E-cigarette aerosol constituents modulate Leydig cell steroidogenic pathways: Evidence from experimental models

Area of Science:

• Reproductive Endocrinology
• Toxicology
• Male Reproductive Health

Background:

• E-cigarette use is increasing, raising concerns about male reproductive and endocrine health.
• The specific impact of e-cigarettes on testosterone regulation and the hypothalamic-pituitary-gonadal axis is not well understood.

Purpose of the Study:

• To review and synthesize existing evidence on e-cigarette exposure and its effects on testosterone homeostasis.
• To evaluate the influence of e-cigarette use on male reproductive endocrine function.

Main Methods:

• Narrative review of preclinical (in vivo, in vitro) and human observational studies.
• Critical synthesis of evidence on mechanisms of testosterone disruption.

Main Results:

• Preclinical models show e-cigarette aerosols impair Leydig cell function and testosterone biosynthesis via oxidative stress, inflammation, and epigenetic changes.
• Some mechanisms are shared with combustible cigarettes, while others are specific to e-cigarette constituents like solvents, flavorings, and metals.
• Human studies are limited, yielding inconsistent findings; large studies show no significant difference in testosterone levels between users and non-users.

Conclusions:

• There is biological plausibility for e-cigarettes disrupting testosterone production.
• Current human evidence is insufficient to establish a causal link between e-cigarette use and testosterone disruption.
• Longitudinal, biomarker-focused human studies are needed to determine clinical relevance and reversibility.