Hypogonadism in exercising men: dysfunction or adaptive regulatory adjustment? (2024)

table 1

The main clinical conditions associated with the development of primary and secondary hypogonadism in men (9,12).

table 2

Reference range for clinical assessment of testosterone from selected sources for non-obese men (i.e. Body Mass Index [BMI] <30 kg m)²).

What about training men?

Perhaps more relevant for sporting or athletic men are the recent findings reported by Handelsman et alEndocrine Assessments(16). These authors have provided a comprehensive review of the available research literature and of the International Association of Athletics Federation (IAAF) extensive database of athletes who have competed for many years at the elite level of athletics (i.e. track and field). They concluded that there was a reference range (95%) of 223–849 ng/dl (7.7–29.4 nmol/l) in healthy adult athletic men and 0–144 ng/dl (0–5.0 nmol/ l) in athletic women. . On this last point, Handelsman et al. However, the area of ​​reference is a point of contention as it has been challenged by the legal team involved in the Caster sem*nya vs. IAAF at the Tribunal Arbitral du Sport (Court of Arbitration for Sport) on male and female categorical standards for acceptable sex-based testosterone levels (16,17).

Nevertheless, and importantly, there is currently no universal agreement in the global medical community on what exactly constitutes normal testosterone levels. Furthermore, the clinical definition of what constitutes "low testosterone" and the diagnostic threshold for diagnosing hypogonadism also vary. Until this last pointtable 3illustrates this lack of agreement by showing what hypogonadism can be based on testosterone levels as defined by various medical organizations (18).

It should be noted that for some doctors and medical professionals, hypogonadism is not only characterized by low testosterone levels, but also includes at least one clinical sign or symptom (9). Obvious signs of hypogonadism include the absence or regression of secondary sexual characteristics, anemia, muscle wasting, decreased bone mass or bone mineral density, oligospermia, and abdominal fat. Symptoms include sexual dysfunction (e.g., erectile dysfunction, decreased libido, decreased penile sensation, difficulty achieving org*sm, and decreased ejacul*tion), decreased energy and stamina, depressed mood, increased irritability, difficulty concentrating, changes in cholesterol levels, anemia , osteoporosis and hot flashes. (9,12,13).

In the absence of any clinical signs or symptoms, the presence of low testosterone alone may lead to the diagnosis of "androgen deficiency" (also called testosterone deficiency) and not definitive hypogonadism. That said, many leading medical sources define hypogonadism based solely on the presence of low circulating testosterone (9,12).

How is exertional hypogonadism defined?

The term exercise hypogonadism has been used in a number of exercise studies reporting low testosterone levels, but researchers have rarely applied the criteria described intable 3for their definition of hypogonadism. In fact other criteria have been used, for example:

• If the study was cross-sectional in design, there was typically a matched control group (sedentary) to which the exercising men were compared to determine whether testosterone status was low or decreased;

• If the research design of the study was prospective or longitudinal in nature, the exercising men are usually compared with themselves at a time before exercise, when their testosterone was unaffected; And,

• Some studies have compared testosterone levels in exercising men to a clinical reference range of values ​​to determine testosterone status.

In addition, some research groups have been reluctant to use the term hypogonadism in its entirety, and have referred to exercising men as having conditions of "low testosterone," "testosterone deficiency," or "androgen deficiency."6,19–22). Although, again, what is onelavaoflacklevel is not clearly defined or has used endocrine standards according to professional organization guidelines as stated in setable 3. And while the term hypogonadism is not strictly used, some published exercise reports based on testosterone findings have hinted at consequences associated with hypogonadal states.

In short, there is a lack of consistency in the exercise literature defining what exactly constitutes exercise hypogonadism. Furthermore, few researchers have attempted to establish or use a threshold or cut-off value to indicate when testosterone levels are reduced enough to use the “exercise hypogonadism” distinction. Regardless of the terms used to refer to testosterone levels in exercising men, it is important to note that even when testosterone is reduced, it is low for many of these individuals, but within the normal range and rarely exceeds the clinical definitions of achieved hypogonadism.table 3). Although there are reports of subclinical findings and testosterone levels well below those established for clinical hypogonadism (23–25).

In particular, in 2005 Hackney and colleagues outlined criteria for the level of testosterone reduction required to designate an athlete as suffering from what they termed the 'male hypogonadal state of exertion' (see later discussion) (19,26). These researchers suggested that sustained reductions of 25-50% or more in testosterone were necessary to distinguish this as a relative form of hypogonadism.

Table 4

Signs and symptoms of low testosterone and hypogonadism commonly reported by both men, non-athletes and athletes (39).

Background

Systematic and scientific research into the influence of exercise on testosterone levels in men began in the 1970s. Animal research was significantly outdated during this period, and 'doping experiments' with human anabolic steroids, conducted by athlete-trainers, also took place before this period. Although evidence that the latter actually occurred was hidden from public and scientific scrutiny for decades due to concerns about legal and ethical breaches. Perhaps the first systematic study of human movement was conducted by the late Dr. John Sutton from Australia in the 1970s. He and his colleagues published a paper on the testosterone responses in men and women to acute submaximal and maximal training sessions (40). They reported that maximal exercise increased testosterone levels, and with this finding, a plethora of studies were initiated by the scientific community investigating testosterone, exercise, and training modifications.

In the mid-1980s, several important studies were published reporting that men who engaged in endurance training had significantly lower resting testosterone levels (41–44), and/or disruption of the HPG axis [potentially affecting testosterone levels (historically, the vast majority of these studies have examined total testosterone; although a few research groups have also examined free testosterone and found that both total and free testosterone can be reduced)] (45). These studies involved distance runners, and at the time these researchers did not speculate on the cause of the low resting testosterone. Nevertheless, these studies served as a basis for subsequent work attempting to investigate causality (see the following discussions).

In the context of exercise endocrinology, it is important to understand the distinction between the effect of an acute exercise session on hormones and the more chronic effect of exercise on hormones. In the acute scenario, almost all forms of exercise cause changes in circulating hormone concentrations – almost universally elevated levels that are usually proportional to the intensity at which the exercise is performed and/or the duration of the exercise. Although the form of exercise used creates some variation in the degree of response (e.g. swimming vs. running, vs. weight lifting) (46–48). Furthermore, some hormones exhibit a 'threshold' level of training volume (i.e. intensity X duration of training sessions) before a response is detected in the blood (49). These acute exercise-induced changes diminish relatively quickly during the recovery period unless the training session is extremely long (e.g. hours) (49).Table 5provides a basic summary of the general effects of exercise on key hormones related to clinical research interests in exercise physiology and exercise.

Conversely, when examining the chronic effect of exercise, one can examine the (basal) effects at rest and/or responses to a subsequent training session, after a period of exercise has been performed. At rest, basal hormone levels are usually unchanged, slightly increased or perhaps slightly decreased after extensive exercise. Regarding the latter, the phenomena of the "basem*nt effect" prevent some aspects of observable reductions from being observed; it is a hormone value close to zero and which cannot be reduced significantly further (50). In response to performing an acute exercise session after chronic exercise training, many hormonal responses are reduced compared to performing a similar exercise session before the exercise intervention; although the direction (↑ or ↓) of the hormone change remains the same. These reduced responses are usually a function of reduced stress reactivity to a given exercise bout and of improved sensitivity of the target tissue as an adaptation to the exercise (51,52). In general, these endocrine principles of acute-chronic exercise apply to the hormonal response to the reproductive and non-reproductive hormones (52). Finally, and important to the current discussion, in most clinical diagnostic settings, much of the assessment and detection of reproductive dysfunction relies on the evaluation of hormone status in a resting, basal state and not in response to an exercise session.53). In such assessments, the gold standard for biological measurements is blood serum or plasma. Other fluids are occasionally assessed, such as saliva or sweat; but these fluids may produce a variation in results. For example, Adebero and colleagues compared salivary and serum concentrations of testosterone and cortisol at rest and in response to intense exercise in boys and men; and found that testosterone was reduced in serum but not in saliva after exercise (54). VanBruggen and colleagues have attributed such a discrepancy in blood-salivary findings to be due to changes in the hormonal diffusion rate in the salivary gland-salivary gland that is influenced by the physiological consequences of exercise (e.g.55).

