At a glance
Effects
- Appetite stimulation: Clinically demonstrated increases in appetite in patients with cancer- or AIDS-related anorexia/cachexia; a positive dose-response relationship has been observed across trials [8][9].
- Weight gain: Associated with increases in fat mass and body cell mass rather than fluid retention; approximately 1-in-12 patients experience meaningful weight gain in cancer cachexia studies [5][6].
- Antigonadotropic / hormone suppression: Suppresses LH via its progestogenic activity, reducing gonadal steroid production; used therapeutically in hormone-sensitive breast and endometrial cancers [1][3].
- Antineoplastic (palliative): Modifies oestrogen receptor action and exerts direct cytotoxic effects on hormone-dependent tumour cells in breast and endometrial carcinoma [3][4].
- Adrenal androgen suppression: May suppress adrenal androgens and inhibit 5α-reductase, which has been exploited in prostate cancer contexts [7].
Synthetic progestin / antineoplastic hormone
~34 h (range 13–105 h)
Oral (tablet or suspension)
Peak plasma: 1–3 h (mean 2.2 h)
FDA Category X — absolute contraindication
About Megestrol Acetate
Every point here is drawn from public medical and harm-reduction sources. A bracketed number after a claim — like [1]— is a reference: tap it to open the exact source it's based on (numbered list at the bottom). It is not a rating or score. Educational information, not medical advice.
Product specifics
- Est. delivery
- 3–7 business days · EU tracked
Product details as stated by the vendor (claims, not independently verified). Delivery is our standard EU estimate.
What it is
Megestrol acetate is a synthetic progestin (progesterone derivative) classified as an antineoplastic hormone and appetite stimulant [1][2]. It is FDA-approved for palliative treatment of advanced breast and endometrial carcinoma, and as an oral suspension to treat anorexia, cachexia, and unexplained significant weight loss in patients with AIDS or cancer [3][4].
How it works
Megestrol acetate works primarily by binding to progesterone receptors, exerting antigonadotropic effects (suppressing LH release from the pituitary) and, in cancer contexts, modifying estrogen receptor signalling and exerting a direct cytotoxic effect on hormone-sensitive tumour cells [1][2][3]. Its appetite-stimulant mechanism is not fully understood, but evidence points to stimulation of neuropeptide Y release in the hypothalamus, possible neurosteroid-like calcium channel modulation, increased IGF-1 levels, and interference with cachectin (TNF-α) signalling — collectively increasing appetite and promoting fat and body cell mass accrual [5][6][7]. It also carries antiandrogen activity and may suppress adrenal androgens via inhibition of 5α-reductase [7].
Risks & side effects
Most important: Venous thromboembolism (VTE) — including deep vein thrombosis and potentially fatal pulmonary embolism — is the single most serious risk; thromboembolic events occur in approximately 4.9% of nursing-home patients on megestrol therapy and the risk is higher when used concurrently with chemotherapy [10][11]. Prolonged use also carries a significant risk of adrenal insufficiency (HPA-axis suppression), which can be life-threatening upon abrupt discontinuation [12][13].
Common
- Weight gain (incidence 15–70% at high doses) [5]
- Oedema / fluid retention [14]
- Nausea, diarrhoea, flatulence [15]
- Hypertension [15][13]
- Asthenia / fatigue / malaise [14]
- Hyperglycaemia / glucose intolerance [13]
- Rash [15]
- Mood changes, hot flashes [14]
- Impotence / decreased libido in men [15]
- Breakthrough vaginal bleeding in women [12]
Serious
- Venous thromboembolism — DVT and pulmonary embolism (in some cases fatal) [10][14]
- Adrenal insufficiency / HPA suppression (especially with long-term or high-dose use; risk on withdrawal) [12][13]
- New-onset or worsening diabetes mellitus; Cushing's-like syndrome with chronic use [13]
- Heart failure / dyspnoea [14]
- Severe hypertension [13]
- Carpal tunnel syndrome [14]
- Tumour flare with hypercalcaemia [14]
Safety & harm reduction
- Known or suspected pregnancy — FDA Category X; causes fetal harm including feminisation of male fetuses [1][17]
- Known hypersensitivity to megestrol acetate or formulation components [5][16]
- Active or history of venous thromboembolism (DVT or pulmonary embolism) [16][11]
- Severe hepatic impairment — megestrol is primarily hepatically metabolised and impaired clearance may lead to toxicity [16]
- Breastfeeding — adverse effects on the newborn have been reported; breastfeeding should be discontinued if megestrol is required [13][17]
- Signs and symptoms of venous thromboembolic events (DVT, pulmonary embolism) throughout therapy [12][11]
