endurance exercise training and reproductive endocrine dysfunction in men alterations in the...

Current Pharmaceutical Design, 2001, 7, 261-273 261

Endurance Exercise Training and Reproductive Endocrine Dysfunction inMen: Alterations in the Hypothalamic-Pituitary-Testicular Axis

A.C. Hackney*

Endocrine Section - Applied Physiology Laboratory, Department of Exercise & Sport Science,University of North Carolina, Chapel Hill, North Carolina, USA

INTRODUCTION [1, 2]. However, it is generally accepted that themost important cause for the improvement inhuman performance is the level of exercise trainingthat athletes are undergoing [1, 2, 3, 4]. Forexample, it is not uncommon now for distancerunners to complete 150 to 250 kilometers ofintensive running during their weekly training. Thislarge volume of exercise training results inphysiological changes and adaptations that arehighly beneficial to the human organism (e.g.,enhanced cardiac output, arterial-venous oxygendifference, increased erythrocytes, decreased bodyadiposity … etc.) [3]. However, this volume oftraining can also place a tremendous amount ofstress on the organism and result in detrimental ormal-adaptations physiologically. Onephysiological system that is extremely sensitive tothe stress of exercise training is the reproductiveendocrine system. Research indicates that chronic

Athletes who compete in endurance sportingevents are swimming, running, cycling, and skatingfaster than ever before [1]. Thus the world recordsin many sporting events are being broken on anearly annual basis and the trend seems to becontinuing. Many factors are contributing to thisimprovement in human performance. The coachesworking with athletes have more knowledgebecause of advances in the fields of SportsMedicine and Exercise Science. In some case,athletic equipment changes have also led toimmediate improvements in some events (e.g.,running shoe design or track surface composition)

*Address correspondence to this author at the CB # 8700 – UNC-CH,Chapel Hill, NC 27599-8700, USA; Tel: 919-962-0334; Fax: 919-962-0489; Email: [email protected]

1381-6128/01 $28.00+.00 © 2001 Bentham Science Publishers Ltd.

Abstract: Research indicates that endurance exercise training has significant effects upon the reproductiveendocrine system of humans. Until recently, this effect was thought to be limited primarily to women.However, a growing body of evidence demonstrates that the male reproductive endocrine system is alsoeffected. Specifically, the circulating hormonal levels of testosterone are found to be at low concentrations;and, the hypothalamic-pituitary-testicular axis that regulates testosterone production is altered in endurance trained men. The physiological mechanism inducing the lower testosterone is currently unclear;but in many respects, these men display hypogonadotropic hypogonadism characteristics. Currently, thetime course of the changes in the reproductive endocrine system is unresolved and in need of much furthersscientific investigation. The evidence available, however, suggests that a slowly developing process requiring years of exercise training results in these changes. Potentially, the lowered testosterone levels ofthe endurance-trained male could disrupt some of their anabolic or androgenic dependent processes. Todate, there are only a limited number of findings suggesting that a consistent disruption of testosteronedependent processes occur due to endurance exercise training (e.g., oligo-spermatogenesis). Conversely,the alterations in testosterone concentration brought about by endurance training could have cardiovascularprotective effects and thus be beneficial to the health of these men.

262 Current Pharmaceutical Design, 2001, Vol. 7, No. 4 A.C. Hackney

exposure to endurance exercise training can resultin dysfunction developing within the reproductiveendocrinological system of humans [5, 6, 7, 8, 9].

from production within the Leydig cells of thetesticles. Although within the male, the adrenalgland also produces small amounts of the hormone.Regulation of testicular production occurs via anegative feedback regulatory loop systeminvolving the anterior pituitary, hypothalamus,and testicles; referred to as the hypothalamic-pituitary-testicular axis [3, 6, 12, 13, 15, 16].

Most research within the Sports Medicine andExercise Science community has primarily focusedupon the reproductive endocrine dysfunctionassociated with athletic women [10, 11]. However,recently studies have seriously started to addressthe question of how exercise training affects themale reproductive endocrine system. Researchfindings in this area have led some investigators tosuggest that the effect of endurance exercisetraining on the male reproductive system may becomparable (to some degree) to that found inathletic women. For example, endurance-trainedathletes of both sexes have abnormally low levelsof their major sex hormones: testosterone in men,and estrogen - progesterone in women.

The hypothalamus releases pulses ofgonadoliberin (also called gonadotrophin-releasinghormone, GnRH) into the hypophysealcirculation, which supplies the hypothalamus andanterior pituitary. The GnRH stimulates theanterior pituitary to produce and release lutropin(i.e., luteinizing hormone) and follitropin (i.e.,follicle-stimulating hormone). The pulsatile releaseof GnRH results in lutropin and follitropin alsobeing released into the systemic circulation in asimilar pulsatile manner. For normal, healthymales, approximately 2 to 4 lutropin andfollitropin pulses are observed over a 6- to 8-hourperiod, however the amplitudes of the lutropinpulses are much greater than those observed forfollitropin. At the level of the testicles, lutropinand follitropin interact with their primary targettissue receptors (lutropin, Leydig cells; follitropin,Sertoli cells) located on the respective cellmembranes. After a hormone-receptor complex isformed, there is an adenyl cyclase-mediatedincrease of cyclic AMP, which produces aphosphorylation of intracellular proteins byactivation of a protein kinase mechanism. In theLeydig cells, this protein kinase activation leads toa mobilization of steroid precursors, in particularthe activation of pregnenolone synthesis fromcholesterol. Pregnenolone serves as the parentcompound from which testosterone isbiochemically derived [12, 14, 15]. Several otherhormones participate in these regulatory eventswithin the biosynthesis pathway. One worthnoting is the anterior pituitary hormone prolactin,which in low concentrations seems to act as apotentiator of lutropin at the Leydig cells. Anotherregulatory is the adipocyte produced cytokine –hormone leptin; although, the exact aspects of itrole in regulation is an area of much currentresearch [17, 18].

This paper is to serve as a mini-review andpresent an overview of how endurance exercisetraining affects the male reproductive endocrinesystem. The material is divided into four majorsections. The first section deals with the basicendocrinology-physiology of testosterone in themale and methodological issues surrounding theinterpretation of hormonal research. The secondsection covers the basal changes in testosterone inresponse to exercise training and the affects ofacute or prolonged exercise bouts on testosterone.The third section deals with overtraining and theovertraining syndrome relative to testosterone. Inthe fourth and final section, the physiologicalconsequences of the changes observed intestosterone levels associated with enduranceexercise training are discussed.

OVERVIEW OF BASIC ENDOCRINOLOGYAND PHYSIOLOGY

Regulation of Testosterone Production

Testosterone is one of the steroid hormones(chemical designation = 4-Androsten-3-on-17β-ol).Other steroids substances in the body, hormonalor otherwise, are cholesterol, bile acids, vitamin D,and hormones of the adrenal glands and ovary. Themajority of circulating testosterone in men comes

Reproductive Endocrine Dysfunction in Male Athletes Current Pharmaceutical Design, 2001, Vol. 7, No. 4 263

The synthesized testosterone diffuses from theLeydig cells into the testicular vascular systemand/or into adjacent testicle compartmentscontaining the Sertoli cells. Once within the Sertolicells, testosterone plays an essential role in thefacilitation of the spermatogenesis process. Thefollitropin receptor-hormone formation at theSertoli cell results in the initiation of thespermatogenesis process [see reference 12].

Maintenance of testosterone levels within theSertoli cells is essential for the development ofadequate numbers of mature, viable sperm that arenecessary for a male to be fertile [3, 12, 15, 21].

Testosterone also assists in the developmentand function of the male accessory sex glands(prostate, seminal vesicles, and epididymides);that, aid in the sperm development and function,as well as in the act of copulation. Also attributedto the influence of testosterone are the secondarysex characteristics of males, such as the typicaldeeper male voice, increased levels of body hair,penile growth, sex drive (libido), and moreaggressive behavior patterns [3, 15, 21].

The pulsatile release of lutropin results influctuations of testosterone levels in the circulationand additionally there are large circadian cycles inwhich nocturnal elevations in testosterone can beobserved in comparison to daytime levels [19, 20].The majority of the circulating testosterone istransported bound to various carrier proteins(sometimes referred to as binding proteins). Sexhormone-binding globulin (SHBG) is the principalcarrier protein, however other plasma proteins canalso bind and carry testosterone to a lesser degree(e.g., albumin, and cortisol-binding globulin). Theremaining non-bound circulating testosterone isreferred to as free testosterone. This freetestosterone is considered the biologically activeform of the hormone, as this portion of thehormone can interact at the target tissue receptors.The circulating bound and free testosterone arecollectively referred to as total testosterone;although, sometimes in the literature the term"testosterone" is used interchangeably for thephrase total testosterone [12, 14, 15].

Testosterone and dihydroxytestosterone (DHT,derived from intracellular testosterone) arepowerful anabolic hormones that stimulatenitrogen retention and protein synthesis within thebody. Testosterone acts in concert with otherhormones to help initiate the pubertal growthspurt as well as activates the cessation of lineargrowth by closure of the epiphyseal growthcenters in bones. In the adult, the anabolic aspectsof testosterone allow the hormone to facilitate themaintenance of protein anabolism and therebymaintain many functional - structural proteins.Athletes who use anabolic steroid (i.e.,pharmacologically derived testosterone-likecompounds) take advantage of this lastphysiologic point to aid in the development ofskeletal muscle mass [3, 6, 12, 15]. Finally,testosterone also assists in the hematopoiesisprocess and increases sodium reabsorption in thekidneys. Animal based research has also suggestedtestosterone plays a role in increasing skeletalmuscle glycogen synthesis and storage [12, 14].

Physiological Roles of Testosterone

Testosterone has several physiological roleswithin the male. These roles can be divided intotwo major categories: "androgenic effects", relatedto reproductive function and the development of amale's secondary sex characteristics, and "anaboliceffects", pertaining more generally to stimulationof tissue growth.

Factors Affecting Circulating TestosteroneLevels

The concentration of testosterone in thecirculation is a function of the amount of hormoneentering (testicular production and secretion) andthe amount leaving (metabolic clearance) the bloodpool. The rates for these processes are affected byany changes in the physiological state that altermetabolic turnover of the hormone [12].

A major reproductive role of testosteroneinvolves the development of the sperm cell. At theSertoli cells of the testicles, testosterone induces anuclear activation process which stimulates andcatalyses the maturation and development ofsperm during the process of spermatogenesis.


Testicular production of testosterone in thenormal, average male is approximately 7 mg perday. Circulating production stimulators (lutropin),testicle lutropin-receptor numbers, and synthesissubstrate availability affect this rate. Lutropin andtestosterone levels are directly related [12, 22].However, it is believed that only a smallpercentage of the total testicular receptors need tobe occupied to achieve maximum stimulation of theLeydig cells. Reductions in the numbers oftesticular lutropin receptors can result in reducedlevels of testosterone production even in thepresence of elevated lutropin. Receptor numberscan be reduced by certain pathological conditions(e.g. hypergonadotrophic hypogonadism) or a"down-regulation phenomena" related state.Persistent elevations in circulating lutropin canproduce a down-regulation of receptor numbersand thereby reduce testicular sensitivity to furtherchanges in blood lutropin levels [12, 22]. Theconditions of hyperprolactinemia andhypercortisolemia can also produce loweredtestosterone levels. The exact mechanism for thislower testosterone effect is uncertain, but may bedue to interference with Leydig cell receptorsand/or direct inhibition of the steroidogenicsynthesis pathway. Finally, any reduction inavailability of steroid hormone precursors(cholesterol, and pregnenolone) can produce alower rate of testosterone synthesis. Secretion isaffected mainly by testicular blood flow throughthe testicular area, since testosterone is lipidsoluble and thus freely diffusible. Furthermore, thetesticles apparently have little or no storagecapacity for testosterone. Testicular blood flowmoreover is a function of the levels of vascularvasoconstriction or vasodilatation [22, 23].Therefore, anything that influences vascular tonecan affect the rate of testosterone secretion (i.e.,increase sympathetic nervous system activity)[23].

14, 15]. The hepatic removal process is primarily afunction of hepatic blood flow. Thus, any changesin the hepatic blood flow can result in concomitantchanges in the removal rate of testosterone.Additionally, a small portion of the testosterone isremoved from the circulation by select bodytissues and then converted to estrogens via theamortization process [12]. It is also important torealize that the changes observed in blood levels oftestosterone may not necessarily reflect alterationsin production, secretion, or metabolic clearancerates. A prime example, relative to exercise studies,involves the effect of shifts in plasma. Owing tothe binding of testosterone to carrier proteins,increases or decreases in plasma volume lead to adilution or concentration effect that is notindicative of changes in the normal hormonalturnover rate [14]. Whether these changes inconcentration due to plasma volume shifts have aphysiological impact is a point of debate.

When discussing factors affecting blood levelsof testosterone, consideration must be given tonon-physiological factors that could be sources ofvariation between research studies. Examplesinclude blood sampling method, diurnal variationsin hormone concentrations, hormone detectionmethodology, and research protocol (each of whichare discussed briefly below).

The timing and method of blood sampling areconsiderations that must be carefully addressedwhen comparing and evaluating testosteroneresults of different studies. The pulsatile release oflutropin produces fluctuations in the circulatinglevels of testosterone. Furthermore, as notedearlier there is a large daily circadian pattern inblood testosterone levels. A single blood samplewill therefore provide an imprecise estimate of theaverage hormonal level. Use of multiple or serialblood sampling will provide a more accurateassessment. Thus, the use of a serial method ofblood sampling would be preferred and consideredmore informative of the true status of circulatingtestosterone [12, 14].

The metabolic clearance rate of testosterone isestimated to be approximately 100 L per day [12,15]. This process involves target tissue uptake aswell as degradation of the hormone at the liver.The degradation process involves the conversionof testosterone into 17-ketosteroids andglucuronide, which are excreted into the urine [12,

The hormonal biochemical assay methodologymust also be considered a source of variability intestosterone results. Currently, radioimmuno-


assays and chemi-luminescence assays are themost popular means of assessing testosteroneconcentrations in blood samples (although,radioimmunoassays are probably the mostprevalent method). Since the development of theradioimmunoassay technique, over 40 years ago,tremendous refinements in the procedure-technicalaspects have occurred. Hence, comparison ofhormonal values between studies becomescomplicated if a number of years separate theexperiments. A comparison problem may alsodevelop if the radioimmunoassay for the hormoneis via a commercial kit versus a laboratorydeveloped technique. In such comparisons,absolute numbers are difficult to contrast directlyto one another and the reader must look at relativechanges for the most part and observe trendswithin the data. The radioimmunoassay techniqueis a relatively easy bioassay to use, as well asinexpensive, and has a high degree of reliability[12]. However, there is a limitation: the resultsrepresent the immunological activity of thehormone and not necessarily the biologicalactivity. The total biological activity depends notonly on hormonal levels but also on receptoravailability and sensitivity within the individualsubject [12, 14, 22].

research may indicate that a five-year or greaterperiod is necessary. Additionally, one of theprincipal assumptions made within theseretrospective studies is that the observed effectson testosterone levels are the results of the exercisetraining performed by the subject. Obviously, thisassumption is not completely valid unless suchthings as psychological stresses, sleep loss, diet,weight loss, and hereditary factors, all of whichaffect testosterone level, are controlled [14, 16, 24,25, 26, 27]. However, seldom are these factorsconsidered.

Collectively, all of the aforementioned must becarefully reflected on and examined whencomparing the hormonal results of research studiesif a valid interpretation of the endocrine system’sresponse to exercise is to be made.

EXERCISE AND TESTOSTERONE

Basal Change - Response Findings

Retrospective comparative studies examiningisolated (single) blood samples have found lowertestosterone levels in chronically endurance-trainedmales. The subjects in these studies have typicallybeen distance runners who had been involved withthe physical training aspects of their sport for 1 to15 years. In these studies, testosterone levels ofthe endurance-trained men were found to be only60-85% of the levels of matched untrained controlmen subjects [7, 25, 28, 29, 30, 31, 32]. Many ofthe early studies reporting this finding sufferedfrom small sample sizes, however, recent workwith large subject numbers have substantiated thefinding [33]. In addition, work by Gulledge et al.reported that the low resting testosterone findingsare highly reproducible and not just an aberrationof the athletes’ seasonal training regime [34]. Itshould be noted that typically the level of the lowtestosterone values reported in these studies arenot outside of the clinical norm (but, at the verylow end of this range) [35].

Finally, examination of the research protocolsof studies that compare the hormonal status ofexercising and non-exercising subjects revealsseveral problems. For example, to examine theeffects of endurance training most studies havecompared aerobically trained men with untrainedsedentary-control men, in a retrospective fashion.The problem with this approach is the trained menhave subjected themselves to the rigors of thetraining program (typically for years) and theinvestigator is observing the end result. Because ofthe wide variations in response to training, as wellas variations in the exact type of training,considerable divergence can be observed in thetestosterone responses of these subjects. Anotherproblem develops from the large discrepancy inwhat individual authors define as exercise trainingand exercise-trained states. For example, someresearchers may consider an individual aschronically trained if they have performed regularexercise for as little as one year, while other

Prospective studies have also been conducted inwhich blood samples have been collected overdays or weeks while exposing subjects toendurance training regimens. Findings thus far from


such studies have been inconsistent. Some reportsreveal significant reductions (decreases of 20-40%)in resting testosterone following 1 to 6 months ofintensive training, while others studies have foundno significant change in resting testosterone after 2to 3 months of training [36, 37, 38, 39, 40, 41, 42].Differences in the initial training status of thesubjects, or the training dosage administered withinthese studies may explain the discrepant findings.An additional possibility is these studies havebeen conducted for too short a period of time (i.e.,months, where as in the retrospective studies themen with low testosterone have been training foryears).

endurance trained men with low testosterone havebeen interpreted by some researchers as indicatinga dysfunction of the hypothalamic-pituitary-testicular regulatory axis. These findings withprolactin and lutropin have been reported inseveral studies both of the retrospective andprospective type [7, 25, 29, 30, 32, 41].

A number of investigators have also conductedretrospective investigations where resting bloodsamples were collected every 20 or 30 min for 4 to8-hour periods from chronically endurance-trainedmen and untrained controls. Results are similar tothose of the isolated-sampling studies: restingtestosterone concentration of the trained subjectswere typically only 60-80% of those found innon-exercising control men [29, 31, 39]. As withthe isolated blood sampling studies, restinglutropin levels were not significantly elevated inthese studies [29, 31, 39]. Again, these findingshave been cited as representative of a dysfunctionin the hypothalamic-pituitary-testicular axispossibly existing.

Endurance-trained males with loweredtestosterone also display other reproductivehormonal abnormalities. The most frequentlyreported changes involve no significant elevationsin resting lutropin although there are significantdecreases in testosterone. Additionally, it isreported that resting levels of prolactin aredecreased in these men too. These findings ofaltered prolactin and lutropin levels at rest in

Fig. (1). Mean (+SEM) integrated area under the response curve 3-hours for lutropin following the injection of GnRH(gonadorelin hydrochloride). This challenge to the pituitary was performed in groups of endurance exercise-trained male runnersand age-matched sedentary controls. Significant between group differences (P<0.05) are denoted with an asterisk. These data arere-drawn from that contained in reference 45.


Fig. (2). Mean (+SEM) integrated area under the response curve 3-hours for prolactin following the injection of a dopamineantagonist (metoclopramide hydrochloride). This challenge to the pituitary was performed in groups of endurance exercise-trained male runners and age-matched sedentary controls. Significant between group differences (P<0.05) are denoted with anasterisk. These data are re-drawn from that contained in reference 45.

To date, the hormonal findings reported abovehave primarily been found in endurance athletes;i.e., distance and marathon runners. It is highlyunlikely; however, that these hormonal alterationsare limited to this athletic group alone. Theprevalence of the occurrences in distance runnersmost likely represents the tendency of researchersto focus upon this group, since the finding wereinitially reported in these athletes in the1980’s. Asscientists studying exercise expand theirendocrinological studies to include other athleticgroups involved with endurance training; it ishighly likely that comparable data will comeforward.

The research work addressing centralmechanisms has focused upon alterations inlutropin release and, or prolactin release.Alterations in lutropin and prolactin release havebeen an area of extensive research relative to thestudy of exercising women who developreproductive dysfunction. Thus, the male-basedresearch is being modeled on that in females [10,16, 43, 44]. An exaggerated prolactin release to anexogenous stimulus of drugs or synthetichormones has been found in endurance-trainedmales with low testosterone. Conversely, anattenuated release of lutropin due to injections ofGnRH has been detected in endurance-trainedmales with low testosterone [31, 45]. Prolactinpresents an interesting paradox relative toreproductive physiological function. Smallamounts of prolactin seem necessary to worksynergistically at the testicle with lutropin, whileexcessive levels disrupt both central and peripheralaspects of the hypothalamic-pituitary-testicularaxis [12, 13]. Several investigators have found thisaltered prolactin and lutropin release in responseto exogenous stimuli and, or an exercise bout [10,

Mechanistic Studies

Some studies have attempted to elucidatewhether a dysfunction exists in the hypothalamic-pituitary-testicular axis of endurance-trained men;and, what the mechanism for the developmentmight be. These studies have focused on examiningwhether the dysfunction is central (hypothalamicor pituitary) or peripheral (testicular) in nature.


19, 45, 46]. Figs. 1 and 2 illustrates the findings ofHackney and associates for this unusual lutropinand prolactin hormonal response in trained males[45]. Interestingly, although overall lutropinresponse is decreased, results are contradictory asto whether lutropin pulsatile characteristics (i.e.,pulse frequency and amplitude) are affected byendurance training [14, 16, 32, 42, 47].

and cortisol levels in response to exercise [4, 19,48, 49, 50, 51, 52, 53, 54, 55]. Furthermore,generally the lowered testosterone associated withincreased prolactin or cortisol is due to chronicsupra-physiological elevations of these hormonesthat usually result from pathological states such aspituitary or adrenal tumors [12, 55, 56]. Theexercise-induced changes in prolactin and cortisolare well within the clinical normal ranges for thesehormones, regardless of whether the exercise is of amoderate or high intensity. This point is illustratedwith respect to cortisol in Fig. 3 [57].

Peripherally, alterations in the sensitivity of thetestes to lutropin changes have been the essentialresearch focus. Evaluations of testicular sensitivityto an exogenous stimulus have shown trained anduntrained males have comparable responses [31,45]. Thus, these overall findings would suggest thedevelopment of a central problem in thehypothalamic-pituitary-testicular axis; however,data in this area are limited and not yet definitive.

Exercise Changes – Response

It is generally accepted that short-term maximalexercise results in an elevation of circulationtestosterone levels [16, 44, 51, 52, 58, 59]. It isstill an issue of some debate whether this effect isdue simply to hemoconcentration (i.e., plasmavolume shifts) effects, reduced metabolic clearanceand/or possibly a hormone-mediated increase intesticular production. Interestingly, few studieshave performed direct comparisons of exercisetestosterone responses between endurance-trained(with low testosterone levels) and untrainedcontrol men. There appear to be no major

A single, acute exercise bout at high intensity(>60% of maximal aerobic capacity) could inducetransient increases in circulating prolactin andcortisol, which could bring about the observedreductions in testosterone via the inhibitoryactions of each hormone. The likelihood, however,of either of these increased hormonal states viaexercise being a causative factor is doubtful. Thereare relatively small, transient changes in prolactin

Fig. (3). Mean cortisol responses for 24-hours in endurance athletes on three separate occasions; (a) control – baseline day withno exercise, (b) exercise day involving two moderate intensity exercise sessions morning and afternoon, and (c) exercise dayinvolving two high intensity exercise sessions morning and afternoon. Significant increases (P<0.05) in cortisol occurred onexercise days; however, the changes were transient in nature. The data are re-drawn from that contained in reference 57.


differences in response between the two types ofsubjects for testosterone, although the lutropinresponses seem blunted while prolactin isaugmented in the endurance-trained men with lowtestosterone [25]. Nevertheless, this area is in needof much further investigation.

between endurance-trained men (with lowtestosterone levels) to that of untrained controlmen. There is no evidence to suggest extensiveresponse differences between the two types ofsamples exist. Again, however, more research isnecessary on the issue.

Testosterone responses to submaximal exerciseare variable and strongly influenced by theduration and intensity of an exercise bout [16, 44,51, 52, 60]. A progressive increase in testosteroneoccurs during moderate exercise lasting 45 to 90minutes, but 90 minutes of submaximal exercisehas also been reported to produce no change orslight decreases in testosterone concentration [16,44]. Exercise of a moderate to hard intensityperformed until exhaustion (or for more than 2hours duration) results in lowered testosteronelevels [16, 44, 49, 51, 52].

OVERTRAINING AND THE OVERTRAININGSYNDROME

Several researchers have indicated that thefindings of suppressed reproductive hormones inendurance-trained males may exist because theyare “overtraining” and, or are developing the“overtraining syndrome” [2, 8, 9]. Thisterminology can be confusing to non-ExerciseScience researchers, thus some explanation iswarranted. The terms overtraining syndrome andovertraining are frequently used interchangeably.The term "overtraining" actually refers to theprocess of heavier than usual exercise training,while the term "overtraining syndrome" refers tothe product of the overtraining process [2, 4, 7, 9,62, 63]. The overtraining syndrome is apathological disorder, where there is consistent andpersistent exercise performance incompetence inan athlete that does not reverse itself after a fewdays of rest and recovery. Furthermore, there is nounderlying medical reason or explanation for thefinding of declining performance. This exerciseperformance impairment can manifest its selfwithin athletic competition as well as duringexercise training. Concurrent along with thedeclining physical performance is a host of otherpsycho-physiologic consequences that are adverseand negative in nature. Some of the most generaland commonly reported consequences –symptoms are given in Table 1. In addition to thepsycho-physiological characteristics reported inTable 1, one commonly reported endocrine changeis suppressed or extremely low circulating levels oftestosterone [2, 4, 8, 9, 58, 60, 62, 63].Furthermore, in some cases suppressed levels oflutropin, follitropin, and inhibin have also beenreported [14, 59, 60, 63]. While these changesappear nearly identical to those reported above, itdoes not seem to represent the same mal-adaptation. The hormone changes that are found in

This disparity in the findings in testosteroneduring submaximal exercise may be due to theinteraction of several factors. Initially withsubmaximal exercise, hemoconcentration mayproduce elevations in testosterone levels.However, as the exercise continues, there arereductions in the testicular production andsecretion of testosterone. Theseproduction/secretion reductions appear to beprincipally the effects of declining testicular bloodflow. Concurrently with the reduced testicle bloodflow, hepatic blood flow may also becompromised, resulting in a declining hepaticclearance, which may elevate testosterone levels.This latter change may be offset by an increaseduptake by skeletal muscle as exercise durationcontinues, resulting in gradual reduction intestosterone levels.

The acute effects of maximal and submaximalexercise on testosterone levels last a relativelyshort period (~1 to 48 hours). Although, in a fewcases where prolonged intensive exercise has beenperformed, reductions in testosterone have beenreported for longer than 72 hours (e.g., 100-kilometer cross-country ski race, iron mantriathlon, ultra-marathon running) [16, 44, 61].

Again, few studies seem to have comparedsubmaximal exercise testosterone responses


overtraining athletes appear to be only temporaryin nature. When the exercise-training load of theseathletes is reduced or increased levels of rest areincorporated into the training program, theirhormonal profile return to normal. In theendurance-trained males reporting reproductivehormonal abnormalities, they do not displayovertraining syndrome symptoms. Furthermore,most researchers studying this issue have beencareful to insure that their subjects underinvestigation are not going through periods ofintensive training; and, that when they areevaluated they are well rested.

(i.e., a resetting of the regulatory axis) while thosein overtrained athletes are transient.

CONSEQUENCES - PHYSIOLOGICALIMPACT OF LOW TESTOSTERONE

There is evidence to suggest that thedevelopment of low resting testosterone levels inmen doing endurance training have somedetrimental effect on the testosterone-dependentphysiological processes of the body. However, theamount of evidence is scant.

There is the potential for disruption in any ofthe processes influenced by testosterone, andreproductive capacity is of essential concern. Fewstudies have systematically studied this issue andcurrently only a few reports of decreasedspermatogenesis or oligospermic conditionsexisting in endurance trained, males have beenpublished [21, 28, 64]. Additionally, someinvestigators have reported endurance trained menmay have a lowered sex drive; but a direct cause-and-effect linkage between a lower sex drive andtestosterone did not exist in these data [21, 26].Researchers feel that other facts may be affectingthe libido status of these athletes (e.g., overallfatigue, and psychological stress) [65].

Table 1. General Consequences and Symptoms ofthe Overtraining Syndrome [references 4, 5,61, 63].

↓ Physical performance

Severe constant fatigue

Persistent muscle soreness

Overuse muscular-skeletal injuries

Reduced appetite

Lethargy

Depression

Disturbed sleep patterns

Overall Mood disturbances - shifts Relative to the androgenic-anabolic actions oftestosterone, there are apparently no significantdetrimental effects of the lower testosterone levels(i.e., decreased protein synthesis and muscle massdevelopment). However, this area has not beenexamined thoroughly by the Exercise Sciencecommunity. An additional area in need of researchconcerns the impacts of low testosterone levels onbone demineralization in men. Clinically, there isstrong evidence indicating hypogonadal and hypo-testosteronemic men have severe mineral loss fromtheir bones [66]. There are no conclusive findingsof mineral content change in endurance trained menwith low testosterone [67]. Although, severalcompelling case study reports have appeared inthe literature which have found hypo-testosteronemic male athletes and low bonemineral density levels [21, 68, 69].

Immune system deficits

Mental concentration difficulties

∆ Submaximal - maximal heart rates responses to exercise

↓ Maximal oxygen uptake

∆ Submaximal - maximal lactate response to exercise

↓ = Decrease

∆ = Change - decrease and, or increase

Thus, the hormonal changes betweenovertrained and chronic endurance trained malesare similar. Nevertheless, the hormonal changesthat are reported for chronic endurance trainedmales seem to be a more stable accommodationwithin the hypothalamic-pituitary-testicular axis


On the other hand, there could be beneficialphysiologic adaptations from the loweredtestosterone. Some researchers indicate thatlowering testosterone may have cardiovascularprotective effects and decrease the risk of coronaryheart disease [70]. A recent study out of Germanyhas provided strong evidence supporting thisclaim. This research has demonstrated thatchemically induced reduction in endogenoustestosterone levels results in significant increasesin high-density lipoprotein in men [71]. Whetherthe lowering of testosterone in men performingendurance training will produce the same effectremains to be determined, but presents aninteresting point for future research studies toconsider.

is unresolved and in need of much furthersscientific investigation. Potentially, the loweredtestosterone levels of the endurance-trained malecould disrupt some of their anabolic or androgenicdependent processes. To date, however, there areonly a limited number of reports to indicate thatany consistent disruption of the testosteronedependent processes in the male occurs due toendurance exercise training. Conversely, thealterations in testosterone levels brought about byendurance training could have cardiovascularprotective effects and thus be beneficial to thesemen.

There is a large volume of research literaturelooking at the reproductive endocrine dysfunctionin exercising females. However, the total number ofstudies looking at males is relatively small. Manyquestions remain unanswered and are in need ofinvestigation. Consequently, this area of exerciseendocrinology is in need of continued study andinvestigation by the research community.

Is it necessary for endurance trained males tosupplement with testosterone-like substances toas a safeguard against loss of androgenic-anabolicprocesses? There are many opportunities for theseathletes to obtain prescriptions for testosteronefrom the medical community; or, to use ‘black-market’ means of obtaining similar pharmacologicalagents (e.g., anabolic steroids). The answer to thequestion, at this time, is no. The body of researchevidence does not support that disruptions inthese processes are sufficient to warrant suchaction. However, physicians will have to reviewsuch situations on a case by case basis. In extremecases, such steps may be necessary and a well-developed pharmacological course of therapycould be highly advantageous and efficacious.

ACKNOWLEDGMENT

The help of Grace, Sarah and Zachary Hackneywas invaluable in the preparation of thismanuscript. The author wishes to acknowledgetheir efforts and is deeply appreciative.

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Endurance exercise training does have significanteffects upon the major male reproductive hormone,testosterone and the hypothalamic-pituitary-testicular axis that regulates its production. Agrowing body of evidence suggests at rest,testosterone is lowered in the endurance-trainedmale. The mechanism of this lowering is currentlyunclear. It may be related to dysfunction withinthe hypothalamic-pituitary-testicular regulatoryaxis brought about by months or years ofendurance training. Currently, the time course ofthe changes in the reproductive endocrine system

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