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Try out PMC Labs and tell us what you think. Learn More. 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 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.

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

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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. It is widely accepted that elite athletic competitions should have separate male and female events. Prior to puberty, there is no sex difference in circulating testosterone concentrations and athletic performance.

From male puberty onward, the sex difference in athletic performance emerges as circulating testosterone concentrations rise as the testes produce 30 times more testosterone than before puberty, resulting in men having to fold greater circulating testosterone than children or women at any age.

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This wide, bimodal sex difference in circulating testosterone concentrations and the clear dose-response relationships between circulating testosterone and muscle mass and strength, as well as the hemoglobin level, largely for the sex differences in athletic performance. Virtually all elite sports are segregated into male and female competitions. The main justification is to allow women a chance to win, as women have major disadvantages against men who are, on average, taller, stronger, and faster and have greater endurance due to their larger, stronger muscles and bones as well as a higher circulating hemoglobin level.

Hence, elite female competition forms a protected category with entry that must be restricted by an objective eligibility criterion related, by necessity, to the relevant sex-specific physical advantages. The practical need to establish an eligibility criterion for elite female athletic competition led the International Association of Athletic Federations IAAF to establish a rule inendorsed by the International Olympic Committee IOC infor hyperandrogenic women.

The Court for Arbitration in Sports suspended the rule pending receipt of such evidence. In that context, the present review presents the available evidence on the hormonal basis for the sex difference in athletic performance. If sports are defined as the organized playing of competitive games according to rules 1fixed rules are fundamental in representing the boundaries of fair sporting competition. Rule breaking, whether by breaching eligibility or competition rules, such as use of banned drugs, illegal equipment, or match fixing, creates unfair competitive advantages that violate fair play.

Cheating constitutes a fraud against not just competitors but also spectators, sponsors, the sport, and the public.

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In the absence of genuine fair competition, elite sports would lose their wide popular appeal and ability to captivate and inspire with the authentic attraction of genuine contest between highly trained athletes. Nevertheless, fairness is an elusive, subjective concept with malleable boundaries that may change over time as social concepts of fairness evolve.

For example, until the late 19th century when organized sports trainers emerged, training itself was considered a breach of fairness because competition was envisaged at that time as a contest based solely on natural endowments. Similarly, sports once distinguished between amateurs and professionals.

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The concept of fairness has deep and complex philosophical roots mainly focused on notions of distributive justice. These considerations affect sports through the universal application of antidiscrimination and human rights legislation. Less attention is given to the philosophical basis of fair competition in elite sports, where the objectives are not egalitarian but aim to discover a hierarchy of achievement derived from a mixture of unequal natural talent and individual training effort.

Excellent, insightful discussion of the legal and moral complexities of sex and fair competition in elite sports from a legal scholar and former elite female athlete is available 2. The terms sex and gender are often confused and used as if interchangeable.

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Sex is an objective, specific biological state, a term with distinct, fixed facets, notably genetic, chromosomal, gonadal, hormonal, and phenotypic including genital sex, each of which has a characteristic defined binary form. Whereas all facets of biological sex are almost always aligned so that asment of sex at birth is straightforward, rare instances in which two or more facets of biological sex conflict constitute an intersex state, now referred to as disorders or differences of sex development DSDs 3.

Prompted by biological, personal, and societal factors, volitional expression of gender can take on virtually any form limited only by the imagination, with some individuals asserting they have not just a single natal gender but two genders, none, a distinct third gender, or gender that varies fluidly from time to time. Hence, whereas gender is usually consistent with biological sex as ased at birth, in a few it can differ during life.

For example, if gender were the basis for eligibility for female sports, an athlete could conceivably be eligible to compete at the same Olympics in both female and male events. These features render the unassailable personal assertion of gender identity incapable of forming a fair, consistent sex classification in elite sports. The strongest justification for sex classification in elite sports is that after puberty men produce 20 times more testosterone than women 4—7resulting in circulating testosterone concentrations fold higher than in children or women of any age.

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. 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.

In concert, these render women, on average, unable to compete effectively against men in power-based or endurance-based sports. Sex classification in sports therefore requires proof of eligibility to compete in the protected female category. This deceptively simple requirement for fairness is taken for granted by peer female competitors who regard participation by males, or athletes with physical features closely resembling males, as unfair. This makes policing of eligibility inescapable for sports, to avoid unfair male participation in female events.

