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Raloxifene

Extensively Studied

Second-generation benzothiophene SERM — bone agonist, breast/uterus antagonist — FDA-approved for postmenopausal osteoporosis (1997) and…

Aliases (6)

Evista · Optruma · LY139481 · raloxifene hydrochloride · keoxifene · raloxifene HCl

TYPICAL DOSE

60 mg orally once daily, with or without food, …

Daily

ROUTE

Oral (tablet)

Oral

CYCLE

N/A — designed for continuous daily use in post…

As prescribed

STORAGE

Room temp; original container

Room temp

Overview

What is Raloxifene?

Raloxifene (Evista) is a second-generation selective estrogen receptor modulator (SERM), FDA-approved for prevention and treatment of postmenopausal osteoporosis and reduction of invasive breast cancer risk in postmenopausal women. It was developed by Eli Lilly.

Key Benefits

Increases bone mineral density and reduces vertebral fracture risk in postmenopausal women, while reducing risk of estrogen-receptor-positive invasive breast cancer. Used off-label by men for gynecomastia treatment and as cycle support in AAS use.

Mechanism of Action

Tissue-selective estrogen receptor modulator: agonist at ERα in bone (preserving bone density) and on lipid metabolism, antagonist at ERα in breast tissue (preventing proliferation) and uterine endometrium (no endometrial cancer risk unlike tamoxifen).

▸Brand options3 known

EvistaOptrumaLY139481

StatusRx (FDA-approved 1997 for postmenopausal osteoporosis prevention; 1999 for treatment; 2007 for invasive breast cancer risk reduction in postmenopausal women). Not WADA-prohibited as a hormone modulator class entry per se — but anti-estrogenic effects in females are listed under S4 (Hormone and Metabolic Modulators) in some interpretations; for males, off-label SERM use lands under S4 hormone-axis manipulation.

Research Indications

Most Effective

Bone (ERα + ERβ): full agonist

mimics estrogen's anti-resorptive effect, preserves BMD in postmenopausal women, reduces vertebral fracture risk by ~30-50% in MORE trial…

Effective

Breast tissue (ERα): antagonist

blocks endogenous estrogen at breast ER, prevents proliferation, reduces invasive breast cancer incidence by ~44% in STAR / MORE trial fo…

Investigational

Uterus / endometrium: neutral / weak antagonist

does NOT cause endometrial proliferation unlike tamoxifen, which has partial endometrial agonism and confers small but real endometrial c…

Investigational

Hypothalamus / brain: weak antagonist

does antagonize hypothalamic ER but with less hot-flash-driving severity than tamoxifen (still reports hot flushes ~9-29% of users, but m…

Investigational

Vasomotor / thermoregulatory: variable antagonist

produces hot flushes via hypothalamic ER blockade.

Investigational

Liver: complex

slight LDL reduction (estrogen-agonist-like effect on hepatic LDL receptor); no significant HDL or triglyceride effect (different from or…

Research Protocols

Disclaimer: These are commonly discussed research protocols and not medical advice.

Goal

Dose

Frequency

Solo Use

Cycle

Goal:60 mg orally once daily

Dose:60 mg in cosmetic male use

Frequency:—

Solo:—

Cycle:8-26 week

Goal:Do not stack with aromatase inhibitors (anastrozole, letrozole, exemestane) without clinician supervision

Dose:—

Frequency:—

Solo:Stack

Cycle:—

Goal:Do not stack with other SERMs (tamoxifen, enclomiphene, clomiphene)

Dose:—

Frequency:—

Solo:—

Cycle:—

Goal:Do not use during AAS cycles in men with documented thrombophilia or family history of VTE/DVT/PE

Dose:—

Frequency:—

Solo:—

Cycle:—

Goal:Do not use in men with active prostate cancer

Dose:—

Frequency:—

Solo:—

Cycle:—

Goal:Do not exceed 120 mg/day

Dose:—

Frequency:—

Solo:—

Cycle:—

Peptide Interactions

Calcium + Vitamin D3 + K2:

Synergistic

Cofactors for bone formation; standard add-on with raloxifene for osteoporosis. the user's V stack D3+K2 is unrelated to this use case.

