The Testosterone Trials and the T4DM trial were placebo-controlled studies that measured both benefits and harms. The Testosterone Trials found testosterone gel improved sexual activity, desire and erectile function in men 65 or older, with slight mood benefit, but no significant benefit on vitality. The T4DM trial found fewer men on testosterone injections had diabetes-range glucose at 2 years, while far more reached a hematocrit safety trigger. Neither trial used testosterone cypionate.
The Testosterone Trials: who and how
The Testosterone Trials randomized 790 men aged 65 or older with testosterone below 275 ng/dL and symptoms suggesting low testosterone. Men used testosterone gel or placebo gel for 1 year. The main work was split into sexual function, physical function and vitality trials, with further studies on blood, bone, heart and memory.
Sex, mood, energy and walking
Testosterone significantly increased sexual activity, sexual desire and erectile function, and slightly improved mood and depressive symptoms. It had no significant benefit on vitality, measured with a fatigue scale.
In the Physical Function Trial, the share of men gaining at least 50 m in 6-minute walk distance did not differ between groups. Adverse event rates were similar, but the authors said the trial was too small to draw conclusions about risks.
Blood, bone, heart and memory
| Study | What the source says |
|---|---|
| Anemia | Hemoglobin rose by at least 1.0 g/dL in 54% of men with unexplained anemia on testosterone versus 15% on placebo. 6 men who were not anemic reached hemoglobin above 17.5 g/dL. |
| Bone | In 211 men (mean age 72), spine trabecular volumetric bone density rose 7.5% versus 0.8% on placebo. The authors said a larger, longer trial is needed to show whether fractures are reduced. |
| Heart | In 170 men (138 analyzed), testosterone gel was associated with a significantly greater increase in noncalcified coronary plaque volume than placebo (estimated difference 41 mm3, 95% CI 14 to 67). |
| Memory | In 493 men with age-associated memory impairment, testosterone was not associated with improved memory or other cognitive functions. |
On bone, a later result is worth placing beside the density gain. In the TRAVERSE fracture subtrial of 5,204 men, which also used a gel, clinical fractures occurred in 3.50% on testosterone and 2.46% on placebo (hazard ratio 1.43, 95% CI 1.04 to 1.97), and testosterone did not lower fracture incidence.
T4DM: who and how
T4DM was a 2-year randomized, double-blind, placebo-controlled trial at six Australian centers. It enrolled 1,007 men aged 50 to 74 with a waist of 95 cm or more, testosterone of 14.0 nmol/L or lower, and impaired glucose tolerance or new type 2 diabetes. All men took part in a lifestyle program.
Men received an intramuscular injection of testosterone undecanoate (1000 mg) or placebo at baseline, 6 weeks, and then every 3 months for 2 years.
What T4DM found
At 2 years, 12% of the testosterone group versus 21% of the placebo group had a 2-hour glucose of 11.1 mmol/L or higher, a level indicating type 2 diabetes (relative risk 0.59, 95% CI 0.43 to 0.80).
On safety, a hematocrit safety trigger above 54% occurred in 22% of the testosterone group versus 1% on placebo. Prespecified serious adverse events occurred in 10.9% versus 7.4%. The authors said hematocrit increases might be treatment limiting.
What this does not tell you
The Testosterone Trials used a gel in men 65 or older for 1 year, and T4DM used testosterone undecanoate injections in men with a large waist and blood sugar problems, alongside a lifestyle program. Neither tested testosterone cypionate, and neither describes younger men or men outside those groups.
A rise in bone density does not show fewer fractures, and the plaque finding does not by itself show heart events. The Physical Function Trial authors said it was too small to judge risks. These results describe groups, not any one man, and a licensed provider decides whether treatment fits a given person.