Can Depo-Provera (medroxyprogesterone acetate) cause nipple discharge?

Can Depo-Provera Cause Nipple Discharge?

Yes, Depo-Provera (depot medroxyprogesterone acetate/DMPA) can cause nipple discharge, listed as "mastalgia" (breast tenderness) in pediatric guidelines, though nipple discharge itself is not explicitly documented as a common side effect in the major contraceptive guidelines reviewed. 1

Understanding the Mechanism

• DMPA causes a hypo-estrogenic state by suppressing ovulation and maintaining serum estradiol levels in the early to midfollicular phase range (mean approximately 50 pg/mL initially, declining to 10-92 pg/mL with long-term use) 2
• This hormonal alteration can affect breast tissue, as evidenced by the documented side effect of mastalgia (breast pain/tenderness) in DMPA users 1
• The progestin-dominant environment created by DMPA theoretically could stimulate breast tissue changes that might lead to nipple discharge, though this is not a prominently reported adverse effect in the literature

Clinical Evaluation Required

If nipple discharge occurs while using Depo-Provera, you must determine whether it is physiologic or pathologic:

Physiologic Discharge (Benign - No Imaging Needed)

• Bilateral discharge from multiple ducts 1
• White, green, or yellow in color 1
• Only occurs when provoked (non-spontaneous) 1
• If routine screening mammography is up to date and discharge is physiologic, no radiologic investigation is needed 1

Pathologic Discharge (Requires Workup)

• Unilateral discharge from a single duct 1
• Spontaneous (occurs without manipulation) 1
• Serous or blood-stained 1
• Any one of these features warrants imaging evaluation 1

Management Algorithm

For patients on Depo-Provera who develop nipple discharge:

1. Characterize the discharge using the criteria above to distinguish physiologic from pathologic 1

2. If physiologic and screening mammography is current: Reassure the patient and continue DMPA if desired 1

3. If pathologic or any concerning features:

   • Age ≥40 years: Obtain diagnostic mammography or digital breast tomosynthesis (DBT) plus breast ultrasound 1
   • Age 30-39 years: Obtain diagnostic mammography or DBT plus breast ultrasound 1
   • Age <30 years (females): Breast ultrasound is usually appropriate as initial imaging 1
   • Males (any age): Diagnostic mammography or DBT, as cancer incidence is 23-57% in males with nipple discharge 1

4. Consider discontinuing or switching contraception if the discharge is bothersome to the patient, even if benign, as DMPA's hormonal effects may be contributing 1

Key Clinical Pitfalls

• Do not dismiss nipple discharge as "just a side effect" without proper characterization - pathologic features require imaging regardless of contraceptive use 1
• Do not assume all discharge in DMPA users is benign - the 5-21% malignancy rate in pathologic nipple discharge applies to all patients, including those on hormonal contraception 1
• Do not order imaging for clearly physiologic discharge if screening mammography is current, as this leads to unnecessary procedures and patient anxiety 1
• Remember that DMPA causes multiple breast-related effects including mastalgia, and patients should have been counseled about potential adverse effects before the first injection to improve continuation rates 1