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The Amenorrheic Athlete

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S. R. Wall A. N. Belcastro D. C. Cumming
 The Amenorrheic Athlete
SUMMARY                                                          SOMMAIRE
With the growing number of women who                             Avec le nombre croissant de femmes qui s'adonnent
undertake strenuous physical exercise, an                        a des exercices physiques d'endurance, 1'effet de
effect of such activity on reproductive                          telles activit6s sur la fonction de reproduction est
                                                                 devenu apparent. Ceci peut etre dd a une alteration
function has become apparent. This may be                        du m6tabolisme st6roidien periph6rique.
due to many factors including low body fat                       L'insuffisance de lib6ration de prolactine peut etre
and altered peripheral steroid metabolism.                       un facteur, mais tous les facteurs doivent etre
Impaired prolactin release may also be a                         consid6r6s dans leur ensemble. La ligne de conduite
factor, but all factors must be considered                       comprend la diminution de la charge de travail et le
                                                                 retour d un poids normal en plus d'une m&dication
together. Management includes decrease of                        si necessaire.
workload and return to ideal body weight,
plus medication if necessary. (Can Fam
Physician 1983; 29:157-160).

                         I                  I
   Mr. Wall is a research associate         may characterize those women who          Since the conversion of androgen to
in the Department of Obstetrics and         may become amenorrheic, although          estrogen is accomplished partly in
Gynecology, Dr. Belcastro is                the problem is not restricted to these    body fat, reduction of fat mass may re-
director of the Exercise                    two groups. The exact incidence of the    sult in altered peripheral steroid me-
Biochemistry Laboratory, and Dr.            problem is unclear, but evidence sug-     tabolism. Yet the methods of measur-
Cumming is an assistant professor           gests that about 6-18% of recreational    ing body fat are relatively inaccurate;
in the Departments of Obstetrics            runners't6 and up to 50% of women         there is a remarkable variability in es-
and Gynecology and Medicine, all            running about 80 miles per week2 have     timates based on the various for-
at the University of Alberta in             experienced cessation of menstrual        mulas.10 Amenorrhea has been de-
Edmonton. Reprint requests to: Dr.          periods.                                  scribed in women with normal body
D. C. Cumming, Department of                                                          composition subjected to exercise in
Obstetrics and Gynecology, 5-121            Factors in Exercise-Related               the U.S. Military Academy.11 Others
Clinical Sciences Building,                 Amenorrhea                                failed to find a difference between
University of Alberta, Edmonton,                                                      amenorrheic and normally menstruat-
AB. T6G 2G3.                                   Amenorrheic athletes have been as-
                                            sumed to have a form of "hypothala-       TABLE 1
    INCE MORE women are partici-            mic amenorrhea",7 but many factors        Pathophysiologic Factors In
 I2pating in strenuous sports activity,     may be important in the patho-            Exercise-induced Changes In
more physicians are being confronted        genesis of reproductive dysfunction       Reproductive Function
by the woman athlete whose menstrual        (Table 1).8
periods have been interrupted. Re-             Many women with secondary amen-        Changes in lean-fat ratio
cently, delayed puberty, 1 secondary        orrhea are below ideal weight and have    Loss of weight
amenorrhea 2 and short luteal phase 3                                                 Energy drain
                                            altered lean/fat ratio. Body composi-     Dietary changes
have all been described in association      tion in malnourished women is clearly     Age
with athletic activity. Many women          different from that in the healthy ath-   Predisposition
are enquiring just what it is about exer-   lete, who has low body fat but in-        Physical stress of training and/or
cise that- can disrupt cyclic menstrual     creased muscle mass. However, sev-        competing
function and result in amenorrhea. In-      eral studies have suggested that          Emotional stress of training and/or
vestigations into the etiological factors   amenorrheic athletes have lower           competing
have focussed on distance runners and       weight and lower percent body fat than    Acute endocrine effects of exertion
ballet dancers to seek patterns which       those normally menstruating.4-6 9         Chronic effects of repeated exertion

CAN. FAM. PHYSICIAN Vol. 29: JANUARY 1983                                                                                    157
ing runners.12 Cyclic menstrual func-
tion may return in ballet dancers who
stop dancing through injury without
                                            creases with other stress hormones
                                            (growth hormone and cortisol) but a
                                            progressive maximal exercise test sug-
                                                                                        liosone®
                                                                                         erythromycin estolate
gaining weight.'3 Dietary differences       gested that prolactin release is im-        DESCltll: lbosne is the lauryl sulate salt of the propionyl ester of
                                                                                        erythromycin.
