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Cited by 594Hormonal and reproductive studiesDoping in SportsSexual Differentiation and Disorders

Circulating Testosterone as the Hormonal Basis of Sex Differences in Athletic Performance

Open access
Handelsman, David J, Hirschberg, Angelica L, Bermon, Stephane·2018·Endocrine Reviews
DOI 10.1210/er.2018-00020PMC PMC6391653
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Abstract

Elite athletic competitions have separate male and female events due to men's physical advantages in strength, speed, and endurance so that a protected female category with objective entry criteria is required. Prior to puberty, there is no sex difference in circulating testosterone concentrations or athletic performance, but from puberty onward a clear sex difference in athletic performance emerges as circulating testosterone concentrations rise in men because testes produce 30 times more testosterone than before puberty with circulating testosterone exceeding 15-fold that of women at any age. There is a wide sex difference in circulating testosterone concentrations and a reproducible dose-response relationship between circulating testosterone and muscle mass and strength as well as circulating hemoglobin in both men and women. These dichotomies largely account for the sex differences in muscle mass and strength and circulating hemoglobin levels that result in at least an 8% to 12% ergogenic advantage in men. Suppression of elevated circulating testosterone of hyperandrogenic athletes results in negative effects on performance, which are reversed when suppression ceases. Based on the nonoverlapping, bimodal distribution of circulating testosterone concentration (measured by liquid chromatography-mass spectrometry)-and making an allowance for women with mild hyperandrogenism, notably women with polycystic ovary syndrome (who are overrepresented in elite athletics)-the appropriate eligibility criterion for female athletic events should be a circulating testosterone of <5.0 nmol/L. This would include all women other than those with untreated hyperandrogenic disorders of sexual development and noncompliant male-to-female transgender as well as testosterone-treated female-to-male transgender or androgen dopers.

AI snapshot

Written from the paper’s full text.

TL;DR

This review argues that circulating testosterone is the hormonal basis of sex differences in athletic performance and that a female-event eligibility threshold of <5.0 nmol/L measured by LC-MS is justified. It synthesizes reference-range, dose-response, observational, and interventional evidence showing testosterone effects on muscle, hemoglobin, and bone.

Key findings

  • Before puberty there is no sex difference in circulating testosterone or athletic performance; after male puberty the testes produce 30 times more testosterone than before puberty, and men have 15- to 20-fold higher circulating testosterone than children or women at any age. LC-MS reference ranges are 7.7–29.4 nmol/L in healthy men and 0–1.7 nmol/L in healthy premenopausal women.
  • Testosterone shows dose-response effects on muscle mass and strength. In postmenopausal women, the highest testosterone dose (25 mg/week) raised mean circulating testosterone to 7.3 nmol/L and increased lean muscle mass by 4.4%, chest press by 26%, leg press by 12%, and loaded stair-climb power by 14%. In men, the lowest dose (1.25 g/day gel) raised testosterone to 6.9 nmol/L and increased total lean mass by 2.3%, thigh muscle area by 3.0%, and leg press strength by 5.5%.
  • Postpubertal male athletic advantage is 10%–12% in running and swimming and 20% in jumping. Suppressing circulating testosterone in elite DSD athletes from the male range to <10 nmol/L reduced performance by an average of 5.7%; hemoglobin was 12% lower after suppression and comparable with nondoped, non-DSD females.
  • The proposed female eligibility criterion is circulating testosterone <5.0 nmol/L by LC-MS. Pooled PCOS data show an upper limit of 3.1 nmol/L (95% one-sided CI) or 4.8 nmol/L (99.99% one-sided CI), so a 5 nmol/L threshold would identify <1:10,000 women with PCOS as false positives.

Methods

  • Review/synthesis of observational, interventional, genetic mouse, transgender, DSD, PCOS, and reference-range studies, with no new primary data reported.
  • Pooled LC-MS serum testosterone data from 8 studies of healthy men aged 18–40 years, 9 studies of healthy menstruating women under 40 years, and 16 studies of women with PCOS (n = 4032), using number-weighted means and 95% confidence limits.
  • Main analysis is qualitative dose-response synthesis linking circulating testosterone to muscle mass/strength, hemoglobin, bone, and athletic performance, including data from randomized testosterone dose-response trials and transgender hormone-treatment studies.

Limitations

  • The paper states that well-designed studies replicating adult male circulating testosterone concentrations in women are lacking, largely for ethical and safety reasons, and that most evidence is observational or from sparse, mostly uncontrolled intersex/DSD data. It also states that extrapolation of male testosterone dose-response relationships to women at male-range concentrations remains unproven, even if plausible.
  • The paper states that reference limits do not control for oral contraceptive use, menstrual phase, SHBG, overweight, fasting, smoking, diet, or physical activity, though it says these have small effects without materially influencing the male-female bimodal separation.
  • Evident from the text: this is a narrative review rather than a systematic review or meta-analysis, and some key interventional evidence in women comes from small samples, such as the highest-dose testosterone group in the Huang et al. study (n = 11).

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1210/er.2018-00020

Cites

189 of 189 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 170 cited sources checked · 0 supported · 0 flagged

  • Findingreasoning

    Most women's circulating testosterone never reaches consistently >5 nmol/L.

    “As shown above, the circulating testosterone of most women never reaches consistently >5 nmol/L”
    Quote in the paperNot a substantial claim
  • Findingreasoning

    Circulating testosterone in adults has a nonoverlapping bimodal distribution with wide and complete separation between men and women.

    “Using LC-MS measurement, circulating testosterone in adults has a strikingly nonoverlapping bimodal distribution with wide and complete separation between men and women.”
    Quote in the paperSubstantial claim
  • Findingown data

    The reference range for healthy menstruating women under 40 years is 0 to 1.7 nmol/L.

    “the 95% (two-sided) reference range is 0 to 1.7 nmol/L”
    Quote in the paperSubstantial claim
  • Findingown data

    The reference range for healthy young men (18 to 40 years) is 7.7 nmol/L to 29.4 nmol/L.

    “the reference range for healthy young men (18 to 40 years) is 7.7 nmol/L to 29.4 nmol/L”
    Quote in the paperSubstantial claim
  • Findingcitation

    In 17 transmen treated for the first time with testosterone for 12 months, which increased circulating testosterone to a mean of 31 nmol/L, muscle mass increased by 19.2%.

