Clinical Concerns on Sex Steroids Variability in Cisgender and Transgender Women Athletes

Abstract

In the female athletic community, there are several endogenous and exogenous variables that influence the status of the hypothalamus-pituitary-ovarian axis and serum sex steroid hormones concentrations (e. g., 17β-estradiol, progesterone, androgens) and their effects. Moreover, female athletes with different sex chromosome abnormalities exist (e. g., 46XX, 46XY, and mosaicism). Due to the high variability of sex steroid hormones serum concentrations and responsiveness, female athletes may have different intra- and inter-individual biological and functional characteristics, health conditions, and sports-related health risks that can influence sports performance and eligibility. Consequently, biological, functional, and/or sex steroid differences may exist in the same and in between 46XX female athletes (e. g., ovarian rhythms, treated or untreated hypogonadism and hyperandrogenism), between 46XX and 46XY female athletes (e. g., treated or untreated hyperandrogenism/disorders of sexual differentiation), and between transgender women and eugonadal cisgender athletes. From a healthcare perspective, dedicated physicians need awareness, knowledge, and an understanding of sex steroid hormones’ variability and related health concerns in female athletes to support physiologically healthy, safe, fair, and inclusive sports participation. In this narrative overview, we focus on the main clinical relationships between hypothalamus-pituitary-ovarian axis function, endogenous sex steroids and health status, health risks, and sports performance in the heterogeneous female athletic community.

Key words

sex steroid hormones - female athletes - hyperandrogenism - testosterone - transgender woman

Publication History

Received: 01 February 2022

Accepted: 08 July 2022

Article published online:
29 September 2022

• References

• 1 Borgen NT. Collider bias (aka sample selection bias) in observational studies: why the effects of hyperandrogenism in elite women's sport are likely underestimated. Br J Sports Med 2020; 54: 750-752
• 2 Camporesi S.. A question of ’fairness’: why ethics should factor in the court of arbitration for sport’s decision on the IAAF Hyperandrogenism Regulations. Br J Sports Med 2019; 53: 797-798
• 3 Franklin S, Ospina Betancurt J, Camporesi S.. What statistical data of observational performance can tell us and what they cannot: the case of Dutee Chand v. AFI & IAAF. Br J Sports Med 2018; 52: 420-421
• 4 Harper J, Lima G, Kolliari-Turner A. et al. The fluidity of gender and implications for the biology of inclusion for transgender and intersex athletes. Curr Sports Med Rep 2018; 17: 467-472
• 5 Harper J, Martinez-Patino M-J, Pigozzi F. et al. Implications of a third gender for elite sports. Curr Sports Med Rep 2018; 7: 42-44
• 6 Hirschberg AL.. Hyperandrogenism in female athletes. J Clin Endocrinol Metab 2019; 104: 503-505
• 7 Sönksen PH, Bavington LD, Boehning T. et al. Hyperandrogenism controversy in elite women’s sport: an examination and critique of recent evidence. Br J Sports Med 2018; 52: 1481-1482
• 8 Sonksen P, Ferguson-Smith MA, Bavington LD. et al. Medical and ethical concerns regarding women with hyperandrogenism and elite sport. J Clin Endocrinol Metab 2015; 100: 825-827
• 9 Sönksen PH, Holt RIG, Böhning W. et al. Why do endocrine profiles in elite athletes differ between sports?. Clin Diabetes Endocrinol 2018; 4: 3
• 10 Tannenbaum C, Bekker S.. Sex, gender, and sports. BMJ 2019; 364: I1120
• 11 Holesh JE, Bass AN, Lord M.. Physiology, Ovulation. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022. Jan. 2022 May 8
• 12 Cano Sokoloff N, Misra M, Ackerman KE.. Exercise, training, and the hypothalamic-pituitary-gonadal axis in men and women. Front Horm Res 2016; 47: 27-43
• 13 Haines M, McKinley-Barnard SK, Andre TL. et al. Skeletal muscle estrogen receptor activation in response to eccentric exercise up-regulates myogenic-related gene expression independent of differing serum estradiol levels occurring during the human menstrual cycle. J Sports Sci Med 2018; 17: 31-39
