Relationship between testosterone, estradiol and circulating PCSK9: Cross-sectional and interventional studies in...

Area of Science:

• Endocrinology
• Cardiovascular Science
• Lipid Metabolism

Background:

• Circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) levels exhibit sex-based and menopausal status-based variations.
• These variations suggest a potential role for sex hormones, specifically estradiol (E2) and testosterone (T), in regulating PCSK9 levels.

Purpose of the Study:

• To investigate the relationship between serum E2 and T levels and circulating PCSK9 in men and women.
• To assess the impact of E2 replacement therapy in women and T replacement/ablation therapy in men on serum PCSK9.

Main Methods:

• Cross-sectional analysis correlating serum T (males) and E2 (females) with PCSK9.
• Interventional studies evaluating hormonal therapy effects on PCSK9 levels.

Main Results:

• In men, serum T did not correlate with PCSK9 or LDL cholesterol (LDLC) basally; T replacement therapy had no effect, while T ablation therapy yielded mixed results.
• In women, E2 inversely correlated with PCSK9 and directly with LDLC, but E2 replacement therapy did not alter PCSK9 levels.

Conclusions:

• Significant sex-based differences exist in the relationship between major sex hormones and PCSK9.
• Circulating PCSK9 in men is largely independent of T, except possibly during T ablation.
• The inverse relationship between E2 and PCSK9 in women, without a change in PCSK9 during E2 therapy, suggests E2 influences PCSK9 clearance rather than production.