Dose-Response Relationships Between Gonadal Steroids and Bone, Body Composition, and Sexual Function in Aging Men.
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ABSTRACT: Context
Most labs set the lower limit of normal for testosterone at the 2.5th percentile of values in young or age-matched men, an approach that does not consider the physiologic changes associated with various testosterone concentrations.Objective
To characterize the dose-response relationships between gonadal steroid concentrations and measures regulated by gonadal steroids in older men.Design, participants, and intervention
177 men aged 60 to 80 were randomly assigned to receive goserelin acetate plus either 0 (placebo), 1.25, 2.5, 5, or 10 grams of a 1% testosterone gel daily for 16 weeks or placebos for both medications (controls).Primary outcomes
Changes in serum C-telopeptide (CTX), total body fat by dual energy X-ray absorptiometry, and self-reported sexual desire.Results
Clear relationships between the testosterone dosage (or the resulting testosterone levels) and a variety of outcome measures were observed. Changes in serum CTX exceeded changes in the controls in men whose testosterone levels were 0 to 99, 100 to 199, 200 to 299, or 300 to 499 ng/dL, whereas increases in total body fat, subcutaneous fat, and thigh fat exceeded controls when testosterone levels were 0 to 99 or 100 to 199 ng/dL. Sexual desire and erectile function were indistinguishable from controls until testosterone levels were <100 ng/dL.Conclusion
Changes in measures of bone resorption, body fat, and sexual function begin at a variety of testosterone concentrations with many outcome measures remaining stable until testosterone levels are well below the stated normal ranges. In light of this variation, novel approaches for establishing the normal range for testosterone are needed.
SUBMITTER: Finkelstein JS
PROVIDER: S-EPMC7337183 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The influence of sex steroids on bone in both men and women has long been recognized. In men, however, the relative contribution of androgens versus estrogens in the regulation of bone metabolism remains uncertain. Animal studies demonstrate that both estradiol (E2), via activation of estrogen receptor-α, and testosterone (T), via activation of the androgen receptor, regulate bone mass in male rodents. The main focus of this review is to summarize and discuss recent findings from the osteoporotic fractures in men (MrOS) cohorts regarding the impact of serum sex steroids on bone health in elderly men. Collectively, these data demonstrate that serum E2 is directly associated with bone mineral density (BMD) and that low serum E2 associates with higher rates of bone loss and fracture. In addition, they substantiate the concept of a threshold E2 level that determines fracture risk in elderly men. We propose that the effect of E2 on fracture risk is at least partly mediated by its effect on BMD, whereas the more modest effect of T on fracture risk mainly is mediated by effects on muscle strength and risk of falls. Findings from the MrOS cohorts also demonstrate that racial and genetic variations in aromatase activity influence serum E2 levels in men. In conclusion, there is compelling evidence that not only androgens, but also estrogens, are important regulators of bone health in men. Consequently, E2 should not exclusively be regarded as the 'female hormone' but as a sex steroid that is necessary for maintenance of bone health in men.
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