have been suggested between amen-           paired in exercise in women with exer-      ACTOUIS Erythromycin inhibits protein synthesis without affecting nucleic
                                                                                        acid synthesis. Some strains of Hemophilus influenzae and staphyococci
orrheic and normocyclic athletic            cise-related amenorrhea. 14, 15 It          have demonstrated resistance to erythmmycin.
                                                                                            Orally administered erythromycin estolate is readily and reliably
women.6, 13 The various studies there-      remains unclear precisely what role         absDrbed. Because of acid stability, serum levels are comparable whether
                                                                                        the estolate is taken in the fasting state or after food. After a single 250-mg
fore suggest a complex interplay of         either of these hormones plays in           dose, blood concentrations at two, four and six hours average 0.29, 1.2, and
factors related to energy supply and        amenorrhea.                                  1.2 mcg/ml, respectively. Following a 500-mg dose, blood concentrations at
                                                                                        two, six and twelve hours average 3, L9, and 0.7 mcg/ml respectively.
utilization, of which low body fat is          Many factors may be involved in          INDIWfON: Streptococcus pyogenes (Group A Beta-Hemolytic)-Upper
                                                                                        and lower-respiratory tract, skin, and soft-tissue infections of mild to
only one.                                   exertional amenorrhea. The complex          moderate severity. A therapeutic dose should be administered for at least
                                                                                        ten days.
   Stress, both physical and psycho-        interplay of physical, psychological,           Alpha-Hemolytic Steptococci (Viridans Group)-Short-term prophylaxis
                                                                                        against bacterial endocarditis prior to dental or other operative procedures
logical, may also be involved, but both     hormonal, nutritional and environmen-       in patients with a history of rheumatic fever or congenital heart disease who
                                                                                        are hypersensitive to penicillin.
are difficult to evaluate. Minor injuries   tal factors is difficult to unravel, and        Staphybcoccus aureus-Acute infections of skin and soft tissue which are
                                                                                        mild to moderately severe. Some strains have demonstrated resistance.
were much more common in women              such factors probably interact with an          Diplcoccus pneumoniae-Upper respiratory tract infections and bwer
                                                                                        respiratory tract infections of mild to moderate severity.
than men recruits to the U.S. Military      innate predisposition, since young age          Mycoplasma pneumoniae (Eaton Agent, PPLO)-In the treatment of
Academy during the first six months,                                                    primary atypical pneumonia when due to this organism.
                                            and previous history of menstrual               Treponema pallidum-Erythromycin is an alternate choice of treatment of
and over the same period the incidence      disruption are more common in amen-         primary syphilis in penicillin-allergic patients. In primary syphilis, spinal-fluid
                                                                                        examinations should be done before treatment and as part of follow-up
of amenorrhea was highest.10 Investi-       orrheic athletes.5' 6, 12 Perhaps the       after therapy.
                                                                                            Corynebacterium diphtheriae-As an adjunct to antitoxin, to prevent
gation of the role of psychological         most important factor of all is the in-     establishment of carriers, and to eradicate the organism in carriers.
                                                                                            Corynebacterium minutissimum-In the treatment of erythrasma.
stress failed to find any objective evi-    nate capacity of the hypothalamic-              Entamoeba histolytica-In the treatment of intestinal amebiasis only.
                                                                                        Extra enteric amebiasis requires treatment with other agents.
dence of increased stress in amenorr-       pituitary-gonadal axis to function, and         Listeria monocytogenes-Infections due to this organism.
