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.
Pre-filled with a typical Progesterone setup. Edit any field — the draw updates live.
Insulin syringe — 100 units = 1 mL
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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 FreeBioidentical micronized progesterone (Prometrium, generics) is structurally identical to what ovaries produce. Synthetic progestins like medroxyprogesterone (MPA) and norethindrone have different receptor and metabolic profiles. The negative cardiovascular and breast cancer signals in older HRT trials were predominantly linked to synthetic progestins, not bioidentical progesterone. The French E3N cohort found that bioidentical progesterone plus estradiol had no increase in breast cancer risk versus estrogen alone — a meaningfully different signal than the WHI synthetic-progestin data.
Each route has a different use case. Oral micronized progesterone at bedtime is the standard for menopausal HRT (100 mg/day continuous, or 200 mg/day cyclically 12-14 days per month) and is the form that drives the sleep benefit. Vaginal progesterone (Endometrin, Crinone) is used primarily in fertility treatment for luteal-phase support. Over-the-counter progesterone creams are generally too low-dose for endometrial protection and should not substitute for prescription micronized progesterone.
Yes. Oral progesterone at bedtime meaningfully improves sleep quality through a well-documented GABA-mediated mechanism. The metabolite allopregnanolone is a positive allosteric modulator of GABA-A receptors — similar mechanism to benzodiazepines, much milder. This is why providers typically prescribe oral progesterone at bedtime rather than in the morning, and why daytime sedation can be a complaint if dosing or timing is off.
For women with an intact uterus, yes — progesterone is required to protect the endometrium from unopposed estrogen, which can drive endometrial hyperplasia and cancer. The two standard regimens are continuous (100 mg progesterone nightly, no monthly bleed) and cyclic (200 mg progesterone 12-14 days per month, with a monthly bleed). Women who have had a hysterectomy don't need progesterone for endometrial protection, but some still take it for sleep and mood support.
Yes, substantially. A high-fat meal increases peak progesterone concentration roughly 22x and AUC roughly 7x compared with fasted dosing. That's enough to meaningfully amplify sedation and dose-dependent side effects if paired with a big fatty dinner and then a bedtime dose. Pick a consistent pattern (with food or without) and stick with it.
Common dose-dependent effects include drowsiness and sedation (a feature, not a bug, at bedtime), dizziness, breast tenderness, bloating, and mood changes during initial titration. Prometrium capsules contain peanut oil, so known peanut allergy is a contraindication — compounded versions avoid this. Active DVT/PE, active liver disease, known or suspected breast cancer, and undiagnosed vaginal bleeding are contraindications. Use caution with history of depression, gallbladder disease, and migraines.
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