- Blood pressure — megestrol can cause or worsen hypertension [13][15]
- Blood glucose / HbA1c — risk of new-onset diabetes or exacerbation of existing diabetes [13]
- Body weight — expected gain should be monitored; distinguish fluid oedema from true mass gain [14]
- Adrenal function — monitor for signs of insufficiency (dizziness, fatigue, hypotension) especially after long-term use or on discontinuation [12][13]
- Renal function in elderly patients — megestrol is substantially renally excreted; impaired clearance increases toxicity risk [13]
- Serum cortisol if HPA suppression is suspected, particularly at doses ≥400 mg/day [18]
- Warfarin — megestrol may enhance anticoagulant effects, increasing bleeding risk; monitor INR closely [11][19]
- Immunosuppressants (e.g., siponimod, etrasimod) — additive immunosuppressive effects; avoid combination or use with extreme caution [19]
- Indinavir — reduced antiretroviral plasma levels reported [16]
- Maitake mushroom extract — minor pharmacodynamic synergism reported; clinical significance unclear [19]
- Adrenal-suppressing drugs — additive risk of HPA axis suppression with concurrent corticosteroids or other progestins [13]
- Taper dose gradually after prolonged use to avoid acute adrenal insufficiency; do not abruptly discontinue after long-term therapy [12][13]
- Evaluate pregnancy status before initiating therapy in females of reproductive potential and advise effective contraception throughout [1][17]
- Use the lowest effective dose for the shortest duration necessary; 160 mg/day is a commonly used initial dose for cachexia, with escalation guided by response [8]
- Optimise hydration and consider prophylactic anticoagulation assessment in patients with additional VTE risk factors (immobility, prior clots, cancer chemotherapy) [10][11]
- Monitor for adrenal suppression symptoms (pallor, dizziness, weakness, nausea) — especially at doses ≥400 mg/day or after long-term use [12][18]
Dosage context
Commonly reported clinical dosage ranges (not a prescription; ranges vary widely by indication): For cancer anorexia/cachexia — 160 mg/day orally is a frequently used starting dose, with clinical trials using 160–1,280 mg/day; the dose with maximum appetite-stimulant effect has been reported as 800 mg/day [8][9]. For palliative treatment of breast or endometrial carcinoma — 40–320 mg/day (tablets) in divided doses is the typical range cited in prescribing information [3][4]. For AIDS-related cachexia — 800 mg/day (oral suspension, 20 mL) is the marketed dose; the concentrated suspension (Megace ES, 625 mg/5 mL) is NOT interchangeable mg-per-mg with standard formulations [1][20]. Cortisol suppression is common at higher doses and may persist; clinical utility at very high doses is controversial [18].
Sources
- 1.PharmaCompass – Megestrol Acetate EP Monograph (pharmacology, half-life, mechanism)
- 2.Boehringer Ingelheim – Megestrol Acetate Tablets USP Prescribing Information
- 3.FDA.report / DailyMed – Megestrol Acetate Tablet
- 4.DailyMed NLM – Megestrol Acetate Tablets USP 20 mg and 40 mg
- 5.Medicine.com – Megestrol Dosage, Mechanism, Half-Life
- 6.Wikipedia – Megestrol acetate
- 7.iKanEat Clinical Trial Protocol – Megestrol Pharmacokinetics & Side Effects (NIH ClinicalTrials)
- 8.ASCO Journal of Clinical Oncology – Phase III: Four Doses of Megestrol for Cancer Anorexia/Cachexia
- 9.PMC – Systematic Review & Meta-Analysis: Megestrol for Cancer-Related Anorexia/Cachexia
- 10.PMC – Megestrol Acetate Induced Paradoxical Embolism (thromboembolic risk data)
- 11.The Kingsley Clinic – Megestrol Acetate: Uses, Dosage, Side Effects, Contraindications
- 12.StatPearls / NCBI Bookshelf – Megestrol (NIH)
- 13.RxList – Megestrol Acetate Tablets: Side Effects, Warnings, Dosage
- 14.ClinicalTrials NCT03671811 ICF – Megestrol Acetate Side Effect Profile (IRB-approved informed consent)
- 15.ClinicalTrials NCT03077698 – Adverse Reactions Reported with Megestrol Acetate
- 16.Medscape – Megace (Megestrol) Dosing, Interactions, Adverse Effects
- 17.Mayo Clinic – Megestrol (Oral Route): Side Effects & Dosage
- 18.DrOracle / AAFP – Megestrol Dosing: Appetite Stimulation & Cortisol Suppression
- 19.Medscape – Megestrol Drug Interactions (warfarin, immunosuppressants)
- 20.AAFP – Megestrol for Palliative Care in Cancer (VTE risk, adrenal suppression)
This information is provided for educational and harm-reduction purposes only. It is not medical advice. These substances can carry serious health risks; effects and safe use vary by individual. Consult a qualified healthcare professional before use. Legal status varies by country — it is your responsibility to know your local law. We do not encourage misuse.