Bisphosphonates (alendronate, risedronate):

Synergistic

Sometimes combined for severe osteoporosis; not first-line stacking.

Antipsychotics (in schizophrenia adjunct use):

Synergistic

Olanzapine, risperidone, etc. — concomitant with antipsychotic continuation, not replacement.

Other SERMs (tamoxifen, enclomiphene, clomiphene, toremifene):

Avoid

Redundant ER antagonism; unpredictable additive effects. Avoid.

Aromatase inhibitors (anastrozole, letrozole, exemestane) without clinical supervision:

Avoid

Combined with raloxifene → can crash systemic E2 and tissue E2 simultaneously → severe hypoestrogenic phenotype (bone loss accelerated despite raloxifene's b…

Cholestyramine (bile-acid sequestrant):

Avoid

Reduces raloxifene absorption ~60% via interference with enterohepatic recirculation. Major interaction. Avoid.

Warfarin:

Avoid

Modest reduction in prothrombin time when raloxifene added; INR adjustment may be needed. Monitor.

Estrogen / hormone replacement therapy:

Avoid

Combined use is generally not done — purpose conflict.

Anabolic-androgenic steroids (AAS) without thrombophilia screening:

Avoid

AAS-induced hematocrit elevation + raloxifene VTE risk = compounded thrombosis risk. (For the user: he doesn't use AAS, so not relevant; for the AAS-using au…

Smoking:

Avoid

Smoking is a strong VTE risk factor; raloxifene + smoking = avoidable additive risk. (the user: zero smoking, not applicable.)

Most non-hormonal nootropics in the user's V stack/the canonical stack:

Compatible

Modafinil, citicoline, NAC, magnesium, fish oil, theanine, rhodiola, curcumin, beta-alanine — no PD/PK conflict with raloxifene. (Theoretical interaction sur…

Caffeine:

Compatible

No interaction.

Quality Indicators

✓

Pharmacy-dispensed, intact packaging

Prescription tablets in original sealed packaging from a licensed pharmacy.

Generic vs branded

Generics are usually fine but bioavailability can vary slightly; track if you switch.

✗

Unbranded blister or counterfeit risk

Counterfeit pharmaceuticals are a known issue; verify pharmacy and lot if buying internationally.

What to Expect

Onset
of bone effects: months — BMD changes detectable on DEXA at 12-24 months
Onset
of breast tissue effect: 4-12 weeks for noticeable reduction in glandular tissue

Side Effects & Safety 13

Side Effects

1Hot flushes ~9-29% (in women; lower in men)
2Leg cramps / muscle cramps ~7-12%
3Peripheral edema ~3-7%
4Flu-like symptoms / mild infections ~10-15% (mechanism unclear, possibly immune modulation by ERα antagonism)
5Arthralgia / joint pain ~10%
6Headache ~6-9%
7Nausea, dyspepsia ~6-8%
8Insomnia / sleep disturbance ~3-6%
9Decreased libido (in men, off-label use) ~5-15% per anecdotal reports; not formally tracked in female clinical trials
10Erectile dysfunction (in men) ~5-10% per anecdotal reports
11Weight gain mild ~3-5%
12Vaginal dryness / atrophy (in women)
13Sweating ~2-3%

