4.1 Anthropometrics
Given its importance for the general health of the transgender population, there are multiple studies of bone health, and reviews of these data. To summarise, transgender women often have low baseline (pre-intervention) bone mineral density (BMD), attributed to low levels of physical activity, especially weight-bearing exercise, and low vitamin D levels [
52,
53]. However, transgender women generally maintain bone mass over the course of at least 24 months of testosterone suppression. There may even be small but significant increases in BMD at the lumbar spine [
54,
55]. Some retrieved studies present data pertaining to maintained BMD in transgender women after many years of testosterone suppression. One such study concluded that “BMD is preserved over a median of 12.5 years” [
56]. In support, no increase in fracture rates was observed over 12 months of testosterone suppression [
54]. Current advice, including that from the International Society for Clinical Densitometry, is that transgender women, in the absence of other risk factors, do not require monitoring of BMD [
52,
57]. This is explicable under current standard treatment regimes, given the established positive effect of estrogen, rather than testosterone, on bone turnover in males [
58].
Given the maintenance of BMD and the lack of a plausible biological mechanism by which testosterone suppression might affect skeletal measurements such as bone length and hip width, we conclude that height and skeletal parameters remain unaltered in transgender women, and that sporting advantage conferred by skeletal size and bone density would be retained despite testosterone reductions compliant with the IOC’s current guidelines. This is of particular relevance to sports where height, limb length and handspan are key (e.g. basketball, volleyball, handball) and where high movement efficiency is advantageous. Male bone geometry and density may also provide protection against some sport-related injuries—for example, males have a lower incidence of knee injuries, often attributed to low quadriceps (
Q) angle conferred by a narrow pelvic girdle [
59,
60].
4.2 Muscle and Strength Metrics
As discussed earlier, muscle mass and strength are key parameters underpinning male performance advantages. Strength differences range between 30 and 100%, depending upon the cohort studied and the task used to assess strength. Thus, given the important contribution made by strength to performance, we sought studies that have assessed strength and muscle/lean body mass changes in transgender women after testosterone reduction. Studies retrieved in our literature search covered both longitudinal and cross-sectional analyses. Given the superior power of the former study type, we will focus on these.
The pioneer work by Gooren and colleagues, published in part in 1999 [
61] and in full in 2004 [
62], reported the effects of 1 and 3 years of testosterone suppression and estrogen supplementation in 19 transgender women (age 18–37 years). After the first year of therapy, testosterone levels were reduced to 1 nmol/L, well within typical female reference ranges, and remained low throughout the study course. As determined by MRI, thigh muscle area had decreased by − 9% from baseline measurement. After 3 years, thigh muscle area had decreased by a further − 3% from baseline measurement (total loss of − 12% over 3 years of treatment). However, when compared with the baseline measurement of thigh muscle area in transgender men (who are born female and experience female puberty), transgender women retained significantly higher thigh muscle size. The final thigh muscle area, after three years of testosterone suppression, was 13% larger in transwomen than in the transmen at baseline (
p < 0.05). The authors concluded that testosterone suppression in transgender women does not reverse muscle size to female levels.
Including Gooren and Bunck [
62], 12 longitudinal studies [
53,
63‐
73] have examined the effects of testosterone suppression on lean body mass or muscle size in transgender women. The collective evidence from these studies suggests that 12 months, which is the most commonly examined intervention period, of testosterone suppression to female-typical reference levels results in a modest (approximately − 5%) loss of lean body mass or muscle size (Table
4). No study has reported muscle loss exceeding the − 12% found by Gooren and Bunck after 3 years of therapy. Notably, studies have found very consistent changes in lean body mass (using dual-energy X-ray absorptiometry) after 12 months of treatment, where the change has always been between − 3 and − 5% on average, with slightly greater reductions in the arm compared with the leg region [
68]. Thus, given the large baseline differences in muscle mass between males and females (Table
1; approximately 40%), the reduction achieved by 12 months of testosterone suppression can reasonably be assessed as small relative to the initial superior mass. We, therefore, conclude that the muscle mass advantage males possess over females, and the performance implications thereof, are not removed by the currently studied durations (4 months, 1, 2 and 3 years) of testosterone suppression in transgender women. In sports where muscle mass is important for performance, inclusion is therefore only possible if a large imbalance in fairness, and potentially safety in some sports, is to be tolerated.
Table 4
Longitudinal studies of muscle and strength changes in adult transgender women undergoing cross-sex hormone therapy
| N = 12 TW 18–36 yr (age range) | T suppression + E supplementation | < 2 nmol/L at 4 mo | LBM 4 mo − 2.2% | LBM 4 mo 16% |
| N = 19 TW 26 ± 6 yr | T suppression + E supplementation | ≤ 1 nmol/L at 1 and 3 yr | Thigh area 1 yr − 9% / 3 yr -12% | Thigh area 1 yr 16%/3 yr 13% |
| N = 12 TW 29 ± 8 yr | E supplementation | < 10 nmol/L at 3 mo and 1 yr | LBM 3 mo/1 yr—small changes, unclear magnitude | |
| N = 84 TW 36 ± 11 yr | T suppression + E supplementation | ≤ 1 nmol/L at 1 and 2 yr | LBM 1 yr − 4%/2 yr − 7% | |
| N = 53 TW 31 ± 14 yr | T suppression + E supplementation | < 10 nmol/L at 1 yr | LBM 1 yr − 5% | LBM 1 yr 39% |
(and Van Caenegem et al. [ 76]) | N = 49 TW 33 ± 14 yr | T suppression + E supplementation | ≤ 1 nmol/L at 1 and 2 yr | LBM 1 yr − 4%/2 yr − 0.5% Grip strength 1 yr − 7%/2 yr − 9% Calf area 1 yr − 2%/2 yr − 4% Forearm area 1 yr − 8%/2 yr − 4% | LBM 1 yr 24%/2 yr 28% Grip strength 1 yr 26%/2 yr 23% Calf area 1 yr 16%/2 yr 13% Forearm area 1 yr 29%/2 yr 34% |
| N = 40 TW 31 ± 10 yr | T suppression + E supplementation | < 5 nmol/L at 6 mo and ≤ 1 nmol/L at 1 yr | LBM 1 yr − 2% | |
| N = 45 TW 35 ± 1 (SE) yr | T suppression + E supplementation | < 5 nmol/L at 1 yr | LBM 1 yr − 3% | LBM 1 yr 27% |
| N = 179 TW 29 (range 18–66) | T suppression + E supplementation | ≤ 1 nmol/L at 1 yr | LBM 1 yr Total − 3% Arm region − 6% Trunk region − 2% Android region 0% Gynoid region − 3% Leg region − 4% | LBM 1 yr Total 18% Arm region 28% Leg region 19% |
| N = 46 TW 34 ± 10 | E supplementation with or without T suppression | < 5 nmol/L at 3 mo ≤ 1 nmol/L at 31 mo | ALM 31 mo − 4% from the 3 mo visit | |
| N = 249 TW 28 (inter quartile range 23–40) | T suppression + E supplementation | ≤ 1 nmol/L at 1 yr | Grip strength 1 yr − 4% | Grip strength 1 yr 21% |
| N = 11 TW 27 ± 4 | T suppression + E supplementation | ≤ 1 nmol/L at 4 mo and at 1 yr | Thigh volume 1 yr − 5% Quad area 1 yr − 4% Knee extension strength 1 yr 2% Knee flexion strength 1 yr 3% | Thigh volume 1 yr 33% Quad area 26% Knee extension strength 41% Knee flexion strength 33% |
To provide more detailed information on not only gross body composition but also thigh muscle volume and contractile density, Wiik et al. [
71] recently carried out a comprehensive battery of MRI and computed tomography (CT) examinations before and after 12 months of successful testosterone suppression and estrogen supplementation in 11 transgender women. Thigh volume (both anterior and posterior thigh) and quadriceps cross-sectional area decreased − 4 and − 5%, respectively, after the 12-month period, supporting previous results of modest effects of testosterone suppression on muscle mass (see Table
4). The more novel measure of radiological attenuation of the quadriceps muscle, a valid proxy of contractile density [
74,
75], showed no significant change in transgender women after 12 months of treatment, whereas the parallel group of transgender men demonstrated a + 6% increase in contractile density with testosterone supplementation.
As indicated earlier (e.g. Table
1), the difference in muscle strength between males and females is often more pronounced than the difference in muscle mass. Unfortunately, few studies have examined the effects of testosterone suppression on muscle strength or other proxies of performance in transgender individuals. The first such study was published online approximately 1 year prior to the release of the current IOC policy. In this study, as well as reporting changes in muscle size, van Caenegem et al. [
53] reported that hand-grip strength was reduced from baseline measurements by − 7% and − 9% after 12 and 24 months, respectively, of cross-hormone treatment in transgender women. Comparison with data in a separately-published, parallel cohort of transgender men [
76] demonstrated a retained hand-grip strength advantage after 2 years of 23% over female baseline measurements (a calculated average of baseline data obtained from control females and transgender men).
In a recent multicenter study [
70], examination of 249 transgender women revealed a decrease of − 4% in grip strength after 12 months of cross-hormone treatment, with no variation between different testosterone level, age or BMI tertiles (all transgender women studied were within female reference ranges for testosterone). Despite this modest reduction in strength, transgender women retained a 17% grip strength advantage over transgender men measured at baseline. The authors noted that handgrip strength in transgender women was in approximately the 25th percentile for males but was over the 90th percentile for females, both before and after hormone treatment. This emphasizes that the strength advantage for males over females is inherently large. In another study exploring handgrip strength, albeit in late puberty adolescents, Tack et al. noted no change in grip strength after hormonal treatment (average duration 11 months) of 21 transgender girls [
72].
Although grip strength provides an excellent proxy measurement for general strength in a broad population, specific assessment within different muscle groups is more valuable in a sports-specific framework. Wiik et al., [
71] having determined that thigh muscle mass reduces only modestly, and that no significant changes in contractile density occur with 12 months of testosterone suppression, provided, for the first time, data for isokinetic strength measurements of both knee extension and knee flexion. They reported that muscle strength after 12 months of testosterone suppression was comparable to baseline strength. As a result, transgender women remained about 50% stronger than both the group of transgender men at baseline and a reference group of females. The authors suggested that small neural learning effects during repeated testing may explain the apparent lack of small reductions in strength that had been measured in other studies [
71].
These longitudinal data comprise a clear pattern of very modest to negligible changes in muscle mass and strength in transgender women suppressing testosterone for at least 12 months. Muscle mass and strength are key physical parameters that constitute a significant, if not majority, portion of the male performance advantage, most notably in those sports where upper body strength, overall strength, and muscle mass are crucial determinants of performance. Thus, our analysis strongly suggests that the reduction in testosterone levels required by many sports federation transgender policies is insufficient to remove or reduce the male advantage, in terms of muscle mass and strength, by any meaningful degree. The relatively consistent finding of a minor (approximately − 5%) muscle loss after the first year of treatment is also in line with studies on androgen-deprivation therapy in males with prostate cancer, where the annual loss of lean body mass has been reported to range between − 2 and − 4% [
77].
Although less powerful than longitudinal studies, we identified one major cross-sectional study that measured muscle mass and strength in transgender women. In this study, 23 transgender women and 46 healthy age- and height-matched control males were compared [
78]. The transgender women were recruited at least 3 years after sex reassignment surgery, and the mean duration of cross-hormone treatment was 8 years. The results showed that transgender women had 17% less lean mass and 25% lower peak quadriceps muscle strength than the control males [
78]. This cross-sectional comparison suggests that prolonged testosterone suppression, well beyond the time period mandated by sports federations substantially reduces muscle mass and strength in transgender women. However, the typical gap in lean mass and strength between males and females at baseline (Table
1) exceeds the reductions reported in this study [
78]. The final average lean body mass of the transgender women was 51.2 kg, which puts them in the 90th percentile for women [
79]. Similarly, the final grip strength was 41 kg, 25% higher than the female reference value [
80]. Collectively, this implies a retained physical advantage even after 8 years of testosterone suppression. Furthermore, given that cohorts of transgender women often have slightly lower baseline measurements of muscle and strength than control males [
53], and baseline measurements were unavailable for the transgender women of this cohort, the above calculations using control males reference values may be an overestimate of actual loss of muscle mass and strength, emphasizing both the need for caution when analyzing cross-sectional data in the absence of baseline assessment and the superior power of longitudinal studies quantifying within-subject changes.
