At a glance
Effects
- Endometrial protection: Converts oestrogen-primed endometrium to a secretory state, preventing hyperplasia and protecting against endometrial cancer when used alongside oestrogen HRT [2].
- Pregnancy support: Prevents endometrial shedding, reduces uterine contractility, and modulates immune tolerance to support implantation and early pregnancy [6].
- Anxiolytic / sleep support: Oral micronised progesterone is metabolised to allopregnanolone, a GABA-A receptor agonist, producing mild sedative, anxiolytic, and sleep-promoting effects [5].
- Menstrual regulation: Used to manage secondary amenorrhea and dysfunctional uterine bleeding by restoring a normal secretory phase and allowing controlled withdrawal bleeding [2].
- Neuroprotection (emerging): Progesterone and its metabolites are under investigation as neuroprotectors and immunomodulators, though clinical evidence remains preliminary [1].
Endogenous progestogen / steroid hormone
~13–25 h (route-dependent; oral ~1–2 h peak, vaginal ~6 h peak, absorption t½ 25–50 h for gel)
Oral (micronised capsule), vaginal (gel / pessary), intramuscular injection, transdermal (compounded)
Prescription-only (FDA Rx); not a DEA scheduled substance
Oral: peak ~1–2 h; vaginal: peak ~6 h; effect on endometrium within days
About Progesterone
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
Progesterone is an endogenous 21-carbon steroid sex hormone classified as a progestogen, naturally synthesised from cholesterol in the corpus luteum of the ovaries, placenta, adrenal cortex, and (to a lesser extent) in male testes [1]. It is used medically for hormone replacement therapy (HRT), prevention of endometrial hyperplasia, maintenance of pregnancy, contraception, secondary amenorrhea, abnormal uterine bleeding, and assisted reproductive technology (ART) procedures [2].
How it works
Progesterone primarily acts via nuclear progesterone receptors (PR), binding to progesterone response elements (PRE) in target gene promoter regions to regulate transcription — the classical "genomic" mechanism [3]. It also activates membrane-associated PRs and several intracellular signalling pathways via non-genomic mechanisms [3]. It weakly agonises glucocorticoid and androgen receptors and fully antagonises the mineralocorticoid receptor, helping prevent water retention [4]. Oral micronised progesterone is metabolised to neuroactive metabolites (e.g. allopregnanolone) that act as GABA-A receptor agonists, producing sedative and anxiolytic effects [5]. It suppresses LH pulse frequency via the hypothalamic pulse generator [6].
Risks & side effects
Most important: Long-term use — particularly in combination with oestrogen — is associated with an increased risk of blood clots (DVT, pulmonary embolism), stroke, and heart attack; this risk persists even after stopping the medication and is compounded by high blood pressure, diabetes, high cholesterol, obesity, or smoking [7]. Rare but serious thromboembolic events are the single most critical harm to be aware of before use.
Common
Serious
- Thromboembolic events: DVT, pulmonary embolism, stroke, myocardial infarction [7]
- Increased risk of breast cancer with prolonged combined oestrogen + progestogen HRT [7]
- Risk of probable dementia reported in postmenopausal women ≥65 on combined HRT [10]
- Elevated risk in patients with liver impairment — should not be used if liver function is compromised [11]
Rare
Safety & harm reduction
- History of or active blood clots (DVT, pulmonary embolism, stroke, myocardial infarction) [7]
- Hepatic impairment or liver disease — progesterone is extensively hepatically metabolised [11]
- Hormone-sensitive cancers (e.g. breast or uterine cancer) unless specifically directed by an oncologist [7]
- Known or suspected pregnancy (outside medically supervised ART/fertility treatment) [8]
- Peanut allergy — some oil-based progesterone capsules use peanut oil as excipient; always check product labelling [11]
- Breastfeeding — progesterone passes into breast milk; risk to nursing infant not fully established [8]
- Baseline and periodic liver function tests, especially with long-term use [11]
- Blood pressure monitoring — elevated BP amplifies cardiovascular / clot risk [7]
- Regular breast examination and mammography with long-term combined oestrogen + progestogen HRT [7]
- Monitor for signs of thromboembolism: leg swelling, chest pain, shortness of breath, sudden visual changes [7]
- Serum progesterone levels if using for ART/luteal support to confirm adequate supplementation [2]
- Anticonvulsants (e.g. carbamazepine, phenytoin, phenobarbital) may accelerate progesterone metabolism and reduce efficacy [8]
- Antibiotics (rifampicin in particular) may reduce progesterone levels [8]
- Progesterone may potentiate anticoagulants — close INR monitoring required [8]
- CNS depressants, sedatives, anxiolytics, and alcohol: additive drowsiness risk with oral micronised progesterone [9]
- CYP3A4 inhibitors (e.g. ketoconazole, grapefruit juice) may increase progesterone exposure [11]
- Oral micronised progesterone capsules are best taken at bedtime to leverage sedative metabolite effects and reduce daytime drowsiness [8]
- When used in HRT: progesterone must be co-administered with oestrogen in women with an intact uterus to protect the endometrium [2]
- In ART/IVF: dosing protocols are individually prescribed and strictly supervised; do not self-adjust [2]
- Avoid driving or operating heavy machinery, especially at initiation of oral therapy [9]
- Inform all healthcare providers (including surgeons and dentists) of progesterone use prior to any procedure [7]
- If switching between routes of administration (oral → vaginal → IM), do not attempt dose conversion without medical guidance as bioavailability differs substantially by route [12]
Dosage context
Commonly-reported clinical doses (not a prescription — always follow prescriber guidance): Oral micronised capsules: 100–400 mg/day at bedtime (e.g. 200 mg/day for HRT endometrial protection; 400 mg/day for 10 days for secondary amenorrhoea) [13]. Vaginal gel: 45–90 mg every other day up to 6 doses for assisted reproduction [13]. Intramuscular injection: 5–10 mg/day for 6–8 consecutive days for secondary amenorrhoea [13]. Bioavailability is markedly lower via oral route than IM injection; serum levels are not always a reliable surrogate for tissue-level effect, particularly in uterine tissue with vaginal administration [12].
Sources
- 1.Fedotcheva TA — Clinical Use of Progestins and Their Mechanisms of Action (PMC, 2021)
- 2.DrugBank — Progesterone DB00396
- 3.PMC — Non-genomic mechanisms of progesterone action in the brain
- 4.MDPI — Progesterone: A Steroid with Wide Range of Effects (2022)
- 5.PMC — Progesterone: A Steroid with Wide Range of Effects (full text)
- 6.Pharmacy180 — Progestins: Mechanism of Action, Pharmacokinetics
- 7.Mayo Clinic — Progesterone (oral route) side effects & warnings
- 8.Drugs.com — Progesterone: Uses, Dosage, Side Effects & Warnings
- 9.ClinicalTrials.gov — Perimenopausal Effects of Estradiol (progesterone side-effect data)
- 10.RxList — Prometrium (Progesterone) Prescribing Information
- 11.WebMD — Progesterone (Prometrium): Uses, Side Effects, Interactions, Warnings
- 12.Fagron Academy — Progesterone: Switching Between Routes of Administration
- 13.Drugs.com — Progesterone Dosage Guide
- 14.FDA — Crinone (Progesterone Gel) Prescribing Information
- 15.PubMed — Pharmacokinetics of natural progesterone vaginal tablet
- 16.PMC — Pharmacokinetics of micronised progesterone capsules oral vs vaginal
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.