Table 3.
Comparative safety of patch versus topical gel testosterone among new testosterone initiators by data source
| Crude | Adjusted | PS Matched | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Datasource | Outcome | Treatment | N | Rate / 1,000 PY |
HR | (95% CI) | HR | (95% CI) | N | Rate / 1,000 PY |
HR | (95% CI) |
| MarketScan | MI | Gel | 290,525 | 3.3 | -- | -- | -- | -- | 68,505 | 4.0 | -- | -- |
| Patch | 34,735 | 5.2 | 1.56 | (1.31, 1.85) | 1.20 | (1.00, 1.44) | 34,718 | 5.2 | 1.28 | (1.05, 1.57) | ||
| Unstable angina |
Gel | 290,525 | 1.7 | -- | -- | -- | -- | 68,505 | 2.9 | -- | -- | |
| Patch | 34,735 | 2.9 | 1.73 | (1.37, 2.19) | 1.04 | (0.82, 1.33) | 34,718 | 2.9 | 0.99 | (0.76, 1.28) | ||
| Stroke | Gel | 290,494 | 4.2 | -- | -- | -- | -- | 68,450 | 5.9 | -- | -- | |
| Patch | 34,701 | 6.8 | 1.61 | (1.38, 1.87) | 1.13 | (0.96, 1.32) | 34,683 | 6.8 | 1.15 | (0.96, 1.36) | ||
| Composite | Gel | 289,931 | 8.8 | -- | -- | -- | -- | 68,249 | 12.6 | -- | -- | |
| Patch | 34,596 | 14.1 | 1.60 | (1.44, 1.78) | 1.06 | (0.89, 1.27) | 34,579 | 14.1 | 1.13 | (1.00, 1.27) | ||
| Hospitalization | Gel | 277,572 | 86.3 | -- | -- | -- | -- | 63,974 | 105.5 | -- | -- | |
| Patch | 32,373 | 108.2 | 1.26 | (1.21, 1.31) | 1.04 | (1.00, 1.08) | 32,373 | 108.2 | 1.03 | (0.98, 1.07) | ||
| VTE | Gel | 290,953 | 0.003 | -- | -- | -- | -- | 68,677 | 0.003 | -- | -- | |
| Patch | 34,818 | 0.003 | 0.99 | (0.70, 1.42) | 1.03 | (0.71, 1.48) | 34,799 | 0.003 | 1.14 | (0.75, 1.74) | ||
| Medicare | MI | Gel | 9,552 | 9.5 | -- | -- | -- | -- | 2,610 | 10.6 | ||
| Patch | 1,305 | 15.9 | 1.67 | (0.99, 2.82) | 1.25 | (0.72, 2.18) | 1,305 | 15.9 | 1.50 | (0.80, 2.81) | ||
| Unstable angina |
Gel | 9,552 | 3.9 | -- | -- | -- | -- | 2,610 | 4.6 | |||
| Patch | 1,305 | 4.6 | 1.18 | (0.46, 3.02) | 1.13 | (0.42, 3.04) | 1,305 | 4.6 | 1.01 | (0.35, 2.96) | ||
| Stroke | Gel | 9,558 | 10.5 | -- | -- | -- | -- | 2,599 | 15.7 | -- | -- | |
| Patch | 1,302 | 14.9 | 1.42 | (0.83, 2.43) | 1.25 | (0.72, 2.18) | 1,302 | 14.9 | 1.14 | (0.62, 2.10) | ||
| Composite | Gel | 9,510 | 23.1 | -- | -- | -- | -- | 2,590 | 28.9 | -- | -- | |
| Patch | 1,296 | 34.9 | 1.51 | (1.06, 2.15) | 1.22 | (0.84, 1.76) | 1,295 | 35.0 | 1.21 | (0.81, 1.82) | ||
| Death | Gel | 9,600 | 32.2 | -- | -- | -- | -- | 2,618 | 44.5 | -- | -- | |
| Patch | 1,311 | 58.2 | 1.81 | (1.37, 2.38) | 1.06 | (0.79, 1.42) | 1,311 | 58.2 | 1.24 | (0.90, 1.69) | ||
| Hospitalization | Gel | 9,392 | 45.2 | -- | -- | -- | -- | 2,546 | 60.0 | |||
| Patch | 1,274 | 57.4 | 1.24 | (0.94, 1.65) | 0.99 | (0.74, 1.33) | 1,273 | 57.4 | 0.98 | (0.72, 1.35) | ||
| VTE | Gel | 9,592 | 0.006 | -- | -- | -- | -- | 9,415 | 0.007 | -- | -- | |
| Patch | 11,458 | 0.008 | 1.36 | (0.74, 2.50) | 1.23 | (0.65, 2.32) | 7,914 | 0.008 | 1.43 | (0.75, 2.72) | ||
| CPRD | MI | Gel | 2,793 | 2.5 | -- | -- | -- | -- | 1,998 | 1.8 | -- | -- |