• 14 Hirschberg AL.. Female hyperandrogenism and elite sport. Endocr Connect 2020; 9: R81-R92
• 15 Chidi-Ogbolu N, Baar K.. Effect of estrogen on musculoskeletal performance and injury risk. Front Physiol 2019; 9: 1834
• 16 Guillaume M, Montagner A, Fontaine C. et al. Nuclear and membrane actions of estrogen receptor alpha: contribution to the regulation of energy and glucose homeostasis. Adv Exp Med Biol 2017; 1043: 401-426
• 17 Oosthuyse T, Bosch AN.. The effect of the menstrual cycle on exercise metabolism: implications for exercise performance in eumenorrhoeic women. Sports Med 2010; 40: 207-227
• 18 Rettberg JR, Yao J, Brinton RD.. Estrogen: a master regulator of bioenergetic systems in the brain and body. Front Neuroendocrinol 2014; 35: 8-30
• 19 Smith JR, Koepp KE, Berg JD. et al. Influence of sex, menstrual cycle, and menopause status on the exercise pressor reflex. Med Sci Sports Exerc 2019; 51: 874-881
• 20 Melanson EL, Lyden K, Gibbons E. et al. Influence of estradiol status on physical activity in premenopausal women. Med Sci Sports Exerc 2018; 50: 1704-1709
• 21 Minahan C, Joyce S, Bulmer AC. et al. The influence of estradiol on muscle damage and leg strength after intense eccentric exercise. J Appl Physiol (1985) 2015; 115: 1493-1500
• 22 Hansen M.. Female hormones: do they influence muscle and tendon protein metabolism?. Proc Nutr Soc 2018; 77: 32-41
• 23 Klinge CM.. Estrogenic control of mitochondrial function and biogenesis. J Cell Biochem 2008; 105: 1342-1351
• 24 Kraemer RR, Francois M, Castracane VD.. Estrogen mediation of hormone responses to exercise. Metabolism 2012; 61: 1337-1346
• 25 Spangenburg EE, Geiger PC, Leinwand LA. et al. Regulation of physiological and metabolic function of muscle by female sex steroids. Med Sci Sports Exerc 2012; 44: 1653-1662
• 26 da Silva SB, de Sousa Ramalho Viana E. et al. Changes in peak expiratory flow and respiratory strength during the menstrual cycle. Respir Physiol Neurobiol 2006; 150: 211-219
• 27 Stachenfeld NS.. Sex hormone effects on body fluid regulation. Exerc Sport Sci Rev 2008; 36: 152-159
• 28 Sgrò P, Di Luigi L.. Sport and male sexuality. J Endocrinol Invest 2017; 40: 911-923
• 29 Julian R, Hecksteden A, Fullagar HH. et al. The effects of menstrual cycle phase on physical performance in female soccer players. PLoS One 2017; 12: e0173951
• 30 Cristina-Souza G, Santos-Mariano AC, Souza-Rodrigues CC. et al. Menstrual cycle alters training strain, monotony, and technical training length in young. J Sports Sci 2019; 37: 1824-1830
• 31 Janse DE, Jonge X, Thompson B, Han A.. Methodological recommendations for menstrual cycle research in sports and exercise. Med Sci Sports Exerc 2019; 51: 2610-2617
• 32 Findlay RJ, Macrae EHR, Whyte IY. et al. How the menstrual cycle and menstruation affect sporting performance: experiences and perceptions of elite female rugby players. Br J Sports Med 2020; 54: 1108-1113
• 33 Foster R, Vaisberg M, Bachi ALL. et al. Premenstrual syndrome, inflammatory status, and mood states in soccer players. Neuroimmunomodulation 2019; 26: 1-6
• 34 Hakimi O, Cameron LC.. Effect of exercise on ovulation: a systematic review. Sports Med 2017; 47: 1555-1567
• 35 Ackerman KE, Holtzman B, Cooper KM. et al. Low energy availability surrogates correlate with health and performance consequences of relative energy deficiency in sport. Br J Sports Med 2019; 53: 628-633
• 36 De Souza MJ, Koltun KJ, Williams NI.. The role of energy availability in reproductive function in the female athlete triad and extension of its effects to men: an initial working model of a similar syndrome in male athletes. Sports Med 2019; 49: 125-137
• 37 Dipla K, Kraemer RR, Constantini NW. et al. Relative energy deficiency in sports (RED-S): elucidation of endocrine changes affecting the health of males and females. Hormones (Athens) 2021; 20: 35-47