    “Conversely, in 17 transmen (F2M transgender) treated for the first time with testosterone for 12 months (which increased circulating testosterone levels to a mean of 31 nmol/L), muscle mass increased by 19.2% and hemoglobin by 15% (114).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [114] Elbers, 1999, Effects of sex steroid hormones on regional fat depots as assessed by magnetic resonance imaging in transsexuals, Am J Physiol

      Not checked in the free run.

  • May combine two claims. 64
  • The quote only partly states this claim. 1
  • Classified as probably not a substantial claim. 14

  • May combine two claims.

    Findingown data

    The upper limit of serum testosterone in women with PCOS is 3.1 nmol/L (95% CI, one-sided) or 4.8 nmol/L (99.99% CI, one-sided).

    “The pooled data reveal that the upper limit of serum testosterone in women with PCOS is 3.1 nmol/L (95% CI, one-sided) or 4.8 nmol/L (using a 99.99% CI, one-sided) (Table 3).”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    The winning margin in elite athletic or swimming events during the last three Olympics is <1% equally for both male and female events.

    “Finally, to put these competitive advantages into context, the winning margin (the difference in performance by which a competitor misses a gold medal, any medal, or making the final) in elite athletic or swimming events during the last three Olympics is <1% equally for both male and female events (Table 5).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There were no significant differences in winning margin between years (2008, 2012, 2016) and sexes.

    “Years (2008, 2012, 2016) and sexes were combined as there were no significant differences in winning margin between them.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The limited available prospective evidence from initiation of transgender cross-sex hormone treatment suggests that the advantageous increases in muscle and hemoglobin due to male circulating testosterone concentrations are induced or reversed during the first 12 months and the androgenic effects may plateau after time.

    “The limited available prospective evidence from initiation of transgender cross-sex hormone treatment suggests that the advantageous increases in muscle and hemoglobin due to male circulating testosterone concentrations are induced or reversed during the first 12 months and the androgenic effects may plateau after time.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Nonclassical adrenal hyperplasia has a population prevalence of 1:1000 vs 1:16,000 for classical congenital adrenal hyperplasia.

    “Nonclassical adrenal hyperplasia is a milder and later (adult) onset variant of classical congenital adrenal hyperplasia (48) with a much higher but still rare population prevalence (1:1000 vs 1:16,000 for the classical variant) (49).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [48] Falhammar, 2015, Nonclassic congenital adrenal hyperplasia due to 21-hydroxylase deficiency: clinical presentation, diagnosis, treatment, and outcome, Endocrine source

      Not checked in the free run.

    • cites [49] Auchus, 2015, The classic and nonclassic concenital adrenal hyperplasias, Endocr Pract source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In female athletes with PCOS, higher performance has been shown, and their muscle mass and power performance correlate with androgen levels.

    “In female athletes with the mild hyperandrogenism of PCOS, higher performance has been shown (47), with their muscle mass and power performance correlating with androgen levels (36).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [47] Rickenlund, 2003, Hyperandrogenicity is an alternative mechanism underlying oligomenorrhea or amenorrhea in female athletes and may improve physical performance, Fertil Steril source

      Not checked in the free run.

    • cites [36] Eklund, 2017, Serum androgen profile and physical performance in women Olympic athletes, Br J Sports Med source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The postpubertal increase in circulating testosterone in men creates larger and stronger bones, greater muscle mass and strength, higher circulating hemoglobin, and possibly psychological differences.

    “The striking male postpubertal increase in circulating testosterone provides a major, ongoing, cumulative, and durable physical advantage in sporting contests by creating larger and stronger bones, greater muscle mass and strength, and higher circulating hemoglobin as well as possible psychological (behavioral) differences.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    Suppression of elevated circulating testosterone in hyperandrogenic athletes results in negative effects on performance, which are reversed when suppression ceases.

    “Suppression of elevated circulating testosterone of hyperandrogenic athletes results in negative effects on performance, which are reversed when suppression ceases.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Mild hyperandrogenism is a key clinical feature of PCOS.

    “in which mild hyperandrogenism is a key clinical feature”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    The dose-response relationship for testosterone is usually a sigmoidal curve with lower and upper plateaus joined by a monotonically rising middle region.

    “Similar to all hormones and drugs, over their effective range of biological activity the dose-response relationship for testosterone is usually a sigmoidal curve with lower and upper plateaus joined by a monotonically rising middle region”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Testosterone immunoassays have limited specificity due to antibody cross-reactivity, causing method-specific bias.

    “The inherently limited specificity of testosterone immunoassays arises from antibody cross-reactivity with structurally related steroids (such as precursors and metabolites) other than the intended target. As a result, all steroid immunoassays, including for testosterone, display method-specific bias”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [25] Sikaris, 2005, Reproductive hormone reference intervals for healthy fertile young men: evaluation of automated platform assays, J Clin Endocrinol Metab source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    PCOS prevalence is 6% to 10% among women of reproductive ages.

    “PCOS is a relatively common disorder among women of reproductive ages with a prevalence of 6% to 10%, depending on the diagnostic criteria used (44)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [44] Bozdag, 2016, The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-analysis, Hum Reprod source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    From male puberty onward, a clear sex difference in athletic performance emerges, with a strong and ongoing male advantage.

    “from puberty onward a clear sex difference in athletic performance emerges as circulating testosterone concentrations rise in men”
    • Also stated in: § Sex, Fairness, and Segregation in Sport · boosted
      “Age-grade competitive sporting records show no sex differences prior to puberty, whereas from the age of male puberty onward there is a strong and ongoing male advantage (8).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [8] Handelsman, 2017, Sex differences in athletic performance emerge coinciding with the onset of male puberty, Clin Endocrinol (Oxf) source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Circulating testosterone higher than 5 nmol/L in women is likely due to testosterone-secreting adrenal or ovarian tumors, intersex/DSD, badly controlled or noncompliant male-to-female transgender athletes, or testosterone doping.

    “Circulating testosterone higher than this threshold is likely to be due to testosterone-secreting adrenal or ovarian tumors, intersex/DSD, badly controlled or noncompliant male-to-female (M2F) transgender athletes, or testosterone doping.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisereasoning

    LC-MS methods are highly specific and allow a fixed consensus lower reference limit.

