SPORTS AND PERFORMANCE IN THE TRANSGENDER POPULATION: A SYSTEMATIC REVIEW AND META-ANALYSIS

Nahon, Roberto Lohn; Silva, Ana Paula Simões da; Muniz-Santos, Renan; Novaes, Rayanne Carneiro Torres de; Pedroso, Laura Souza Prado Lobrigati

doi:10.1590/1517-8692202127062021_0054

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Revista Brasileira de Medicina do Esporte

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Systematic Review, General Sports Medicine • Rev Bras Med Esporte 27 (6) • 2021 • https://doi.org/10.1590/1517-8692202127062021_0054 copy

SPORTS AND PERFORMANCE IN THE TRANSGENDER POPULATION: A SYSTEMATIC REVIEW AND META-ANALYSIS

DEPORTE Y RENDIMIENTO EN LA POBLACIÓN TRANSGÉNERO: REVISIÓN SISTEMÁTICA Y METANÁLISIS

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Introduction:

The debate surrounding the regulations on the participation of transgender individuals in sports is not recent, but it is still ongoing. Some sports organizations are more flexible in this regard, while others are more conservative.

Objective:

Through a systematic review and meta-analysis, this study summarizes the scientific evidence of the effects of cross-sex hormone therapy on muscle strength, hematocrit, and hemoglobin measurements, parameters that seem to be linked to sports performance.

Methods:

We conducted electronic searches for manuscripts published before November 20^th, 2020. Studies published in three different databases (PubMed, SciELO, and Lilacs) were included, without any time or language restriction, and using keywords such as “transgender”, “gender dysphoria”, “strength”, “hematocrit”, and “hemoglobin”. The PRISMA systematization was used for the elaboration of this review, while a meta-analysis was conducted to mathematically evidence the results. The meta-analysis was performed using the random effect model, to find the pooled estimate effect of cross-sex hormone therapy on the parameters analyzed.

Results:

The electronic search retrieved 21 articles that were eligible for inclusion. Cross-sex hormone therapy influenced the three parameters analyzed in almost all the studies. Overall, there was a significant increase in muscle strength in female-to-males (FtMs), per muscle group analyzed: +17.7% (95% confidence interval [CI]14.9;20.6). In male-to-females (MtFs) the results of the muscle strength analysis were more controversial, but the pooled estimate effect showed a decrease: −3.6% (95% confidence interval [CI] −6.6; −0.6).

Conclusion:

Muscle strength, hematocrit, and hemoglobin were altered as a result of cross-sex hormone therapy in both FtMs and MtFs. However, there was a lack of studies comparing the transgender individuals to the population of the same desired gender. Such studies are needed, to better infer rules for the participation of transgender athletes in Olympic sports. Level of Evidence I; Systematic Review and Meta-analysis.

Keywords:
Sports medicine; Transgender; Athletic performance

Year	Design	Subjects	Country	Drugs and route of administration	T levels at the end (mean)	Assessment	Follow up	Results & Conclusion*
E Van Caenegem et al., 2015³⁸38 Van Caenegem E, Wierckx K, Taes Y, Schreiner T, Vandewalle S, Toye K, et al. Body composition, bone turnover, and bone mass in trans men during testosterone treatment: 1-year follow-up data from a prospective case-controlled study (ENIGI). Eur J Endocrinol. 2015;172(2):163-71.	Prospective	n= 23 FtMs 27 ± 9 years	Norway and Belgium	T undecanoate 1000mg (sometimes preceded by progestogens)	FtMs: 21.8nmol/L	Grip strength	12 months	Increase in grip strength
M Scharff et al., 2019³⁹39 Scharff M, Wiepjes CM, Klaver M, Schreiner T, t’Sjoen G, Den Heijer M. Change in grip strength in trans people and its association with lean body mass and bone density. Endocrine connections. 2019;8(7):1020-8.	Prospective	n= 278 FtMs 23 (20-30) years n= 249 MtFs 28 (23-40) years	Norway, Belgium, and Netherlands	FtMs: T gel (50 mg), T esters (250 mg i.m) or T undecanoate (1000 mg i.m). MtFs: Cpa 50 mg, in combination with 2–4 mg oral estradiol valerate or 100 μg/24 h estradiol patch	FtMs: 22 nmol/L MtFs: 0.6 nmol/L	Grip strength	12 months	Increase grip strength in FtMs and decrease in MtFs
E Van Caenegem et al., 2015⁴⁰40 Van Caenegem E, Wierckx K, Taes Y, Schreiner T, Vandewalle S, Toye K, et al. Preservation of volumetric bone density and geometry in trans women during cross-sex hormonal therapy: a prospective observational study. Osteoporosis International. 2015;26(1):35-47.	Prospective	n= 49 FtMs 33 ± 12 years	Norway and Belgium	Estradiol valerate 4mg or transdermal estradiol 100mg, with cpa 50mg	MtFs: 0.5 nmol/L	Grip strength	12/24 months	Decrease grip strength in MtFs
LJW Tack et al., 2018⁴¹41 Tack LJ, Craen M, Lapauw B, Goemaere S, Toye K, Kaufman J-M, et al. Proandrogenic and antiandrogenic progestins in transgender youth: differential effects on body composition and bone metabolism. The Journal of Clinical Endocrinology & Metabolism. 2018;103(6):2147-56.	Prospective	n= 44 FtMs 16.2 ± 1.05 years n= 21 MtFs 16.3 ± 1.2 years	Belgium	FtMs: L 5-10 mg MtFs: Cpa 50 mg	FtMs: 8.8 nmol/L MtFs: 0.8 nmol//L	Grip strength	FtMs:11.6 months MtFs:10.6 months	Increase in FtMs and no difference in MtFs
A Wiilk et al., 2020⁴²42 Wiik A, Lundberg TR, Rullman E, Andersson DP, Holmberg M, Mandić M, et al. Muscle strength, size, and composition following 12 months of gender-affirming treatment in transgender individuals. The Journal of Clinical Endocrinology & Metabolism. 2020;105(3):e805-e13.	Prospective	n= 12 FtMs 25 years n= 11 MtFs 27 years	Sweden	GnRH antagonist with; FtMs: T undecanoate 1000 mg i.m. MtFs: Estradiol transdermally (1-2 mg as gel, or 100-200 mg with a patch), orally (4-8 mg), or i.m (80mg)	Shown in graphic	Knee extensor and flexor strength	12 months	Increase in FtMs and no difference in MtFs
A. Muller et al., 2010⁴³43 Mueller A, Haeberle L, Zollver H, Claassen T, Kronawitter D, Oppelt PG, et al. Effects of intramuscular testosterone undecanoate on body composition and bone mineral density in female-to-male transsexuals. The journal of sexual medicine. 2010;7(9):3190-8.	Prospective	n=45 FtMs 30.4± 9.1 years	Germany	T undecanoate 1,000 mg intramuscularly	FtMs: 22.6 nmol/L	Hb and Hct	12, 24 months	Increase in Hb and Hct
JW Jacobelt et al., 2007⁴⁴44 Jacobeit JW, Gooren LJ, Schulte HM. Endocrinology: long-acting intramuscular testosterone undecanoate for treatment of female-to-male transgender individuals. The journal of sexual medicine. 2007;4(5):1479-84.	Prospective	n = 12 FtMs 33±6 years	Germany and Netherlands	T undecanoate 1,000 mg intramuscularly	FtMs: 19.1 nmol/L	Hb and Hct	12 months	Increase in Hb and Hct
JD Fernandes et al., 2016⁴⁵45 Fernandez J, Tannock L. Metabolic effects of hormone therapy in transgender patients. Endocrine Practice. 2016;22(4):383-8.	Retrospective	n=19 FtMs (baseline) and 10 FtMs (end) 22.1 ± 6.9 years	United States	T intramuscularly (11 mg/day)	Not shown	Hb and Hct	3-6, 6-18 months	Increase in Hb and Hct
JW Jacobelt et al., 2009⁴⁶46 Jacobeit J, Gooren L, Schulte H. Safety aspects of 36 months of administration of long-acting intramuscular testosterone undecanoate for treatment of female-to-male transgender individuals. European journal of endocrinology. 2009;161(5):795.	Prospective	n=17 FtMs 34±7 years	Germany and Netherlands	T undecanoate 1,000 mg intramuscularly	FtMs: 21.1 nmol/L	Hb and Hct	6,12,18,24,30,36 months	Increase in Hb and Hct
R Abdala et al., 2018⁴⁷47 Abdala R, Nagelberg A, Silveira F, Otero P, Mormandi E. Short-term safety profile of cross-hormonal therapy in trans-male subjects. Medicina. 2018;78(6):399-402.	Retrospective	n= 30 FtMs 27 years	Argentina	T undecanoate 1,000mg or T enanthate 250mg, or gel 1% (5g)	FtMs: 22.1 nmol/L	Hb and Hct	6-12 months	Increase in Hb and Hct
LJW Tack et al., 2016⁴⁸48 Tack LJ, Craen M, Dhondt K, Bossche HV, Laridaen J, Cools M. Consecutive lynestrenol and cross-sex hormone treatment in biological female adolescents with gender dysphoria: a retrospective analysis. Biology of sex Differences. 2016;7(1):1-11.	Retrospective	n=37 FtMs 15.8 years	Belgium	L monotherapy in all participants, followed by L+T esters (50-125mg) in a subset of them (n=25)	FtMs: 19.5 nmol/L	Hb and Hct	6,12,18,24 months	Increase in Hb and Hct
IE Stoffers et al., 2019⁴⁹49 Stoffers IE, de Vries MC, Hannema SE. Physical changes, laboratory parameters, and bone mineral density during testosterone treatment in adolescents with gender dysphoria. The journal of sexual medicine. 2019;16(9):1459-68.	Retrospective	n=62 FtMs (baseline) and 15 FtMs (end) 16.5 years	Netherlands	GnRHa followed by T esters (250mg)	FtMs: 13.9nmol/L	Hb and Hct	6,12,24 months	Increase in Hb and Hct
J Jarin et al., 2017⁵⁰50 5Jarin J, Pine-Twaddell E, Trotman G, Stevens J, Conard LA, Tefera E, et al. Cross-sex hormones and metabolic parameters in adolescents with gender dysphoria. Pediatrics. 2017;139(5).	Retrospective	FtMs: n=52 for Hct and 41 for Hb (baseline) n = 40 for Hct and Hb (end) 16 years MtFs: n=13 for Hct and Hb (baseline) n=12 for Hct and 13 for Hb (end) 18 years.	United States	FtMs: T subcutaneous at a dose of 25-100mg MtFs: Estrogen orally at 1-8 mg; or intramuscularly at 20-80 mg; or transdermally at 0.025-0.200 mg, with or without spironolactone (50-200mg)	FtMs: 14.7nmol/L FtMs:6.9nmol/L	Hb and Hct	1-3,4-6,6+ months	FtMs: Increase in Hb and Hct MtFs: No difference in Hb and Hct
K Wierckx et al., 2014⁵¹51 Wierckx K, Van Caenegem E, Schreiner T, Haraldsen I, Fisher A, Toye K, et al. Cross-sex hormone therapy in trans persons is safe and effective at short-time follow-up: results from the European network for the investigation of gender incongruence. The journal of sexual medicine. 2014;11(8):1999-2011.	Prospective	n=53 FtMs Ghent (27) 27.3 ± 8.5 years Oslo (26) 21.7 ± 5.1 years n=53 MtFs Ghent (47) 31.7 ± 14.8 years Oslo (6) 19.3 ± 2.4 years	Belgium, Norway, and Italy	FtMs: T undecanoate 1,000mg intramuscularly MtFs: 50 mg of cpa, with 4 mg of estradiol valerate or 100 μg/24 hours transdermal 17-β estradiol patch	FtMs: 20.7nmol/L MtFs: 0.4nmol/L (oral) 0.5nmol/L (transdermal)	Hct	12 months	FtMs: Increase in Hct MtFs: Decrease in Hct
J Olson-Kennedy et al., 2018⁵²52 Olson-Kennedy J, Okonta V, Clark LF, Belzer M. Physiologic response to gender-affirming hormones among transgender youth. Journal of Adolescent Health. 2018;62(4):397-401.	Prospective	n= 34 FtMs 18 years	United States	FtMs: T cypionate via subcutaneous. Two were on simultaneous GnRHa MtFs: 17 β estradiol (orally 1-6mg, or injectable 20-30mg) with or without spironolactone (100–200 mg orally) or a GnRH analog, and in some cases, the addition of progesterone.	FtMs 18.5nmol/L MtFs 5.9nmol/L	Hb	24 months	FtMs: Increase in Hb MtFs: Decrease in Hb
