Does Hydrocortisone Cause GI Bleeding?
Yes, hydrocortisone and other corticosteroids increase the risk of gastrointestinal bleeding by approximately 40-100%, though the absolute risk remains relatively low in most clinical contexts. 1, 2
Quantifying the Risk
The evidence demonstrates a clear dose-response relationship:
- Corticosteroid use increases GI bleeding risk by approximately 2-fold compared to non-users across multiple studies 3, 1, 4
- A comprehensive meta-analysis of 159 randomized controlled trials (N=33,253 patients) found corticosteroids increased the risk of GI bleeding or perforation by 40% (OR 1.43,95% CI 1.22 to 1.66) 2
- The absolute risk varies dramatically by clinical setting: hospitalized patients show significantly elevated risk (OR 1.42), while ambulatory patients have very low absolute occurrence (0.13% or 11 events among 8,651 patients) 2, 5
Risk Stratification by Patient Population
High-Risk Patients (Require Gastroprotection)
History of peptic ulcer or prior GI bleeding represents the single most important risk factor, increasing risk 2.5-4 fold 1, 4:
- Patients with prior ulcer history: 15.9 cases per 10,000 person-months 5
- Combined with anticoagulants: 23.0 cases per 10,000 person-months 5
Advanced age significantly amplifies risk, increasing approximately 4% per year of advancing age 3, 1
Concomitant medications create multiplicative risk 3:
- NSAIDs combined with corticosteroids: 2-4 fold increased risk 3, 1
- Anticoagulants (warfarin/heparin): approximately 3-fold increase 3, 5
- Low-dose aspirin plus corticosteroids: relative risk >10-fold when combined with NSAIDs 3
Low-Risk Patients
Ambulatory patients without risk factors have minimal absolute risk (2.8 cases per 10,000 person-months) 5:
- Young patients without ulcer history
- Short-term corticosteroid courses
- No concurrent NSAIDs, anticoagulants, or aspirin
Clinical Context: When Hydrocortisone is Appropriately Used Despite GI Risk
The British Society of Gastroenterology 2025 guidelines explicitly recommend intravenous hydrocortisone 100 mg four times daily as cornerstone therapy for acute severe ulcerative colitis, despite these patients having active GI bleeding 3. This demonstrates that the therapeutic benefit often outweighs bleeding risk in appropriate clinical contexts.
Similarly, hydrocortisone is recommended for septic shock (200 mg/day IV) and critical illness-related corticosteroid insufficiency, with monitoring for GI bleeding as an expected adverse effect rather than a contraindication 3, 6.
Risk Mitigation Strategies
Proton pump inhibitors (PPIs) are highly effective, reducing GI bleeding risk by 75-85% in high-risk patients 3, 1, 4:
- Mandatory for patients with prior ulcer/bleeding history
- Strongly recommended when combining corticosteroids with NSAIDs or anticoagulants
- Consider for elderly patients (>60-65 years) on prolonged courses
H. pylori testing and eradication further reduces risk in appropriate patients 1, 4
Avoid prolonged high-dose therapy when possible, as risk increases with both dose and duration 3, 6, 4:
- Limit IV hydrocortisone courses to 7-10 days maximum 3
- Taper gradually over 6-14 days rather than abrupt discontinuation 6
Common Pitfalls to Avoid
Do not withhold necessary corticosteroid therapy solely due to GI bleeding concerns in conditions like acute severe ulcerative colitis or septic shock—instead, implement gastroprotection 3, 6
Do not assume prophylaxis is needed for all patients—the absolute risk in young, healthy ambulatory patients without risk factors is extremely low (0.13%), making routine prophylaxis unnecessary 2, 5
Do not overlook over-the-counter NSAID or aspirin use when assessing risk, as these are frequently unreported by patients but dramatically increase bleeding risk when combined with corticosteroids 3, 7
Monitor for GI bleeding during therapy as it represents a known adverse effect requiring surveillance, particularly in hospitalized and critically ill patients 3, 6