For hormone replacement therapy (HRT), does the Depo-Provera (medroxyprogesterone) injection cover the need for progesterone and what is the typical starting dose of estrogen?

Depo-Provera for Hormone Replacement Therapy

Depo-Provera (depot medroxyprogesterone acetate) is NOT appropriate for hormone replacement therapy in postmenopausal women—it is a contraceptive formulation that delivers supraphysiologic doses of progestin without estrogen, and therefore cannot serve as progesterone replacement in HRT. 1

Why Depo-Provera is Inappropriate for HRT

• Depo-Provera delivers 150 mg of medroxyprogesterone acetate intramuscularly every 13 weeks, which is designed for contraception through ovulation suppression, not hormone replacement. 1

• This contraceptive dose maintains serum MPA levels around 1.0 ng/mL for three months and actually suppresses estradiol to early follicular phase levels (mean ~50 pg/mL), which would worsen menopausal symptoms rather than treat them. 2

• The formulation causes endometrial atrophy and is specifically designed to prevent pregnancy, not to provide physiologic hormone replacement. 2

Correct Progesterone Options for HRT

For postmenopausal hormone replacement therapy, micronized progesterone is the preferred progestogen due to its superior cardiovascular and thrombotic safety profile compared to synthetic progestins like medroxyprogesterone acetate. 3, 4

Sequential Regimen (if uterus present):

• Micronized progesterone 200 mg orally daily for 12-14 days per month is the recommended first-line approach. 3
• Alternative: Vaginal micronized progesterone 200 mg daily for 12-14 days per month. 3
• Other options include medroxyprogesterone acetate 10 mg daily for 12-14 days per month or dydrogesterone 10 mg daily for 12-14 days per month. 3

Continuous Combined Regimen:

• Micronized progesterone 100 mg orally daily continuously when combined with transdermal estradiol. 3, 4
• Alternative: Medroxyprogesterone acetate 2.5 mg daily continuously. 3
• Alternative: Dydrogesterone 5 mg daily continuously. 3

Starting Estrogen Dose for HRT

Begin with transdermal 17β-estradiol 50 mcg daily (0.05 mg patch) as the lowest effective dose. 3, 4

Rationale for Starting Dose:

• The principle of "lowest effective dose for shortest duration" is paramount given the cardiovascular and thrombotic risks that emerge within the first 1-2 years of therapy. 5, 3

• Transdermal estradiol is preferred over oral formulations because it avoids first-pass hepatic metabolism, resulting in lower thrombotic risk. 3

• The dose range is 50-100 mcg daily for transdermal patches, with 50 mcg being the appropriate starting point. 4

Dose Titration:

• Reassess at 3 months to evaluate symptom control and adjust upward to 100 mcg daily only if menopausal symptoms persist. 4

• Never start with high doses, as the Women's Health Initiative demonstrated that for every 10,000 women taking estrogen-progestin for 1 year, there are 7 additional CHD events, 8 more strokes, 8 more pulmonary emboli, and 8 more invasive breast cancers. 5, 3

Critical Clinical Pitfalls

• Do not confuse contraceptive formulations with HRT formulations—Depo-Provera is a contraceptive that suppresses ovarian function, while HRT aims to replace physiologic hormone levels. 1, 2

• Women with an intact uterus require progestogen for endometrial protection when taking estrogen—unopposed estrogen increases endometrial cancer risk. 5

• Micronized progesterone provides better sleep quality and quality of life outcomes compared to medroxyprogesterone acetate when used in HRT regimens. 6, 7

• Annual clinical review is mandatory to assess compliance, side effects, and ongoing risk-benefit balance. 3