No controlled longitudinal study has explored the effects of testosterone suppression on endurance-based performance. Sex differences in endurance performance are generally smaller than for events relying more on muscle mass and explosive strength. Using an age grading model designed to normalize times for masters/veteran categories, Harper [
81] analyzed self-selected and self-reported race times for eight transgender women runners of various age categories who had, over an average 7 year period (range 1–29 years), competed in sub-elite middle and long distance races within both the male and female categories. The age-graded scores for these eight runners were the same in both categories, suggesting that cross-hormone treatment reduced running performance by approximately the size of the typical male advantage. However, factors affecting performances in the interim, including training and injury, were uncontrolled for periods of years to decades and there were uncertainties regarding which race times were self-reported vs. which race times were actually reported and verified, and factors such as standardization of race course and weather conditions were unaccounted for. Furthermore, one runner improved substantially post-transition, which was attributed to improved training [
81]. This demonstrates that performance decrease after transition is not inevitable if training practices are improved. Unfortunately, no study to date has followed up these preliminary self-reports in a more controlled setting, so it is impossible to make any firm conclusions from this data set alone.
Circulating hemoglobin levels are androgen-dependent [
82] and typically reported as 12% higher in males compared with females [
4]. Hemoglobin levels appear to decrease by 11–14% with cross-hormone therapy in transgender women [
62,
71], and indeed comparably sized reductions have been reported in athletes with DSDs where those athletes are sensitive to and been required to reduce testosterone [
47,
83]. Oxygen-carrying capacity in transgender women is most likely reduced with testosterone suppression, with a concomitant performance penalty estimated at 2–5% for the female athletic population [
83]. Furthermore, there is a robust relationship between hemoglobin mass and
VO
2max [
84,
85] and reduction in hemoglobin is generally associated with reduced aerobic capacity [
86,
87]. However, hemoglobin mass is not the only parameter contributing to
VO
2max, where central factors such as total blood volume, heart size and contractility, and peripheral factors such as capillary supply and mitochondrial content also plays a role in the final oxygen uptake [
88]. Thus, while a reduction in hemoglobin is strongly predicted to impact aerobic capacity and reduce endurance performance in transgender women, it is unlikely to completely close the baseline gap in aerobic capacity between males and females.
The typical increase in body fat noted in transgender women [
89,
90] may also be a disadvantage for sporting activities (e.g. running) where body weight (or fat distribution) presents a marginal disadvantage. Whether this body composition change negatively affects performance results in transgender women endurance athletes remains unknown. It is unclear to what extent the expected increase in body fat could be offset by nutritional and exercise countermeasures, as individual variation is likely to be present. For example, in the Wiik et al. study [
71], 3 out of the 11 transgender women were completely resistant to the marked increase in total adipose tissue noted at the group level. This inter-individual response to treatment represents yet another challenge for sports governing bodies who most likely, given the many obstacles with case-by-case assessments, will form policies based on average effect sizes.
Altogether, the effects of testosterone suppression on performance markers for endurance athletes remain insufficiently explored. While the negative effect on hemoglobin concentration is well documented, the effects on VO2max, left ventricular size, stroke volume, blood volume, cardiac output lactate threshold, and exercise economy, all of which are important determinants of endurance performance, remain unknown. However, given the plausible disadvantages with testosterone suppression mentioned in this section, together with the more marginal male advantage in endurance-based sports, the balance between inclusion and fairness is likely closer to equilibrium in weight-bearing endurance-based sports compared with strength-based sports where the male advantage is still substantial.