Reproductive failure in women who practice weight control*

Transcription

1 FERTILITY Aim STERIUTY Cpyright c 1982 The American Fertility Sciety Vl. 37, N.3, March 1982 Printed in U.SA. Reprductive failure in wmen wh practice weight cntrl* G. William Bates, M.D.t Susanne R. Bates, M.Ed. Neil S. Whitwrth, Ph.D. Divisin f Reprductive Endcrinlgy, Department f Obstetrics and Gyneclgy, The University f Mississippi Medical Center, Jacksn, Mississippi Frty-seven wmen (29 with unexplained infertility and 18 with menstrual dysfunctin) practiced weight cntrl by calric restrictin in rder t maintain a fashinable bdy habitus. All f these wmen were belw ideal bdy weight (lbw) when cmpared with Metrplitan Life Insurance Cmpany tables fr height and weight. When 36 f these wmen fllwed a dietary regimen designed t increase their weight t predicted IBW, 19 f 26 infertile wmen (73%) cnceived spntaneusly; 9 f 10 wmen (90%) with secndary amenrrhea resumed menstruatin. Eleven wmen (23%) wuld nt accept their practice f weight cntrl as the cause f reprductive failure and did nt participate in the study. Differences in the serum gnadtrpin luteinizing hrmne:fllicle-stimulating hrmne (LH:FSH) rati were fund t be significantly related t differences in the percentage f IBW. The practice f weight cntrl may be a cause f unexplained infertility and menstrual disrders in therwise healthy wmen. Fertil Steril37:373, 1982 The nset f menstrual cycles in wmen and the sustenance f menstrual cycles depend ften upn achieving and maintaining an adequate amunt f bdy fat as a percentage f ttal bdy mass. l - 3 Simple weight lss may result in amenrrhea; extreme weight lss results in the mre cmplex metablic changes characteristic f anrexia nervsa. 4 Current Western fashin trends dictate that wmen maintain a svelte bdy habitus, and the ppularity f jgging and distance running further emphasizes this desired bdy image. We bserved that a grup f wmen wh practiced weight cntrl by calric restrictin in rder t maintain a fashinable bdy image had unexplained infertility r menstrual dysfunctin; Received September 8, 1981; revised and accepted Nvember 13, *Presented in part at the Thirty-Seventh Annual Meeting f The American Fertility Sciety, March 14 t 18, 1981, Atlanta, Gergia. treprint requests: G. William Bates, M.D., 2500 Nrth. State Street, Jacksn, Mississippi Vl. 37, N.3, March 1982 hwever, these wmen were belw ideal bdy weight (IBW) as determined by the Metrplitan Life Insurance Cmpany tables fr bdy weight and surface area. In this reprt we present the effects f weight cntrl n menstrual cycles, serum gnadtrpins, and fertility, and the effects f weight gain n restring reprductive functin. MATERIALS AND METHODS Frm August 1978 thrugh April 1981, 47 wmen wh practiced strict weight cntrl were referred t the Reprductive Endcrinlgy Clinic fr evaluatin f previusly unexplained infertility r menstrual dysfunctin. These wmen ranged frm 16 t 36 years f age; all had nrmal sexual develpment at puberty and had established cyclic menses during their teen-age years. Twenty-nine wmen (grup A) had unexplained infertility, althugh we subsequently fund that 93% f these wmen had abnrmal menstrual cycles. Eighteen wmen (grup B) had abnrmal menstrual cycles but n desire fr pregnancy. Bates et ai. Reprductive failure in wmen 373