• 38 Mountjoy M, Sundgot-Borgen JK, Burke LM. et al. IOC consensus statement on relative energy deficiency in sport (RED-S): 2018 update. Br J Sports Med 2018; 52: 687-697
• 39 Toufexis D, Rivarola MA, Lara H. et al. Stress and the reproductive axis. J Neuroendocrinol 2014; 26: 573-586
• 40 Vorona E, Nieschlag E.. Adverse effects of doping with anabolic androgenic steroids in competitive athletics, recreational sports and bodybuilding. Minerva Endocrinol 2018; 43: 476-488
• 41 Tornberg ÅB, Melin A, Koivula FM. et al. Reduced neuromuscular performance in amenorrheic elite endurance athletes. Med Sci Sports Exerc 2017; 49: 2478-2485
• 42 Witchel SF.. Congenital adrenal hyperplasia. Pediatr Adolesc Gynecol 2017; 30: 520-534
• 43 Moran C, Azziz R, Weintrob N. et al. Reproductive outcome of women with 21-hydroxylase-deficient nonclassic adrenal hyperplasia. J Clin Endocrinol Metab 2006; 91: 3451-3456
• 44 Bidet M, Bellanne-Chantelot C, Galand-Portier MB. et al. Fertility in women with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Endocrinol Metab 2010; 95: 1182-1190
• 45 Aversa A, La Vignera S, Rago R. et al. Fundamental concepts and novel aspects of polycystic ovarian syndrome: expert consensus resolutions. Fornt Endocrinol (Lausanne) 2020; 11: 516
• 46 Kogure GS, Silva RC, Miranda-Furtado CL. et al. Hyperandrogenism enhances muscle strength after progressive resistance training, independent of body composition, in women with polycystic ovary syndrome. J Strength Cond Res 2018; 32: 2642-2651
• 47 Dos Santos IK, de Lima Nunes R, Soares GM. et al. Exercise and reproductive function in polycystic ovary syndrome: protocol of a systematic review. Syst Rev 2017; 6: 264
• 48 Kogure GS, Silva RC, Picchi Ramos FK. et al. Women with polycystic ovary syndrome have greater muscle strength irrespective of body composition. Gynecol Endocrinol 2015; 31: 237-242
• 49 Speiser PW, Dupont B, Rubinstein P. et al. High frequency of nonclassical steroid 21-hydroxylase deficiency. Am J Hum Genet 1985; 37: 650-667
• 50 Moran C, Azziz R, Carmina E. et al. 21-hydroxylase-deficient nonclassic adrenal hyperplasia is a progressive disorder: a multicenter study. Am J Obstet Gynecol 2000; 183: 1468-1474
• 51 Pignatelli D.. Non-classic adrenal hyperplasia due to the deficiency of 21-hydroxylase and its relation to polycystic ovarian syndrome. Front Horm Res 2013; 40: 158-170
• 52 Oncul M, Sahmay S, Tuten A. et al. May AMH levels distinguish LOCAH from PCOS among hirsute women?. Eur J Obstet Gynecol Reprod Biol 2014; 178: 183-187
• 53 Martin KA, Anderson RR, Chang RJ. et al. Evaluation and treatment of hirsutism in premenopausal women: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2018; 103: 1233-1257
• 54 Escobar-Morreale HF, Carmina E, Dewailly D. et al. Epidemiology, diagnosis and management of hirsutism: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome Society. Hum Reprod Update 2012; 18: 146-170
• 55 Di Luigi L, Pigozzi F, Sgrò P. et al. The use of prohibited substances for therapeutic reasons in athletes affected by endocrine diseases and disorders: the therapeutic use exemption (TUE) in clinical endocrinology. J Endocrinol Invest 2020; 43: 563-573
• 56 World Anti-doping Agency (WADA). Therapeutic Use Exemption (TUE Available from https://www.wada-ama.org/en/what-we-do/science-medical/therapeutic-use-exemptions Accessed: May 2022
• 57 Clark RV, Wald JA, Swerdloff RS. et al. Large divergence in testosterone concentrations between men and women: frame of reference for elite athletes in sex-specific competition in sports, a narrative review. Clin Endocrinol (Oxf) 2019; 90: 15-22
• 58 Handelsman DJ, Hirschberg AL, Bermon S.. Circulating testosterone as the hormonal basis of sex differences in athletic performance. Endocr Rev 2018; 39: 803-829
• 59 Ristori J, Cocchetti C, Romani A. et al. Brain sex differences related to gender identity development: genes or hormones?. Int J Mol Sci 2020; 21: 2123
• 60 Eklund E, Berglund B, Labrie F. et al. Serum androgen profile and physical performance in women Olympic athletes. Br J Sports Med 2017; 51: 1301-1308
