Trends in blood-based metabolic and cardiovascular risk profiles in men during treatment for testosterone deficiency: a longitudinal, retrospective cohort study.

HDL cholesterol decreased significantly over 12 months of testosterone deficiency treatment.

• Cohort comprised 4307 men with median age 41 years and baseline BMI 28.4 kg/m2.
• Average HDL at baseline was 1.26 mmol/L (95% CI: 1.25 to 1.26), decreasing to 1.15 mmol/L (95% CI: 1.10 to 1.20) at 12 months.
• Relative change in HDL was -8.73% (P < 0.001).
• Mixed effects models were used to assess marker trajectories.

HbA1c showed a statistically significant reduction over 12 months of treatment for testosterone deficiency.

• Average reduction in HbA1c was 1.55 mmol/mol (95% CI: -2.74 to -0.36) over 12 months.
• Relative change in HbA1c was -4.46% (P = 0.011).
• This suggests potential improvement in glycemic control during treatment.

Triglyceride levels decreased substantially over 12 months of testosterone deficiency treatment.

• Average triglyceride level at baseline was 2.25 mmol/L (95% CI: 2.20 to 2.28), falling to 1.79 mmol/L (95% CI: 1.55 to 2.04) at 12 months.
• Relative change in triglycerides was -20.09% (P < 0.001).
• Men with elevated baseline triglycerides showed marked reductions from 3.13 mmol/L (95% CI: 3.67 to 3.79) to 2.29 mmol/L (95% CI: 1.90 to 2.68), a relative change of -26.84% (P < 0.001).

The triglyceride:HDL ratio showed the greatest relative reductions in men with the highest baseline values.

• There was a positive relationship between baseline triglyceride:HDL elevation and the magnitude of relative reductions observed.
• In men with a baseline triglyceride:HDL ratio > 6, values decreased from 8.99 (95% CI: 8.80 to 9.18) at baseline to 1.90 (95% CI: 0.19 to 3.61) at month 12.
• Relative change in this high-baseline subgroup was -78.86% (P < 0.001).

LDL cholesterol did not change significantly during 12 months of testosterone deficiency treatment.

• No significant changes were observed in LDL over the 12-month study period.
• This finding contrasts with the significant changes seen in HDL, triglycerides, HbA1c, and triglyceride:HDL ratio.
• The study used mixed effects models to assess LDL trajectories along with all other markers.

The study design was retrospective and non-randomized, limiting causal inference about the effects of testosterone deficiency treatment.

• This was a retrospective cohort study using data from a single healthcare provider.
• The study was non-randomized, meaning contributions from TD treatment strategies versus lifestyle changes on biochemical marker improvements could not be distinguished.
• Authors note that 'large, prospective, controlled studies are needed to identify the causal contributions from TD treatment strategies and lifestyle changes on biochemical marker improvements.'
• Despite limitations, the study used a large cohort of 4307 men and explored clinically relevant sub-groups.