However, such policing inevitably Girls looking for sex in Monaco va into highly personal matters so that it must be achieved with respect for dignity and privacy, demanding use of the least invasive, scientifically reliable means.

Unsurprisingly, this dilemma has always been highly contentious since it first entered international elite sports in the early 20th century, and it has become increasingly prominent and contentious in recent decades; nevertheless, the requirement to maintain fair play in female events will not disappear as long as separate female competitions exist. During recent decades, there has been progressively better understanding of the complex biology of genetic sex determination and the impact of pubertal sexual maturation in establishing phenotypic sexual dichotomy in physical capabilities.

These sex-dichotomous physical features form the basis of, but remain quite distinct from, adult gender roles and identity. During the last century, as knowledge grew, the attempts to formalize a scientific basis for the unavoidable necessity of policing eligibility for the female category have been continually challenged. Allowing subjective gender self-identification to become the sole criterion of sports sex would allow for gaming and perceptions of systematic unfairness to grow.

Separate male and female events in sports is a dominant form of classification that is superimposed on other graduated age group and weight classifications e. Age and weight classifications rely on objective criteria birth date, weigh-in weight for eligibility, and so should sex classification. Nevertheless, some power sports dependent on explosive strength and power e. If sex classification were eliminated, such open or mixed competitions would be dominated almost exclusively by men.

An androgen is a hormone capable of developing and maintaining masculine characteristics in reproductive tissues notably the genital tract, as well as in other tissues and organs associated with secondary sexual characteristics and fertility and contributing to the anabolic status of nonreproductive body tissues The two dominant bioactive androgens circulating in mature mammals, including humans—testosterone and its more potent metabolite DHT— for the development and maintenance of all androgen-dependent characteristics, and their circulating levels in men and nonpregnant women arise from steroids synthesized de novo in the testes, ovary, or adrenals The sexually undifferentiated gon in the embryo develop into either ovaries or testes according to whether a Y chromosome or at least the sry gene is present.

After birth and until puberty commences, circulating testosterone concentrations are essentially the same in boys and girls, other than briefly in the neonatal period of boys when higher levels prevail. The onset of male puberty, a brain-driven process triggered by a still mysterious hypothalamic or higher cerebral mechanism 13initiates a hormonal cascade.

In males, this le to enhanced pituitary LH secretion that stimulates the million Leydig cells in the testes to secrete 3 to 10 mg mean, 7 mg of testosterone daily 46714 This creates a very high local concentration of testosterone within the testis as well as a steep downhill concentration gradient into the bloodstream that maintains circulating testosterone levels at adult male levels, which are tightly regulated by strong negative hypothalamic feedback of circulating testosterone.

In the absence of testes, these mechanisms do not function in females. In adult women, circulating testosterone is derived from three roughly equal sources: direct secretion from the adrenal gland or Girls looking for sex in Monaco va ovary and indirect extraglandular conversion in liver, kidney, muscle, fat, skin from testosterone precursors secreted by the adrenal and ovary. Only when circulating testosterone concentrations rise in male adolescents above the prepubertal concentrations does the virilization characteristic of men commence, progress, and endure throughout adult life, at least until old age Circulating testosterone concentrations in women are subject to little dynamic physiological regulation.

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As a result, circulating testosterone concentrations in healthy premenopausal women are stable nonfluctuating and not subject to strong negative feedback by exogenous testosterone as happens in men. A reliable threshold for circulating testosterone must be set using measurement by the reference method of liquid chromatography—mass spectrometry LC-MS rather than using one of the various available commercial testosterone immunoassays.

The necessary reliance on steroid mass spectrometry for clinical applications in endocrinology, reproductive medicine, and sports medicine is widely recognized. It has been standard for decades in antidoping science 20and the growing consensus is that it is required for high-quality clinical research and practice recognized by cognate professional societies 2122 and editorials in leading clinical endocrinology 23 and reproductive medicine 24 journals. The inherently limited specificity of testosterone immunoassays arises from antibody cross-reactivity with structurally related steroids such Girls looking for sex in Monaco va precursors and metabolites other than the intended target.