• 61 Hirschberg AL, Elings Knutsson J, Helge T. et al. Effects of moderately increased testosterone concentration on physical performance in young women: a double blind, randomised, placebo-controlled study. Br J Sports Med 2020; 54: 599-604
• 62 Labrie F, Martel C, Bélanger A. et al. Androgens in women are essentially made from DHEA in each peripheral tissue according to intracrinology. J Steroid Biochem Mol Biol 2017; 168: 9-18
• 63 Huang G, Basaria S.. Do anabolic-androgenic steroids have performance-enhancing effects in female athletes?. Mol Cell Endocrinol 2018; 15: 56-64
• 64 Miller KK, Biller BM, Beauregard C. et al. Effects of testosterone replacement in androgen-deficient women with hypopituitarism: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab 2006; 91: 1683-1690
• 65 Huang G, Basaria S, Travison TG. et al. Testosterone dose-response relationships in hysterectomized women with or without oophorectomy: effects on sexual function, body composition, muscle performance and physical function in a randomized trial. Menopause 2014; 21: 612-623
• 66 Eliakim A, Nemet D.. Endogenous hyperandrogenism and exercise capacity lessons from the exercise-congenital adrenal hyperplasia model. J Pediatr Endocrinol Metab 2010; 23: 1213-1219
• 67 Hagmar M, Berglund B, Brismar K. et al. Hyperandrogenism may explain reproductive dysfunction in olympic athletes. Med Sci Sports Exerc 2009; 41: 1241-1248
• 68 Kogure GS, Miranda-Furtado CL, Silva RC. et al. Resistance exercise impacts lean muscle mass in women with polycystic ovary syndrome. Med Sci Sports Exerc 2016; 48: 589-598
• 69 Costa EC, Sá JCF DE, Stepto NK. et al. Aerobic training improves quality of life in women with polycystic ovary syndrome. Med Sci Sports Exerc 2018; 50: 1357-1366
• 70 Knochenhauer ES, Key TJ, Kahsar-Miller M. et al. Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study. J Clin Endocrinol Metab 1998; 83: 3078-3082
• 71 Ferguson-Smith MA, Bavington LD.. Natural selection for genetic variants in sport: the role of Y chromosome genes in elite female athletes with 46,XY DSD1. Sports Med 2014; 44: 1629-1634
• 72 Bermon S, Garnier PY, Hirschberg AL. et al. Serum androgen levels in elite female athletes. J Clin Endocrinol Metab 2014; 99: 4328-4335
• 73 Caliskan Guzelce E, Eyupoglu D, Torgutalp S. et al. Is muscle mechanical function altered in polycystic ovary syndrome?. Arch Gynecol Obstet 2019; 300: 771-776
• 74 Cardinale M, Stone MH.. Is testosterone influencing explosive performance?. J Strength Cond Res 2006; 20: 103-107
• 75 Douchi T, Yamamoto S, Oki T. et al. Serum androgen levels and muscle mass in women with polycystic ovary syndrome. Obstet Gynecol 1999; 94: 337-340
• 76 Rickenlund A, Carlström K, Ekblom B. et al. Hyperandrogenicity is an alternative mechanism underlying oligomenorrhea or amenorrhea in female athletes and may improve physical performance. Fertil Steril 2003; 79: 947-955
• 77 Bermon S.. Androgens and athletic performance of elite female athletes. Curr Opin Endocrinol Diabetes Obes 2017; 24: 246-251
• 78 Conte D, Romanelli F, Fillo S. et al. Aspirin inhibits androgen response to chorionic gonadotropin in humans. Am J Physiol 1999; 277: e1032
• 79 Di Luigi L, Rossi C, Sgrò P. et al. Do non-steroidal anti-inflammatory drugs influence the steroid hormone milieu in male athletes?. Int J Sports Med 2007; 28: 809-814
• 80 Di Luigi L, Guidetti L, Romanelli F. et al. Acetylsalicylic acid inhibits the pituitary response to exercise-related stress in humans. Med Sci Sports Exerc 2001; 33: 2029-2035
• 81 Di Luigi L, Guidetti L, Pigozzi F. et al. Acute amino acids supplementation enhances pituitary responsiveness in athletes. Med Sci Sports Exerc 1999; 31: 1748-1754
• 82 Di Luigi L.. Supplements and the endocrine system in athletes. Clin Sports Med 2008; 27: 131-51
• 83 Hilton EN, Lundberg TR.. Transgender women in the female category of sport: perspectives on testosterone suppression and performance advantage. Sports Med 2021; 51: 199-214