                                                                                        CONTWA DICNKA . Erthromycin is contraindicated in patients with known
heic women runners, but subjective          this cannot at present be evaluated.        hypersensitivity to this antibiotic.
perception of stress was greater.6 The                                                  WANKNGS: The administration of erythromycin estolate has been asso-
                                                                                        ciated in adults with an infrequent occurrence of intrahepatic cholestasis.
stress of the goal-oriented lifestyle of    Management of the                               Hepatic dysfunction, with or without jaundice, has occurred in association
                                                                                        with the administration of erythromycin estolate. It may be accompanied by
young musicians is similar to ballet        Amenorrheic Athlete                         malaise, nausea, vomiting, abdominal colic, and fever. In seme instances,
                                                                                        severe abdominal pain may simulate the pain of biliary colic, pancreatitis,
dancers in training, but menarche                                                       perforate ulcer, or an acute abdominal surgical problem. In other instances,
occurs at the normal time in the musi-         Few authors have made specific rec-      clinical symptoms and results of liver function tests have resembled findings
                                                                                        in extrahepatic obstructive jaundice. If abnormalities occur, discontinue
cians.13 This suggests that exercise it-    ommendations for investigating and          IlosDne promptly.
                                                                                            The syndrome seems to result from a form of sensitization, occurs chiefly
self is a specific component in delay of    treating the athlete with reproductive      in adults, and has been reversible when medication is discontinued.
                                                                                            In some cases, initial symptoms have developed after a few days of
menarche, further supported by evi-         dysfunction. All women presenting           treatment, but generally they have followed one or too weeks of continuous
                                            with amenorrhea require at least a min-     therapy. If the above findings occur. discontinue IlosDne promptly. After the
dence that amount and duration of pre-                                                  drug is readministered to sensitive patients, symptoms reappear, usually
menarcheal training are important in        imal investigation to exclude life-         within forty-eight hours.
                                                                                            Usage in Pregnancy-Safety of this drug for utse during pregnancy has not
timing of menarche. '3 14 Levels of         threatening causes of amenorrhea. The       been established.
                                                                                        PRECAIUTflO: Since erythromycin is excreted principally by the liver,
betaendorphin increase in athletes dur-     majority of women presenting with           caution should be exercised in administering the antibiotic to patients with
                                                                                        impaired hepatic function.
ing exercise and training, and since        secondary amenorrhea induced by ex-             Surgical procedures shouild be performed when indicated.
                                                                                        ADVERSE REACNOI The most frequent side-effects of erythromycin pre-
betaendorphin may inhibit gonadotro-        ercise will appear as healthy women of      parations are gastro-intestinal (e.g., abdominal cramping and discomfort)
                                                                                        and are dose related. Nausea, vomiting, and diarrhea occur infrequently
pin release, this may result in amenorr-    normal stature but low body fat, with-      with usual oral doses.
                                            out galactorrhea, hirsutism or hyper-           During prolnged or repeated therapy, there is a possibility of overgrowth
hea.7 However, there is evidence that       tension. An organized, rational use of
                                                                                        of nonsusceptible bacteria or fungi. If such infections arise, the drug should
                                                                                        be discontinued and appropriate therapy instituted.
amenorrheic athletes do not have an         investigative procedures will exclude
                                                                                            Mild allergic reactions, such as urticaria and other skin rashes, have
                                                                                        occurred. Serious allergic reactions, including anaphylaxis, have been
excess of beta-endorphin suppressing                                                    reported rarely.
gonadotropins. 15, 16                       significant lesions. Minimal investiga-     DOWE ADMINIRAT1O : Ilsone is administered orally. For infants and
                                                                                        children under 25 pounds of body weight, the usual dosage is 5 mg per
                                            tions should include measurement of         pound every six hours; for children 25-50 pounds, 125 mg every six hours.
                                                                                            For adults and children over 50 pounds, the usual dosage of Ilosone is
   Other hormonal changes have been         LH,FSH, prolactin, appropriate sex          250 mg every six hours or 500 mg every twelve hours.
