What is the recommended progesterone (hormone replacement therapy) dosing regimen for postmenopausal women?

Progesterone Dosing for Postmenopausal Women

For postmenopausal women requiring progesterone as part of hormone replacement therapy, the recommended dosage is 200 mg oral micronized progesterone daily at bedtime for 12 continuous days per 28-day cycle when used with estrogen therapy. 1

Dosing Regimens Based on Treatment Goals

Sequential (Cyclic) Regimen

• Standard dose: 200 mg oral micronized progesterone daily at bedtime for 12-14 days per 28-day cycle 1, 2
• This regimen typically induces withdrawal bleeding between cycles
• First-line choice for women who have recently entered menopause

Continuous Combined Regimen

• Standard dose: 100 mg oral micronized progesterone daily for 25 days per month 3, 4
• Designed to achieve amenorrhea (no bleeding) in 91-93% of women 4
• Better suited for women who prefer to avoid monthly bleeding
• Studies show this regimen effectively protects the endometrium by inhibiting mitoses 4

Formulation Considerations

Oral Micronized Progesterone

• First-line choice for postmenopausal hormone therapy 3
• Advantages:
  • Bioidentical to endogenous progesterone
  • Lower cardiovascular risk compared to synthetic progestins 2
  • Fewer metabolic side effects than synthetic progestins 3
  • Minimal impact on the beneficial lipid effects of estrogen 3
• Dosing considerations:
  • Should be taken at bedtime due to potential drowsiness 1
  • Should be taken with a glass of water while standing to improve swallowing 1

Alternative Progestins

• Medroxyprogesterone acetate (MPA): 2.5 mg daily for continuous regimens or 10 mg daily for 12-14 days per month for sequential regimens 5
• Dydrogesterone: 5 mg daily for continuous regimens or 10 mg daily for 12-14 days per month for sequential regimens 5
• Norethisterone: 1 mg daily for continuous regimens 5

Important Clinical Considerations

Endometrial Protection

• The primary purpose of progesterone in postmenopausal HRT is endometrial protection 2
• Inadequate progesterone dosing increases risk of endometrial hyperplasia and cancer 1
• Dose-response studies show that 300 mg daily of oral micronized progesterone achieves optimal endometrial protection, but 200 mg is generally sufficient when used for 12-14 days 6

Transdermal Progesterone Creams

• Not recommended for endometrial protection
• Studies show that transdermal progesterone creams (even at doses of 16-64 mg daily) fail to induce secretory changes in the endometrium 7
• Plasma levels achieved with transdermal application are insufficient for endometrial protection 7

Side Effects and Monitoring

• Common side effects include drowsiness, dizziness, and breakthrough bleeding 1
• Serious but rare side effects include venous thromboembolism and stroke 1
• Annual clinical review is necessary to assess symptom control and compliance 2
• Patients should report any persistent or recurring abnormal vaginal bleeding for appropriate diagnostic evaluation 2

Contraindications

• History of breast cancer or other hormonally-mediated cancers 2, 1
• Undiagnosed vaginal bleeding 1
• Active thromboembolic disorders 1
• History of arterial thrombotic disease 1
• Peanut allergy (some progesterone capsules contain peanut oil) 1

Duration of Therapy

• HRT should use the lowest effective dose for the shortest duration consistent with treatment goals 2
• The USPSTF recommends against using HRT for primary prevention of chronic conditions in postmenopausal women 5
• For women with premature ovarian insufficiency, HRT should be continued until the average age of natural menopause (45-55 years) 5

Remember that progesterone therapy should always be administered with estrogen in women with an intact uterus to prevent endometrial hyperplasia and cancer. The choice between sequential and continuous regimens should be based on the woman's preference regarding withdrawal bleeding and time since menopause.