What are the secondary effects of monthly Depo‑Provera (medroxyprogesterone acetate) in older post‑menopausal women?

Depo-Provera in Postmenopausal Women: Not Indicated and Potentially Harmful

Depo-Provera (depot medroxyprogesterone acetate, DMPA) is not indicated for use in postmenopausal women and should not be prescribed for this population. This injectable contraceptive is FDA-approved solely for pregnancy prevention in reproductive-age women, not for hormone replacement therapy in older postmenopausal individuals 1.

Why DMPA Is Inappropriate for Postmenopausal Women

Mechanism and Intended Use

• DMPA works by suppressing ovarian estrogen production through inhibition of pituitary gonadotropins, creating a state of estrogen deficiency 2
• This mechanism is the opposite of what postmenopausal women need—postmenopausal women already have low estrogen and require estrogen supplementation, not further suppression 3
• DMPA is designed as a contraceptive for women of reproductive age (typically administered every 3 months at 150 mg IM or 104 mg subcutaneously), not as hormone therapy 4

Serious Adverse Effects in This Population

Bone Mineral Density Loss

• The FDA issued a black-box warning specifically highlighting that DMPA causes significant bone mineral density (BMD) loss, with mean decreases of 5-6% in spine and hip over 5 years of use 1
• Postmenopausal women already face accelerated bone loss (approximately 2% annually in the first 5 years after menopause) and are at high baseline risk for osteoporosis 3
• Adding DMPA would compound this risk catastrophically, with lumbar spine BMD decreasing by -2.86% after 1 year, -4.11% after 2 years, and -5.38% after 5 years 1
• While some BMD recovery occurs after discontinuation, recovery is incomplete, especially with longer duration of use 1, 2

Breast Cancer Risk

• DMPA combined with estrogen in older women shows a small but significant increase in breast cancer risk (relative risk 2.0 for recent users) and stroke risk 5, 6
• A population-based study found that recent DMPA use for ≥12 months was associated with a 2.2-fold increased risk of invasive breast cancer in younger women (ages 20-44), raising concerns about cumulative exposure 7
• Combined estrogen-progestogen therapy already adds approximately 8 invasive breast cancers per 10,000 women-years; using DMPA as the progestogen component would likely worsen this profile 3

Cardiovascular and Cognitive Effects

• Research suggests DMPA may contribute to increased stroke risk and cognitive decline in older women when combined with estrogen for postmenopausal hormone therapy 5, 6
• The FDA label documents increased risks of stroke, venous thromboembolism, and cardiovascular events with DMPA use 1

What Should Be Used Instead

For Postmenopausal Women Requiring Hormone Therapy:

• Transdermal estradiol (50 μg patch applied twice weekly) is the evidence-based first-line estrogen formulation because it bypasses hepatic first-pass metabolism and reduces cardiovascular and thromboembolic risks 3
• Micronized progesterone (200 mg orally at bedtime for 12-14 days per month, or 100-200 mg daily continuously) is the preferred progestogen for endometrial protection, with superior breast safety compared to synthetic progestins like medroxyprogesterone acetate 3, 8
• This combination reduces vasomotor symptoms by approximately 75%, prevents bone loss, and has a more favorable risk profile than DMPA-containing regimens 3

Key Contraindications to Any Hormone Therapy:

• Personal history of breast cancer, venous thromboembolism, stroke, coronary artery disease, or active liver disease 3
• Women >60 years or >10 years past menopause have less favorable risk-benefit profiles and should use the absolute lowest dose for the shortest duration if continuation is essential 3

Critical Clinical Pitfalls to Avoid

• Never prescribe DMPA to postmenopausal women—it is a contraceptive that suppresses estrogen, not a hormone replacement therapy 4, 1
• Never use DMPA as the progestogen component of postmenopausal hormone therapy—micronized progesterone or other oral progestogens are appropriate, but injectable DMPA is not 3, 8, 9
• Do not confuse "medroxyprogesterone acetate" formulations—oral MPA (2.5-10 mg daily) can be used in hormone therapy, but injectable depot MPA (150 mg every 3 months) cannot 3, 8
• Avoid custom compounded bioidentical hormones—the FDA has not approved any bioidentical hormone therapy, and data supporting safety claims are lacking 9

Bottom Line

If an older postmenopausal woman is currently receiving monthly Depo-Provera injections, this represents a prescribing error that should be corrected immediately. The medication should be discontinued, and if hormone therapy is indicated for menopausal symptoms, she should be transitioned to an appropriate regimen of transdermal estradiol plus oral micronized progesterone (if she has an intact uterus) or estradiol alone (if post-hysterectomy) 3, 9. The use of DMPA in this population exposes patients to unnecessary bone loss, potential breast cancer risk, and cardiovascular harm without providing appropriate hormone replacement 1, 5, 6.