As a result, all steroid immunoassays, including for testosterone, display method-specific bias whereby, for example, the lower limit of a testosterone reference range in healthy young men varies from 7. Furthermore, testosterone immunoassays are optimized for circulating levels in men but display increasing inaccuracy at the lower, by an order of magnitude, circulating testosterone concentrations in women or children.

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. Hence, for the precision required in sports medicine, whether for eligibility criteria or antidoping applications, testosterone in serum must be measured by LC-MS methods.

Prior to puberty, levels of circulating testosterone as determined by LC-MS are the same in boys and girls However, from the onset of male puberty the testes secrete 20 times more testosterone resulting in circulating testosterone levels that are 15 times greater in healthy young men than in age-similar women. Using LC-MS measurement, circulating testosterone in adults has a strikingly nonoverlapping bimodal distribution with wide and complete separation between men and women. Table 1 25—36 summarizes data from appropriate reported studies using mass spectrometry—based methods to measure serum testosterone in healthy men and women.

These reference limits do not control for factors such as oral contraceptive use 3536menstrual phase 19SHBG 3738overweight 3940fasting and smoking 41diet 40and physical activity 4243 in women and men, all of which have small effects on circulating testosterone but without materially influencing the divergence between the nonoverlapping bimodal distribution of male and female reference ranges of circulating testosterone.

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In creating a threshold for eligibility for female events it is also necessary to make allowance for women with polycystic ovary syndrome PCOS and nonclassical 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 vsfor the classical variant Data taken directly from paper or interpolated from other data e.

The pooled data reveal that the upper limit of serum testosterone in women with PCOS is 3. Testosterone, whether of a natural endogenous or manufactured Girls looking for sex in Monaco va source, has an identical chemical structure and biological effects, aside from minor differences in isotopic composition, which are biologically inificant.

At equivalent doses and circulating levels, exogenous testosterone exerts the same biological and clinical effects on every known androgen-responsive tissue or organ as endogenous testosterone, apart from effects on spermatogenesis, which as discussed below is only a matter of degree. Consequently, exogenous testosterone is a fully effective substitute for endogenous testosterone in therapeutic use, countering the effects of testosterone deficiency due to hypogonadism reproductive system disorders. Any purported differences between endogenous and exogenous testosterone are due to corresponding differences in the endogenous production rate or exogenous dose.

Such differences in effective exposure lead to corresponding differences in circulating testosterone levels and its effects according to the dose-response curves for testosterone. 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 ed by a monotonically rising middle region, which may be linear in the natural scale but more often log-linear linear on the log or similar transformed scale.

In the middle portion of the typical sigmoidal dose-response curve for the same increase in testosterone dose or concentrationthe response would be increased in simple proportional i. In contrast, at the lower and upper plateaus of dose or concentrations, changes in testosterone exposure may evoke minimal or no response on the endpoint. For example, in women of any age circulating testosterone concentrations are along the lower plateau of the dose-response curve, so that increases in circulating testosterone concentrations within that lower plateau may have minimal or no effect.

In female athletes with the mild hyperandrogenism of PCOS, higher performance has been shown 47with their muscle mass and power performance correlating with androgen levels In addition, the effects of testosterone are modulated in a form of fine tuning by the patterns of exposure, such as whether the circulating testosterone is delivered in the unphysiological steady-state format e.

However, these latter pattern effects are subtle and the dominant effect remains that of dose and average testosterone concentrations in blood, however they arise. Furthermore, there is evidence that the androgen sensitivity of responsive tissues differs and may be optimal at different 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. For example, in a well-controlled prospective study of older men with prostate cancer 66androgen deprivation achieving castrate levels of circulating testosterone sustained during 12 months markedly suppressed sexual desire and function, whereas those effects did not occur in age-matched men having nonhormonal treatment of prostate cancer or those without prostate cancer.

In healthy younger men whose endogenous testosterone was fully suppressed, sexual function completely recovered when circulating testosterone was restored to the physiological male range by administration of exogenous testosterone Similar effects were also observed in healthy, middle-aged men in whom male sexual function was fully maintained compared with placebo during 2 years of treatment with an exogenous androgen DHT despite that treatment causing sustained, complete suppression of endogenous testosterone This further supports the key interpretation that the biological effects of exogenous or endogenous testosterone are the same at comparable circulating levels.

Clinically, exogenous testosterone replicates fully all effects of endogenous testosterone on every reproductive and nonreproductive organ or tissue, with the sole exception of the testis.

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