    “In contrast to immunoassays, LC-MS–based methods are highly specific and do not depend on proprietary antibodies. Using LC-MS–based measurements, method-specific bias can be avoided and a fixed consensus lower reference limit defined (Table 1).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationnone given

    The greater magnitude of sex difference in testosterone production (20-fold) compared with circulating levels (15-fold) is due to women's higher circulating SHBG, which retards testosterone clearance, creating a slower circulating half-time of testosterone.

    “The greater magnitude of sex difference in testosterone production (20-fold) compared with circulating levels (15-fold) is due to women’s higher circulating SHBG, which retards testosterone clearance, creating a slower circulating half-time of testosterone.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    On average, women have 50% to 60% of men's upper arm muscle cross-sectional area and 65% to 70% of men's thigh muscle cross-sectional area, and women have 50% to 60% of men's upper limb strength and 60% to 80% of men's leg strength.

    “On average, women have 50% to 60% of men’s upper arm muscle cross-sectional area and 65% to 70% of men's thigh muscle cross-sectional area, and women have 50% to 60% of men’s upper limb strength and 60% to 80% of men’s leg strength (106).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [106] Sale, 1999

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    At least up to average circulating testosterone concentrations of 7.3 nmol/L, women display a dose-response relationship similar to that of men, with supraphysiological doses of testosterone leading to significant gains in muscle mass and power.

    “These findings provide salient direct evidence of the ergogenic effects of hyperandrogenism in female athletes confirming that at least up to average circulating testosterone concentrations of 7.3 nmol/L, women display a dose-response relationship similar to that of men, with supraphysiological doses of testosterone leading to significant gains in muscle mass and power.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Androgen sensitivity of responsive tissues differs and may be optimal at different circulating testosterone concentrations.

    “Furthermore, there is evidence that the androgen sensitivity of responsive tissues differs and may be optimal at different circulating testosterone concentrations (65).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [65] Finkelstein, 2013, Gonadal steroids and body composition, strength, and sexual function in men, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Confirmatory evidence in humans from rare cases of men with an activating mutation of the chorionic gonadotropin/LH receptor shows that high testosterone without gonadotropin stimulation induced sperm production and allowed natural paternity.

    “Nevertheless, confirmatory evidence in humans is available from rare cases of men with an activating mutation of the chorionic gonadotropin/LH receptor (73, 74).”
    • Also stated in: § The physiological effects of testosterone depend on the circulating testosterone, not its source (endogenous or exogenous) · plain
      “In this illustrative case the testis was exposed to nonphysiologically high testosterone concentrations (but without any gonadotropin stimulation) that induced sperm production and allowed for natural paternity (73).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [73] Juel Mortensen, 2017, Germ cell neoplasia in situ and preserved fertility despite suppressed gonadotropins in a patient with testotoxicosis, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [74] Cunha-Silva, 2018, Spontaneous fertility in a male patient with testotoxicosis despite suppression of FSH levels, Hum Reprod source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In postmenopausal women, muscle mass and strength showed a flat response at three lower testosterone doses when circulating testosterone remained <5 nmol/L, and a significant increase only when the highest dose first increased circulating testosterone >5 nmol/L.

    “In the Huang et al. (112) study (Fig. 3), muscle mass and strength in postmenopausal women displayed a flat response at the three lower doses, when circulating testosterone concentrations remain <5 nmol/L, and displayed a significant increase only when the mean circulating testosterone concentration produced by the highest testosterone dose first increased circulating testosterone concentrations >”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Huang et al. (112) Huang, 2014, 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 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Following puberty, testosterone production increases but remains <2 nmol/L in women, whereas in men testosterone production increases 20-fold (from 0.3 mg/d to 7 mg/d), leading to 15-fold higher circulating testosterone concentrations (15 vs 1 nmol/L).

    “Following puberty, testosterone production increases (16) but remains <2 nmol/L in women, whereas in men testosterone production increases 20-fold (from 0.3 mg/d to 7 mg/d), leading to 15-fold higher circulating testosterone concentrations (15 vs 1 nmol/L).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [16] Courant, 2010, Assessment of circulating sex steroid levels in prepubertal and pubertal boys and girls by a novel ultrasensitive gas chromatography-tandem mass spectrometry method, J Clin Endocrinol Metab source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Male sexual function is maintained by endogenous testosterone at adult male circulating concentrations, and these effects can be replicated by exogenous testosterone if and only if it achieves comparable circulating testosterone concentrations.

    “Male sexual function is maintained by endogenous testosterone at adult male circulating concentrations. These effects can be replicated by exogenous testosterone if and only if it achieves comparable circulating testosterone concentrations.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisereasoning

    Athletes with DSDs who were raised and identify as women can have circulating testosterone levels comparable to those of men and greatly exceeding those of non-DSD (and nondoped) women, including those with PCOS.

    “This can cause athletes who were raised and identify as women to have circulating testosterone levels comparable to those of men and greatly exceeding those of non-DSD (and nondoped) women, including those with PCOS.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In men, the lowest testosterone dose (1.25 g/d) increased mean serum testosterone to 6.9 nmol/L and significantly increased total body lean mass (2.3%), thigh muscle area (3.0%), and leg press strength (5.5%) compared with placebo (0.7 nmol/L).

    “In men, the lowest testosterone dose (1.25 g/d) increased mean serum testosterone to 6.9 nmol/L (equivalent to levels seen in early to middle male puberty), resulting in significant increases of total body lean (muscle) mass (2.3%), thigh muscle area (3.0%), and leg press strength (5.5%) compared with the placebo dose that resulted in a serum testosterone of 0.7 nmol/L.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Finkelstein et al. (65) Finkelstein, 2013, Gonadal steroids and body composition, strength, and sexual function in men, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Corresponding to endogenous circulating testosterone increasing in males after puberty to 15 to 20 nmol/L (sharply diverging from the circulating levels that remain <2 nmol/L in females), male athletic performances go from being equal on average to those of age-matched females to 10% to 12% better in running and swimming events, and 20% better in jumping events.

    “Corresponding to the endogenous circulating testosterone increasing in males after puberty to 15 to 20 nmol/L (sharply diverging from the circulating levels that remain <2 nmol/L in females), male athletic performances go from being equal on average to those of age-matched females to 10% to 12% better in running and swimming events, and 20% better in jumping events (8) (Fig. 1).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [8] Handelsman, 2017, Sex differences in athletic performance emerge coinciding with the onset of male puberty, Clin Endocrinol (Oxf) source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    There is a clear sex difference in both muscle mass and strength even adjusting for sex differences in height and weight.

