Progesterone

HRT MEMBERS ONLY

INDICATIONS FOR USE

Progesterone is used for hormone replacement therapy (HRT) in postmenopausal women, managing abnormal uterine bleeding, preventing endometrial hyperplasia, and supporting pregnancy in women with luteal phase defects.

ROUTE OF ADMINISTRATION

  • Available as oral capsules, topical creams, or intravaginal gels and suppositories.

COMMON INITIAL DOSING REGIMENS

  • Oral: 100–200 mg daily, typically taken at bedtime to reduce side effects.

  • Topical: Applied as 10–40 mg daily to thin skin areas.

  • Intravaginal: Doses range from 45–400 mg daily, depending on the indication (e.g., luteal phase support or endometrial protection).

MECHANISM OF ACTION

  • Progesterone binds to progesterone receptors, influencing gene expression to regulate menstrual cycles, support pregnancy, and maintain endometrial stability. It opposes the proliferative effects of estrogen on the endometrium.

COMMON SIDE EFFECTS

  • Neurological: Drowsiness, dizziness, or mood changes, particularly with oral administration.

  • Endocrine: Breast tenderness, bloating, or weight changes.

  • Gastrointestinal: Nausea, abdominal discomfort, or diarrhea.

  • Rare: Allergic reactions or severe mood disturbances such as depression.

CONTRAINDICATIONS

  • Absolute: Known or suspected breast cancer, active thromboembolic disorders, undiagnosed vaginal bleeding, or pregnancy (except when used to support pregnancy).

  • Relative: Use cautiously in women with a history of depression, migraines, or liver dysfunction.

MORE INFORMATION

  • FDA Safety Data Sheet may be found here

  • Stute P. The impact of micronized progesterone on the endometrium: a systematic review. Climacteric. 2016 [PubMed Link]

  • Memi E. Diagnostic and therapeutic use of oral micronized progesterone in endocrinology. Rev Endocr Metab Disord. 2024 [PubMed Link]

  • Taraborrelli S. Physiology, production and action of progesterone. Acta Obstet Gynecol Scand. 2015 [PubMed Link]

  • Stute P. The impact of micronized progesterone on breast cancer risk: a systematic review. Climacteric. 2018 [PubMed Link]

  • Giordano Imbroll M. A current perspective into young female sex hormone replacement: a review. Expert Rev Endocrinol Metab. 2020 [PubMed Link]

  • Marjoribanks J. Long-term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev. 2017 [PubMed Link]

  • Genazzani AR. Hormone therapy in the postmenopausal years: considering benefits and risks in clinical practice. Hum Reprod Update. 2021 [PubMed Link]

  • Prior JC. Oral micronized progesterone for perimenopausal night sweats and hot flushes a Phase III Canada-wide randomized placebo-controlled 4 month trial. Sci Rep. 2023 [PubMed Link]

  • Capozzi A. Clinical pharmacology of progestins. Minerva Obstet Gynecol. 2022 [PubMed Link]

  • Gordon JL. Efficacy of Transdermal Estradiol and Micronized Progesterone in the Prevention of Depressive Symptoms in the Menopause Transition: A Randomized Clinical Trial. JAMA Psychiatry. 2018 [PubMed Link]

  • Nolan BJ. Efficacy of Micronized Progesterone for Sleep: A Systematic Review and Meta-analysis of Randomized Controlled Trial Data. J Clin Endocrinol Metab. 2021 [PubMed Link]

  • Piette PCM. The pharmacodynamics and safety of progesterone. Best Pract Res Clin Obstet Gynaecol. 2020 [PubMed Link]

  • Kaemmle LM. The impact of micronized progesterone on cardiovascular events - a systematic review. Climacteric. 2022 [PubMed Link]