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She has received grant support from the IAAF for a study on testosterone and physical performance in women. Comparable longitudinal studies of muscle loss, strength, and performance following castration for prostate cancer are well summarized (185), showing progressive loss for 24 months (see Fig. 4). Although these studies of older men with prostate cancer must be extrapolated with caution, age, stage of disease, race, and baseline circulating testosterone concentration did not affect the rate or extent of decline in hemoglobin (179, 181). In these circumstances, it could only be justifiable to replicate in women the salient testosterone dose-response studies available from men if the available evidence of dose-response relationship in men was not sufficiently convincing and/or there was reason to think that these dose-response characteristics would be substantially different in women. In men, analogous ethical concerns over short- and long-term adverse effects delayed the definitive studies of supraphysiological testosterone doses to healthy young and older men but were eventually overcome.
Data corroborating the Huang et al. study results comes from another well-controlled study in which postmenopausal women who were administered methyl testosterone following a run-in period of estrogen replacement displayed a significant increase in lean (muscle) mass as well as upper and lower limb power during a 16-week double-blind, parallel group study (113). Strong dose-response relationship between testosterone dose and circulating concentration with muscle mass and strength in men. The studies showed a consistent dose response for muscle mass and strength that was clearly related to testosterone dose and consequential blood testosterone concentrations (Fig. 2, upper panel). The lower panels from Finkelstein et al. (65) show the strong dose-response relationships of (B) whole-body muscle mass, (E) thigh muscle mass, and (F) leg press strength with increasing testosterone dose. The upper panels from Bhasin et al. (111) display the strong dose-response relationships of muscle mass shown as (A) "lean" or "fat-free" mass or volume of (D) thigh and (E) quadriceps muscle and (C) of leg muscle strength with increasing testosterone dose (upper row) or circulating concentration (middle row). These sex differences render women unable to compete effectively against men, especially (but not only) in power sports.Open in a new tabSex differences in performance (in percentage) according to age (in years) in running events, including 50 m to 2 miles (upper left panel), and in jumping events, including high jump, pole vault, triple jump, long jump, and standing long jump (upper right panel) for details, see Ref. (8).
Sex differences in height have been the most thoroughly investigated measure of bone size, as adult height is a stable, easily quantified measure in large population samples. It may be estimated that as a result the average maximal oxygen transfer will be ∼10% greater in men than in women, which has a direct impact on their respective athletic capacities. The sex difference in pulmonary function may be largely explained by the androgen-sensitive sex difference in height, which is a strong predictor of lung capacity and function (149). These changes create an advantage of greater bone strength and stronger fulcrum power from longer bones. As a result, on average men are 7% to 8% taller with longer, denser, and stronger bones, whereas women have shorter humerus and femur cross-sectional areas being 65% to 75% and 85%, respectively, those of men (106). Bone grows in length due to epiphyseal chondral growth plates that provide cartilage, forming the matrix for lengthening of long bone, which is terminated by an estrogen-dependent mechanism that depends on aromatization of testosterone to estradiol.
The proposal that the sex difference in muscle mass and function might be due to sex differences in endogenous GH secretion (116) is refuted by the extensive and conclusive clinical evidence that endogenous GH secretion in young women is consistently higher (typically twice as high) as in young men of similar age (163–170). It has also been proposed that the sex difference in athletic performance may be due to genetic effects of an unspecified Y chromosome gene that may dictate taller stature (154), as height is correlated with men’s greater muscle mass. One proposal has been that, as men are taller than women, height differences may explain the sex differences in muscle mass and function, which explains some athletic success (116). Additionally, whereas passing through puberty enhances male physical performance, the widening of the female pelvis during puberty, balancing the evolutionary demands of obstetrics and locomotion (136, 137), retards the improvement in female physical performance, possibly driven by ovarian hormones rather than the absence of testosterone (138, 139). Analogous findings were reported for testosterone treatment effects in postmenopausal women where the highest dose (25 mg weekly) of testosterone, which increased mean serum testosterone to 7.3 nmol/L, had the largest increase (3%) in blood hemoglobin and hematocrit (112).
Additionally, there is experimental evidence that testosterone increases skeletal muscle myostatin expression (94), mitochondrial biogenesis (95), myoglobin expression (96), and IGF-1 content (97), which may augment energetic and power generation of skeletal muscular activity. However, the limited knowledge of the magnitude and hormonal mechanisms involved, specifically the degree of androgen dependence of these mechanisms, means that it is difficult to estimate their contribution, if any, toward the sex difference in athletic performance. Examples include sex differences in exercise-induced cardiac (147, 148) and lung (149) function and mitochondrial biogenesis and energetics (95). The greater cortical bone density and thereby resistance to long bone fractures is unlikely to be relevant to the athletic performance of young athletes, in whom fractures during competition are extremely rare and not expected to be linked to sex. Women with CAH require glucocorticoid replacement therapy but exhibit widely varying levels of hormonal control (79). The increasing doses of testosterone produced an expected dose response in serum testosterone concentrations (by LC-MS), with the highest testosterone dose (25 mg/wk) producing a mean nadir concentration of 7.3 nmol/L.