In this pilot prospective cohort study, cardiometabolic outcomes of six months of testosterone therapy in men with late-onset hypogonadism differed by vitamin E intake: men with adequate intake improved in most parameters, those with low intake improved only in HOMA-IR, and those with high intake showed no significant changes except a decrease in HDL cholesterol.
Key Findings
Results
Compared with controls, men with late-onset hypogonadism had a worse baseline cardiometabolic profile.
Men with LOH had higher HOMA-IR, LDL cholesterol, uric acid, fibrinogen, homocysteine, hsCRP, and urinary albumin-to-creatinine ratio (UACR).
They also had greater carotid intima-media thickness and higher estimated 10-year cardiovascular risk.
The study included three LOH cohorts (n = 29 each) matched for age, smoking status, BMI, and baseline testosterone, plus 29 men without LOH as controls.
Results
Baseline elevations in homocysteine, hsCRP, and UACR were more pronounced in men with low or high vitamin E intake than in those with adequate intake.
LOH men were classified by vitamin E intake as low, adequate, or high.
The difference was seen for three markers: homocysteine, hsCRP, and UACR.
Results
Testosterone levels increased during treatment in all three LOH groups.
Men with LOH received intramuscular testosterone injections every three weeks for six months.
The rise in testosterone occurred regardless of vitamin E intake category.
Results
Men with adequate vitamin E intake showed improvements in most cardiometabolic parameters during testosterone therapy.
Parameters assessed before and after treatment included biochemical markers, carotid intima-media thickness, retinal vascular sclerotic changes, and estimated 10-year cardiovascular risk.
At study completion, carotid intima-media thickness and retinal vascular sclerotic changes in this group did not differ significantly from those in controls.
Results
In men with low vitamin E intake, the only change during testosterone therapy was an improvement in HOMA-IR.
Other assessed cardiometabolic parameters did not change significantly in this group.
This contrasts with the broad improvements seen in the adequate-intake group.
Results
In men with high vitamin E intake, no significant changes occurred during testosterone therapy except a decrease in HDL cholesterol.
Unlike the adequate-intake group, the high-intake group did not show improvement in the other parameters.
The HDL cholesterol decrease is an unfavorable change.
Results
Changes in the assessed risk factors correlated with both increases in testosterone levels and mean daily vitamin E intake.
The authors interpret this as an association between vitamin E intake and cardiometabolic outcomes during testosterone therapy.
The design was a pilot prospective cohort study, so the findings show association rather than causation.
What This Means
This small pilot study looked at men with late-onset hypogonadism, a condition in which the body makes too little testosterone with age. These men tend to have worse heart and metabolic health than men with normal testosterone, including higher insulin resistance, LDL cholesterol, inflammation markers, and thicker carotid artery walls. The researchers asked whether the benefits of six months of testosterone injections differed depending on how much vitamin E the men got from their diet.
Testosterone levels rose in all groups, but the heart and metabolic effects differed. Men with adequate vitamin E intake improved in most measures, and their artery wall thickness and eye blood-vessel changes ended up similar to men without low testosterone. Men with low vitamin E intake improved only in insulin resistance. Men with high intake showed essentially no improvement, and their HDL ("good") cholesterol fell.
This research suggests that vitamin E intake may be associated with how well testosterone therapy works for cardiometabolic health, with a middle, adequate range appearing most favorable. The study was small (29 men per group) and observational in design, so it cannot show that vitamin E causes these differences. Larger, controlled studies would be needed to confirm the findings.
Krysiak R, Szkróbka W, Kowalcze K, Machnik G, Zapletal-Pudełko K, Okopień B. (2026). The Impact of Vitamin E Intake on Cardiometabolic Outcomes of Testosterone Replacement Therapy in Men with Late-Onset Hypogonadism.. International journal of molecular sciences. https://doi.org/10.3390/ijms27208953