Most Likely Adverse Effect of Intramuscular Medroxyprogesterone
Menstrual irregularities are the most common adverse effect of intramuscular depot medroxyprogesterone acetate (DMPA), experienced by nearly all users initially, with irregular bleeding, spotting, and amenorrhea being the predominant patterns. 1
Understanding the Menstrual Pattern Changes
The FDA drug label explicitly states that "most women using Medroxyprogesterone Acetate Injectable Suspension, USP experience disruption of menstrual bleeding patterns" with altered patterns including irregular or unpredictable bleeding or spotting. 2 This is not merely common—it affects virtually all users at the outset. 1
The pattern evolves predictably over time:
- By month 12, amenorrhea occurs in 55% of users 2
- By month 24, amenorrhea increases to 68% of users 2
- In adolescent populations, 30-40% experience no menstrual bleeding in any 3-month injection period, while those who do bleed average 8-13 days of bleeding between injections 3
Other Common Adverse Effects (In Order of Frequency)
While menstrual irregularities dominate the side effect profile, other effects include:
Weight gain is the second most significant concern:
- Average increase of 6.0 kg at 11 months and 9.0 kg at 17 months of use 3
- Reported by 27% of adolescent users 3
- Weight gain status at 6 months strongly predicts future excessive weight gain with ongoing use 4
Additional side effects reported in clinical studies include:
- Headache (25% of users) 3
- Nervousness 5
- Abdominal pain or discomfort 5
- Fatigue (23% of users) 3
- Dizziness 5
- Decreased sexual desire (15% of users) 3
Bone Mineral Density Concerns
Long-term use causes reductions in bone mineral density (BMD):
- Mean decreases of -5.38% in the spine after 5 years 2
- Similar decreases observed in total hip and femoral neck 2
- The FDA issued a black box warning in 2004 regarding this effect 4
- However, substantial recovery of BMD occurs after discontinuation 4, 2
Clinical Management Recommendations
For menstrual irregularities:
- 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, offer NSAIDs for 5-7 days 1
- If bleeding persists or becomes unacceptable despite treatment, counsel on alternative contraceptive methods 1
For bone health with long-term use (>2 years):
- Counsel about daily intake of 1300 mg calcium and 600 IU vitamin D 4
- Recommend regular weight-bearing exercise 6, 4
- Advise smoking cessation 6, 4
- Note that ACOG does not recommend limiting use to 2 years or routinely monitoring bone density, as benefits of preventing unwanted pregnancy generally outweigh risks 4
Important Clinical Pitfalls
Do not dismiss menstrual irregularities as benign without proper evaluation:
- If abnormal bleeding persists or is severe, investigate to rule out organic pathology 2
- Unscheduled bleeding can be a sign of an STI, and adolescents should be tested accordingly 6
Despite high side effect rates, patient satisfaction remains high: