Hormonal changes in men due to ageing (all hormonal axes)

Abstract

The increase in life expectancy achieved in the last decades has raised the proportion of the elderly in the general population, rendering health problems of the 3rd age more relevant than ever. Ageing is accompanied by adaptations in endocrine functions, most of them in the form of regression, affecting the secretory capacity of the cells that comprise the endocrine system, the corresponding hormone receptors and the post-receptor processes in the target cells. A reduction of the gonadal axis output has been demonstrated in both cross-sectional and longitudinal studies in healthy men, predicting a fall of Testosterone concentrations by approximately 110 ng/dL per decade, after the age of 60 yrs. The primary event of this gradually established, mild form of hypogonadism (late-onset; LOH) has not been elucidated as yet and is believed to be a combined result of reduced hypothalamic GnRH secretion, decreased testicular responsiveness to hCG/LH, and blunted androgenic negative feedback. Similarly, a decline in circulating Growth hormone (GH) and IGF-I levels is observed with ageing, due principally to decreased GH secretion. This decline starts at young adulthood and progresses exponentially until advanced age, when it may even reach cessation. Many of the manifestations of normal ageing resemble those of pathologic GH deficiency, implying a crucial role of hyposomatotropism in the process of ageing. The functionality of the thyroid axis is also characterized by regression with increasing age, concerning both the production of thyroid hormones, as well as their metabolism: TRH secretion is blunted, resulting in a decrease of the TSH drive on the thyroid, while conversion of T4 to T3 from deiodinases D1 and D2 is reduced. The net result of these changes is a frank reduction of the active T3 metabolite, an increase of the inactive reverse T3 metabolite (rT3), while T4 levels remain relatively unchanged. On the contrary, cortisol secretion from the adrenal glands remains relatively unaffected, while the secretion of androgens and in particular DHEA, show a gradual decline since the age of 40, reaching almost 20% of the young adult levels by the age of 80 yrs. Whether these changes reflect the failure of the endocrine glands to fulfill their mission or normal adaptations to protect the frail ageing body is still a matter of considerable debate.