What is micronized progesterone?

Micronized Progesterone: Clinical Applications and Benefits

Micronized progesterone is a bioidentical form of progesterone that is chemically identical to the natural hormone produced by the ovaries, processed into tiny particles to improve oral absorption and bioavailability. Natural micronized progesterone has a more favorable safety profile compared to synthetic progestogens, particularly regarding cardiovascular effects, thrombotic risk, and breast tissue effects. 1

Pharmacology and Formulation

• Micronized progesterone is available in oral capsules (100mg and 200mg) and vaginal gel formulations 2
• The micronization process increases bioavailability by reducing particle size
• Maximum serum concentrations are achieved within 3 hours of oral administration 2
• Bioavailability is increased when taken with food 2
• Contains peanut oil as an inactive ingredient in many oral formulations (important contraindication for patients with severe peanut allergies) 1, 2

Clinical Applications

Hormone Replacement Therapy (HRT)

Micronized progesterone is a preferred option for HRT in women with intact uterus:

• Protects the endometrium from hyperplasia when combined with estrogen 1, 3
• Recommended dosing:
  • 200 mg orally for 12-14 days per month in sequential regimens 4
  • 100 mg daily for continuous regimens 5
• European Society for Human Reproduction and Embryology (ESHRE) includes micronized progesterone among recommended progestogens for HRT in women with ovarian insufficiency due to its safer pharmacological profile 1

Premature Ovarian Insufficiency (POI)

For women with POI, micronized progesterone offers:

• Lower cardiovascular risk compared to synthetic progestogens 1
• Neutral or beneficial effect on blood pressure 1
• Better safety profile regarding thrombotic risk 1
• Dosing for adolescents with POI: Begin with 100-200 mg/day during 12-14 days of the month after 2 years of estrogen therapy or when breakthrough bleeding occurs 1

Advantages Over Synthetic Progestogens

1. Cardiovascular effects:

   • Minimizes hormone-related cardiovascular risks 1
   • Neutral or beneficial effect on blood pressure 1

2. Thrombotic risk:

   • One of the best safety profiles regarding thrombotic risk 1

3. Breast tissue effects:

   • Does not increase cell proliferation in breast tissue (unlike synthetic progestogens like medroxyprogesterone acetate) 3
   • May be associated with lower breast cancer risk compared to synthetic progestogens 3

4. Metabolic effects:

   • Less negative impact on lipid metabolism compared to synthetic progestogens 1
   • Less androgenic effects 1

Side Effects and Contraindications

• Main side effect: mild and transient drowsiness (minimized by taking at bedtime) 5
• Contraindications:
  • Severe peanut allergies (for formulations containing peanut oil) 1, 2
  • Hormone receptor-positive breast cancer 1
  • Active liver disease 4
  • History of venous thromboembolism or stroke 4

Clinical Pearls

• For optimal absorption, oral micronized progesterone should be taken with food 2
• Vaginal gel formulations are available for patients with peanut allergies 1
• When used for HRT, micronized progesterone should be combined with estrogen in women with an intact uterus to prevent endometrial hyperplasia 4, 3
• The Postmenopausal Estrogen/Progestin Intervention trial recommended oral micronized progesterone as the first choice for opposing estrogen therapy in non-hysterectomized postmenopausal women 5

Micronized progesterone represents an important advancement in hormone therapy, offering the benefits of natural progesterone with improved bioavailability and a favorable safety profile compared to synthetic alternatives.