    “There is a clear sex difference in both muscle mass and strength (102–104) even adjusting for sex differences in height and weight (104, 105).”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [102] Morrow, 1981, Strength comparisons in untrained men and trained women athletes, Med Sci Sports Exerc source

      Not checked in the free run.

    • cites [103] Miller, 1993, Gender differences in strength and muscle fiber characteristics, Eur J Appl Physiol Occup Physiol source

      Not checked in the free run.

    • cites [104] Janssen, 2000, Skeletal muscle mass and distribution in 468 men and women aged 18–88 yr, J Appl Physiol source

      Not checked in the free run.

    • cites [105] Hosler, 1982, Arm and leg strength compared between young women and men after allowing for differences in body size and composition, Ergonomics source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Athletes with CAIS can compete fairly as females because the circulating testosterone, although at adult male levels, has no physiological effect, so that affected individuals are indistinguishable from females and gain no benefits of the sex difference arising from unimpeded testosterone action.

    “Athletes with CAIS can compete fairly as females because the circulating testosterone, although at adult male levels, has no physiological effect so that, in terms of androgen action and the ensuing physical somatic advantages of male sex, affected individuals are indistinguishable from females and gain no benefits of the sex difference arising from unimpeded testosterone action.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [83] Strickland, 1969, Absence of response to dihydrotestosterone in the syndrome of testicular feminization, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [84] Rosenfield, 1971, Androgens and androgen responsiveness in the feminizing testis syndrome. Comparison of complete and “incomplete” forms, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [85] Hamilton, 1971, Anabolic effect of dihydrotestosterone in testicular feminization syndrome, Metabolism source

      Not checked in the free run.

    • cites [86] Zachmann, 1977, Influence of testosterone on urinary 15N-balance in normal subjects and patients with testicular feminization, Clin Chim Acta source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    When exogenous testosterone is administered to men, pituitary LH is suppressed by negative feedback and sperm production halts for as long as exogenous testosterone or androgen exposure continues, after which it recovers.

    “When exogenous testosterone (or any other androgen) is administered to men, pituitary LH is suppressed by negative feedback and the sperm production halts for as long as exogenous testosterone or androgen exposure continues, after which it recovers (69).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [69] Liu, 2006, Rate, extent, and modifiers of spermatogenic recovery after hormonal male contraception: an integrated analysis, Lancet source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Age-grade competitive sports records show minimal or no female disadvantage prior to puberty, whereas from the age of male puberty onwards there is a strong and ongoing male advantage.

    “Age-grade competitive sports records show minimal or no female disadvantage prior to puberty, whereas from the age of male puberty onwards there is a strong and ongoing male advantage.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [8] Handelsman, 2017, Sex differences in athletic performance emerge coinciding with the onset of male puberty, Clin Endocrinol (Oxf) source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In 23 transmen administered adult male testosterone doses, total body muscle size and limb muscle size increased by 6.5% to 16.6% and grip strength by 18% compared with age-matched untreated control women.

    “In a second study, 23 transmen administered adult male testosterone doses also produced striking increases in total body muscle size and limb muscle size (by 6.5% to 16.6%) and grip strength (by 18%) compared with age-matched untreated control women (115).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [115] Van Caenegem, 2015, 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 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    If such an increase in hemoglobin were produced by any chemical substance, it would be considered doping according to the World Anti-Doping Code.

    “If such an increase in hemoglobin were produced by any chemical substance, it would be considered doping, according to the World Anti-Doping Code.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisereasoning

    Men have distinctively greater bone size, strength, and density than do women of the same age.

    “Men have distinctively greater bone size, strength, and density than do women of the same age.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    An 11% increase in circulating hemoglobin translates to a 10% difference in maximal oxygen transfer, which may account for virtually all the 12% sex difference in male and female circulating hemoglobin.

    “An 11% increase in circulating hemoglobin translates to a 10% difference in maximal oxygen transfer (124), which may account for virtually all the 12% sex difference in male and female circulating hemoglobin (125).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [124] Ekblom, 1972, Response to exercise after blood loss and reinfusion, J Appl Physiol source

      Not checked in the free run.

    • cites [125] Murphy, 2014, The sex difference in haemoglobin levels in adults—mechanisms, causes, and consequences, Blood Rev source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Increasing the amount of hemoglobin in the blood increases oxygen transport from lungs to tissues, where increased oxygen availability enhances aerobic energy expenditure.

    “Increasing the amount of hemoglobin in the blood has the biological effect of increasing oxygen transport from lungs to tissues, where the increased availability of oxygen enhances aerobic energy expenditure. This is exploited to its greatest effect in endurance sports (1).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [1] Handelsman, 2015

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Any drug that achieved such increases in hemoglobin would be prohibited in sports for blood doping, as this difference is sufficient to have ergogenic effects.

    “To put this into context, any drug that achieved such increases in hemoglobin would be prohibited in sports for blood doping, as this difference is sufficient to have ergogenic effects, even without taking into account any testosterone effects on muscle mass or strength (for which data were not available in that study).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The average maximal oxygen transfer is estimated to be ~10% greater in men than in women, with direct impact on athletic capacities.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Interpolating from the dose-response regression, increases in circulating testosterone from 0.9 nmol/L to 5, 7, 10, and 19 nmol/L were associated with increases in circulating hemoglobin of 6.5%, 7.8%, 8.9%, and 11%, respectively, establishing a strong dose-response relationship.

    “Interpolating from the dose-response regression, increases in circulating testosterone measured by LC-MS from 0.9 nmol/L to 5 nmol/L, 7 nmol/L, 10 nmol/L, and 19 nmol/L were associated with increases in circulating hemoglobin of 6.5%, 7.8%, 8.9%, and 11%, respectively, establishing a strong dose-response relationship.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [92] Karunasena, 2017, Androgens correlate with increased erythropoiesis in women with congenital adrenal hyperplasia, Clin Endocrinol (Oxf) source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    There is convincing evidence that sex differences in muscle mass and strength are sufficient to account for the increased strength and aerobic performance of men compared with women and are in keeping with differences in world records between the sexes.

    “There is convincing evidence that the sex differences in muscle mass and strength are sufficient to account for the increased strength and aerobic performance of men compared with women and is in keeping with the differences in world records between the sexes (116).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [116] Sonksen, 2018, Determination and regulation of body composition in elite athletes, Br J Sports Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In women with CAH, the degree of poor hormonal control is associated with increasing circulating testosterone ranging from normal female concentrations up to 36 nmol/L, and these levels correlate closely (r = 0.56) with circulating hemoglobin.

    “The degree of poor control is associated with increasing levels of circulating testosterone ranging from normal female concentrations up to 36 nmol/L, and these levels correlate closely (r = 0.56) with levels of circulating hemoglobin (Fig. 5).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [92] Karunasena, 2017, Androgens correlate with increased erythropoiesis in women with congenital adrenal hyperplasia, Clin Endocrinol (Oxf) source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Testosterone increases secretion of and sensitivity to erythropoietin and suppresses hepcidin.

    “Testosterone increases secretion of and sensitivity to erythropoietin, the main trophic hormone for erythrocyte production and thereby hemoglobin synthesis, as well as suppressing hepcidin (122), a crucial iron regulatory protein that governs the body’s iron economy.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [122] Bachman, 2014, Testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin: evidence for a new erythropoietin/hemoglobin set point, J Gerontol A Biol Sci Med Sci source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Experimental evidence in mice shows that testosterone increases myoglobin content of muscle with potential for augmenting aerobic exercise performance, but this has not been evaluated in humans.

    “Experimental evidence in mice shows that testosterone increases myoglobin content of muscle with potential for augmenting aerobic exercise performance (96), but this has not been evaluated in humans.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [96] Mänttäri, 2008, Testosterone stimulates myoglobin expression in different muscles of the mouse, J Comp Physiol B source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    Earlier onset of puberty and growth spurt in girls and earlier estrogen-dependent epiphyseal fusion explains shorter stature of girls than boys.

    “The earlier onset of puberty and the related growth spurt in girls as well as earlier estrogen-dependent epiphyseal fusion explains shorter stature of girls than boys.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationcitation

    Psychological differences between men and women on mental function as well as mood, motivation, and behavioral effects may involve androgen-sensitive effects during prenatal and perinatal as well as postpubertal effects.

    “Psychological differences between men and women on mental function (e.g., rotational orientation) (150) as well as mood, motivation, and behavioral effects may involve androgen-sensitive effects during prenatal and perinatal as well as postpubertal effects (151, 152).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [150] Levine, 2016, Sex differences in spatial cognition: advancing the conversation, Wiley Interdiscip Rev Cogn Sci source

      Not checked in the free run.

    • cites [151] Hines, 2006, Prenatal testosterone and gender-related behaviour, Eur J Endocrinol source

      Not checked in the free run.

    • cites [152] Hines, 2016, The early postnatal period, mini-puberty, provides a window on the role of testosterone in human neurobehavioural development, Curr Opin Neurobiol source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    There is no evidence supporting dosage-dependent Y chromosomal gene effects on height independent of SHOX gene copy number, nor does men's possession of a Y chromosome explain the height difference between adult men and women.

    “Hence, there is no evidence supporting dosage-dependent Y chromosomal gene effects on height independent of SHOX gene copy number, nor does men’s possession of a Y chromosome explain the height difference between adult men and women.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The major effects of men's larger and stronger bones would be manifest via their taller stature as well as the larger fulcrum with greater leverage for muscular limb power exerted in jumping, throwing, or other explosive power activities.

    “The major effects of men’s larger and stronger bones would be manifest via their taller stature as well as the larger fulcrum with greater leverage for muscular limb power exerted in jumping, throwing, or other explosive power activities.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisereasoning

    Similar eunuchoidal features and taller stature are evident in 46,XY men with congenital hypogonadotropic hypogonadism with comparable congenital onset of androgen deficiency, also manifest as pubertal delay and long bone overgrowth.

    “Similar eunuchoidal features and taller stature are evident in 46,XY men with congenital hypogonadotropic hypogonadism (Kallmann syndrome and its variants) with comparable congenital onset of androgen deficiency, also manifest as pubertal delay and long bone overgrowth.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    The widening of the female pelvis during puberty retards the improvement in female physical performance, possibly driven by ovarian hormones rather than the absence of testosterone.

    “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).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [136] Sharma, 2016, Age related changes in pelvis size among adolescent and adult females with reference to parturition from Naraingarh, Haryana (India), Homo source

      Not checked in the free run.

    • cites [137] Fischer, 2017, Allometry and sexual dimorphism in the human pelvis, Anat Rec (Hoboken) source

      Not checked in the free run.

    • cites [138] Riesenfeld, 1978, Functional and hormonal control of pelvic width in the rat, Acta Anat (Basel) source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    These bone changes create an advantage of greater bone strength and stronger fulcrum power from longer bones.

    “These changes create an advantage of greater bone strength and stronger fulcrum power from longer bones.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In a randomized placebo-controlled study of testosterone administration in postmenopausal women, the highest dose (the only one causing circulating testosterone levels to exceed the normal female range) produced an increase in muscle mass (4.4%) and a strikingly greater increase in muscle strength (12% to 26%).

    “In a randomized placebo-controlled study of testosterone administration in postmenopausal women (112), in case of those receiving the highest dose (the only one causing circulating testosterone levels to exceed the normal female range), there was not only an increase in muscle mass (4.4%) but a strikingly greater increase in muscle strength (12% to 26%), suggesting an enhanced mental motivational”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [112] Huang, 2014, 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 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    With the onset of puberty, girls aged 11 and 12 years are transiently taller than peer-aged boys due to earlier female pubertal growth spurt, but from age 14 years onward taller stature in males emerges and stabilizes.

    “However, with the onset of puberty, girls aged 11 and 12 years are transiently taller than peer-aged boys due to their earlier onset of the female pubertal growth spurt, but from the age of 14 years onward the taller stature in males emerges and stabilizes (141).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [141] Jelenkovic, 2016, Genetic and environmental influences on height from infancy to early adulthood: an individual-based pooled analysis of 45 twin cohorts, Sci Rep source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The small human Y chromosome has few functional genes and none with a known effect on height other than the SHOX gene.

    “The small human Y chromosome has few functional genes and none with a known effect on height other than the short stature homeobox (SHOX) gene, located in the pseudoautosomal regions of the tip of the short arms of X and Y chromosomes (161).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [161] Oliveira, 2011, The role of the SHOX gene in the pathophysiology of Turner syndrome, Endocrinol Nutr source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Bone density is increased in women with CAH with variably elevated serum testosterone when it is only partially suppressed by glucocorticoid treatment, although more effective glucocorticoid suppression lowers bone density.

    “Bone density (total and medullary cross-sectional area) is increased in women with CAH with variably elevated serum testosterone (including into the male range) when it is only partially suppressed by glucocorticoid treatment (143), although more effective glucocorticoid suppression lowers bone density (144).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [143] Bechtold, 2014, Sexual difference in bone geometry of adult patients with classical congenital adrenal hyperplasia: data using peripheral quantitative computed tomography, Horm Res Paediatr source

      Not checked in the free run.

    • cites [144] Falhammar, 2007, Fractures and bone mineral density in adult women with 21-hydroxylase deficiency, J Clin Endocrinol Metab source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    Many if not most other aspects of physiology exhibit sex differences and may therefore enhance the impact of the male advantage in sports performance of the dominant determinants (muscle and hemoglobin).

    “Many if not most other aspects of physiology exhibit sex differences and may therefore enhance the impact of the male advantage in sports performance of the dominant determinants (muscle and hemoglobin).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Stress fractures in athletes, mostly involving the legs, are more frequent in females, with the male protection attributable to their larger and thicker bones.

    “Alternatively, stress fractures in athletes, mostly involving the legs, are more frequent in females with the male protection attributable to their larger and thicker bones (146).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [146] Moreira, 2017, Stress fractures: concepts and therapeutics, J Clin Endocrinol Metab

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    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.

    “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).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [106] Sale, 1999

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Extensive twin studies show that adult height is highly heritable with predominantly additive genetic effects that diverge in a sex-specific manner from the age of puberty onwards, and these effects are likely due to sex differences in adult circulating testosterone concentrations.

    “Extensive twin studies show that adult height is highly heritable with predominantly additive genetic effects (140) that diverge in a sex-specific manner from the age of puberty onwards (141, 142), the effects of which are likely to be due to sex differences in adult circulating testosterone concentrations.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [140] Polderman, 2015, Meta-analysis of the heritability of human traits based on fifty years of twin studies, Nat Genet source

      Not checked in the free run.

    • cites [141] Jelenkovic, 2016, Genetic and environmental influences on height from infancy to early adulthood: an individual-based pooled analysis of 45 twin cohorts, Sci Rep source

      Not checked in the free run.

    • cites [142] Jelenkovic, 2016, Genetic and environmental influences on adult human height across birth cohorts from 1886 to 1994, eLife source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Carefully controlled, graded-dose studies in F2M transgender individuals might be informative but are largely lacking at this time.

    “Alternatively, carefully controlled, graded-dose studies in F2M transgender individuals might be informative but are largely lacking at this time.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The rise in testosterone from male puberty is associated with a 10% to 12% better performance in running and swimming events and 20% enhancement in jumping events.

    “This is associated with a 10% to 12% better performance in running and swimming events and 20% enhancement in jumping events (8).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [8] Handelsman, 2017, Sex differences in athletic performance emerge coinciding with the onset of male puberty, Clin Endocrinol (Oxf) source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    In men, there is no known disease state due to pathologically excessive testosterone secretion.

    “This was despite the fact that, uniquely among hormones, there is no known disease state in men due to pathologically excessive testosterone secretion.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    With the exception of one interventional study administering a relatively low testosterone dose to women, the available evidence comprises observational studies that can only examine effects of serum testosterone within physiological female limits or sparse and mostly uncontrolled data from intersex/DSD athletes.

    “With the exception of one interventional study administering a relatively low testosterone dose (i.e., low for males) to women (112), the available evidence comprises observational studies that can only examine the effects of serum testosterone within physiological female limits or sparse and mostly uncontrolled data from intersex/DSD athletes.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [112] Huang, 2014, 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 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    According to the Huang et al. study, reducing circulating testosterone to a mean of 7.3 nmol/L would still deliver a 4.4% increase in muscle size and a 12% to 26% increase in muscle strength compared with circulating testosterone at the normal female mean value of 0.9 nmol/L.

    “For example, according to the Huang et al. (112) study, reducing circulating testosterone to a mean of 7.3 nmol/L would still deliver a 4.4% increase in muscle size and a 12% to 26% increase in muscle strength compared with circulating testosterone at the normal female mean value of 0.9 nmol/L.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [112] Huang, 2014, 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 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    After 24 weeks of testosterone treatment, the increase in circulating testosterone concentrations led to significant increases in muscle size of 4.4% and in muscle strength of 12% to 26%.

    “After 24 weeks of testosterone treatment, the increase in circulating testosterone concentrations led to significant increases in muscle size of 4.4% and in muscle strength of 12% to 26%.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [112] Huang, 2014, 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 source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    In women, circulating testosterone originates from three different sources (adrenal, ovary, extraglandular conversion of androgen precursors), none of which is subject to tight testosterone negative feedback control.

    “However, similar mechanisms do not operate in women, in whom circulating testosterone originates from three different sources (adrenal, ovary, extraglandular conversion of androgen precursors), none of which is subject to tight testosterone negative feedback control.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationnone given

    The major limitation on scientific knowledge of the impact of adult male circulating testosterone concentrations on the sex difference in athletic performance is the lack of well-designed studies.

    “The major limitations on scientific knowledge of the impact of adult male circulating testosterone concentrations on the sex difference in athletic performance is the lack of well-designed studies.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The finding that young women have higher endogenous GH secretion than young men cannot explain the male advantage in muscle mass and strength unless GH retards muscle growth/function, for which there is no evidence.

    “Those findings cannot explain the male advantage in muscle mass and strength unless GH retards muscle growth/function, for which there is no evidence.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    There is anecdotal evidence that testosterone dose-response curves may be left shifted so that testosterone has greater potency in women than in men at comparable doses and circulating levels.

    “Although the dose-response relationship in women may be similar to what is seen in men, there is also anecdotal evidence that the dose-response curves may be left shifted so that testosterone has greater potency in women than in men at comparable doses and circulating levels.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [120] Franke, 1997, Hormonal doping and androgenization of athletes: a secret program of the German Democratic Republic government, Clin Chem source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    When the IAAF hyperandrogenism rule was suspended in 2015, these elite athletes could train and compete with unsuppressed serum testosterone levels, and their athletic performances increased by a similar amount.

    “Subsequently, when the IAAF hyperandrogenism rule was suspended in 2015, and so these elite athletes could train and compete with unsuppressed serum testosterone levels, their athletic performances increased by a similar amount.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    When circulating testosterone was suppressed to <10 nmol/L, the levels of circulating hemoglobin were 12% lower and comparable with nondoped, non-DSD females, corresponding to the 12% magnitude of the sex difference in hemoglobin between men and women.

    “However, when circulating testosterone was suppressed to <10 nmol/L the levels of circulating hemoglobin were 12% lower and again comparable with nondoped, non-DSD females, corresponding to the 12% magnitude of the sex difference in hemoglobin between men and women (125).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [125] Murphy, 2014, The sex difference in haemoglobin levels in adults—mechanisms, causes, and consequences, Blood Rev source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Daily GH administration for 8 weeks to healthy recreational athletes produced only marginally significant improvement in exercise performance of men and none in women.

    “Finally, the evidence that endogenous GH plays no role in sex differences in muscle mass and function is supported by evidence from the most extensive interventional study of GH treatment to non-GH–deficient adults, daily GH administration for 8 weeks to healthy recreational athletes produced only marginally significant improvement in exercise performance of men and none in women (174).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [174] Meinhardt, 2010, The effects of growth hormone on body composition and physical performance in recreational athletes: a randomized trial, Ann Intern Med source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Population data on the ontogeny of puberty show that prior to puberty boys and girls have comparable athletic performance, whereas sex differences in athletic performance emerge coinciding with the rise in circulating testosterone from the onset of male puberty.

    “Population data on the ontogeny of puberty show that prior to puberty boys and girls have comparable athletic performance, whereas sex differences in athletic performance emerge coinciding with the rise in circulating testosterone from the onset of male puberty.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationnone given

    In both intersex/DSD and transgender individuals, the developmental effects of adult male circulating testosterone concentrations will have established the sex difference in muscle, hemoglobin, and bone, some of which is fixed and irreversible (bone size) and some of which is maintained by the male circulating testosterone concentrations (muscle, hemoglobin).

    “In both intersex/DSD and transgender individuals, the developmental effects of adult male circulating testosterone concentrations will have established the sex difference in muscle, hemoglobin, and bone, some of which is fixed and irreversible (bone size) and some of which is maintained by the male circulating testosterone concentrations (muscle, hemoglobin).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    Circulating testosterone has dose-response effects to increase muscle mass and strength, bone size and strength (density), and circulating hemoglobin, each of which alone increases athletic capacity.

    “This is based on the dose-response effects of circulating testosterone to increase muscle mass and strength, bone size and strength (density), and circulating hemoglobin, each of which alone increases athletic capacity, as well as other possible sex dichotomous, androgen-sensitive contributors such as mental effects (mood, motivation, aggression) and muscle myoglobin content.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    These facts explain the clear sex difference in athletic performance in most sports, on which basis it is commonly accepted that competition has to be divided into male and female categories.

    “These facts explain the clear sex difference in athletic performance in most sports, on which basis it is commonly accepted that competition has to be divided into male and female categories.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Maintaining clearly supraphysiological testosterone concentrations would require treatment of months (muscle) or years (bone) and would replicate a known hyperandrogenic disease state (PCOS) and potentially increase risk of hormone-dependent cancers.

    “However, maintaining clearly supraphysiological testosterone concentrations would require treatment of months (muscle) or years (bone) and would replicate not only a known hyperandrogenic disease state (PCOS) but also potentially increasing risk of hormone-dependent cancers.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    The 2 to 5 nmol/L range remains below the circulating testosterone levels of middle male puberty when the major biological effects of men's higher circulating testosterone begin to be fully expressed.

    “This is so even though the range remains below the circulating testosterone levels of middle male puberty when the major biological effects of men’s higher circulating testosterone begin to be fully expressed.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    Estrogen-based suppression of circulating testosterone, typically using daily administered estrogen products, has a rapid onset and offset.

    “Ongoing compliance with the eligibility criterion is also an important variable because the estrogen-based suppression of circulating testosterone, typically using daily administered estrogen products, has a rapid onset and offset.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisenone given

    This threshold was based on serum testosterone measurements by immunoassays.

    “This threshold was based on serum testosterone measurements by immunoassays.”
    Quote in the paperSubstantial claim
78 of 78

  • The paper relies on this without support.

    Elite athletic competitions should have separate male and female events, and a protected female category with objective entry criteria is required.

    “Elite athletic competitions have separate male and female events due to men’s physical advantages in strength, speed, and endurance so that a protected female category with objective entry criteria is required.”
    “It is widely accepted that elite athletic competitions should have separate male and female events”

  • The paper relies on this without support.

    Sperm production in the testis requires a very high concentration of testosterone (typically 100-fold greater than in the general bloodstream), which is produced in nature only by the action of the pituitary hormone LH.

    “Sperm production in the testis requires a very high concentration of testosterone (typically 100-fold greater than in the general bloodstream), which is produced in nature only by the action of the pituitary hormone LH.”

  • The paper relies on this without support.

    LH stimulates the Leydig cells in the interstitial space of the testis to produce high intratesticular concentrations of testosterone, which are necessary and sufficient to initiate and maintain sperm production in the adjacent seminiferous tubules.

    “LH stimulates the Leydig cells in the interstitial space of the testis between seminiferous tubules to produce high intratesticular concentrations of testosterone, which are necessary and sufficient to initiate and maintain sperm production in the adjacent seminiferous tubules.”

  • The paper relies on this without support.

    The characteristic clinical features of masculinization appear only if and when circulating testosterone concentrations rise into the range of males at mid-puberty, which are higher than in women at any age even after the rise in circulating testosterone in female puberty.

    “The characteristic clinical features of masculinization (e.g., muscle growth, increased height, increased hemoglobin, body hair distribution, voice change) appear only if and when circulating testosterone concentrations rise into the range of males at mid-puberty, which are higher than in women at any age even after the rise in circulating testosterone in female puberty.”

  • The paper relies on this without support.

    If male puberty fails, testosterone replacement therapy is fully effective in replicating all of the distinctive masculine features apart from spermatogenesis.

    “If male puberty fails, testosterone replacement therapy is fully effective in replicating all of the distinctive masculine features apart from spermatogenesis.”

  • The paper relies on this without support.

    The dose-response effects of testosterone on muscle mass and strength observed in postmenopausal women and transmen are representative of effects in athletes and can be used to estimate athletic performance advantages.

