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

Abstract

Background: Cross-sectional analyses demonstrate associations between lower endogenous testosterone, poorer metabolic health, and cardiovascular risk. However, the longitudinal associations between treating testosterone deficiency (TD) and key markers are unclear.

Aim: To examine 12-month trends in total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), haemoglobin A1c (HbA1c), triglycerides, and triglyceride:HDL ratios during treatment for TD.

Methods: This retrospective cohort study used mixed effects models to assess marker trajectories.

Outcomes: Absolute and percentage changes calculated from average marker values at 0 and 12 months (overall and sub-groups).

Results: The cohort comprised 4307 men (median age 41 years; baseline BMI 28.4 kg/m2). No significant changes were observed in LDL. The average HDL level at baseline was 1.26 mmol/L (95% CI: 1.25 to 1.26), decreasing to 1.15 (95% CI: 1.10 to 1.20) at 12 months, a relative change of -8.73% (P < 0.001). There was a 1.55 mmol/mol (95% CI: -2.74 to -0.36) average reduction in HbA1c over 12 months (relative change -4.46%, P = 0.011). The average triglyceride level was 2.25 mmol/L at baseline (95% CI: 2.20 to 2.28) and 1.79 mmol/L (95% CI: 1.55 to 2.04) at 12 months, a relative change of -20.09% (P < 0.001). Men with elevated baseline triglycerides had marked reductions, from 3.13 mmol/L at baseline to (95% CI: 3.67 to 3.79) to 2.29 mmol/L at 12 months (95% CI: 1.90 to 2.68), relative change -26.84% (P < 0.001). There was a positive relationship between baseline triglyceride:HDL elevation and relative reductions; in men with a baseline ratio > 6, values went from 8.99 at baseline (95% CI: 8.80 to 9.18) to 1.90 (95% CI: 0.19 to 3.61) at month 12, a relative change of -78.86% (P < 0.001).

Clinical implications: In this non-randomized study, significant reductions in HDL, HbA1c, triglycerides, and the triglyceride:HDL ratio were observed during the course of treatment for TD.

Strengths & limitations: The study used a large cohort of men and explored clinically relevant sub-groups, albeit from a single healthcare provider.

Conclusions: Interventions for TD could have potential to improve longer-term cardiometabolic health in hypogonadic men. Large, prospective, controlled studies are needed to identify the causal contributions from TD treatment strategies and lifestyle changes on biochemical marker improvements.