Adverse events associated with testosterone administration.
BACKGROUND
Testosterone supplementation has been shown to increase muscle mass and strength in healthy older men. The safety and efficacy of testosterone treatment in older men who have limitations in mobility have not been studied.


METHODS
Community-dwelling men, 65 years of age or older, with limitations in mobility and a total serum testosterone level of 100 to 350 ng per deciliter (3.5 to 12.1 nmol per liter) or a free serum testosterone level of less than 50 pg per milliliter (173 pmol per liter) were randomly assigned to receive placebo gel or testosterone gel, to be applied daily for 6 months. Adverse events were categorized with the use of the Medical Dictionary for Regulatory Activities classification. The data and safety monitoring board recommended that the trial be discontinued early because there was a significantly higher rate of adverse cardiovascular events in the testosterone group than in the placebo group.


RESULTS
A total of 209 men (mean age, 74 years) were enrolled at the time the trial was terminated. At baseline, there was a high prevalence of hypertension, diabetes, hyperlipidemia, and obesity among the participants. During the course of the study, the testosterone group had higher rates of cardiac, respiratory, and dermatologic events than did the placebo group. A total of 23 subjects in the testosterone group, as compared with 5 in the placebo group, had cardiovascular-related adverse events. The relative risk of a cardiovascular-related adverse event remained constant throughout the 6-month treatment period. As compared with the placebo group, the testosterone group had significantly greater improvements in leg-press and chest-press strength and in stair climbing while carrying a load.


CONCLUSIONS
In this population of older men with limitations in mobility and a high prevalence of chronic disease, the application of a testosterone gel was associated with an increased risk of cardiovascular adverse events. The small size of the trial and the unique population prevent broader inferences from being made about the safety of testosterone therapy. (ClinicalTrials.gov number, NCT00240981.)
Basaria
Shehzad
S
Section of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts 02118, USA.
Coviello
Andrea D
AD
Travison
Thomas G
TG
Storer
Thomas W
TW
Farwell
Wildon R
WR
Jette
Alan M
AM
Eder
Richard
R
Tennstedt
Sharon
S
Ulloor
Jagadish
J
Zhang
Anqi
A
Choong
Karen
K
Lakshman
Kishore M
KM
Mazer
Norman A
NA
Miciek
Renee
R
Krasnoff
Joanne
J
Elmi
Ayan
A
Knapp
Philip E
PE
Brooks
Brad
B
Appleman
Erica
E
Aggarwal
Sheetal
S
Bhasin
Geeta
G
Hede-Brierley
Leif
L
Bhatia
Ashmeet
A
Collins
Lauren
L
LeBrasseur
Nathan
N
Fiore
Louis D
LD
Bhasin
Shalender
S
D000279:Administration, Cutaneous; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D004311:Double-Blind Method; D005080:Exercise Test; D005782:Gels; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications; D006973:Hypertension / Q000150:complications; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D053580:Muscle Strength / Q000187:drug effects; D009765:Obesity / Q000150:complications; D012307:Risk Factors; D013739:Testosterone / Q000009:adverse effects* / Q000097:blood / Q000172:deficiency / Q000627:therapeutic use; D016138:Walking
D005782:Gels; D013739:Testosterone