Overtraining syndrome

In their comprehensive review, Kuiper and Keizer provide a thorough historical background on the use of the concept of overtraining and comment on the early research on this topic. Many trainers and exercise scientists would be surprised to discover that this topic has been recognized and discussed for almost 100 years (56). That said, in recent decades there have been attempts to change the language and nomenclature used to describe the problem and to shift explanations to some extent in the operational definitions of the terms associated with it.57). For example, in their recent innovative EROS (Endocrine and Metabolic Responses on Overtraining Syndrome) study, Cadegiani and Kater proposed a new term for “Paradoxical Deconditioning Syndrome” instead of overtraining syndrome (58,59). Nevertheless, regardless of what it is called, for the most part the indicators of the condition are essentially the same subject as when they were first mentioned in a 1939 sports medicine article by Jezler (60). To help the reader progress from a normal and appropriate level of training to overtrainingfigure 3(61) are provided and references 56 and 61 are recommended for reading.

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figure 3

Schematic representation of the progression of training loads leading to the development of overtraining syndrome in athletes. Adapted from information given in reference (61). Used with permission.

Because of testosterone's critical physiological role, researchers early in the pursuit of exercise adaptation began asking the question, "Can monitoring circulating changes in testosterone serve as a viable biomarker of exercise adaptation?". Research work in the late 1970s and early 1980s by groups of several Scandinavian and Baltic researchers reported that intense training sessions and training loads resulted in significant reductions in blood testosterone levels (62–67). These numerous findings led Aldercreutz and colleagues to publish their seminal paper in 1986, which suggested that testosterone, cortisol and/or the ratio of the two (T:C ratio) could be used as a way to access to 'overload' (i.e. overtraining) in an athlete and monitor whether his training was progressing favorably (68). Shortly thereafter, reports began to emerge of overtrained athletes with low testosterone levels and, in some cases, elevated cortisol levels, which were linked to the testosterone reductions (69–73).

To this end, a large number of studies are reported over the next 30 years in which training loads increase, testosterone is reduced, and this generally coincides with stagnation or decline in performance in athletes as they become overtrained (i.e., especially in men; see the review). articles - references (74–76)); although this is not a universal finding (25).Table 6shows some signs, symptoms and health consequences of athletes diagnosed with overtraining syndrome. The syndrome results in chronic underperformance and negative health consequences (seeTable 6), and can typically end or limit an athlete's competitive season (56,57,77). The development of overtraining syndrome has been reported in a wide variety of sports, regardless of emphasis on the training method used (e.g., runners vs. weightlifters vs. tennis players), although the specific symptoms and frequency of selected symptoms may vary somewhat. sport specific (74,75).

Researchers have proposed two main reasons and mechanisms for the decrease in testosterone seen with overtraining; (1) testosterone production is disrupted by inhibitory factors such as other hormones in a cascade of stress responses; and (2) insufficient energy intake disruption of the regulatory function of the HPG axis.

Regarding the first mechanism, Doerr and Pirke, as well as Cummings and colleagues, have shown that elevated blood cortisol levels disrupt testosterone production peripherally at the gonads (testicl*s) when cortisol levels are elevated.78,79). There are numerous research studies reporting results of exercise-induced short-term increases in cortisol levels (see Review Articles - References (74,78)), as well as these acute increases in cortisol from a training session that are accompanied by decreases in testosterone (72,80,81). Furthermore, there is evidence that circulating testosterone and cortisol are negatively associated in athletes, even in a resting, basal state (82). In these scenarios, the inhibitory effect of cortisol occurs in two ways; to influence LH and FSH via suppression of GnRH, as well as compromise of Leydig cell function via direct inhibition of steroidogenesis (79,83). Prolactin is another hormone that can cause a decrease in testosterone levels, and the release of this hormone is also stimulated by exercise (see review article-(84)). The evidence convincingly shows that increased prolactin concentrations inhibit GnRH secretion and thereby reduce gonadotropins (LH, FSH) secretion and affect central aspects of the HPG axis.85). In addition, prolactin can also directly inhibit the action of gonadotropins on the gonads (86). Acute exercise-induced increases in prolactin have been associated with decreases in testosterone (87), which have exercise-induced increases in resting basal prolactin associated with decreases in testosterone (73,88); but the latter is not universally reported (41,89).

