RAD-140

Selective Androgen Receptor Binding#

RAD-140 is a non-steroidal small molecule that binds the androgen receptor (AR) with high affinity (Ki ≈ 7 nM) and activates it in a tissue-selective manner. It fully agonizes AR in skeletal muscle and bone while behaving as a partial or weak agonist in prostate and seminal vesicle tissue — the split that defines a SARM and the reason you get most of the anabolic signal of testosterone with a fraction of the androgenic load.

"RAD140 was shown to deliver anabolic activity comparable to testosterone propionate in castrated male rats, with considerably reduced stimulation of the prostate and seminal vesicles." — Miller CP, Shomali M, Lyttle CR, et al., ACS Medicinal Chemistry Letters (2011)

Practically, this is what drives the strength and lean-mass gains users report from week 3 onward: AR activation in muscle triggers the same core anabolic cascade as testosterone — increased myofibrillar protein synthesis, IGF-1 upregulation, and myostatin suppression — without needing to inject.

No Aromatization, No 5α-Reduction#

Because RAD-140 is non-steroidal, it is not a substrate for aromatase or 5α-reductase. That means:

• No estrogen conversion — no gyno risk, no water retention, no need for an AI
• No DHT conversion — oral finasteride / dutasteride do nothing to protect your scalp on RAD, because there's no DHT pathway to block in the first place. Scalp-prone users need topical AR antagonists (RU58841, pyrilutamide) if they want local protection.

This is also why RAD feels "dry" compared to testosterone — gains come in without the bloat, which is part of why recomp-focused users and looksmaxxers gravitate to it.

HPTA Suppression via AR Feedback#

The same AR activity that builds muscle also signals the hypothalamus and pituitary to shut down endogenous testosterone production. LH and FSH drop, natural T falls, and testicular output winds down within the first few weeks — this happens even at 10 mg and is why PCT is non-negotiable. RAD is not a "mild suppression" SARM; it's the most suppressive one in common circulation, which is the trade-off for its potency.

Hepatic Stress at the Metabolic Pass#

RAD-140 is metabolized primarily through hepatic CYP pathways (CYP3A4-dominant), and the liver is where the compound's main downside shows up. The Phase 1 oncology trial in breast cancer patients characterized both the long half-life and the dose-dependent transaminase elevations:

"RAD140 demonstrated a half-life of 44.7 hours, with dose-proportional pharmacokinetics observed across the 50–150 mg range and reversible elevations in AST/ALT at higher doses." — LoRusso P, Hamilton E, Ma C, et al., Clinical Cancer Research (2022)

Recreational doses are an order of magnitude lower (5–30 mg), but published case reports of cholestatic drug-induced liver injury at bodybuilding doses confirm the hepatic signal is real at normal cycle doses — not just at oncology exposure. Mid-cycle LFTs and a cap of 8 weeks per cycle are the standard mitigations.

Neuroprotective and Cardiac AR Activity#

RAD-140 shows meaningful off-target AR activity in the brain and heart, which cuts both ways. In hippocampal neurons it activates AR-mediated MAPK signalling and protects against apoptotic insult:

"RAD140 robustly reduced cell death induced by apoptotic insult in rat hippocampal neurons, indicating a neuroprotective action through androgen receptor-mediated mechanisms." — Jayaraman A, Christensen A, Moser VA, et al., Brain Research (2014)

That same AR activation in cardiac tissue is why long-term cardiovascular safety remains a legitimate open question — the heart expresses AR, and potent agonism there is mechanistically plausible as a driver of the lipid shifts (notably HDL suppression) and blood-pressure changes users see on cycle. Keeping cycles short, monitoring lipids, and not stacking RAD with oral 17α-alkylated steroids is how experienced users stay on the right side of that risk.

Common (most users)#

• HPTA suppression — near-universal even at 10 mg. Expect lower libido, softer erections, and smaller testicles by week 3–4. Mitigation: keep cycles to 8 weeks, run a proper SERM PCT (tamoxifen 20 mg or enclomiphene 12.5–25 mg × 4 weeks starting the day after last dose), and don't stack it with other suppressive compounds unless you're also running exogenous testosterone.
• HDL suppression — often dramatic (30–50% drops are common on bloodwork). LDL creeps up modestly. Mitigation: cardio 3×/week, 2–4 g EPA/DHA daily, citrus bergamot 1000 mg/day, keep saturated fat moderate. Lipids normalize within 4–8 weeks post-cycle.
• Mild LFT elevation — AST/ALT drift upward on most users by week 4–6. Mitigation: TUDCA 500 mg/day, zero alcohol on cycle, no acetaminophen, no stacked 17-aa orals. Check labs at week 4.
• Aggression / irritability ("RAD rage") — dose-dependent, kicks in noticeably at 20 mg+. Mitigation: drop to 10–15 mg if it's affecting relationships or workplace behavior. Some users actually want this for training; know which camp you're in.
• Headaches and lethargy in week 1–2 — usually resolve as steady-state is reached (~day 8–10). Mitigation: hydration, electrolytes, don't panic-bump the dose.
• Nausea on an empty stomach — dose with food if it bothers you.
• Rebound low libido during PCT — normal while LH/FSH recover. Resolves 4–8 weeks post-PCT in most users running a clean protocol.

