No Clinically Significant Drug Interaction Between Depo-Provera and Aspirin
There is no documented pharmacokinetic or pharmacodynamic interaction between Depo-Provera (medroxyprogesterone acetate) and aspirin, and these medications can be used together safely without dose adjustments.
Mechanism and Safety Profile
- Depo-Provera is a progestin-only contraceptive administered as a 150 mg intramuscular injection every 12 weeks that does not affect platelet function, coagulation pathways, or prostaglandin synthesis 1
- Aspirin works through irreversible inhibition of cyclooxygenase-1, blocking thromboxane A2 formation and platelet aggregation—a mechanism completely independent of progestin activity 2
- Unlike combined oral contraceptives containing estrogen, progestin-only methods like Depo-Provera have no appreciable effects on thrombosis risk or coagulation factors 3
Key Clinical Considerations
Bleeding patterns may be affected by each medication independently, but not through interaction:
- Depo-Provera causes menstrual irregularities in most users, with 57% experiencing amenorrhea by one year of use 1
- Aspirin increases gastrointestinal bleeding risk (OR 1.59,95% CI 1.32-1.91) and adds 0.29 bleeding events per 1,000 person-years of exposure 2
- Any bleeding observed in patients taking both medications should be attributed to aspirin's antiplatelet effects or Depo-Provera's hormonal effects on the endometrium, not to a drug interaction 3
No contraindications exist for concurrent use:
- Aspirin is contraindicated in patients with active peptic ulcer, bleeding disorders, recent GI or intracranial bleeding, severe liver disease, or thrombocytopenia 2
- Depo-Provera is contraindicated in undiagnosed vaginal bleeding, known breast malignancy, thromboembolic disorders, cerebral vascular disease, and liver dysfunction 1
- Neither medication's contraindications are affected by the presence of the other drug
Practical Management
When prescribing both medications together:
- Use the lowest effective aspirin dose (75-100 mg daily) for cardiovascular or stroke prevention indications 2, 4
- Consider adding a proton pump inhibitor if aspirin is combined with other risk factors for GI bleeding, though this is based on aspirin's bleeding risk alone, not interaction with Depo-Provera 4
- Counsel patients that irregular bleeding from Depo-Provera is expected and unrelated to aspirin use 3, 5
- Monitor for excessive or prolonged bleeding that would warrant evaluation regardless of medication use 5
Common clinical scenarios requiring both medications:
- Women using Depo-Provera for contraception who require aspirin for cardiovascular disease prevention can safely use both 2
- Patients on aspirin for stroke prevention in atrial fibrillation can initiate Depo-Provera without concern for interaction 2
- No dose adjustment of either medication is needed when used concurrently 1, 3