                                                                                            For severe infections these dosages may be doubled.
described, but do not clarify the patho-    steroids, thyroid hormone screening             If administration is desired on a twice-a-day schedule in either adufts O
                                                                                        children, one-halt of the total daily dose may be given every twelve hours.
physiology.15 Differences are apparent      and a pituitary X-ray. The occasional           Streptococcal Infections-In the treatment of group A beta-hemolytic
between hypothalamic amenorrhea             runner will present with a definable        streptococcal infections, a therapeutic dosage of erythmomycin should be
                                                                                        administered for at least ten days. In continuous prophylaxis of streptococcal
and exertional amenorrhea,6 and it          syndrome and must be dealt with ac-         infections in persons with a history of rheumatic heart disease, the dosage is
                                                                                        250 mg twice a day.
seems likely that the latter results from   cordingly.                                      When Ilosxne is used prior to surgery to prevent endocarditis caused by
                                                                                        alpha-hemolytic streptococci (viridans group), a recommended schedule for
alterations arising specifically in the        If significant lesions (e.g. hyperpro-   adults is 500 mg before the procedure and 250 mg every eight hours for
                                                                                        four doses afterward; for children, 30 to 50 mg per kg per day divided into
periphery with secondary effects on         lactinemia, thyroid dysfunction, hy-        three or four evenl spaced doses.
                                                                                            Primary Syphilis-20 to 30 g given in divided doses over a period of ten
the hypothalamic-pituitary axis. Acute      perandrogenism, gonadal failure and         to fifteen days.
                                                                                            Amebic Dysentery-250 mg four times daily for ten to fourteen days for
hormonal changes with exercise have         pituitary tumor) are excluded, the          adults; 30 to 50 mg per kg per day in divided doses for ten to fourteen days
                                                                                        br children.
been described in detail, and may be        management of the runner's problem          OVERDOSA Symptoms-nausea, vomiting, and diarrhea.
involved in the genesis of amenorr-          depends upon her current goals.            Treatment-general management may consist in supportive therapy.
                                                                                        HDV SUPPlEDIblosone, Capsules, Pulvules No. 375, 250 mg (equivalent to
hea. 15, 16                                 Speroff advised that estrogen supple-       base), (No. 0, Ivory Opaque Body, Red Opaque Cap), in bottles of 100.
                                                                                         Identi-code: H09.
   Testosterone and prolactin have          mentation was necessary to avoid os-            llosne, Tablets No. 1863, 500 mg, contain erythromycin estolate (equiv-
                                                                                        alent to 500 mg erythromycin), in a pink film-coated tablet; in bottles of 50.
been considered particularly impor-         teoporosis .7 However, no evidence          Identi-code: U26.
                                                                                           Ilosone Liquid 125, M-1U8, Oral Suspension, in 100 ml and 500 ml
tant, since both increase during exer-      has suggested bone demineralization         battles. Identi-code: W15. Each 5 ml contains erythrompcin estolate equiv-
                                                                                        alent to 125 mg erythromycin base in an orange-flavored vehicle. Shake well
cise. We have recently found that ex-       in this group. Exercise itself has an ef-   before using. Avoid freezing.
                                                                                            Ilosone Liquid 250, M-153, Oral Suspension, in 100 ml and 500 ml
ercise induces an increment in free          fect on bone deposition and resorption     hottles. Idonti-codo: W17. Each 5 ml contains erythromycin estolate equiv-
                                                                                        alent ho 250mg erythromyrcin base in a cheery flavored vehicle. Shake well
(non-SHBG bound) testosterone               patterns, and such therapy may not be       before using. Atvoid freezing.
beyond that anticipated from changes         warranted. The levels of estrogen tend
in total testosterone. Prolactin in-         to be in the low normal range above                               Toronto, Ontario

158                                                                                       CAN. FAM. PHYSICIAN Vol. 29: JANUARY 1983
 the post-menopausal level, and thus
 calcium supplementation may be a
preferred form of treatment, if indeed
                                            Profiles of selected hormones during men.
                                            strual cycles of teenage athletes. J App,
                                            Physiol: Respirat Environ Exercise Phy-
                                                                                           Sudafed* DM ;
                                                                                           (pseudoephedrine HCI/
 any is necessary.                          siol. 1981; 50:545-551.
