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Progesterone binds to progesterone receptors throughout the body, balancing estrogen effects, supporting uterine health, calming the nervous system, promoting sleep, and supporting thyroid function.
The only FDA-approved bioidentical oral progesterone (Prometrium) contains peanut oil — unsuitable for patients with peanut allergies. Compounding allows custom doses, peanut-free capsules, creams, and vaginal/rectal suppositories not commercially available.
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Progesterone is a steroid hormone produced primarily by the corpus luteum after ovulation and by the placenta during pregnancy. It plays a critical role in the menstrual cycle, pregnancy maintenance, and as a counterbalance to estrogen's proliferative effects.
Bio-identical progesterone (chemically identical to human progesterone) is distinct from synthetic progestins (medroxyprogesterone acetate, norethindrone) used in older HRT formulations. Research suggests bio-identical progesterone has a more favorable safety profile, particularly regarding breast cancer and cardiovascular risk.
Compounded progesterone is widely used in BHRT protocols, for peri-menopausal hormone balance, insomnia, anxiety, and as uterine protection for women on estrogen therapy.
Progesterone Receptor Activation
Progesterone binds to nuclear progesterone receptors (PR-A and PR-B), modulating gene expression in the uterus, breast, brain, and cardiovascular tissue.
GABA Modulation
Progesterone metabolizes to allopregnanolone — a potent positive allosteric modulator of GABA-A receptors. This is why progesterone promotes relaxation, reduces anxiety, and improves sleep.
Estrogen Counterbalance
Progesterone downregulates estrogen receptors, preventing estrogen-driven endometrial proliferation and reducing breast tissue stimulation.
BHRT: Essential component of bio-identical hormone replacement therapy — uterine protection with estrogen
Menstrual: PMS, PMDD, luteal phase deficiency, heavy periods
Perimenopause: Irregular cycles, mood swings, sleep disruption
Sleep and Anxiety: Leverages GABA-modulating effects for improved sleep and reduced anxiety
Pregnancy Support: Luteal phase support in fertility protocols
BHRT / Uterine Protection: 100–200mg oral capsule at bedtime for 12–14 days/cycle or continuously
Sleep / Anxiety: 50–100mg at bedtime
Vaginal Suppository: 25–200mg daily or per protocol
Transdermal Cream: 20–40mg/day typically (absorption variable)
Dosing individualized based on hormone labs and symptoms. Higher oral doses leverage GABA effects for sleep.
Oral progesterone has a significant first-pass metabolism effect that enhances its sedating/sleep-promoting properties — this is often desirable when used at bedtime. Transdermal progesterone has lower and more variable absorption but avoids first-pass metabolism. Providers often start low and adjust based on symptom response and serum progesterone levels.
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