The endocrine system is intimately involved in modulating lifespan and quality of life. Facing an ever increasing proportion of aged people in the western society, there is great interest in understanding the complex interrelations between increasing age and hormonal regulation. Age-associated endocrinological changes comprise the decline of basal hormonal levels, pulsatile hormone distribution, and activity of hormonal axis, which result in changes in body composition. Men and women experience different age-associated alterations of the hormonal system. Aging per se is a risk factor for diseases like diabetes mellitus type 2, thyroid disorders, osteoporosis, frailty, and sarcopenia. Gender-specific differences with respect to symptoms, interactions, diagnosis, and therapy must be taken into consideration. Current data do not allow a general recommendation for hormonal substitution, neither for women nor for men. New research approaches following a multifactorial pathway are required to elucidate the complexity of age-associated endocrinological changes and to develop gender-specific therapies for endocrinological diseases.