Polymorphisms in androgen and estrogen receptor genes: effects on male aging

Besides lifestyle and environmental factors, the life-long exposure to the endocrine milieu of gonadal steroids is a determining factor to gender specific features of aging. In contrast to women, men do not experience a sudden cessation of gonadal function comparable to menopause. However, cross-sectional and longitudinal population studies demonstrate that the hormones with anabolic actions (e.g. testosterone [T], growth hormone, insulin-like growth factor [IGF]-1, dehydroepiandrosterone) do decrease progressively with aging in healthy men, and chronic systemic illnesses accelerate this process. In addition, estrogen has recently been established to be essential for normal physiology of the male. The slow progressive decline of the hypothalamic-pituitary-gonadal (HPG) function is thought to be responsible for many common signs and symptoms of aging men, such as general weakness, sexual dysfunction, and increased fat mass. There is a large inter-individual variation in sex hormone levels cross-sectionally within given age groups as well as longitudinally with aging. A contributing factor to this variability are the numerous functionally significant polymorphisms that have been detected in the receptors for androgen and estrogen. In this review, we summarize the recent information on some common polymorphisms in androgen and estrogen receptor genes and their effect on gender specific and aging-related symptoms and diseases of men.