The often-underrated half of menopause HRT — protects the uterus from unopposed estrogen, supports sleep, and is available as bioidentical micronized progesterone.
Progesterone is the primary gestagen hormone, produced by the ovaries after ovulation and by the placenta during pregnancy. Modern HRT uses micronized progesterone (Prometrium, generics) — bioidentical, orally bioavailable, and distinct from synthetic progestins (medroxyprogesterone, norethindrone) which carry different risk profiles.
Prescription-only. Primary uses: endometrial protection when taking estrogen, perimenopausal sleep and mood support, luteal-phase support in fertility treatment, and prevention of preterm birth in at-risk pregnancies.
FDA approved. Prescription only. Over-the-counter "progesterone cream" products exist but are generally too low-dose for endometrial protection — don’t substitute for prescription micronized progesterone.
Binds PR-A and PR-B in the endometrium, breast, brain, and other tissues. The endometrial effect is why it’s required alongside estrogen in women with a uterus.
Metabolite allopregnanolone is a positive allosteric modulator of GABA-A receptors — which is why oral progesterone at bedtime often improves sleep (similar mechanism to benzodiazepines, much milder).
Medroxyprogesterone (MPA) and other synthetic progestins have different receptor and metabolic profiles. The negative CV and breast cancer signal in older HRT trials was predominantly linked to synthetic progestins, not bioidentical progesterone.
| Benefit | Evidence |
|---|---|
| Endometrial protection | Prevents endometrial hyperplasia / cancer in women on estrogen with intact uterus |
| Sleep | Oral bedtime dose meaningfully improves sleep quality; well-documented GABA-mediated effect |
| Anxiety / mood | Calming effect; useful in perimenopausal mood symptoms |
| Breast cancer risk | Unlike synthetic progestins, E6N French cohort: bioidentical progesterone + estradiol had no increase in breast cancer risk vs estrogen alone |
| Preterm birth prevention | Vaginal or IM progesterone reduces preterm birth in women with short cervix or prior preterm history |
Build your protocol, log every dose, monitor your body's response, and get reminders so you never miss a dose.
Start Tracking FreeFood matters — take oral progesterone consistently with respect to meals: PMID 34806331 shows that a high-fat meal increases peak progesterone concentration roughly 22× and AUC roughly 7× compared with fasted dosing. That’s enough to meaningfully amplify sedation and dose-dependent side effects if you pair it with a big fatty dinner and then drop the dose at bedtime. Pick a consistent pattern (with food or without) and stick with it.
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Progesterone is a prescription medication. StackTrax does not sell, prescribe, or facilitate purchase of prescription drugs.
Find a clinician who can order baseline lab work, screen for contraindications, monitor your response, and adjust dosing over time. Options to consider:
Before starting, you’ll typically want:
Avoid sources that offer prescription medications without labs, medical history, or licensed-provider oversight. If a telehealth service promises a prescription after a 5-minute questionnaire, that’s a red flag.
Build your protocol, log every dose, monitor your body's response, and get reminders so you never miss a dose.
Start Tracking FreeDisclaimer: This guide is for educational and informational purposes only and is not intended as medical advice, diagnosis, or treatment. The compounds discussed are not FDA approved for human use. Always consult a qualified healthcare provider before starting any new supplement or peptide protocol. StackTrax does not sell peptides or supplements directly — purchase links go to third-party vendors. StackTrax is not responsible for the products, quality, or business practices of any third-party vendor. This page contains affiliate links — StackTrax may earn a commission on purchases at no extra cost to you.
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StackTrax guides cover peptides and compounds that are not FDA-approved for the uses discussed. The dosing, reconstitution, and safety information is compiled from published research and community protocols for educational purposes only.
Before using any compound mentioned here, consult a qualified healthcare provider. StackTrax does not sell, prescribe, or recommend these substances for personal use.
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