Our data suggest that total and free estradiol, % IBW, and fat-free mass are important positive determinants of BMD, while VO2 max is an important negative determinant of BMD at the spine in male collegiate athletes. In contrast and contrary to our hypothesis, we could not detect an important role for IGF-1. We demonstrated lower total and free estradiol levels in male long-distance runners compared to wrestlers. These relationships may contribute to the below average spine BMD in long-distance runners and higher-than-average BMD at all skeletal sites measured in the wrestlers studied. Higher estradiol levels in the wrestlers may reflect their higher mean fat mass, as estradiol is synthesized primarily in adipose cells by aromatases in men. This hypothesis is supported by our data demonstrating that fat mass is a predictor of free estradiol levels. Our data are the first to demonstrate that estrogen levels may be a significant determinant of BMD in collegiate athletes. Our findings that free and total estradiol are stronger predictors of BMD than testosterone in male athletes may have important implications and certainly merit further study. This cross-sectional study provides the basis for larger longitudinal studies to investigate whether intensive running training results in diminished bone density over time and whether this effect is mediated, at least in part, by a reduction in estradiol levels.
Although the female athlete triad is established as a prevalent syndrome of bone loss and fractures, mechanistically related to restrictive eating behavior that results in amenorrhea,(1
)no such syndrome has been established in their male counterparts. Because female long-distance runners are specifically affected with this syndrome,(2
) we chose to study male long-distance runners. We demonstrate lower than average-for-age spine BMD, but not hip BMD in male collegiate long-distance runners. A study of 65 female and 44 male endurance runners, ages 19–50, demonstrated a similar proportion and degree of bone loss in men as in women.(3
) In addition, in men, multiple regression models determined that weekly running distance and training years were both negative predictors and, together, best predicted lumbar BMD; number of years of training was the best (negative) predictor of hip BMD.(3
) These previously published data are consistent with our data demonstrating VO2
max as an important negative predictor of BMD in male athletes. We did not find a correlation with hours of cardiovascular exercise per week, and this may be because levels of exertion and fitness could not be interpreted simply from hours of training. The preservation of hip BMD in our runners is likely related to the positive weight-bearing effects of running in moderation on the hip, as has been shown in prior work, where training volume and energy availability have not been analyzed.(27
The failure of other studies to identify an endocrine predictor of low bone density in male runners may be due to the prior focus of investigators on androgens rather than estrogens. Androgen levels have been shown to be normal or low-normal in studies of male athletes.(4
) Of note, one study demonstrated an inverse relationship between androgen levels, all within the normal range, and training volumes of more than 64 km weekly.(5
) In the same study, a positive association was reported between training volumes less than 80 km weekly and BMD at the proximal femur, but no association was observed between either testosterone or free testosterone and BMD.(5
) This is consistent with our data in which neither total nor free testosterone levels were important determinants of bone density at any site, except for free testosterone’s positive relationship with bone density at the radius. Mean testosterone and free testosterone levels were similar in the runners and wrestlers, despite the difference in mean bone density between the groups, and very few of the athletes were hypogonadal.
The lack of a high prevalence of hypogonadism in male athletes, in contrast to their female counterparts, raises the issue of whether there are sex-specific effects, with less sensitivity of the hypothalamic-pituitary-gonadal (HPG) axis to physical stress in men. However, some studies investigating the differential effects of fasting on the HPG axis have suggested that the male HPG axis may be more sensitive to starvation than that of females.(29
) Sex-specific effects of exercise on the HPG axis have not been as well characterized. Such studies are often confounded by differences in body fat and/or prevalence of eating disordered behavior in females compared to males, as in a study in which delayed menarche was reported in young elite female gymnasts but normal pubertal development in their male counterparts.(32
) Although percent body fat was reduced in both genders, it was more severely reduced in girls than boys, possibly contributing to the more profound effects on the HPG axis in the girls. Body fat may also impact endocrine mechanisms of bone maintenance in males through its central role in the conversion of androgens to estrogens by aromatases. This hypothesis is supported by our data demonstrating both free testosterone and body fat mass to be significant positive predictors of free estradiol levels.