| Patch | 1,189 | 3.5 | 1.42 | (0.40, 5.02) | 18.62 | (0.07, 4706) |
1,132 | 3.2 | 1.07 | (0.30, 3.79) | ||
| Unstable angina |
Gel | 2,793 | 0.4 | -- | -- | -- | -- | 1,998 | 0.0 | -- | -- | |
| Patch | 1,189 | 2.6 | 6.62 | (0.69, 63.62) |
1,132 | 3.2 | 4.99 | (0.52, 47.95) |
||||
| Stroke | Gel | 2,790 | 5.0 | -- | -- | -- | -- | 1,976 | 4.4 | -- | -- | |
| Patch | 1,190 | 6.2 | 1.14 | (0.36, 2.86) | 1.50 | (0.52, 4.31) | 1,133 | 4.8 | 1.01 | (0.39, 2.60) | ||
| Composite | Gel | 2,783 | 8.0 | -- | -- | -- | -- | 1,977 | 6.2 | -- | -- | |
| Patch | 1,186 | 11.5 | 1.39 | (0.69, 2.79) | 1.43 | (0.67, 3.07) | 1,129 | 11.2 | 1.60 | (0.74, 3.45) | ||
| Death | Gel | 2,800 | 13.7 | -- | -- | -- | -- | 1,986 | 13.4 | -- | -- | |
| Patch | 1,193 | 10.5 | 0.79 | (0.41, 1.53) | 0.77 | (0.37, 1.61) | 1,137 | 16.0 | 0.86 | (0.43. 1.73) | ||
| Hospitalization | Gel | 2,771 | 12.7 | -- | -- | -- | -- | 2,000 | 11.8 | -- | -- | |
| Patch | 1,185 | 14.2 | 1.11 | (0.60, 2.03) | 1.30 | (0.57, 2.96) | 1,126 | 17.6 | 1.49 | (0.67, 3.33) | ||
| VTE | Gel | 2,800 | 0.4 | -- | -- | -- | -- | 1,986 | 0.0 | -- | -- | |
| Patch | 1,193 | 0.0 | 1,137 | 0.0 | ||||||||
MI: myocardial infarction; VTE: venous thromboembolism; composite: MI, unstable angina, or stroke; HR: hazard ratio; CI: confidence interval
Covariates included in the final adjusted and PS models were: patient age; year; presence of serum tests for total and free testosterone levels; a diagnosis of low testosterone or hypogonadism; prior angina, arrhythmia, MI, revascularization, stroke, or VTE; fracture; prostate and any cancer; hospitalization; deficiency and blood loss anemia; peripheral arterial disease; arthritis; asthma; inflammatory bowel disease; chronic obstructive pulmonary disease; diabetes; fatigue; gout; heart failure; hypertension; other ischemic heart disease; liver disease of cirrhosis; lupus; obesity; osteoporosis; osteo- and rheumatoid arthritis; other heart disease; psoriasis; psychological disorders; percutaneous transluminal coronary angioplasty; pulmonary circulatory disease; peripheral vascular disease; rheumatic heart disease; sexual dysfunction; substance abuse; thyroid disease; peptic ulcer disease; screening tests and preventive health services including lipid tests, bone mineral density tests, colonoscopy, fecal occult blood test, flu vaccination; and prescription medication use, including angiotensin-converting-enzyme inhibitors, alpha blockers, anti-platelet drugs, anti-coagulant drugs, angiotensin II receptor blockers, beta blockers, calcium channel blockers, erectile dysfunction drugs, ezetimibe, fibrates, loop diuretics, niacin, nonsteroidal anti-inflammatory drugs, potassium sparing diuretics, proton-pump inhibitors, statins, and thiazide diuretics. Additional covariates included in the CPRD analysis include smoking status and BMI category.