Can Depomedrol Injection Cause Vaginal Bleeding?
Yes, corticosteroid injections including Depomedrol (methylprednisolone) can cause abnormal vaginal bleeding, particularly in postmenopausal women, though the mechanism is not fully understood and this represents an uncommon but documented adverse effect.
Evidence for Corticosteroid-Associated Vaginal Bleeding
Postmenopausal Women
- Postmenopausal women receiving outpatient corticosteroid injections have significantly higher rates of abnormal vaginal bleeding compared to matched controls (17% vs. 7%, p=0.02), with the association remaining independent of body mass index and hormone use 1.
- Multiple case reports document postmenopausal bleeding following epidural corticosteroid injections and other corticosteroid administration routes 2, 3.
Premenopausal Women
- Premenopausal women show similar baseline rates of abnormal bleeding whether or not they receive corticosteroid injections (50% vs. 43%, p=0.39), making the association less clear in this population 1.
- Case series document abnormal vaginal bleeding in both pre- and postmenopausal women following epidural steroid injections and facet medial branch blocks 2.
Clinical Approach
Risk Assessment Before Injection
- Identify patients with pre-existing risk factors for abnormal uterine bleeding, including hormone use, body mass index, and underlying gynecologic conditions 1, 2.
- Consider menopausal status, as postmenopausal women appear at higher risk for this adverse effect 1.
Patient Counseling
- Inform all women, both pre- and postmenopausal, during the consent process that abnormal vaginal bleeding is a potential risk following corticosteroid injections 2.
- Explain that while uncommon, this side effect has been documented and typically resolves spontaneously 3.
Evaluation of Post-Injection Bleeding
When vaginal bleeding occurs after corticosteroid injection:
- Rule out pregnancy, sexually transmitted infections, and new pathologic uterine conditions (fibroids, polyps, malignancy) before attributing bleeding to the corticosteroid 4, 5.
- Consider transvaginal ultrasonography and endometrial evaluation in postmenopausal women to exclude malignancy 3.
- Recognize that symptoms often settle spontaneously without specific intervention 3.
Important Caveats
The evidence base for this association is limited to case series and one prospective case-control study, so the true incidence and causative mechanism remain unclear 1, 2, 3. The proposed mechanism involves disruption of the hypothalamic-pituitary-ovarian axis by exogenous corticosteroids 2.
Do not assume all post-injection bleeding is benign—appropriate gynecologic evaluation remains essential, particularly in postmenopausal women where bleeding should always prompt investigation for malignancy 5, 3.