Aging and the Male Reproductive System.

This narrative review presents an overview of current knowledge on fertility and reproductive hormone changes in aging men, the factors driving and modulating these changes, their clinical consequences, and the benefits and risks of testosterone (T) therapy. Aging is accompanied by moderate decline of gamete quality and fertility. Population mean levels show a mild total T decline, an SHBG increase, a steeper free T decline, and a moderate LH increase with important contribution of comorbidities (e.g., obesity) to these changes. Sexual symptoms and lower hematocrit are associated with low T and are partly responsive to T therapy. The relationship of serum T with body composition and metabolic health is bidirectional; limited beneficial effects of T therapy on body composition have only marginal effects on metabolic health and physical function. Skeletal changes are associated primarily with estradiol and SHBG. Cognitive decline is not consistently linked to low T and is not improved by T therapy. Although limited evidence links moderate androgen decline with depressive symptoms, T therapy has small beneficial effects on mood, depressive symptoms, and vitality in elderly patients with low T. Suboptimal T (and/or DHT) has been associated with increased risk of stroke, but not of ischemic heart disease, whereas an association with mortality probably reflects that low T is a marker of poor health. Globally, neither severity of clinical consequences attributable to low T nor the nature and magnitude of beneficial treatment effects justify the concept of some broadly applied "T replacement therapy" in older men with low T. Moreover, long-term safety of T therapy is not established.