Normative Hypogonadism and Depression: Does 'Andropause' Exist?

S. N. Seidman


Int J Impot Res. 2006;18(5):415-422. 

Abstract and Introduction

The progressive decline in testosterone level has been demonstrated in both cross-sectional and longitudinal studies, and overall at least 25% of men over the age of 70 years meet laboratory criteria for hypogonadism (i.e., testosterone deficiency). Such age-associated HPG hypofunctioning, which has been termed 'andropause', is thought to be responsible for a variety of symptoms experienced by elderly men, including sexual dysfunction and depression. Although, it has been difficult to establish correlations between 'andropausal' symptoms and plasma testosterone levels, there is some evidence that testosterone replacement leads to improvement in muscle strength, bone mineral density, and erectile dysfunction. There is little evidence of a link between HPG-axis dysfunction and depressive illness, and exogenous androgens have not been consistently shown to be antidepressant. This article reviews the relationship between androgens and depression in aging men.

Male hypothalamic-pituitary-gonada (HPG) function declines progressively with age and a substantial proportion of men older than age of 50 years have testosterone levels below the threshold values used to define testosterone deficiency in younger men.[1] Mild testosterone deficiency in middle-aged and elderly men can, therefore, be considered physiological (i.e., a para-aging phenomenon) or pathological (i.e., a deficit state). Since age-adjusted norms are not used, it is treated as pathological. Yet, even if it is considered physiological, this 'normative' decline may be clinically significant, as is the case with the age-associated decline in female gonadal hormones.

Whether the age-dependent decline in androgen levels leads to health problems in men is being debated vigorously.[2,3,4] Some investigators argue that age-associated testosterone deficiency, or 'andropause,' is responsible for many of the typical signs of male aging, such as erectile dysfunction (ED), decreased lean body mass, skin alterations, osteoporosis, and increased visceral fat; as well as for neuropsychiatric problems, such as fatigue, loss of libido, depression, irritability, insomnia, and memory impairment.[4] Furthermore, the application of a testosterone replacement strategy for older men with low or low-normal testosterone levels is thought by some investigators to be especially promising for reversing such presumed 'andropausal' sequelae.[5] Yet, it has not only been difficult to correlate hormone levels with these age-related phenomena,[3,4] but testosterone replacement in elderly men is not especially effective in reversing these symptoms.[6,7] For example, although testosterone replacement in elderly men has been demonstrated to enhance upper limb strength[8,9] and mass,[7] improve bone mineral density,[6] increase hematocrit,[10] and reduce leptin levels (an effect that may improve visceral adiposity),[8] such effects are apparently weak and likely of no clinical consequence. There are few testosterone replacement studies in which psychiatric symptoms of age-related hypogonadism have been considered. Here, we will focus on psychiatric aspects of male HPG-axis hypofunctioning, and consider the relationship between testosterone and depressive illness.