. Selling it with health claims, as a dietary supplement, or for human consumption is illegal under FDA regulations. The 'research chemical' label is a regulatory workaround that does not confer legal status for human use. The FDA has explicitly warned consumers about SARMs and stated that companies marketing SARMs as supplements are breaking federal law. The compound is legal to possess in the US (not a controlled substance) but not legal to sell for human consumption.

This argument is partially valid — SARM product contamination is real and some DILI cases may involve co-contaminants. However, the pharmaceutical-grade RAD-140 Phase 1 clinical trial (verified compound, GMP manufacturing, controlled dose) showed elevated liver enzymes in 59% of participants. This confirms that at least some of the hepatotoxicity is intrinsic to the compound itself rather than exclusively a contamination artifact. Contamination may amplify the risk from community-source products, but it does not explain the clinical trial findings.

LoRusso P, Hamilton E, Ma C, et al. (2022). A first-in-human Phase 1 study of a novel selective androgen receptor modulator (SARM), RAD140, in ER+/HER2- metastatic breast cancer. Clinical Breast Cancer. 22(1):67-77. doi:10.1016/j.clbc.2021.08.003. [n=22; postmenopausal women; stage IV ER+/HER2- breast cancer; elevated AST 59.1%, elevated ALT 45.5%, elevated total bilirubin 27.3%; the primary human safety evidence for RAD-140.]

Yaramada P, Goyal P, Hammami M, Cai C. (2020). S2399 RAD-140: an emerging cause of drug-induced liver injury. American Journal of Gastroenterology. 115:1273. [First published DILI case with RAD-140; established the signal that subsequent reports confirmed.]

Jones RP, et al. (2022). Severe liver injury following use of RAD-140, a selective androgen receptor modulator, for body building. Australian Prescriber. [Severe case; bilirubin 708 μmol/L; near liver transplant criteria; stopped RAD-140 before presentation yet injury continued to worsen for 6 weeks.]

Demangone MR, et al. (2024). Selective Androgen Receptor Modulators Leading to Liver Injury: A Case Report. Cureus. 16(8):e67958. PMC11426965. [Most recent case report; 29-year-old male; jaundice and elevated enzymes after 3 months of 20 mg/day RAD-140; hepatic steatosis and hyperechoic lesion on ultrasound; resolved after discontinuation.]

Padappayil RP, Chandini Arjun A, et al. (2022). Acute myopericarditis from the use of selective androgen receptor modulator (SARM) RAD-140 (testolone). Cureus. 14(1):e21663. [16-year-old male; myopericarditis after first dose of RAD-140; the youngest case and the most alarming adverse event in the RAD-140 literature.]

FDA analysis cited in multiple publications: of 44 SARM products tested, 52.3% contained the labeled SARM; 38.6% contained an unlabeled drug; 9.1% contained nothing. [Source: FDA Health Fraud Warning; establishes the systematic quality control failure in the SARM market.]

• Liver enzyme monitoring: non-negotiable; baseline ALT/AST/bilirubin; repeat at 4 weeks; repeat at cycle end; stop immediately if symptoms or >3x ULN elevation.
• Age restriction: not appropriate for men under 21; developmental HPTA and bone concerns apply.
• Active malignancy: hard stop; oncologist consultation required.
• HPTA suppression management: PCT with tamoxifen 20 mg/day or clomiphene 25 mg/day for 4-6 weeks after every cycle; blood work confirmation of testosterone recovery before starting another cycle.
• vs Ostarine for lower-risk approach: Ostarine has a longer and more favorable human clinical safety database; lower hepatotoxicity signal; appropriate for users prioritizing safety over peak anabolic effect.
• Quality verification: request third-party COA with HPLC + mass spectrometry from any RAD-140 source; acknowledge that the 50% SARM market quality problem means verification is important, not optional.

— End of RAD-140 (Testolone) —

THE PEPTIDE BIBLE | RAD-140 (Testolone) | For Research & Educational Purposes Only