What is the most common side effect of Depo-Provera (medroxyprogesterone acetate) in women of reproductive age?

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Most Common Side Effect of Depo-Provera

Menstrual irregularities are the most common side effect of Depo-Provera, experienced by nearly all users initially, with irregular bleeding, spotting, and amenorrhea being the predominant patterns. 1, 2

Menstrual Changes

  • Menstrual irregularities occur in approximately 92.6% of Depo-Provera users, making this the most frequently reported side effect 3
  • The FDA drug label confirms that change in normal menstrual cycle is "the side effect reported most frequently by women who use medroxyprogesterone acetate injectable suspension for birth control" 2
  • During the first year, users experience irregular or unpredictable bleeding, spotting, increased or decreased menstrual bleeding, or complete absence of bleeding 2
  • Amenorrhea becomes increasingly common with continued use: 55-57% of women report no menstrual bleeding after one year, and 68% after two years 2, 4
  • These menstrual changes are generally not harmful but significantly affect patient satisfaction and continuation rates 1

Other Common Side Effects

Beyond menstrual irregularities, the following side effects occur frequently:

Weight Gain

  • Weight gain is the second most common side effect, reported by approximately two-thirds of users 2
  • Average weight gain is about 5 pounds during the first year and 8 pounds over two years of use 2
  • Weight gain status at 6 months strongly predicts future excessive weight gain with ongoing use 1

Additional Frequent Side Effects

  • Headache, abdominal pain or discomfort, nervousness, dizziness, and weakness are commonly reported 2, 4
  • Non-menstrual side effects collectively occur in 67.6% of users 3

Clinical Implications for Discontinuation

  • The 12-month discontinuation rate for Depo-Provera is approximately 49%, with menstrual side effects accounting for 23.1% of discontinuations and non-menstrual side effects (primarily weight gain and headaches) accounting for 35.6% 3
  • Among adolescents, 26% discontinue due to menstrual irregularities and 18% due to weight gain 5
  • 70% of those discontinuing due to irregular bleeding do so after only one injection, highlighting the importance of early counseling 5

Management Recommendations

  • Counsel all patients before initiation that menstrual irregularities are expected and typically improve over time, as this improves continuation rates 1
  • For persistent irregular bleeding, NSAIDs for 5-7 days can be offered as treatment 6
  • Reassure patients that amenorrhea with regular injections every 3 months is common and does not indicate pregnancy 2
  • If bleeding persists or becomes unacceptable despite treatment, offer counseling on alternative contraceptive methods 6

References

Guideline

Risks of Long-Term Depo Provera Use Beyond 2 Years

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

3-month contraceptive injection approved.

FDA medical bulletin : important information for health professionals from the U.S. Food & Drug Administration, 1993

Research

Long-term depot medroxyprogesterone acetate (Depo-Provera) use in inner-city adolescents.

The Journal of adolescent health : official publication of the Society for Adolescent Medicine, 1998

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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