Nevertheless, hypercortisolmic or hyperprolactinemic states at rest are not commonly encountered in athletes, but consistent daily training sessions can induce frequent transient periods of such hyperexposure during an actual training session, as well as for longer periods during recovery from such training sessions.80,84,90,91).

In the case of the second proposed mechanism, several researchers demonstrated decades ago that short- and long-term calorie deprivation results in a decrease in testosterone in men (92–94). It is known that a common finding is that overtrained athletics lead to weight loss and suppressed appetite/anorexic tendencies.56,61). The effect of insufficient caloric intake on testosterone appears to be more related to suppression of the central HPG axis than to a direct effect on the testes, as both LH and FSH levels are reduced in such scenarios. Bergendahl et al. (95) found that such gonadotropin reductions were caused by suppressed GnRH release from the hypothalamus. Recently, Wong and partners (96) suggest that this dysfunction likely involves hypothalamic suppression due to dysregulation of leptin, ghrelin, and proinflammatory cytokines. The suppression of the gonadal axis is temporary and the axis functional, as the effect may be reversible with weight gain; although the rate at which testosterone returns to normal seems very individualistic (96–98).

Weight-bearing sports

Historically, one of the training activities in which dramatic testosterone reductions were first reported in athletes involved the sport of wrestling (i.e., Olympic freestyle, Greco-Roman, and/or American Scholastic-Collegiate forms). For example, researchers nearly four decades ago described a significant decrease in testosterone in adult male wrestlers during their competitive season, compared to the off-season period.99). Subsequent reports from several other researchers confirmed these findings not only in wrestlers, but also in other weight-restricted sports.100–104).

Mechanistically, the reason for this reduction in testosterone is most likely related to the practice of many athletes in these sports of using extreme weight loss tactics (e.g. semi-starvation) in an attempt to reach a specific competitive weight category. That is, their reduced caloric intake plus high exercise expenditure leads to extremely negative energy balances and a suppression of the HPG axis – in particular a hypogonadotropic hypogonadism state development – ​​see the discussion in the previous section (105). Although this event also appears to be highly reversible, as resumption of adequate caloric intake restores HPG axis function relatively quickly (96,98,105).

Contact – Martial arts

It is known that traumatic brain injury (TBI), such as concussion, can result in the development of low testosterone levels; specifically, secondary hypogonadism usually arises as a result of a pituitary dysfunction (106,107). Much modern research has focused on American football and these types of injuries, because studies of professional and collegiate athletes who have suffered multiple concussions show serious negative long-term health consequences from such repetitive head trauma.108). But there are a number of sporting activities that put participants at increased risk of developing some form of brain injury. Sports activities categorized as "contact sports" (some of which are also called combat sports) pose the greatest risk: boxing, kickboxing, karate, taekwondo, aikido, jujitsu, judo, rugby and Australian rules football. Although these types of sporting activities carry a greater risk of exposure to traumatic brain injury, a wide variety of sports, although not specifically categorized as contact competition, can cause an athlete to develop a traumatic brain injury (for example, wrestling as discussed in the previous sections or football ). ). It is important that physicians examine an athlete's medical history for TBI events if they detect the presence of low testosterone.

Hantriade/RED-S

The Female Athlete Triad refers to a medical condition that is a constellation of three clinical entities: menstrual disorders, low energy availability (with or without an eating disorder), and reduced bone mineral density (7). The triad term for this condition was first coined by the American College of Sports Medicine in 1992 after many experts in the field noticed a pattern among teenage and young adult female athletes. Evidence from groundbreaking work by Dr. Anne Loucks showed that the etiological cause of the triad in women was a persistent state of low energy availability.109).

In connection with this discussion, it is important to define the term "energy availability". Energy availability refers to the amount of energy remaining and available for body functions after the energy used in daily exercise is subtracted from the energy expended from daily caloric intake from food. In other words, in its most basic form:

Extensive research in women has identified cut-off points of low energy availability that indicate the level of risk for developing physiological and performance deficits associated with the triad. These limit values ​​are: risk = ≤30 kcal/kg fat-free mass (LBM); moderate risk = 30-45 kcal/kg body weight; and no risk = ≥45 kcal/kg body weight (109). Whether male athletes share the same risk factors is currently unknown and up for debate.109).

