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

Created on 06/17/2026 – Quick Reference based on Evidence Review created using AI4L / Opus 4.8 – Audit

Progesterone is a hormone made after ovulation that calms the nervous system and supports sleep. Its clearest value is protecting the womb lining in women taking estrogen; it also modestly aids sleep and appears safer for the breast over about five years than older synthetic versions. Its main downside is drowsiness, so it is taken at night. (Full Review)

Protocol

Endometrial Protection
100 mg nightly (continuous)
Or 200 mg nightly for 12–14 days/month (sequential), alongside estrogen in women with a uterus
Sleep / Symptoms
100–200 mg at bedtime
300 mg has been used in sleep research but increases next-morning grogginess
Timing
Bedtime
Single nightly dose; take with food containing some fat to improve absorption
Time to effect
Endometrial Protection
Each dosing cycle
Protection accrues over each dosing cycle
Sleep Effect
Within hours
Sedative and sleep effects felt within hours of the first bedtime dose
Symptom Relief
Days to weeks
Symptom relief develops over days to weeks

Benefits

Contraindications
  • Current or past hormone-receptor-positive breast cancer
  • Known or suspected estrogen/progesterone-dependent tumors
  • Active or recent venous thromboembolism
  • Recent thromboembolic stroke (<12 months)
  • Active liver disease (decompensated cirrhosis, Child-Pugh Class C)
  • Undiagnosed vaginal bleeding
  • Known progesterone hypersensitivity
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Key Interactions
  • Strong CYP3A4 inducers (rifampin, carbamazepine, phenytoin, St. John's Wort)
  • Strong CYP3A4 inhibitors (ketoconazole, ritonavir, clarithromycin, grapefruit juice)
  • Sedating CNS depressants (benzodiazepines, opioids, alcohol)
  • Sedating antihistamines (diphenhydramine, doxylamine)
  • Sedative supplements (melatonin, valerian, magnesium glycinate, kava, ashwagandha)
  • Accompanying estrogen route and dose (transdermal estradiol lower-risk than oral)
    •

Risk & Side Effects

  • High: Sedation, drowsiness, and dizziness
    •
  • Medium: Increased risk of blood clots and stroke; breast cancer risk with prolonged use
    •
  • Low: Mood changes, bloating, and breast tenderness
    •
  • Speculative: Autoimmune progesterone dermatitis; long-term metabolic effects of chronic use
    •

Monitoring

Marker Target Why
Serum progesterone Not routinely targeted for oral therapy Confirms exposure where adherence or absorption is in question
Endometrial thickness (transvaginal ultrasound) <4–5 mm in postmenopausal women on therapy Detects estrogen-driven overgrowth and confirms adequate protection
Liver function (ALT, AST) Within standard reference range Oral hormones are liver-metabolized; flags impaired metabolism
Lipid panel Triglycerides <100 mg/dL (functional target) Oral hormone therapy can raise triglycerides
Complete blood count / clotting review Within standard reference range Supports vascular-risk assessment alongside personal history

Cadence: Baseline, at ~3 months after initiation, then every 6–12 months; promptly evaluate any unscheduled vaginal bleeding and follow age-appropriate breast screening (mammography).

Qualitative Assessment

  • Sleep quality: Faster sleep onset, fewer night awakenings, more restorative sleep
  • Mood and calm: Reduced anxiety or irritability, or early detection of paradoxical low mood
  • Vasomotor symptoms: Reduction in night sweats where present
  • Absence of warning signs: No unscheduled vaginal bleeding, new breast lumps, leg swelling, or signs of a clot
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.