Progesterone

Progesterone is a hormone medication available in multiple forms and brands, each approved for specific uses.

• Progesterone capsules and Prometrium (oral capsules): prevent endometrial hyperplasia in postmenopausal women with a uterus taking conjugated estrogens; also treat secondary amenorrhea
• Progesterone injection: treats amenorrhea and abnormal uterine bleeding due to hormonal imbalance (when structural causes have been ruled out)
• Crinone 8% vaginal gel: progesterone supplementation or replacement as part of ART treatment for infertile women
• Crinone 4% vaginal gel: treatment of secondary amenorrhea; Crinone 8% may be used if Crinone 4% is not effective
• Endometrin and progesterone vaginal inserts: support embryo implantation and early pregnancy as part of ART treatment for infertile women
• P25 Progesterone Cream (transdermal): labeled for external cosmetic use; described as providing temporary relief from menopausal symptoms such as hot flashes
• P50 Progesterone Cream, P75 Lav Progesterone Cream: labeled for external cosmetic use; applied transdermally
• BUNUSS Phyto-Pro Skin Cream: labeled for topical external use

Progesterone is chemically identical to the progesterone your ovaries naturally make. It acts on the lining of the uterus (endometrium) to regulate and protect it — which is why it's paired with estrogen therapy to prevent the uterine lining from becoming abnormally thick. In fertility treatment, it supports the conditions needed for an embryo to implant and a pregnancy to begin. Oral capsules use a micronized form (very finely ground) to improve how well the body absorbs progesterone when taken by mouth.

The right form, dose, and schedule for progesterone depends entirely on what it is being treated and which product is prescribed. Capsules are generally taken at bedtime, and taking them with food improves absorption. Vaginal gels and inserts are placed into the vagina according to a schedule your prescriber sets — frequency and duration differ depending on whether you are in a fertility program or being treated for missed periods. Injections are given into the muscle by a healthcare provider.

• Never adjust your schedule or switch brands or forms without talking to your prescriber first
• If you miss a dose, ask your pharmacist or prescriber what to do — do not double up without guidance

The most commonly reported side effects from progesterone capsule studies include:

• Headache
• Breast tenderness or pain
• Dizziness
• Abdominal bloating or pain
• Vaginal discharge
• Nausea or vomiting
• Depressed mood
• Hot flashes
• Constipation

More serious reactions — such as chest pain, sudden severe headache, vision changes, leg swelling, or signs of a blood clot — require immediate medical attention. Stop the medication and seek emergency care if any of these occur.

• Blood clots, stroke, and heart attack: Using progesterone combined with estrogen increases the risk of deep vein thrombosis (blood clot in a vein), pulmonary embolism (blood clot in the lungs), stroke, and heart attack. These risks were seen within the first year of use in large studies.
• Breast cancer: Combined estrogen plus progestin therapy is associated with an increased risk of invasive breast cancer. Women should have regular breast exams and mammograms as recommended by their provider.
• Dementia: In women 65 and older, combined estrogen plus progestin therapy was linked to an increased risk of probable dementia. It is not known whether this applies to younger postmenopausal women.
• Endometrial and ovarian cancer: Estrogen use alone raises endometrial cancer risk; progesterone is added to reduce this risk. A non-significant trend toward increased ovarian cancer risk was also observed in combined therapy studies.
• Vision changes: Retinal blood clots have been reported. Sudden vision loss or double vision requires immediate evaluation and may mean stopping the medication.
• Not for preventing heart disease or dementia: This medication should not be used to try to prevent cardiovascular disease or dementia — evidence shows it does not help and may cause harm in those contexts.

Progesterone has a limited number of documented interactions from the label, but a few are important to be aware of:

• Ketoconazole (antifungal): This drug can inhibit the liver enzymes that break down progesterone, which could increase progesterone levels in your body — tell your prescriber if you are prescribed an antifungal
• Lab test interference: Estrogen plus progestin therapy can alter results for liver function tests, blood clotting factor tests, thyroid function tests, and certain hormonal measurements — always tell your lab and any treating provider that you are taking this medication

This is not a complete list of interactions. Always talk with your doctor or pharmacist before starting, stopping, or changing any medication.

• Do not use progesterone capsules if you have a peanut allergy — the capsules contain peanut oil
• Do not use if you have known, suspected, or a history of breast cancer
• Do not use if you have or have had deep vein thrombosis, pulmonary embolism, stroke, or heart attack
• Do not use if you have known liver disease or dysfunction
• Do not use if you have undiagnosed abnormal genital bleeding
• Do not use if you are known or suspected to be pregnant, unless specifically prescribed as part of ART fertility treatment
• Older adults (65+): combined estrogen plus progestin therapy carries an increased risk of probable dementia — discuss this carefully with your prescriber
• Kidney or liver impairment: the effect on how progesterone capsules are processed has not been fully studied — inform your prescriber of any kidney or liver conditions
• Allergy to any ingredient in the product: tell your prescriber or pharmacist before starting

There are no human studies specifically on progesterone overdose. If too much is taken, the capsules should be stopped and treatment should focus on managing symptoms. Contact Poison Control or seek emergency medical care right away if you suspect an overdose.

Progesterone acts on the uterine lining (endometrium) to regulate and stabilize it. When used with estrogen, it significantly reduces the risk of endometrial hyperplasia — in one clinical study, only 6% of women using combined progesterone capsules with estrogen developed any degree of hyperplasia, compared to 64% of women on estrogen alone. In secondary amenorrhea, a course of progesterone therapy can trigger withdrawal bleeding (a period-like bleed) within days of completing the treatment. In fertility treatment, it supports corpus luteal function — the hormonal activity needed for embryo implantation and early pregnancy to succeed.

When progesterone capsules are taken by mouth, peak blood levels are reached within about 1.5 to 3 hours. Taking the capsules with food meaningfully increases how much progesterone gets absorbed compared to taking them on an empty stomach. Progesterone is very heavily protein-bound in the bloodstream — about 96–99% is attached to proteins, mainly albumin and a protein called transcortin. The liver breaks progesterone down into metabolites that are then eliminated mainly through the kidneys in urine, with some leaving the body through bile and stool.

Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) . Protect from excessive moisture. Dispense in tight, light-resistant container as defined in USP/NF, accompanied by a Patient Insert.