• 84 Jones BA, Arcelus J, Bouman WP. et al. Sport and transgender people: a systematic review of the literature relating to sport participation and competitive sport policies. Sports Med 2017; 47: 701-716
• 85 International Olympic Committee. Framework on Fairness, Inclusion and Non-discrimination on the Basis of Gender Identity and Sex Variations, 2021 Available from https://stillmed.olympics.com/media/Documents/News/2021/11/IOC-Framework Fairness-Inclusion-Nondiscrimination-2021.pdf Accessed: May 2022
• 86 Pigozzi F, Bigard X, Steinacker J. , on behalf of the International Federation of Sports Medicine (FIMS) and the European Federation of Sports Medicine Associations (EFSMA) et al. Joint position statement of the International Federation of Sports Medicine (FIMS) and European Federation of Sports Medicine Associations (EFSMA) on the IOC framework on fairness, inclusion and non-discrimination based on gender identity and sex variations. BMJ Open Sport Exerc Med 2022; 8: e001273
• 87 Iuliano S, Izzo G, Zagari MC. et al. Endocrine management of transgender adults: a clinical approach. Sexes 2021; 2: 104-118
• 88 Bermon S, Garnier PY.. Serum androgen levels and their relation to performance in track and field: mass spectrometry results from 2127 observations in male and female elite athletes. Br J Sports Med 2017; 51: 1309-1314
• 89 Dubon ME, Abbott K, Carl RL.. Care of the transgender athlete. Curr Sports Med Rep 2018; 17: 410-418
• 90 Gooren LJ, Giltay EJ, Bunck MC.. Long-term treatment of transsexuals with cross-sex hormones: extensive personal experience. J Clin Endocrinol Metab 2008; 93: 19-25
• 91 van Dijk D, Dekker MJHJ, Conemans EB. et al. Explorative prospective evaluation of short-term subjective effects of hormonal treatment in trans people–results from the European network for the investigation of gender incongruence. J Sex Med 2019; 16: 1297-1309
• 92 Zhao H, Zhou L, Li L. et al. Shift from androgen to estrogen action causes abdominal muscle fibrosis, atrophy, and inguinal hernia in a transgenic male mouse model. Proc Natl Acad Sci USA 2018; 115: e10427-e10436
• 93 Catelan RF, Saadeh A, Lobato MIR. et al. Depression, self-esteem, and resilience and its relationship with psychological features of sexuality among transgender men and women from Brazil. Arch Sex Behav 2022; 51: 1993-2002
• 94 Sarno EL, Dyar C, Newcomb ME. et al. Relationship quality and mental health among sexual and gender minorities. J Fam Psychol 2022; 36: 770-779
• 95 Romani A, Mazzoli F, Ristori J. et al. Psychological wellbeing and perceived social acceptance in gender diverse individuals. J Sex Med 2021; 18: 1933-1944
• 96 Allison KF, Keenan KA, Sell TC. et al. Musculoskeletal, biomechanical, and physiological gender differences in the US military. US Army Med Dep J 2015; 22-32
• 97 Ngun TC, Ghahramani N, Sánchez FJ. et al. The genetics of sex differences in brain and behavior. Front Neuroendocrinol 2011; 32: 227-246
• 98 Zheng D, Wang X, Antonson P. et al. Genomics of sex hormone receptor signaling in hepatic sexual dimorphism. Mol Cell Endocrinol 2018; 15: 33-41
• 99 Boldt P, Knechtle B, Nikolaidis P. et al. Sex differences in the health status of endurance runners: results from the NURMI study (step 2). J Strength Cond Res 2019; 33: 1929-1940
• 100 Lepers R, Knechtle B, Stapley PJ.. Trends in triathlon performance: effects of sex and age. Sports Med 2013; 43: 851-863
• 101 Handelsman DJ.. Sex differences in athletic performance emerge coinciding with the onset of male puberty. Clin Endocrinol (Oxf) 2017; 87: 68-72
• 102 Oyola MG, Handa RJ.. Hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes: sex differences in regulation of stress responsivity. Stress 2017; 20: 476-494
• 103 Roberts TA, Smalley J, Ahrendt D.. Effect of gender affirming hormones on athletic performance in transwomen and transmen: implications for sporting organisations and legislators. Br J Sports Med . 2020