    “A minimal estimate of the impact of adult male testosterone concentrations on muscle size and strength in females is provided by the Huang et al. (112) study of postmenopausal women.”

  • The paper relies on this without support.

    The dose-response relationship between testosterone and hemoglobin observed in women with CAH and other clinical populations applies to athletes and DSD athletes.

    “Similarly, according to the Karunasena et al. (92) study, reducing circulating testosterone concentration to 7 nmol/L would still deliver 7.8% more circulating hemoglobin than the normal female mean value.”

  • The paper relies on this without support.

    The performance changes following testosterone suppression in transwomen and DSD athletes are attributable to changes in circulating testosterone rather than other concurrent factors.

    “Among recreational (nonelite) athletes, an observational study showed a consistent deterioration in athletic performance of transwomen (M2F transgender) athletes corresponding closely to the suppression of circulating testosterone concentrations (175).”

  • The paper relies on this without support.

    The time course of androgen effects observed in older men undergoing castration for prostate cancer can be extrapolated to younger athletes and transgender individuals.

    “Although these studies of older men with prostate cancer must be extrapolated with caution”
9 of 9

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Males have superior cardiovascular and respiratory function compared with females, with larger blood and heart volumes, higher hemoglobin concentration, greater cross-sectional area of the trachea and lower oxygen cost of respiration.

    “superior cardiovascular and respiratory function, with larger blood and heart volumes, higher hemoglobin concentration, greater cross-sectional area of the trachea and lower oxygen cost of respiration [3, 4, 39, 40].”

    From Transgender Women in the Female Category of Sport: Perspectives on Testosterone Suppression and Performance Advantage (2021) · cites this paper as [4]

    The Hemoglobin section (page not provided) says men have, on average, 12% higher circulating hemoglobin than women and estimates greater maximal oxygen transfer. The Other androgen-sensitive sex dichotomous effects section notes sex differences in exercise-induced cardiac and lung function, but does not establish the claimed larger blood and heart volumes, greater tracheal cross-sectional area, or lower oxygen cost of respiration. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Many physiological factors differ significantly between biological males and females as a result of genetic differences and androgen-directed development of secondary sex characteristics.

    “Many of these physiological factors differ significantly between biological males and females as a result of genetic differences and androgen-directed development of secondary sex characteristics [3, 4].”

    From Transgender Women in the Female Category of Sport: Perspectives on Testosterone Suppression and Performance Advantage (2021) · cites this paper as [4]

    The sections on muscle and bone link several male–female physiological differences to androgen action, and the section on other androgen-sensitive effects says many aspects of physiology differ by sex. But that section says the androgen dependence of other differences remains uncertain, while the section on genetic effects of the Y chromosome does not support a general genetic explanation for them. Our copy provides no page numbers for these passages. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Individuals assigned female at birth with DSD can possess testosterone concentrations comparable to cisgender males and much higher than non-DSD women, including those with polycystic ovary syndrome.

    “These features can result in individuals assigned female at birth possessing testosterone concentrations comparable to cisgender males and, therefore, much higher than non-DSD women, including those with polycystic ovary syndrome [19].”

    From Integrating Transwomen and Female Athletes with Differences of Sex Development (DSD) into Elite Competition: The FIMS 2021 Consensus Statement (2021) · cites this paper as [19]

  • Healthy premenopausal women typically have a testosterone concentration <5 nmol/L (e.g., <1.7 nmol/L).

    “healthy premenopausal women typically have a testosterone concentration < 5 nmol/L (e.g., < 1.7 nmol/L) [19]”

    From Integrating Transwomen and Female Athletes with Differences of Sex Development (DSD) into Elite Competition: The FIMS 2021 Consensus Statement (2021) · cites this paper as [19]

  • The biological effects of elevated pubertal testosterone are primarily responsible for driving the divergence of athletic performances between males and females.

    “Thus, the biological effects of elevated pubertal testosterone are primarily responsible for driving the divergence of athletic performances between males and females [4].”

    From Transgender Women in the Female Category of Sport: Perspectives on Testosterone Suppression and Performance Advantage (2021) · cites this paper as [4]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Male pubertal testosterone increase is given as both 30-fold and 20-fold

    Minor

    The paper gives two different multipliers for the increase in testicular testosterone production at male puberty relative to before puberty.

  • Claim that winning margins are below 1% conflicts with Table 5

    Minor

    Table 5 reports a 1.93% median margin for winning gold in throwing events, exceeding the stated 1% ceiling.

  • Claim that women's testosterone stays below 2 nmol/L conflicts with Table 1

    Minor

    The categorical claim is inconsistent with a reported upper 95% limit of 2.8 nmol/L in healthy women.

3 of 3

Cites

Flagged first, then by citations

Research works printed but not linked: 2

  1. Handelsman, 2015, Endocrinology, 441
  2. Handelsman, 2015, Endocrinology, 2368

Cited by

Sorted by citations

Related

Authors
Handelsman, D. J., Hirschberg, A. L., & Bermon, S.
Affiliations
  • The University of Sydney (AU)
  • Karolinska University Hospital (SE)
  • Laboratoire Motricité Humaine, Education, Sport, Santé, Université Côte d’Azur, Nice, France
Corresponding author
Handelsman, David J
ORCID
Venue
Endocrine Reviews
Publisher
The Endocrine Society
Published
2018-07-13
Volume
39
Issue
5
Pages
803-829
ISSN
  • 0163-769X (ISSN-L)
  • 1945-7189
DOI
10.1210/er.2018-00020
PMC
PMC6391653
OpenAlex
W2883088360
Semantic Scholar
1083f62e12ae5f37a3e9f9f430a027d6f250360c
Cited by
594
References
189
Citations by year
2026: 92 · 2025: 91 · 2024: 99 · 2023: 92 · 2022: 83 · 2021: 76 · 2020: 41 · 2019: 15 · 2018: 5
FWCI
5.29
Type
journal article
Language
en
Open access
Licence
Locations
  • Endocrine Reviews (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Social Sciences › Sociology and Political Science › Doping in Sports
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
Keywords
circulating testosterone, sex differences in athletic performance, hyperandrogenism, polycystic ovary syndrome, testosterone suppression, muscle mass and strength, hemoglobin, puberty, transgender athletes
MeSH terms
Female, Humans, Male, Sex Characteristics, Testosterone, Athletic Performance, Athletes

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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