Testosterone Therapy in Men With Late-onset Hypogonadism
Testosterone Therapy in Men With Late-onset Hypogonadism
Studies show that the age-related decline in serum testosterone levels occurs as a result of changes both at the level of the testes, reflected in diminished testicular secretory capacity, and the hypothalamic-pituitary unit, including alterations in the pulsatility of the GnRH neurons. In addition to the effect of biological age however, the prevalence of androgen deficiency is also influenced by adiposity and comorbidities, including diabetes, cardiac failure, renal disease and chronic obstructive lung disease. Similarly, medications that suppress testosterone levels, such as glucocorticoids and opioids, also contribute to this decrease. Of all these factors, obesity has the most potent effect on testosterone levels. For example, data from EMAS show that irrespective of age, an obese (body mass index [BMI] >30 kg/m) man has a 30% lower serum testosterone level than a man with a normal BMI (<25 kg/m) (Fig. 4). Longitudinal studies also show that the trajectory of age-related decline in serum testosterone level becomes steeper if a person becomes obese during the course of the follow-up, confirming that health and body composition are major determinants of testosterone level (Fig. 5). Similarly, the prevalence of LOH is increased with poor general health, and is 10-fold higher in men with at least two comorbid conditions compared to men with none (Fig. 4). These observations suggest that healthy lifestyle, treatment of comorbidities, and discontinuation of testosterone-suppressing medications may attenuate the age-related decline in testosterone levels. Indeed, weight loss resulting from gastric bypass surgery or a very low calorie diet is associated with a significant increase in testosterone levels (Fig. 6).
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Figure 4.
Relative influence of age, obesity, and comorbidities on testosterone levels (adapted from Ref. 10).
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Figure 5.
Relative impact of a variety of factors on testosterone levels (adapted from Ref. 21).
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Figure 6.
Increase in total and free testosterone levels after weight loss resulting from gastric bypass surgery (data from Ref. 22).
Influence of Modifiable Risk Factors on LOH
Studies show that the age-related decline in serum testosterone levels occurs as a result of changes both at the level of the testes, reflected in diminished testicular secretory capacity, and the hypothalamic-pituitary unit, including alterations in the pulsatility of the GnRH neurons. In addition to the effect of biological age however, the prevalence of androgen deficiency is also influenced by adiposity and comorbidities, including diabetes, cardiac failure, renal disease and chronic obstructive lung disease. Similarly, medications that suppress testosterone levels, such as glucocorticoids and opioids, also contribute to this decrease. Of all these factors, obesity has the most potent effect on testosterone levels. For example, data from EMAS show that irrespective of age, an obese (body mass index [BMI] >30 kg/m) man has a 30% lower serum testosterone level than a man with a normal BMI (<25 kg/m) (Fig. 4). Longitudinal studies also show that the trajectory of age-related decline in serum testosterone level becomes steeper if a person becomes obese during the course of the follow-up, confirming that health and body composition are major determinants of testosterone level (Fig. 5). Similarly, the prevalence of LOH is increased with poor general health, and is 10-fold higher in men with at least two comorbid conditions compared to men with none (Fig. 4). These observations suggest that healthy lifestyle, treatment of comorbidities, and discontinuation of testosterone-suppressing medications may attenuate the age-related decline in testosterone levels. Indeed, weight loss resulting from gastric bypass surgery or a very low calorie diet is associated with a significant increase in testosterone levels (Fig. 6).
(Enlarge Image)
Figure 4.
Relative influence of age, obesity, and comorbidities on testosterone levels (adapted from Ref. 10).
(Enlarge Image)
Figure 5.
Relative impact of a variety of factors on testosterone levels (adapted from Ref. 21).
(Enlarge Image)
Figure 6.
Increase in total and free testosterone levels after weight loss resulting from gastric bypass surgery (data from Ref. 22).
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