• 104 Elbers JM, de Jong S, Teerlink T. et al. Changes in fat cell size and in vitro lipolytic activity of abdominal and gluteal adipocytes after a one-year cross-sex hormone administration in transsexuals. Metabolism 1999; 48: 1371-1377
• 105 Klaver M, de Blok CJM, Wiepjes CM. et al. Changes in regional body fat, lean body mass and body shape in trans persons using cross-sex hormonal therapy: results from a multicenter perspective study. Eur J Endocrinol 2018; 178: 163-171
• 106 Klaver M, Dekker MJHJ, de Mutsert R. et al. Cross-sex hormone therapy in transgender persons affects total body weight, body fat and lean body mass: a meta-analysis. Andrologia 2017; 49: e12660
• 107 Van Caenegem E, Wierckx K, Taes Y. et al. Preservation of volumetric bone density and geometry in trans women during cross-sex hormonal therapy: a prospective observational study. Osteoporos Int 2015; 26: 35-47
• 108 Wiik A, Lundberg TR, Rullman E. et al. Muscle strength, size, and composition following 12 months of gender-affirming treatment in transgender individuals. J Clin Endocrinol Metab 2020; 105: dgz247
• 109 Gooren LJ, Bunck MC.. Transsexuals and competitive sports. Eur J Endocrinol 2004; 151: 425-429
• 110 Haraldsen IR, Haigh E, Falch J. et al. Cross-sex pattern of bone mineral density in early onset gender identity dsorder. Horm Behav 2007; 52: 334-343
• 111 Mueller A, Zollver H, Kronawitter D. et al. Body composition and bone mineral density in male-to-female transexuals during cross-sex hormone therapy using gonadotrophin-releasing hormone agonist. Exp Clin Endocrinol Diabetes 2011; 119: 95-100
• 112 Wierckx K, Van Caenegem E, Schreiner T. 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. J Sex Med 2014; 11: 1999-2011
• 113 Gava G, Cerpolini S, Martelli V. et al. Cyproterone acetate vs leuprolide acetate in combination with transdermal oestradiol in transwomen: a comparison of safety and effectiveness. Clin Endocrinol (Oxf) 2016; 85: 239-246
• 114 Auer MK, Ebert T, Pietzner M. et al. Effects of sex hormone treatment on the metabolic syndrome in transgender individuals: focus on metabolic cytokines. J Clin Endocrinol Metab 2018; 103: 790-802
• 115 Fighera TM, da Silva E, Lindenau JDR. et al. Impact of cross-sex hormone therapy on bone mineral density and body composition in transwomen. Clin Endocrinol (Oxf) 2018; 88: 856-862
• 116 Scharff M, Wiepjes CM, Klaver M. et al. Change in grip strength in trans people and its association with lean body mass and bone density. Endocr Connect 2019; 8: 1020-1028
• 117 Tack LJW, Craen M, Lapauw B. et al. Proandrogenic and antiandrogenic progestins in transgender youth: differential effects on body composition and bone metabolism. J Clin Endocrinol Metab 2018; 103: 2147-2156
• 118 Polderman KH, Gooren LJG, Asscheman H. et al. Induction of insulin resistance by androgens and estrogens. J Clin Endocrinol Metab 1994; 79: 265-271
• 119 D'Andrea S, Pallotti F, Senofonte G. et al. Polymorphic cytosine-adenine-guanine repeat length of androgen receptor gene and gender incongruence in trans women: a systematic review and meta-analysis of case-control studies. J Sex Med 2020; 17: 543-550
• 120 Egner IM, Bruusgaard JC, Eftestøl E. et al. A cellular memory mechanism aids overload hypertrophy in muscle long after an episodic exposure to anabolic steroids. J Physiol 2013; 591: 6221-6230
• 121 Gundersen K.. Muscle memory and a new cellular model for muscle atrophy and hypertrophy. J Exp Biol 2016; 219: 235-242
• 122 Nicoll JX, Fry AC, Mosier EM.. Sex-based differences in resting MAPK, androgen, and glucocorticoid receptor phosphorylation in human skeletal muscle. Steroids 2019; 141: 23-29
• 123 Scott NL, Abreu MR, Cates BE. et al. Prolonged effects of elevated 17β-estradiol on physical activity after orchidectomy. Med Sci Sports Exerc 2018; 50: 1588-1595
• 124 Hamilton BR, Martinez-Patiño MJ, Barrett J.. et al. Response to the United Nations Human Rights Council’s report on race and gender discrimination in sport: an expression of concern and a call to prioritise research. Sports Med 2021; 51: 839-842