   For the amenorrheic runner seeking
                                            4. Dale E, Gerlach DH, Wilhite AL: Men-        dextromethorphan HBr)
                                            strual dysfunction in distance runners. Ob-
pregnancy, the initial treatment should     stet Gynecol 1979; 54:47-53.                   Cherry-flavoured Syrup
be to decrease the workload and to re-     5. Speroff L, Redwine DB: Exercise and          Decongestant - Antitussive: Pseuldoephed-
turn body weight towards the ideal. In      menstral function. Physician Sports Med        rine hydrochloride is ani orally effective ioasal
                                            1980; 8:42-52.                                 decongestant that provides relief' in 15 - 30
the event that ovulation does not spon-     6. Schwartz B, Cumming DC, Riordan E,          imiinutes after adnministrationi. The muLcouLs iem-
                                                                                           brane of the enitire respiratory tract is genitly
taneously return, clomiphene may be         et al: Exercise-associated amenorrhea: A       retuLrine(i toward noriiial by the action of pseudo-
used. 17 Use of bromocryptine was ad-      distinct entity. Am J Obstet Gynecol 1981;      ephedrinic hydrochloride onl bothl nerve andi
                                            141:662-670.                                   stttooth iiiuscle.
vocated since prolactin levels increase    7. SperoffL: Getting high on running. Fer-      Dext romethorpha n hydrobrom ide possesses aniti-
with exercise in normal women. 18                                                          tuLssive lroperties approximately equivalenit to
                                           til Steril 1981; 36:149-151.                    co(deinie. It does inot have atiy anialgesic or addic-
However, several physiological stim-       8. Rebar RW, Cumming DC: Reproduc-              tive properties. It has beenl demonstrated in anii-
uli such as sleep and feeding also pro-    tive function in women athletes. J Am Med       mal stUdies that dextrormiethorplhan acts as dloes
                                                                                           codeiine throulgh the cenitral inhibition of afferent
mote a rise of prolactin to supraphysio-  Assoc 1981; 246:1590.                            tussal impulses. With the usual hu-man therapeu-
logical levels. As previously observed,    9. Frisch RE, Wyshak G, Vincent LE: De-         tic dosage, no effect has been noted oni the gastro-
                                           layed menarche and amenorrhea in ballet         intestinal, cardiovascular or respiratory systems.
a short but strenuous bout of exercise     dancers. New Eng J Med 1980; 303:17-            INDICATIONS AND CLINICA L USE
                                                                                           SUDAFED DM is irtdicated ftor the proplhylaxis and
capable of elevating prolactin levels in   19.                                             treatment of the symptorns associated with the
normally menstruating women athletes       10. Anderson JL: Women's sports and fit-        comnion cold, acuLte and suLbacute sinusitis, acute
                                           ness programs at the U.S. military aca-         eustachian salpingitis, serouLs otitis media with
did not increase the levels in a group of  demy. Phys Sportsmed 1979; 7:72-78.
                                                                                           euLstachian tube coiigestioin, aerotitis media,
amenorrheic athletes. 15, 16 Therefore,                                                   crouLp1, and siiilar lower respiratory tract diseases.
                                           11. Flint MM, Drinkwater BL, Wells CL,         CONTRA INDICATIONS
in the event of clomiphene failure, we     et al: Validity of estimating body fat offe-   The use of SUDAFED DM is cotitraindicated in pa-
                                                                                          tients known to be sensitive to pseudoephedrinie
would recommend more conventional          males: Effect of age and fitness. Human         hydrochloride   or   dextromethorphan hydrobro-
forms of therapy, such as gonadotro-      Biol 1977; 49:559-572.                          imiide. SUDAFED DM should not be administered
                                           12. Baker ER, Mathur RS, Kirk RF, et al:       to patienlts receiving MAO inihibitors.
pins.                                     Female runners and secondary amenorr-           PRECA UTIONS
   In summary, there is no evidence to                                                    Use with cautioin ii hypertensive patietits.
                                          hea: Correlation with age, parity, mileage      ADVERSE REACTIONS
indicate that management of anovula-      and plasma hormonal and sex-hormone             Mild stimuLlationi, nausea or imiild sedation has
tion in the runner should be different    binding globulin concentrations. Fertil         beeni seen ii a fe'w patients.