Uncommon (dose-dependent or individual)#

• Clinically significant LFT elevations (AST/ALT >3× ULN) — more common at 20–30 mg and past week 8. Drop the compound immediately if you see this; do not "push through." Recheck in 2–4 weeks.

  "RAD140 demonstrated a half-life of 44.7 hours, with dose-proportional pharmacokinetics observed across the 50–150 mg range and reversible elevations in AST/ALT at higher doses." — LoRusso et al., Clinical Cancer Research (2022)

• Blood pressure elevation — AR activity in cardiac and vascular tissue can push BP up, especially when stacked or run long. Monitor with a home cuff; add telmisartan 20–40 mg or low-dose tadalafil 5 mg if needed.

  "The widespread use of SARMs such as RAD140 raises concern about cardiovascular-specific risks due to their potent androgenic receptor activation in cardiac tissue." — Hall & Vrolijk, Nutrients (2023)

• Hair shedding in genetically predisposed users — RAD isn't 5α-reduced, so finasteride doesn't help. Topical RU58841 or pyrilutamide is the rational ancillary if you're already running a hair stack.
• Acne on the back/shoulders — less than on real AAS but not zero. Topical adapalene + benzoyl peroxide handles it.
• Sleep disturbance — occasional, more common at 20 mg+. Mitigation: move dose to AM, magnesium glycinate, cap the cycle earlier if it persists.
• Prolonged HPTA shutdown / slow PCT recovery — more likely after 12+ week cycles or back-to-back runs without adequate time off. Run HCG 500 IU 2×/week for the last 2 weeks on-cycle if you've had recovery issues before.

Rare but serious#

• Cholestatic drug-induced liver injury — jaundice, dark urine, scleral icterus, severe pruritus, bilirubin >10 mg/dL. Documented in multiple published case reports at recreational doses. Some required weeks of hospitalization. This is the real worst-case scenario and it happens at bodybuilder-typical doses, not just oncology doses.

  "We report a case of drug-induced liver injury associated with RAD-140 use for bodybuilding purposes, resulting in jaundice, pruritus, and elevated total bilirubin requiring medical intervention." — Barbara et al., ACG Case Reports Journal (2022)

  Stop immediately and seek care if: yellowing of skin/eyes, persistent right-upper-quadrant pain, severe itching without rash, dark tea-colored urine, pale stools.

• Cardiovascular events — long-term cardiac safety is unknown. The combination of dramatic HDL suppression, potential BP elevation, and direct AR activity on myocardium is a theoretical risk vector that has not been fully characterized in humans.

• Prolonged or incomplete HPTA recovery — rare after a single clean 8-week cycle, more plausible after stacked or back-to-back runs. If LH/FSH and total T haven't returned to baseline 12 weeks post-PCT, that's a clinical problem.

Hard contraindications#

• Pre-existing liver disease, hepatitis, or baseline LFTs >1.5× ULN — do not run RAD-140.
• Heavy alcohol use — incompatible. Pick one.
• Stacking with oral 17α-alkylated steroids (superdrol, anadrol, dianabol, winstrol, anavar) — this is where the hospitalizations happen. The hepatic load compounds.
• Pregnancy, lactation, or plans to conceive in the next 6–12 months — SARM suppression is real and fertility recovery is poorly characterized.
• Tested athletes — WADA-banned. Hydroxylated metabolites are detectable in urine for weeks.
• Pre-existing cardiovascular disease or uncontrolled hypertension — the lipid and BP profile is not compatible with a compromised cardiovascular baseline.
• History of cholestatic drug reactions (past jaundice on oral AAS, etc.) — your liver has already told you it doesn't tolerate this class.

Women and PCT notes#

Women: RAD-140 is not recommended for female users. Despite the 90:1 anabolic:androgenic ratio on paper, virilization (voice deepening, clitoral enlargement, jawline changes, facial hair) has been reported at doses above 5 mg, and voice changes are generally irreversible. Women who run it anyway typically cap at 1–5 mg/day for 6–8 weeks and stop at the first vocal symptom — but S4/andarine and low-dose ostarine are better-characterized choices for female physique users.

PCT is non-negotiable for any cycle ≥6 weeks at ≥10 mg. Standard protocol: tamoxifen 20 mg/day × 4 weeks or enclomiphene 12.5–25 mg/day × 4 weeks, starting the day after the last dose. No taper needed given the 44-hour half-life. If you've had sluggish recovery on prior cycles, add HCG 500 IU 2×/week during the final 2 weeks on-cycle. Confirm recovery with bloodwork at week 4 post-PCT — total T, free T, LH, FSH, E2. If numbers haven't normalized by week 8–12 post-PCT, that's the point to get proper endocrine workup rather than self-treating further.