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

Created on 08/04/2026 – Quick Reference based on Evidence Review created using AI4L / Opus 5 – Audit

Progesterone identical to the body's own protects the uterine lining in people taking estrogen; skin creams do not. Trials support faster, less broken sleep and fewer hot flushes and night sweats. Breast tissue, clotting and metabolism look better than with synthetic versions. Evidence beyond five years thins across the board. Drowsiness is the main drawback, so dosing is at night. (Full Review)

Protocol

Standard endometrial-protection regimen
200 mg oral, 12–14 days per cycle
At bedtime alongside estrogen, or 100 mg nightly continuously. Cyclic dosing brings monthly bleeding; continuous usually none after the first year.
Symptom-directed monotherapy
300 mg at bedtime
Where estrogen is unsuitable or unwanted; tested in randomized trials for hot flushes, night sweats, and sleep. Also cyclic at 300 mg for 14 days in perimenopause.
Best time of day
Bedtime, without exception, for oral dosing
Levels peak 1–3 hours after an oral dose, when sedation is at its maximum. Splitting the dose across the day turns the main benefit into the main side effect.
Time to effect
Endometrial protection
First treated cycle
Route-dependent: oral and, off-label, vaginal dosing achieve it; transdermal creams do not.
Hot flushes and night sweats
4–12 weeks
Benefit builds across this window; trials measured their primary outcome at week 12.
Sleep
First night
The effect appears when sleep is disturbed, not when it is already sound.

Benefits

Contraindications
  • Known or suspected breast cancer or other progesterone-sensitive malignancy
  • Undiagnosed abnormal genital bleeding
  • Active or recent (within 12 months) arterial thromboembolic disease
  • Active deep vein thrombosis or pulmonary embolism
  • Severe hepatic impairment (Child-Pugh Class C)
  • Known hypersensitivity to the product, including peanut allergy for peanut-oil capsules
  • Known or suspected pregnancy outside a supervised fertility protocol
  • Transdermal cream as the sole endometrial protection
  • Personal history of severe hormone-triggered depression
  • Driving or working within several hours of dosing
  • Men and transgender women outside a supervised protocol
  • First-time combined therapy more than 10 years past the final menstrual period
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Key Interactions
  • Strong CYP3A4 inducers (rifampin, carbamazepine, phenytoin, phenobarbital, St John's wort)
  • Strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir, grapefruit juice)
  • Central nervous system depressants (benzodiazepines, "Z-drugs", opioids, gabapentinoids, antihistamines)
  • Alcohol
  • Estrogen therapy (oral or transdermal estradiol, conjugated equine estrogens)
  • Supplements with additive sedative or GABA-ergic effects (valerian, kava, high-dose magnesium glycinate, melatonin, cannabidiol, L-Theanine)
  • Supplements affecting steroid metabolism or clearance (St John's wort, high-dose curcumin, berberine, saw palmetto, diindolylmethane)
  • Anticoagulants and antiplatelet agents (warfarin, apixaban, aspirin)
    •

Risk & Side Effects

  • High: Sedation, dizziness, and residual next-day impairment; no endometrial protection from transdermal creams
  • Medium: Endometrial cancer risk with long-term combined use; breast cancer risk beyond about five years; mood disturbance in susceptible individuals; cyclic bleeding, breast tenderness, and bloating; nausea and gastrointestinal upset; allergic reaction to capsule excipients
  • Low: Small reduction in high-density lipoprotein cholesterol; headache and migraine around hormone withdrawal; hepatic considerations with oral dosing
  • Speculative: Probable dementia carried over from the progestin class boxed warning; meningioma signal attaching to the progestogen class; suppression of endogenous hormones and antiandrogenic effects in men; insulin resistance at exposures above natural levels

Monitoring

Marker Target Why
Progesterone (serum) Mid-luteal >10 ng/mL; 15–20 ng/mL functional target in cycling women Confirms whether ovulation is occurring and quantifies the deficit
Estradiol 30–100 pg/mL on therapy Sets the context progesterone is opposing; unopposed estrogen is the risk being managed
Follicle-stimulating hormone <25 IU/L before menopause; >25–30 IU/L indicates the transition is well advanced Locates the user in the menopausal transition and guides cyclic versus continuous dosing
Endometrial thickness (transvaginal ultrasound) <4–5 mm in postmenopause The only direct measure of whether endometrial protection is working
Lipid panel including HDL cholesterol HDL >50 mg/dL in women, >40 mg/dL in men; triglyceride-to-HDL ratio <2 Progesterone produces a small HDL reduction that matters only if HDL is already low
TSH and free T4 TSH 0.5–2.0 mIU/L; free T4 in the upper half of the reference range Progesterone raises free thyroxine, which can alter dose requirements in treated thyroid disease
HbA1c and fasting insulin HbA1c <5.4%; fasting insulin <6 μIU/mL Confirms the expected metabolic neutrality and detects drift
Liver enzymes (ALT, AST) and bilirubin ALT <25 U/L in women, <30 U/L in men Oral dosing is metabolized hepatically and is contraindicated in active liver disease
Complete blood count with ferritin Ferritin 50–100 ng/mL Heavy perimenopausal bleeding depletes iron before hemoglobin falls
High-sensitivity C-reactive protein <1.0 mg/L General inflammatory marker; randomized data show it should not move on progesterone

Cadence: Symptom review at 4 weeks; lipids, thyroid, and liver enzymes at 3 months, then every 6–12 months. Breast imaging on the standard age-appropriate schedule; endometrial ultrasound only for unscheduled bleeding. Duration revisited at 12 months, then annually.

Qualitative Assessment

  • Time to fall asleep and number of night wakings, logged before starting and again at week four
  • Next-morning alertness, and whether residual sedation persists past the first hour
  • Frequency and severity of hot flushes and night sweats, scored daily rather than recalled monthly
  • Mood, irritability, and emotional flatness in the first two cycles, especially with prior premenstrual mood disturbance
  • Bleeding pattern — timing, duration, and whether it falls within the expected withdrawal window
  • Breast tenderness and bloating, which typically settle after the first cycles
  • Cognitive clarity and daytime energy, which no laboratory value captures
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.