Recently, DeSouza and associates have proposed expanding the scope of the triad condition and the use of the term to include not only the historical population of women, but also men.110). Interestingly, previous researchers had drawn an analogy between the development of menstrual disorders in women's exercise and the observation of low testosterone in men, but they had never applied the Triad terminology to men (111,112).

Although the state of low energy availability (LEA) has a wide range of physiological consequences in women and presumably men, it is specifically associated with the development of low testosterone in men (110). The mechanism of such change appears to be consistent with previous work supporting the development of hypogonadotropic hypogonadism, such as in extensive caloric deprivation, weight loss, and restricted food intake (see previous discussions). Historically, the idea that caloric intake and energy status are associated with low testosterone in exercising men was alluded to in the 1980s, but a systematic investigation of this concept was not thoroughly conducted until recently.44,101).

It is now recognized that a state of LEA can lead not only to the Triad state, but also to the state of “Reduced Energy Deficit in Sport” [RED-S]. RED-S was designated as a separate entity of the triad by an International Olympic Committee medical committee group of physicians; and occurs in both men and women. RED-S differs from the triad because it is seen as broader. It is defined as impaired physiological function, including but not limited to metabolism, menstrual function, bone health, immunity, protein synthesis, and cardiovascular health, caused by a relative energy deficit caused by a state of LEA (113).

The shared etiology and degree of overlapping symptomology of the Triads/RED-S have led some to question whether they truly represent two different conditions (114). That difference of opinion requires more research to be fully resolved. What is clear is that a condition of LEA can lead to low testosterone levels in men. Hooper and colleagues show this clearly in their cross-sectional studies, where LEA was associated with low testosterone in distance runners and triathletes (115,116). For a full discussion of the endocrinological effects of RED-S, the reader is referred to the recent review article by Elliot-Sale and associates (117).

Exercise hypogonadal male fitness

In 2005, Hackney and colleagues proposed the use of the term 'Exercise Hypogonadal Male Condition' (EHMC) for exercise-trained men exhibiting reduced testosterone (19,26). They based this advice on work by their own and other research groups from the 1980s and 1990s. This recommended terminology was intended for exercising men who demonstrated functional hypogonadotropic hypogonadism and met certain criteria, and was not intended for universal application to all exercising men with low testosterone levels. The main features and characteristics of EHMC presented by this research group were (19,26):

• These men had testosterone levels that were at least 25% to 50% lower than expected for their age.

• The reduced testosterone levels did not appear to be a transient phenomenon related to the acute stress load of exercise.

• The men experienced no loss of performance or lack of motivation (overtrained).

• They had not experienced major weight loss in recent months.

• The men had a history of early involvement in sports, resulting in years of almost daily physical activity.

• The most common form of exercise and training involved intensive endurance sports activities such as running, triathlon, cyclo-cross and running.

Unfortunately, there is some confusion within the research community regarding EHMC terminology. That is, many researchers have assumed that the EHMC connotation was the same as training men who exhibited overtraining or Triad/RED-S (...enz) related to reduced testosterone. EHMC, as originally proposed over 15 years ago, was for a different condition and one that represents a potential adaptive response in the HPG axis of the reproductive system from chronic, long-term exercise exposure (see the next section). This point appears to have been overlooked, and as such the use of the EHMC term has been misapplied or completely ignored as a categorical distinction for exercising men with persistently low resting testosterone.

Special considerations

Unfortunately, it is almost impossible to discuss the topic of testosterone and sports activities without mentioning anabolic androgenic steroids (AAS) and athlete doping. AAS, the synthetically produced variants of naturally occurring testosterone, have been associated with certain sports for decades. Although these products have valid and legitimate medical uses, they have been banned or banned by sports governing bodies because they create an unfair physiological advantage (16,21,52). There are a large number of side effects with AAS use, and complications are variable and individual specific; but a common result is that a variant of hypogonadism develops (118). The hypogonadism in this situation can occur during active AAS use, but can also be a long-term side effect when use is stopped (118). When considering some of the possible causes of hypogonadism in athletes, as discussed in previous sections, it is advisable that researchers and physicians rule out the use of AAS as a likely causative factor.

Conflict of interest

The author declares that the research for this article was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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