When to Stop

Venous thromboembolism (VTE) / Deep Vein Thrombosis (DVT) / Pulmonary Embolism (PE): 3× increased risk over placebo in MORE/RUTH trials. Highest risk in first 4 months of therapy. Boxed warning on label. Risk factors: prior VTE/PE, prolonged immobilization, surgery, malignancy, smoking, obesity, oral contraceptives, hormone replacement therapy. Discontinue immediately for prolonged immobilization (e.g., elective surgery, long-haul travel >4 hours).
Stroke (fatal stroke incidence small but elevated in RUTH trial): Particular concern in women with established CV disease or multiple CV risk factors.
Hypertriglyceridemia in women with prior estrogen-induced hypertriglyceridemia: rare but documented.
Hepatic dysfunction: rare; LFT monitoring not routinely required but flag any baseline elevation.
Severe hypersensitivity / rash: rare.
Hot-flush severity in early use: can be debilitating in subset, requiring discontinuation.
First 4 months: Highest VTE risk window. Monitor for unilateral leg swelling/pain (DVT), chest pain / dyspnea / hemoptysis (PE).
Pre-surgery: Discontinue at least 72 hours before any elective surgery or prolonged immobilization to reduce VTE risk.
First 8 weeks: Hot flushes, leg cramps, GI upset most common — usually fade.
Long-term (years): Bone density progressive improvement; CV neutral; breast cancer risk reduction accumulating.
MMA training = repeated soft tissue trauma + impact: trauma is a VTE risk factor; raloxifene compounds that risk multiplicatively
Daily light training: fine, but any ground game involving prolonged static positioning + acute injury creates VTE windows
Long-haul travel for competitions or business: elevated baseline VTE risk on raloxifene; would need discontinuation 72+ hours pre-flight
Eugonadal HPG axis at peak natural function: raloxifene's hypothalamic ER blockade could subtly raise LH/FSH/T (small effect) — unpredictable in a system already at peak; no demonstrated benefit
Net: zero indication, real risk surface, libido downside — unfavorable on every axis

References

Evista (raloxifene HCl) FDA prescribing information

accessdata.fda.gov

official FDA label

Raloxifene

Overview

What is Raloxifene?

Key Benefits

Mechanism of Action

Research Indications

Bone (ERα + ERβ): full agonist

Breast tissue (ERα): antagonist

Uterus / endometrium: neutral / weak antagonist

Hypothalamus / brain: weak antagonist

Vasomotor / thermoregulatory: variable antagonist

Liver: complex

Research Protocols

Peptide Interactions

Quality Indicators

Pharmacy-dispensed, intact packaging

Generic vs branded

Unbranded blister or counterfeit risk

What to Expect

Side Effects & Safety 13

Side Effects

When to Stop

References

Evista (raloxifene HCl) FDA prescribing information

MORE trial — Ettinger et al. 1999 (NEJM)

STAR trial — Vogel et al. 2006 (JAMA)

RUTH trial — Barrett-Connor et al. 2006 (NEJM)

CORE trial — Martino et al. 2004 (J Natl Cancer Inst)

Lawrence et al. 2004 — Beneficial effects of raloxifene and tamoxifen in the treatment of pubertal gynecomastia (J Pediatr)

Hammes & Levin 2007 — Extranuclear steroid receptors (Endocrine Reviews)

Riggs & Hartmann 2003 — Selective estrogen-receptor modulators (NEJM)

Kulkarni et al. 2010 — Estrogen in severe mental illness: a potential new treatment approach (Arch Gen Psychiatry)

Kulkarni et al. 2016 — Effect of raloxifene as adjunct in schizophrenia: PANSS + cognition meta-analysis

de Boer et al. 2018 — The effect of raloxifene augmentation in men and women with a schizophrenia spectrum disorder (NPJ Schizophrenia)

Lapid et al. 2009 — Treatment of gynecomastia (Acta Clin Belg)

Trdan Lušin et al. 2011 — Pharmacogenetics of UGT polymorphisms in raloxifene metabolism

PubChem — Raloxifene

DrugBank — Raloxifene

Cochrane review — SERMs for primary prevention of breast cancer

Iqbal et al. 2013 — Risk of mammographic density and breast cancer (Cancer Epidemiol)

Gennari et al. 2008 — Selective estrogen receptor modulators for postmenopausal osteoporosis (Drugs Aging)

Stuenkel 2017 — Hormone therapy for management of menopause-associated osteoporosis (Endocrinol Metab Clin North Am)

Lasco et al. 2011 — Effect of long-term treatment with raloxifene on mammary density in postmenopausal women (Maturitas)

Pickar et al. 2010 — SERMs: current status and future research (Climacteric)

USADA / WADA Prohibited List 2025-2026

Saudi Med J 2018 — Raloxifene in management of male gynecomastia

Inhouse Pharmacy raloxifene listing

Bodybuilding.com / EliteFitness raloxifene threads (community knowledge)

Khan & Chopra 2024 — Gynecomastia management approaches (StatPearls)

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