                                                                                          SYMPTOMS ANI) TREATMENT OF OVERDOSAGE
from that in non-running women. We        Steril 1981; 36:183-187.                        Symptoms: The clinical picture of acutC poison-
                                           13. Warren MP: The effects of exercise on      ing with SUDAFED DM would probably be
have assumed that the problem is re-      pubertal progression and reproductive           characterized by the toxic eff'ects of pseudoephed-
versible, but this assumption is based    function in girls. J Clin Endocrinol Metab      ritie. Mild stimuLlationi, nausea, or mild sedatioi
                                                                                          has beeni seeni in a fe'w patients. In severe cases,
upon relatively little clearly docu-       1980; 51:1150-1157.                            there may be respiratory depression (fue to the
mented data. Longterm studies of           14. Frisch RE, Gotz-Welbergen AV,              dextromethorphan compotient.
                                          McArthur JW, et al: Delayed menarche, ir-       Treatment: There is no specific antidfote for
amenorrheic athletes are required to       regular cycles and amenorrhea of college       pseudoelphedrine, besides general measures to
assess the significance of exercise-in-                                                   eliminate the drug anid reduLce its absorption.
                                          athletes in relation to the age of onset of     In severe cases of acute poisoning, where the
duced changes in menstrual function,      training. J Am Med Assoc 1981; 248:1559-        respiratory depressive effects of dextromethor-
and to confirm that such changes are       1563.                                          phati imiay be apparenit, the followinig may be
                                                                                          ind icated:
reversible.                                15. Cumming DC, Rebar RW: Exercise
                                          and reproductive function in women. Am J         Levallorplian            - Adults: 1.5       -   2 mg i.v.
                                          Indust Med, in press.                                                     - Children: 0.5         -   mg i.v.
                                                                                          or Nalorphine
References                                16. Cumming DC, Belcastro AN: The re-            (Lethidrone)             - Adults: 5     -   tO mg i.v.
                                          productive effects of exertion. Curr Prob                                 - Children: 2.5 - 5 mg i.v.
1. Malina RM, Harper AB, Avent HH, et Obstet Gynecol 1982; 5:1-42.                        Depending on how the patient's breathing re-
al: Age at menarche in athletes. Med Sci 17. O'Herlihy C: Jogging and suppression         sponds, the dose can be repeated, if necessary, at
Sports 1973; 5:11-13.                                                                     intervals of 20 - 30 mitiutes.
                                          of ovulation. N Eng J Med 1982; 306:50-
2. Feicht CB, Johnson TS, Martin BJ, et 51.                                               or Naloxone (Narcan) - Adults: 400 Imecg s.c.
al: Secondary amenorrhea in athletes. 18. Baker ER: Menstrual dysfunction and                                   - Children: 5 - 10 mcg/kg
Lancet 1978; 2:1145-1146.                 hormonal status in women: A review. Fer-                                            body-weight s.c.
                                                                                          Depending on how the patient's breathing re-
3. Bonen A, Belcastro AN, Ling WY, et al: til Steril 1981; 36:691-696.                    sponds, the dose can be repeated at 2 - 3 minute
                                                                                          intervals.
                                                                                          DOSA GE AND ADMINISTRATION
                                                                                          Children: Ages 2-6 years  2.5 inL (½12 tsp.) t.i.d.
                                                                                                    Ages 6-12 years    5 imtiL (l Isp.) t.i.d.
                                                                                          Adults and
                                                                                             children over 12 years   10 mL (2 tsp.) t.i.d.
                                                                                          AVAILABILITY
                                                                                          Each 5 mL contains 30 mg pseudoephedrine
                                                                                          hydrochloride and 15 mg dextromethorphan
                                                                                          hydrobromide. Available in 100 mL and 250 mL bottles.
                                                                                          Additional prescribing information available
                                                                                          on request.
                                                                                          *Tratde Mark                            FPAABi        W- 1)47
                                                                                                                                   C(.lP

                                                                                                   A'Lt.(O(Ntt
                                                                                                   W             .\tt:t)t( AL1 t)tVttOA(N
                                                                                                   I3BURR()U(II5 WVE-LLU.)ML IN(.
                                                                                                   KtRtKtA,NI), (QUI.


160                                                                                       CAN. FAM. PHYSICIAN Vol. 29: JANUARY 1983

								
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