Progesterone for Health & Longevity - Quick Reference Sheet
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Progesterone for Health & Longevity

Created on 09/12/2026 – Quick Reference based on Evidence Review created using AI4L / Opus 5 – Audit

The body's own hormone, not a synthetic stand-in. Oral capsules at bedtime protect the uterine lining during estrogen therapy; creams do not. Bedtime dosing shortens time to fall asleep and deepens disturbed sleep; higher doses reduce hot flushes after the final period. Safety evidence reassures to five years and thins beyond. Trade-offs: drowsiness, spotting, low mood in a minority. (Full Review)

Protocol

Standard cyclic regimen
200 mg oral, bedtime
12–14 days each month with continuous estradiol; validated for endometrial protection to five years. Scheduled monthly bleed.
Standard continuous regimen
100 mg oral, bedtime
Every day with estradiol. Avoids a scheduled bleed; irregular spotting in the first six months.
Progesterone-alone regimen for symptoms
300 mg, bedtime
Where estrogen is declined or contraindicated. The dose behind the positive hot-flush result.
Time to effect
Endometrial protection
Immediate
Only demonstrable by biopsy or imaging over months.
Sleep changes
First night
Faster sleep onset and deeper sleep where sleep is already disturbed.
Hot-flush reduction
4–12 weeks
Established after the final period; unproven during the transition.

Benefits

Contraindications
  • Known, suspected or past breast cancer; progesterone-receptor-positive malignancy
  • Undiagnosed vaginal bleeding, until malignancy is excluded
  • Active venous or arterial thromboembolism; stroke or myocardial infarction within 12 months
  • Severe liver impairment (Child-Pugh C), or liver enzymes above 3× upper limit of normal
  • Peanut allergy, for the peanut-oil-based capsule
  • Pregnancy outside a supervised obstetric indication
  • Porphyria
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Key Interactions
  • CYP3A4 inducers (rifampin, carbamazepine, St John's wort)
  • CYP3A4 inhibitors (ketoconazole, ritonavir, grapefruit juice)
  • Benzodiazepines (lorazepam), "Z-drugs" (zolpidem), gabapentinoids (pregabalin), opioids, alcohol
  • Over-the-counter sedating antihistamines (diphenhydramine)
  • Sedating supplements (valerian, kava, high-dose melatonin, cannabidiol)
  • Oral estrogen
  • Thyroid hormone replacement (levothyroxine)
  • Antihypertensives (amlodipine) and diuretics (spironolactone)
    •

Risk & Side Effects

  • High: Sedation and next-day psychomotor slowing; failure of endometrial protection with transdermal or under-dosed regimens; bleeding, spotting and headache; bloating, breast tenderness and fluid shifts
    •
  • Medium: Negative mood and irritability in susceptible women; breast cancer risk beyond five years of use
    •
  • Low: Rise in free thyroxine
    •
  • Speculative: Unknown consequences of long-term supraphysiologic dosing
    •

Monitoring

Marker Target Why
Endometrial thickness (transvaginal ultrasound) < 5 mm postmenopausal on therapy Direct read on whether the lining is protected
Serum progesterone No established on-therapy target; track against own pre-treatment value Confirms absorption, especially where response is absent
Estradiol 50–100 pg/mL on transdermal therapy Sets how much opposition the lining needs
TSH and free T4 TSH 0.5–2.0 mIU/L; free T4 upper half of reference range Progesterone raises free thyroxine modestly
HDL-C and LDL-C HDL-C > 60 mg/dL; LDL-C < 100 mg/dL Progesterone preserves the estrogen-driven HDL gain that progestins blunt
Fasting glucose and HbA1c Glucose 75–90 mg/dL; HbA1c < 5.4% Confirms the expected metabolic neutrality holds individually
ALT and AST Both < 25 U/L Progesterone is cleared by the liver; impairment raises exposure and sedation
Blood pressure < 120/80 mmHg Progesterone's mild sodium-losing action can lower it further

Cadence: Baseline panel before the first dose; symptoms and sleep at 4 weeks; thyroid and liver enzymes at 8–12 weeks; full panel with blood pressure at 6 months, then every 6–12 months. Endometrial imaging when bleeding is new, heavy or persistent.

Qualitative Assessment

  • Time to fall asleep and number of night awakenings, logged nightly
  • Frequency and intensity of hot flushes and night sweats, scored daily
  • Next-morning alertness, and whether drowsiness persists past the first hour awake
  • Mood stability and irritability, tracked specifically during the progesterone days of a cyclic regimen
  • Breast tenderness, bloating and any bleeding or spotting, with dates
Not medical advice. Educational distillation of a single evidence review. Confirm any decision with a qualified clinician, especially in the presence of prescription drugs or chronic conditions.