Original article
Normalization of Testosterone Levels After Testosterone Replacement Therapy Is Not Associated With Reduced Myocardial Infarction in Smokers

https://doi.org/10.1016/j.mayocpiqo.2017.05.003Get rights and content
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Abstract

Objective

To examine the effect of cigarette smoking (CS) status and total testosterone (TT) levels after testosterone replacement therapy (TRT) on all-cause mortality, myocardial infarction (MI), and stroke in male smokers and nonsmokers without history of MI and stroke.

Participants and Methods

Data from 18,055 males with known CS status and low TT levels who received TRT at the Veterans Health Administration between December 1, 1999, and May 31, 2014, were grouped into (1) current smokers with normalized TT, (2) current smokers with nonnormalized TT, (3) nonsmokers with normalized TT, and (4) nonsmokers with nonnormalized TT. Combined effect of CS status and TT level normalization after TRT on all-cause mortality, MI, and stroke was compared using propensity score–weighted Cox proportional hazard models.

Results

Normalization of serum TT levels in nonsmokers was associated with a significant decrease in all-cause mortality (hazard ratio [HR]=0.526; 95% CI, 0.477-0.581; P<.001) and MI (HR=0.717; 95% CI, 0.522-0.986; P<.001). Among current smokers, normalization of serum TT levels was associated with a significant decrease in only all-cause mortality (HR=0.563; 95% CI, 0.488-0.649; P<.001) without benefit in MI (HR=1.096; 95% CI, 0.698-1.720; P=.69). Importantly, compared with nonsmokers with normalized TT, all-cause mortality (HR=1.242; 95% CI, 1.104-1.396; P<.001), MI (HR=1.706; 95% CI, 1.242-2.342; P=.001), and stroke (HR=1.590; 95% CI, 1.013-2.495; P=.04) were significantly higher in current smokers with normalized TT.

Conclusion

We conclude that active CS may negate the protective effect of testosterone level normalization on all-cause mortality and MI after TRT.

Abbreviations and Acronyms

BMI
body mass index
DM
diabetes mellitus
CAD
coronary artery disease
CDW
Corporate Data Warehouse
CHF
congestive heart failure
COPD
chronic obstructive pulmonary disease
CS
current smoking
CV
cardiovascular
CVD
cardiovascular disease
HR
hazard ratio
ICD-9
International Classification of Diseases, Ninth Revision
IPTW
inverse probability of treatment weights
LDL
low-density lipoprotein
MI
myocardial infarction
OSA
obstructive sleep apnea
PVD
peripheral vascular disease
TRT
testosterone replacement therapy
TT
total testosterone
VA
Veterans Administration
VHA
Veterans Health Administration

Cited by (0)

Grant Support: The study was supported by the Midwest Biomedical Research Foundation, VA Medical Center, Kansas City, MO. M.S. was supported by grant VA BX001037 from the Veterans Affairs Merit Review, Office of Research and Development, Veterans Health Administration, Department of Veterans Affairs, and through grant RO1DK1074901 from the National Institutes of Health/the National Institute of Diabetes and Digestive and Kidney Diseases.

Potential Competing Interests: The authors report no competing interests.