JA SoRelle et al.,2018⁵³53 SoRelle JA, Jiao R, Gao E, Veazey J, Frame I, Quinn AM, et al. Impact of hormone therapy on laboratory values in transgender patients. Clinical chemistry. 2019;65(1):170-9.	Retrospective	n=56 FtMs (baseline) n= 81 for Hb and 80 for Hct (end) 30 years n=73MtFs (baseline) n=105 for Hb and Hct(end) 33 years	United States	FtMs: T injections, ranging from 35 to 300 mg Oral estradiol 2-8 mg, with or without spironolactone	FtMs: 22.3nmol/L MtFs: 1.9nmol/L	Hb and Hct	6+ months	FtMs: Increase in Hb and Hct MtFs: Decrease in Hb and Hct
R Vita et al., 2018¹⁰10 Vita R, Settineri S, Liotta M, Benvenga S, Trimarchi F. Changes in hormonal and metabolic parameters in transgender subjects on cross-sex hormone therapy: a cohort study. Maturitas. 2018;107:92-6.	Retrospective	n=11 FtMs 25.1+3.7 years n=21 MtFs 25.2+7 years	Italy	FtMs: T enanthate or undecanoate MtFs: Estradiol valerate (2-6 mg/d) with or without cpa (50-100 mg/d). Three patients took progesterone.	FtMs: 17nmol/L MtFs: 1.1nmol/L	Hb and Hct	30 months (mean)	FtMs: Increase in Hb and Hct MtFs: Decrease in Hb and Hct
A Wiik et al., 2020⁴²42 Wiik A, Lundberg TR, Rullman E, Andersson DP, Holmberg M, Mandić M, et al. Muscle strength, size, and composition following 12 months of gender-affirming treatment in transgender individuals. The Journal of Clinical Endocrinology & Metabolism. 2020;105(3):e805-e13.	Prospective	n=12 FtMs ]25+5 years n=11 MtFs 27+4 years	Sweden	GnRH antagonist with; FtMs: T undecanoate 1000 mg i.m.; MtFs: estradiol transdermally (1-2 mg as gel, or 100-200 mg with a patch), orally (4-8 mg), or i.m (80mg)	Shown in graphic	Hb	12 months	FtMs: Increase in Hb MtFs: Decrease in Hb
A Mueller et al., 2007⁵⁴54 Mueller A, Kiesewetter F, Binder H, Beckmann MW, Dittrich R. Long-term administration of testosterone undecanoate every 3 months for testosterone supplementation in female-to-male transsexuals. The Journal of Clinical Endocrinology & Metabolism. 2007;92(9):3470-5.	Prospective	n= 35 FtMs 29.6+ 8.9 years	Germany	T undecanoate 1,000 mg intramuscularly	FtMs: 27.5nmol/L	Hb and Hct	12 months	Increase in Hb and Hct
P Chandra et al., 2010⁵⁵55 Chandra P, Basra SS, Chen TC, Tangpricha V. Alterations in lipids and adipocyte hormones in female-to-male transsexuals. International journal of endocrinology. 2010;2010.	Prospective	n=12 FtMs 29+9years	United States	T esters, cypionate or enanthate	FtMs: 34.6nmol/L	Hct	12 months	Increase in Hct
C. Pelusi et al., 2014⁵⁶56 Pelusi C, Costantino A, Martelli V, Lambertini M, Bazzocchi A, Ponti F, et al. Effects of three different testosterone formulations in female-to-male transsexual persons. The journal of sexual medicine. 2014;11(12):3002-11.	Prospective	n=45 FtMs 23.5 years	Italy	T gel, or undecanoate or esters	FtMs: 20.5nmol/L (gel); 25.7nmol/L (esters); 21.3nmol/L (undecanoate)	Hb and Hct	12 months	Increase in Hb and Hct
LJw Tack et al., 2017⁵⁷57 Tack LJ, Heyse R, Craen M, Dhondt K, Bossche HV, Laridaen J, et al. Consecutive cyproterone acetate and estradiol treatment in late-pubertal transgender female adolescents. The journal of sexual medicine. 2017;14(5):747-57.	Retrospective	n=27 MtFs 16.5 years	Belgium	Cpa (50mg) monotherapy for at least 6 months, and then incremental doses of estrogen	MtFs: 5.82nmol/L	Hb and Hct	24 months	Decrease in Hb and Hct

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[1] Correspondence Roberto Lohn Nahon, LBP – UNIRIO. Rua Dr. Xavier Sigaud, 290 - Urca, Rio de Janeiro, RJ, Brazil. 22290-240. robertonahon@gmail.com