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INTRODUCTION

As a result of the age-related functional impairments of the steroidogenic as well as the gametogenic compartments of the testis, aging of men is associated with an increased risk of sexual dysfunction, reduced fecundity, prostate cancer, lower urinary tract symptoms, and paternal age effect disorders in the offspring.1 These age-related conditions greatly affect men’s well-being and quality of life and are among the major reasons that motivate middle-aged and older men to seek medical care.1 The substantial increase in life expectancy of men around the globe has focused growing attention on these quality-of-life issues associated with reproductive aging of men. Traditionally, the reproductive health of men has not received due attention in the medical school curricula or in typical primary care practices. Therefore, many middle-aged and older men may seek care in one of many men’s health clinics that have mushroomed all around the United States in recognition of this unmet need and which offer specialized care focused on reproductive disorders among men.1

This chapter discusses the age-related decline in testosterone levels and fecundity in men. Sexual dysfunction, lower urinary tract symptoms, and prostate cancer are discussed elsewhere in this book.

CHANGES IN THE STEROIDOGENIC COMPARTMENT OF THE TESTIS

Serum total testosterone levels are lower in older men than in younger men even after accounting for the comorbidities, adiposity, time of sampling, and technical issues related to hormone assays (Fig. 4-1).2–5 Several observational studies have confirmed a gradual but progressive age-related decrease in testosterone concentrations from age 20 to 80.1–9 Total testosterone concentrations reach a peak in the second and third decade of life and decline progressively throughout life without a clear inflection point in the trajectory of age-related change in testosterone concentrations (Fig. 4-1).3,8,9 Therefore, the term andropause has fallen out of favor because it misleadingly implies an abrupt cessation of androgen production in men. The term late-onset hypogonadism has been proposed to reflect the view that in some middle-aged and older men (>65 years), the age-related decline in testosterone concentration is associated with a cluster of symptoms and signs in a syndromic constellation, which resembles that observed in men with classical hypogonadism.5

Key Points

  • Serum total and free testosterone levels in men, after reaching a peak in the second and third decade of life, decline with advancing age.

  • The trajectory of age-related decline is affected by comorbid condition, adiposity, medications, and genetic factors.

  • The age-related decline in circulating testosterone concentrations is primarily due to decreased testosterone production rates in older men because of abnormalities at all levels of the hypothalamic-pituitary-testicular axis.

  • Secondary hypogonadism—low testosterone levels without elevated luteinizing hormone (LH) and follicle-stimulating hormone (FSH)— in older men is associated with obesity and comorbid conditions and is far more prevalent than primary hypogonadism—low testosterone levels with elevated LH and FSH—which is more specific for aging.

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