What causes irregular bleeding with Depo Medroxyprogesterone Acetate (DMPA)?

Causes of Irregular Bleeding with DMPA

Irregular bleeding with DMPA is a direct pharmacologic effect of the progestin causing endometrial changes, not a pathologic condition—it occurs because DMPA induces endometrial atrophy, decreases endometrial vascular density, and disrupts normal menstrual cycling through sustained progestin exposure. 1

Primary Mechanism: Progestin-Induced Endometrial Changes

• DMPA causes the endometrium to become atrophic with small, straight endometrial glands and decidualized stroma, which is the fundamental reason for altered bleeding patterns 2
• Endometrial vascular density significantly decreases from baseline (approximately 150 vessels/mm²) to about 132 vessels/mm² after DMPA use, contributing to unpredictable bleeding episodes 3
• The sustained progestin levels (plateauing at approximately 1.0 ng/mL for about 3 months) continuously suppress normal endometrial development and cycling 2

Expected Bleeding Pattern Evolution

• Unscheduled bleeding or spotting is common with DMPA use, particularly in the initial months 1
• Amenorrhea becomes increasingly common over time: 55% of women report amenorrhea by month 12, and 68% by month 24 1
• These bleeding irregularities are generally not harmful and typically decrease with continued DMPA use 1

When to Suspect Underlying Pathology

While irregular bleeding is expected with DMPA, you must rule out other causes when clinically indicated:

• Pregnancy (DMPA does not guarantee 100% efficacy) 1
• Sexually transmitted infections 1
• Drug interactions with other medications 1
• New pathologic uterine conditions such as fibroids or polyps 1
• Unusually heavy bleeding should raise suspicion of a serious underlying condition 1

Important Clinical Caveat

• DMPA can mask symptoms of underlying pathology because it independently causes irregular bleeding patterns 1
• Before evaluation for unexplained vaginal bleeding suspicious for serious conditions, DMPA receives a Category 3 rating (risks usually outweigh benefits), meaning you should exercise caution in initiating DMPA until pathology is excluded 1
• The effects of DMPA may persist for some time after discontinuation, which can complicate diagnostic evaluation 1

Counseling to Prevent Discontinuation

• Enhanced counseling before DMPA initiation detailing expected bleeding patterns and reassurance that irregularities are generally not harmful has been shown to reduce discontinuation rates in clinical trials 1
• Heavy or "severe" bleeding appears very uncommon, occurring in only 1-2% of users 4