Estrogens have been shown to play a critical role in maintenance of normal BMD in men,(8
) including a report by Falahati-Nini et al., who administered leuprolide and letrozole to 59 elderly men to reduce testosterone levels and prevent conversion of androgens to estrogens.(11
) Study participants were subsequently randomly assigned to receive: 1) estradiol plus placebo patches, 2) testosterone plus placebo patches, 3) testosterone plus estradiol patches or 4) double placebo patches. Serum osteocalcin, a marker of bone formation, decreased in the absence of both testosterone and estradiol, suggesting that both sex steroids were needed to maintain normal osteocalcin levels. However, estradiol, but not testosterone, was necessary to prevent an increase in bone resorption markers. Cross-sectional studies have also demonstrated the importance of estradiol as a determinant of BMD.(13
) Moreover, a case report of a 28-year-old man with estrogen resistance caused by a mutation in the estrogen receptor gene demonstrated that without estradiol action, BMD is extremely low and epiphyses closure is delayed extensively.(12
Limitations of our study include our small sample size. We had sufficient power to detect more significant effects, such as those of estradiol, but we may not have had sufficient power to detect weaker effects of other hormones and determinants on bone that nonetheless may exist, and we cannot rule these out. Another limitation of our study was that we did not include an exhaustive list of potential hormonal and other determinants. Instead, we tested a fairly focused hypothesis that was reasonable to investigate in the available sample size. Thus, we cannot rule out that there may be other important determinants of BMD in male athletes that we did not study, such as PTH or leptin. In fact, bone metabolism is a complex process and important mechanisms, in addition to estrogen’s actions, must also be imputed. We did test a fair number of hypotheses in this exploratory study, and it is conceivable that the results are spurious due to multiple comparisons. We do not intend that this is a definitive study. Rather, we believe that it should generate further investigation in this interesting and novel area, focusing on the role of estrogens in skeletal health in male athletes. Another potential limitation of the study was the lack of a totally sedentary control group. However, we purposefully chose the golfing team as a comparison group because its members share a common “college team” environment and exposures with the other two groups in many regards, but are not involved in organized athletic training – either resistance exercise or endurance training. As indicated in , the golfers engaged in a mean of 1.5 hours of exercise weekly, which is approximately 13 minutes a day. Nevertheless, an entirely sedentary control group may have added additional interesting information. Finally, as this is a cross-sectional study, causation cannot be established. Prospective studies with frequent sampling, more hormonal markers, a larger cohort of athletes in a variety of sports, detailed training histories, a non-athletic control group and additional bone imaging technology such as quantitative computed tomography, are needed to confirm our findings.
Although weight, in the form of BMI and % IBW, was an important predictor of bone density in athletes, the correlation coefficient for fat-free mass at the PA spine was higher. These findings are consistent with published data in healthy male adolescents and adults, in whom lean body mass and resistance exercise,(33
)have been established to be important predictors of bone mass.
Our data suggest that endogenous estrogens are more important determinants of BMD than androgens, which were normal in collegiate long-distance runners. VO2 max and weekly running mileage were important negative predictors of BMD at the spine, likely reflecting a negative effect of high running volume over time. Whether this translates into an elevated risk for fractures is unknown. Percent IBW and fat-free mass were also important predictors of BMD in the athletes studied, reflected in higher BMD at all sites in the wrestlers compared to the runners, and confirming the importance of weight and muscle mass as a determinant of BMD. The exact interactive effects of lean mass, strength training, estradiol, and other mediators of BMD still need to be elucidated. With a better understanding of the interrelationship of fitness, body composition, and the hormonal milieu in male athletes, improved training regimens can be established to optimize both performance and skeletal health.