Table 4.
Risk of Adverse Events with Testosterone Therapy, According to Category.*
| Event Category | Total Risk | Instantaneous Risk | ||
|---|---|---|---|---|
| Odds Ratio (95% CI) | Hazard Ratio (95% CI) | |||
| unadjusted | adjusted | unadjusted | adjusted | |
| MedDRA cardiac† | 10.6 (1.3–84.5) | NA‡ | 10.5 (1.3–82.4) | NA‡ |
| Atherosclerosis-related§ | 7.2 (0.9–59.7) | NA‡ | 7.1 (0.9–57.8) | NA‡ |
| Cardiovascular-related¶ | 5.4 (2.0–14.9) | 5.8 (2.0–16.8) | 5.0 (1.9–13.2) | 5.5 (2.0–14.8) |
| Dermatologic‖ | 2.6 (1.1–6.2) | 4.9 (1.7–14.6) | 2.6 (1.1–5.9) | 4.8 (1.7–13.0) |
| Necessitating referral for medical evaluation | 2.3 (0.98–5.3) | 5.2 (1.8–14.6) | 2.3 (1.1–5.2) | 5.2 (2.0–13.5) |
Total risk refers to the risk of an adverse event occurring over the entire study period after randomization, which included the 24-week treatment period and the subsequent 12-week observation phase. Instantaneous risk refers to the risk of an adverse event occurring at any specific time. Unadjusted odds ratios and hazard ratios were estimated with the use of simple logistic regression. Adjusted odds ratios and hazard ratios were estimated with the use of multiple logistic regression, with adjustment for age group; body-mass index; presence or absence of diabetes, hypertension, and hyperlipidemia; and high-density lipoprotein cholesterol level. Given the small number of subjects in each cell, the ability to adjust for baseline risk factors is limited, and results should be interpreted conservatively. When 104 men with preexisting self-reported cardiovascular, cerebrovascular, or peripheral vascular disease, with or without congestive heart failure and arrhythmias, were excluded, 9 men treated with testosterone had cardiovascular-related events, as compared with 2 men receiving placebo gel (odds ratio, 5.8; 95% confidence level [CI] 1.2 to 28.4; P = 0.03). Three men in the testosterone group had MedDRA cardiac events and two had atherosclerosis-related events, as compared with no men with these events in the placebo group.
Included are adverse events that were classified as cardiac according to the Medical Dictionary for Regulatory Activities (MedDRA) classification system.
Adjusted estimates are not applicable (NA) because there was only one event in the placebo group.
Included are adverse events that were classified, according to the recommendation of the data and safety monitoring board, as having been directly related to atherosclerotic vascular disease (e.g., myocardial infarction, sudden death, angioplasty, coronary-artery bypass grafting, and stroke).
At the recommendation of the data and safety monitoring board, we included in this analysis, in addition to cardiac events in the MedDRA “Cardiac” category, those that were considered to be cardiovascular in nature but which were included in other MedDRA System Organ Class categories: stenting and bypass procedures (included in the MedDRA “Surgical and Medical Procedures” category); peripheral edema (included in the “General Disorders” category); elevated blood pressure, arrhythmias, and electrocardiographic changes (included in the “Investigations” category); and stroke and syncope (included in the “Nervous System Disorders” category).
For dermatologic events, unadjusted odds ratios and hazard ratios were estimated with the use of Cox proportionalhazards models. Adjusted odds ratios and hazard ratios were estimated with the use of multivariate proportional-hazards models, with adjustment for age group, body-mass index, presence or absence of diabetes, hypertension, and hyperlipidemia, and high-density lipoprotein cholesterol level.