Effect of Exercise on Serum Sex Hormones in Men: A 12-Month Randomized Clinical Trial

Vivian N. Hawkins; Karen Foster-Schubert; Jessica Chubak; Bess Sorensen; Cornelia M. Ulrich; Frank Z. Stancyzk; Stephen Plymate; Janet Stanford; Emily White; John D. Potter; Anne Mctiernan

Disclosures

Med Sci Sports Exerc. 2008;40(2):223-233. 

In This Article

Abstract and Introduction

Purpose: The effect of exercise on androgens in middle-aged to older men is poorly understood, and it could have implications for several aspects of health. This analysis was conducted to examine the effects of long-term aerobic exercise on serum sex hormones in middle-aged to older men.
Methods: One hundred two sedentary men, ages 40-75 yr, were randomly assigned to a 12-month exercise intervention or a control group (no change in activity). The combined facility and home-based exercise program consisted of moderate/vigorous-intensity aerobic activity for 60 min·d-1, 6 d·wk-1. Serum concentrations of testosterone, free testosterone, dihydrotestosterone (DHT), 3α-androstanediol glucuronide (3α-Diol-G), estradiol, free estradiol, and sex hormone-binding globulin (SHBG) were measured at baseline, 3, and 12 months.
Results: Exercisers trained a mean of 370 min·wk-1 (102% of goal), with only two dropouts. Cardiopulmonary fitness (V ·O2max) increased 10.8% in exercisers and decreased by 1.8% in controls (PG 0.001). DHT increased 14.5% in exercisers versus 1.7% in controls at 3 months (P = 0.04); at 12 months, it remained 8.6% above baseline in exercisers versus a 3.1% decrease in controls (P = 0.03). SHBG increased 14.3% in exercisers versus 5.7% in controls at 3 months (P = 0.04); at 12 months, it remained 8.9% above baseline in exercisers versus 4.0% in controls (P = 0.13). There were significant trends toward increasing DHT and SHBG, with greater increases in V ·O2max at 3 and 12 months in exercisers. No statistically significant differences were observed for testosterone, free testosterone, 3α-Diol-G, estradiol, or free estradiol in exercisers versus controls.
Conclusions: A yearlong, moderate-intensity aerobic exercise program increased DHT and SHBG, but it had no effect on other androgens in middle-aged to older men.

An age-associated decline of serum testosterone after the fourth to fifth decades of life in men has been observed not only cross-sectionally,[61] but also longitudinally in large cohort studies.[13,65] A combination of changes in testicular function, altered neuroendocrine regulation of Ley dig cells, and increased binding capacity of sex hormone-binding globulin (SHBG) results in approximately 40% lower testosterone levels among men in their 70s compared with men in their 20s.[12,25,28] Given the many health changes that also occur in men as they age, the possibility of a relationship between the decline in androgens and these health changes has, not surprisingly, been an area of active investigation. Low levels of testosterone in men have been associated with decreased sexual function, loss of muscle mass and strength, osteoporosis, declining cognitive function, and poorer quality of life.[28] Further, the age-related decline in testosterone is associated with increased body fat, insulin resistance, and other metabolic risk factors.[36] Despite the common belief to the contrary, cardiovascular disease has been associated with low levels of androgens in older men.[23]

Although treating men with clinical androgen deficiency with testosterone replacement is clearly beneficial for several health and quality-of-life outcomes, administering testosterone to older men with aging-associated relative androgen deficiency is controversial and likely not beneficial.[6,16] Yet, there is some evidence that increasing sex hormone levels in aging men may provide health benefits such as improved cognition, enhanced sexual function, and reduced frailty.[28] Rather than administering pharmacologic doses of exogenous testosterone, interventions that favorably alter endogenous sex hormone levels could be of greater benefit in this setting. One such possible intervention is exercise.

The majority of studies exploring the effects of exercise on androgens have focused on acute effects in short-term exercise protocols, and most of these demonstrate that exercise bouts are associated with an acute transient increase in testosterone, with variable effects on other androgens when these are measured.[8,14,18,20,31,63] The effect of long-term, moderate-intensity, aerobic exercise on hormone levels in men has not been well studied, yet it may be important to differentiate between the acute and chronic effects of exercise, as acute changes may relate more to muscle growth and tissue remodeling, whereas chronic changes may mediate exercise effects on long-term health.[24,32] Some cross-sectional studies conducted in middle-aged and older men indicate that circulating testosterone concentrations may be higher in men who regularly exercise.[3,40] Prospective, nonrandomized studies of resistance exercise over a few weeks either increased testosterone[50] or not,[26,42] whereas one study of daily aerobic exercise together with a low-fat diet increased SHBG, which could counteract the biological activity of testosterone.[60] To our knowledge, no randomized clinical trials have been published that have tested the chronic effects of aerobic exercise on a comprehensive panel of sex hormones in middle-aged to older men. Thus, there is no consensus regarding the physiologic role of long-term exercise to alter hormone levels in men and, in turn, impact age-related diseases.

We conducted a randomized clinical trial to examine the effects of a 12-month, moderate-intensity, aerobic exercise intervention on serum testosterone, free testosterone, dihydrotestosterone (DHT), 3α-androstanediol glucuronide (3α-Diol-G), estradiol, free estradiol, and SHBG in sedentary men. DHT is synthesized from testosterone by two isoenzymes of 5α-reductase (Fig. 1) and is more biologically active at the androgen receptor than testosterone, whereas 3α-Diol-G is its inactive metabolite. Because obesity is associated with sex hormones,[28] we assessed the effects of the exercise intervention on serum hormones by baseline BMI and body fat, and by change in adiposity over 12 months. We additionally evaluated the effects of exercise on sex hormones by baseline age and baseline testosterone level. Among exercisers, the effect of the intervention on serum hormones by adherence and changes in fitness were also evaluated. All of these exploratory subgroup analyses were preplanned.

Testosterone metabolism. Type 2 5α-reductase is found predominantly in the prostate and other genital tissues and is believed to be more important in conversion of testosterone to DHT, whereas type 1 is found throughout the body, including the skin, liver, and prostate.[49] 3α-Diol-G is a metabolite of DHT. Type 3 3α-hydroxysteroid dehydrogenase (3α-HSD-3) converts DHT to 3α-androstanediol (3α-Diol), the immediate precursor of 3α-Diol-G, and is found in abdominal adipose tissue.[46] 3α-Diol is converted to 3α-Diol-G by the glucuro(39)nosyltransferase UGT2B15, an enzyme also present in fat tissue.[57]

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