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Progesterone: 7 things you should know

Written by Carmen Fookes, BPharm on March 17, 2020.

1. How it works

  • Progesterone is a female hormone that has important roles in the regulation of ovulation and menstruation.
  • 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.

2. Upsides

  • 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.
  • Intravaginal gel containing progesterone may be used as part of assisted reproductive technology for infertile women with progesterone deficiency or for 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 reduce the risk of recurrent spontaneous preterm birth.
  • Available as a cream, vaginal gel, oral capsule, and IM formulation.
  • Generic progesterone is available.

3. Downsides

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 abdominal cramps, dizziness, headache, and mood changes. Anxiety, bloating, cough, diarrhea, fluid retention, muscle pain, nausea, and tiredness may also occur.
  • Formulations of progesterone may contain Arachis oil (peanut oil) or sesame oil, which some women may be allergic to.
  • 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.
  • May not be suitable for women with systemic lupus erythematosus, metabolic bone disease, high blood pressure, a history of depression, or a history of endometriosis.
  • 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.
  • Should only be used during pregnancy under specialist advice.
  • 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

4. Bottom Line

Progesterone is a female hormone that is used to treat disorders associated with ovulation, fertility, menstruation, and menopause. It may increase the risk of blood clots.

5. Tips

  • When using the vaginal gel, remove the applicator from the wrapper, push the plunger into place, twist off the cap counterclockwise, then gently insert 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.
  • Report any worrying side effects, such as chest pain, flu-like symptoms, cough, problems with urination, or breast changes to your doctor.
  • Talk to your doctor about stopping progesterone temporarily if you have surgery scheduled (usually discontinued 4 to 6 weeks prior to surgery).

6. Response and Effectiveness

  • 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.

7. Interactions

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
  • 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.


Progesterone Nov 2019

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use progesterone only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Copyright 1996-2021 Revision date: March 17, 2020.