• Progesterone is a synthetic (man-made) hormone that plays important roles in the menstrual cycle, the early stages of pregnancy, and in protecting the uterus.
• Naturally occurring progesterone induces secretory changes in the endometrium, promotes breast development, relaxes the uterus, blocks the maturation and release of a follicle, and maintains pregnancy.
• Although progesterone is known as a female hormone, the adrenal glands and testes in males also produce progesterone which is then converted into testosterone.
• Progesterone belongs to the class of medicines known as progestins.

• Used for the prevention of endometrial hyperplasia (thickening) in postmenopausal women receiving estrogens who have not had a hysterectomy.
• Given for the treatment of secondary amenorrhea (cessation of regular periods for 3 months or irregular periods for 6 months).
• May be given in combination with estrogens as part of menopausal replacement therapy.
• Intramuscular forms may be given for amenorrhea or abnormal bleeding from the uterus.
• Transforms a proliferative endometrium into secretory endometrium.
• Inhibits the secretion of pituitary gonadotropins which in turn prevents follicle maturation and ovulation.
• Intravaginal gel containing progesterone may be used as part of assisted reproductive technology for infertile women with progesterone deficiency or the treatment of secondary amenorrhea.
• Progesterone vaginal inserts may be prescribed to support the implantation of an embryo and early pregnancy.
• May be used for other, unapproved, indications, such as the reducing the risk of recurrent spontaneous preterm birth. Micronized progesterone may be used in gender affirming therapy to improve breast development.
• Available as a cream, vaginal gel, oral capsule, and IM formulation.
• Generic progesterone is available.

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Common side effects include breakthrough bleeding, weight changes (increase or decrease), abdominal cramps, breast tenderness and galactorrhea (milk production), dizziness, headache, and mood changes. Anxiety, bloating, cough, diarrhea, fluid retention, muscle pain, nausea, and tiredness may also occur. Changes in cervical erosion and cervical secretions, acne, hair loss and facial hair growth, rash, and insomnia have also been reported. Progesterone injection can cause pain, redness, and swelling at the site of the injection.
• Progesterone may adversely affect carbohydrate and lipid metabolism.
• Formulations of progesterone may contain Arachis oil (peanut oil) or sesame oil, which some women may be allergic to. Do not use in women with a known sensitivity to sesame oil or seeds or with a known sensitivity to progesterone. Acute eosinophilic pneumonia has been reported in patients receiving progesterone in sesame oil; discontinue immediately.
• Should not be given to women with undiagnosed genital bleeding; a history of, or suspected/current, breast cancer; active deep vein thrombosis or other blood clots or a history of these blood clots; a history of or suspected/current thromboembolic disease (such as a stroke or heart attack), or liver disease. Should not be used in women who have had an abortion or ectopic pregnancy and associated with an increased risk of blood clots, such as pulmonary embolism and stroke when used in combination with an estrogen.
• May not be suitable for women with systemic lupus erythematosus, metabolic bone disease, high blood pressure, a history of depression, kidney disease, or a history of endometriosis. Some people with diabetes may experience a decrease in glucose tolerance when taking estrogen-progestin combination treatment.
• Progesterone use, in association with estrogen, has been associated with an increased risk of developing dementia, particularly in women over the age of 65 years.
• Progesterone should not be given to reduce the risk of cardiovascular disease. Progesterone plus estrogen use has been associated with an increased risk of breast cancer.
• Discontinue progesterone pending examination if there is a sudden partial or complete loss of vision or a sudden onset of proptosis (abnormal protrusion or displacement of an eye), diplopia (double vision), or migraine.
• Should only be used during pregnancy under specialist advice. progesterone at high doses impairs fertility. It is unknown the effect progesterone has on a breastfeeding infant.
• Administration of the injection may cause local irritation.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

• When using the vaginal gel, remove the applicator from the wrapper, push the plunger into place, twist off the cap counterclockwise, then gently insert it into the vagina and push the plunger. A small amount of gel will remain in the applicator following insertion.
• If using the vaginal insert, use the disposable applicator provided.
• Oral capsules are best administered at bedtime with a full glass of water.
• May interact with grapefruit juice and grapefruit products.
• Before starting progesterone your doctor should perform a pretreatment physical examination that should include your breasts and pelvic organs as well as a pap smear.
• Report any worrying side effects, such as chest pain, flu-like symptoms, cough, vision changes, problems with urination, breathing, or breast changes to your doctor.
• You may experience changes in your menstrual flow while taking progesterone. Talk to your doctor about this. Progesterone may also increase your risk of developing a blood clot, which may occur in your legs, lungs, heart, or brain.
• Taking progesterone slightly increases your risk of developing breast cancer and you should perform a breast self-examination every month.
• Talk to your doctor about stopping progesterone temporarily if you have surgery scheduled (usually discontinued 4 to 6 weeks before surgery).
• If you are pregnant or intending to become pregnant tell your doctor. It is not known if it is safe to breastfeed while taking or being administered progesterone.

• Peak levels of progesterone are reported within 3 hours of administration of the oral capsules, 8 hours after administration of the IM injection, 3.5-7 hours after administration of the intravaginal gel, and 17 to 24 hours after administration of the vaginal insert.

Medicines that interact with progesterone may either decrease its effect, affect how long it works for, increase side effects, or have less of an effect when taken with progesterone. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with progesterone include:

• anticoagulants, such as apixaban, edoxaban, or warfarin
• anticonvulsants, such as carbamazepine, fosphenytoin, or lamotrigine
• antidiabetic agents, such as metformin, insulin, and glipizide
• antifungals, such as griseofulvin or ketoconazole (may increase blood levels of progesterone)
• aprepitant
• cyclosporine
• echinacea
• grapefruit products
• HIV medications, such as darunavir
• iloperidone
• ivacaftor
• medications given to treat cancer, such as dabrafenib, or idelalisib
• mitotane
• rifampin
• some heart medications, such as diltiazem
• St. John's Wort
• ubrogepant
• venetoclax.

Note that this list is not all-inclusive and includes only common medications that may interact with progesterone. You should refer to the prescribing information for progesterone for a complete list of interactions.