Effects of Testosterone Treatment in Older Men

Le Trac, Mercer University College of Pharmacy

Research has shown that testosterone levels decrease with age in men. Many conditions that are associated with low testosterone levels in men such as pituitary or testicular disease begin to be more prevalent with increasing age. It is suggested that testosterone treatment increases muscle mass and decrease fat mass. [1]

According to the Institute of Medicine (IOM), there is not enough evidence to suggest that testosterone treatment is beneficial in older men. The effects of testosterone on physical performance, sexual dysfunction, and energy are stated to be inconsistent. Thus, the IOM panel recommended initiating a set of clinical trials in order to determine the benefits of testosterone in older men. [2]

Title: Effects of Testosterone Treatment in Older Men [3]
Design Double-blind, placebo-controlled, multicenter; N = 790
Objective To determine the benefits of testosterone in older men who had low testosterone levels for no known reason other than age and who had clinical conditions due to low level of testosterone
Study Groups Sexual Function Trial: testosterone (n= 193); placebo (n= 193)

Physical Function Trial: Testosterone (n= 172); placebo (n= 165)

Vitality Trial: Testosterone (n= 203); placebo (n= 191)

Methods Men 65 years of age or older with a serum testosterone concentration of less than 275 ng/dL and symptoms suggesting hypoandrogenism receive either testosterone gel or placebo gel for 1 year. Each man participated in one or more of three trials – the Sexual Function Trial, the Physical Function Trial, and the Vitality Trial.
Duration 1 year
Primary Outcome Measure The primary outcome of the Sexual Function Trial was the change from baseline in the score for sexual activity on the Psychosexual Daily Questionnaire (PDQ).

The primary outcome of the Physical Function Trial was the percentage of men who increased the distance walked in the 6-minute walk test by at least 50 m.

The primary outcome of the Vitality Trial was the percentage of men whose score on the FACIT (Functional Assessment of Chronic Illness Therapy)-Fatigue scale increased by at least four points.

Baseline Characteristics
Demographic Placebo Group (n = 395) Testosterone Group (n = 395)
Age 72.3 ± 5.8 72.1 ± 5.7
BMI > 30 (%) 246 (62.3%) 251 (63.5%)
Hypertension (%) 280 (70.9%)

 

286 (72.4%)

 

History of myocardial infarction (%) 63 (16.0%)

 

53 (13.4%)

 

International Prostate Symptom Score (IPSS) 9.6 ± 5.3

 

9.0 ± 5.2

 

Risk (%) of all prostate cancer 17.6 ± 6.0

 

17.3 ± 6.0

 

Testosterone (ng/dL) 236 ± 67

 

232 ± 63

 

Gait speed (m/s) 1.1 ± 0.2 1.1 ± 0.2
Derogatis Interview for Sexual Function – Sexual Desire 14.0 ± 7.8

 

13.9 ± 7.7

 

FACIT-Fatigue 36.8 ± 8.8 37.0 ± 8.6
Results Sexual Function Trial Outcomes

PDQ-Q4 score No. of men Baseline Value Treatment Effect (95% CI) P value
Men enrolled in Sexual Function Trial
Testosterone Group 230 1.4 ± 1.3

 

0.58 (0.38–0.78)

 

<0.001
Placebo Group 229 1.4 ± 1.3

 

All Testosterone Trials participants
Testosterone Group 387 1.5 ± 1.3

 

0.62 (0.45–0.79) <0.001
Placebo Group 384 1.5 ± 1.4

 

 

Physical Function Trial Outcomes

Increase of ≥50 m in 6-min walk test — no./total no. (%) No. of Men Treatment Effect (95% CI) P value
Men enrolled in Physical Function Trial
Testosterone Group 191 1.41 (0.83–2.45) 0.20
Placebo Group 196
All Testosterone Trials participants
Testosterone Group 392 1.76 (1.21–2.57) 0.003
Placebo Group 389

 

Vitality Trial Outcomes

Increase of ≥4 in FACIT–Fatigue score — no./total no. No. of Men Treatment Effect (95% CI) P value
Men enrolled in Physical Function Trial
Testosterone Group 236 1.23 (0.83–1.84) 0.30
Placebo Group 238
All Testosterone Trials participants
Testosterone Group 394 1.23 (0.89–1.70) 0.22
Placebo Group 394
Adverse Events Common Adverse Events: IPSS > 19 (27%), increase in PSA level by ≥1.0 ng/mL (23%), myocardial infarction, stroke, or death from cardiovascular causes (7%)
Serious Adverse Events: hospitalization (68%), death (3%), others (7%)
Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions In symptomatic men 65 years of age or older, raising testosterone concentrations for 1 year from moderately low to the mid-normal range for men 19 to 40 years of age had a moderate benefit with respect to sexual function and some benefit with respect to mood and depressive symptoms but no benefit with respect to vitality or walking distance.

 

 

Results of these trials showed that testosterone treatment had a moderate benefit to sexual function but no significant benefit in walking distance or vitality. Past studies have shown both an increased and decreased risk of cardiovascular side effects in patients who were taking testosterone. The sample size in this trial was too small to draw a definite result, and thus the risks of testosterone treatment should always be considered when initiating therapy.

 

References

[1] Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. J Clin Endocrinol Metab 2001;86:724-31.

[2] Snyder PJ, Ellenberg SS, Cunningham GR, et al. The Testosterone Trials: seven coordinated trials of testosterone treatment in elderly men. Clin Trials 2014;11: 362-75.

[3] Snyder PJ, Bhasin S, Cunningham GR, et al. Effects of Testosterone Treatment in Older Men. N Engl J Med. 2016; 374:611-624

 

 

 

 

 

 

 

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