Male Reproduction and Aging

[madman]

Male Reproduction and Aging (2023)
Maria Gabriela Figueiredo, MD, Thiago Gagliano-Jucá, MD, PhD, Shehzad Basaria, MD


INTRODUCTION

Aging of humans is associated with functional alterations at all levels of the reproductive axis and affects both steroidogenic and spermatogenic compartments. Unlike female reproductive aging (menopause) or organic androgen deficiency in men (due to diseases of the hypothalamus, pituitary, or testes), male reproductive aging does not result in absolute cessation of testosterone production or spermatogenesis (Table 1). In fact, the decline in serum testosterone concentrations due to aging per se is mild, and in most men, testosterone concentrations are in the low-normal range. Nonetheless, in a minority of aging men, testosterone deficiency may occur, which is influenced by the presence of comorbidities. Recent data suggest that older men who remain fit and healthy generally continue to maintain normal serum testosterone levels

Age-related low testosterone in men has been referred to as andropause, viropause, partial androgen deficiency of the aging male, or late-onset hypogonadism (LOH); the latter term is used most often.1 In this article, we review age-related changes in sex steroid levels and their consequences. We also discuss the efficacy and safety of testosterone therapy.




*Epidemiology of Late-Onset Hypogonadism


*Numeric Versus Syndromic Prevalence of Late-Onset Hypogonadism


*Comorbidities Influence Testosterone Levels


*Pathophysiologic Basis of Age-Related Decline in Testosterone Levels


*Clinical Evaluation of Late-Onset Hypogonadism


*Association Between Endogenous Testosterone and Health Outcomes
-Sexual function
-Body composition and physical function
-Cognition and mood
-Skeletal health
-Cardiovascular health
-Metabolic health


*Benefits of Testosterone Treatment
-Sexual function
-Physical function and mobility
-Bone density and quality
-Energy and mood
-Cognition
-Anemia
-Glycemic control


*Risks of Testosterone Therapy
-Cardiovascular safety
-Prostate safety




SUMMARY

Despite the increase in prescription rates of testosterone in middle-aged and older men, the syndromic prevalence of LOH is low. Adiposity and other comorbidities play an important role in influencing the trajectory of a decline in testosterone levels. Thus, testosterone is likely a biomarker of health. Trials of testosterone therapy in older men have shown modest benefits, whereas long-term prostate and cardiovascular safety remains unclear.

Considering the existing evidence, the expert panel of the Endocrine Society recommended against routine testosterone therapy for all men aged 65 years or older with low testosterone. Instead, the panel suggested that testosterone therapy be offered to select older men with unequivocally low morning testosterone and specific symptoms of androgen deficiency on an individualized basis, only after discussion of potential risks and benefits.11 The TRAVERSE trial will likely provide insights regarding the long-term risks of testosterone therapy.

 

[madman]

Table 1
Summary of differences in clinical features of reproductive aging in female menopause, organic male hypogonadism, and late-onset male hypogonadism

 

[madman]

Fig. 1. Effect of adiposity and comorbidities on the prevalence of late-onset hypogonadism. (Data from Wu FC, Tajar A, Pye SR, Silman AJ, Finn JD, O’Neill TW, Bartfai G, Casanueva F, Forti G, Giwercman A, Huhtaniemi IT, Kula K, Punab M, Boonen S, Vanderschueren D; European Male Aging Study Group. Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study. J Clin Endocrinol Metab. 2008 Jul;93(7):2737-45.)

 

[madman]

 

[madman]

Fig. 3. Changes in coronary plaque volume seen in the Cardiovascular Trial of the TTrials. * indicates P<.05 for comparison between testosterone and placebo groups. (Adapted from Gagliano-Juca´ T, Basaria S. Testosterone replacement therapy and cardiovascular risk. Nat Rev Cardiol. 2019 Sep;16(9):555-574.)

 

[madman]

KEY POINTS

*The syndromic prevalence of late-onset hypogonadism is low

*Testosterone can be considered a biomarker of health because comorbidities are associated with low testosterone concentrations

*The efficacy of testosterone therapy in older men is modest

*Testosterone therapy improves bone mass (but there are no fracture data); there is no conclusive evidence that it improves cognition

*The long-term cardiovascular and prostate safety of testosterone therapy in older men remains unclear

 

[madman]

CLINICS CARE POINTS

*The syndromic prevalence of LOH is low (~2%)

*Adiposity and comorbidities influence the trajectory of decline in testosterone levels

*The efficacy of testosterone therapy in older men is modest with improvements in sexual function, anemia (not a primary indication for therapy), and bone mass (no fracture data available)

*The long-term risks of testosterone therapy on the prostate and cardiovascular system remain unknown