Testosterone exerts direct effects on the vascular wall through androgen receptors and by metabolizing into dihydrotestosterone (DHT). It induces rapid vasodilation through non-genomic endothelium-dependent and independent mechanisms, affecting both endothelial cells and arterial smooth muscle cells.
In males, evidence suggests that androgen deficiency is associated with increased oxidative stress and inflammation. Testosterone appears to possess antioxidant and anti-inflammatory properties, as demonstrated in studies where testosterone supplementation improved antioxidant defense systems.
In females, the relationship with testosterone is more complex. Some studies indicate a potential association between higher testosterone levels and increased oxidative stress and inflammation. However, the effects of testosterone administration in women on the oxidative stress and inflammatory environment remain unclear.
Vascular aging involves arterial stiffening and endothelial dysfunction, creating an environment conducive to cardiovascular diseases. Sex differences in vascular aging are often attributed to changes in sex hormones, including estrogen and, to a lesser-explored extent, testosterone.
Available data suggest an association between lower testosterone levels and endothelial dysfunction, as well as increased arterial stiffness in men. However, the effects of testosterone on vascular aging may depend on various factors, such as age, disease status, and the form of testosterone supplementation.
In women, the data are more variable, and the safety of long-term testosterone therapy on cardiovascular health remains uncertain.
Exercise is a potent anti-aging strategy for vascular health, but its effects may vary between sexes. While endurance exercise has shown improvements in endothelial function in older men, the role of testosterone in these adaptations is not entirely clear. Some evidence suggests that testosterone may enhance improvements in endothelial function with exercise training in men with low testosterone levels.
Research on how androgens influence vascular adaptations to exercise in women is limited. Studies in women with polycystic ovary syndrome (PCOS) indicate improvements in endothelial function with exercise training, but more research is needed to understand the specific role of androgens in women.
Understanding the impact of declining sex hormones, including testosterone, on vascular aging is crucial for developing sex-specific therapies to prevent cardiovascular diseases. While associations between testosterone levels and vascular health are evident, further research is needed to elucidate the intricate mechanisms and ensure the safety of long-term testosterone therapy.
In summary, testosterone plays a multifaceted role in vascular health, influencing both endothelial function and arterial stiffness. As we continue to unravel the complexities of this relationship, it becomes clear that a holistic approach, considering individual factors, is essential for developing effective interventions to promote cardiovascular health as we age.