2 Table 1. Physical Characteristics f Wmen with Reprductive Failure Resulting frm Weight Cntrl Practicea Grup A: Infertility (n = 29) Grup B: Menstrual disrder (n = 18) amean ± standard errr f the mean. Age yr 28.5 ± ± 1.4 Height Weight % Ideal weight in lb 65.3 ± ± 2 91 ± ± ± 4 89 ± 1.5 Twenty-eight (97%) f the infertile wmen and their husbands had been evaluated previusly fr infertility. A variety f diagnstic studies (including semen analysis, hystersalpinggraphy, endmetrial bipsy, and diagnstic laparscpy) had been perfrmed by the referring physicians, but n cause fr infertility had been discvered. At initial evaluatin, a histry was btained t ascertain the age f menarche, regularity and frequency f menstrual cycles, cntraceptive practices, pregnancies, maximal adult bdy weight, physical activity, and weight cntrl practices. Height and bdy weight were measured, and the percentage f IBW fr height was btained frm the Metrplitan Life Insurance Cmpany tables fr bdy weight and surface area. Wmen wh ranged between 85% and 95% f IBW were cnsidered t have simple weight lss; wmen wh were less than 85% f IBW were cnsidered t have severe weight lss. Fur wmen had anrexia nervsa as defined by Feighner et al. 5 Single bld samples were cllected by venipuncture n day 10 f the menstrual cycle in thse wmen with cyclic menses and at randm in thse wmen with amenrrhea; the samples were cllected between 9:30 A.M. and 4:30 P.M. The serum was stred at - 20 C until assayed fr luteinizing hrmne (LH) and fllicle-stimulating hrmne (FSH). We determined serum LH and FSH cncentratins by radiimmunassay f duplicate sample aliquts, using materials and prcedures btained frm Sern Labratries, Inc. (Braintree, Mass). The interassay and intraassay variatins fr LH were 9.8% and 6.3%, respective- ly, while the crrespnding values fr FSH were 9.4% and 4.3%. The assay sensitivity fr LH was 1.1 mlulml, and that fr FSH was 0.9 mlui ml. LH values are reprted as mlu equivalents f Internatinal Reference Preparatin (IRP) 68/40; FSH values are stated as mlu equivalents f IRP 69/104. The nrmal gnadtrpin range during the fllicular phase is 2 t 30 mlu/ml fr LH and 6 t 30 mlulml fr FSH. The LH:FSH rati was cmputed fr each subject, and the rati was cmpared with the percentage f IBW. A basal bdy temperature chart (BBT) was maintained by each subject t mnitr the ccurrence f vulatin and t measure the length f the luteal phase f the cycle. 6 The length f the luteal phase was cmputed frm the time f the biphasic temperature shift until menstruatin began. Once the IBW was established, subjects were instructed by a therapeutic dietitian in a weightgaining regimen and encuraged t gain t IBW at a rate f ne-half pund per week. N drug therapy was prescribed t alter the menstrual cycle r t induce vulatin. The data were analyzed fr statistical significance by analysis f variance and Duncan's New Multiple Range Test. 7 RESULTS Twenty-nine wmen in grup A with unexplained infertility were 91 ± 0.8% (mean ± standard errr f the mean) f IBW. Eighteen wmen in grup B with menstrual disrders were 89 ± Table 2. Obstetric Histry f Wmen with Reprductive Failure Resulting frm Weight Cntrl Practice Duratin f infertility Nne Previus pregnancies Term Abrtin yr Grup A: Infertility (n = 29) Grup B: Menstrual disrder (n = 18) 4.3 ± O.4 a 23 (78%) 16 (89%) 3 (11%) 2(11%) 3(11%) amean ± standard errr f the mean. 374 Bates et al. Reprductive failure in wmen Fertility and Sterility

3 Table 3. Characteristics f Menstrual Cycles in Wmen with Reprductive Failure Resulting frm Weight Cntrl Practice Menstrual cycles Absent Irregular Shrt luteal phase Nrmal Grup A: Infertility (n = 29) Befre weight gain After weight gain (n = 26) Grup B: Menstrual disrder (n = 18) Befre weight gain After weight gain (n = 10) 3 (10%) 16 (89%) 1 (10%) 6 (21%) 2 (8%) 2 (11%) 5 (50%) 18 (62%) 2 (8%) 1 (10%) 2 (7%) 22 (84%) 3 (30%) 1.5% f IBW. The age, height, weight, and percentage f IBW fr the tw grups are presented in Table 1. Nne f the wmen in grup A had anrexia nervsa at the time f initial evaluatin, althugh ne wman had been assigned a diagnsis f anrexia nervsa previusly. Fur wmen in grup B (22%) had anrexia nervsa. REPRODUCTIVE HISTORY The reprductive histry is presented in Table 2. Twenty-three wmen (78%) in grup A had never been pregnant; 16 wmen (89%) in grup B had never been pregnant. The duratin f infer tility in grup A was 4.3 years, with a range frm 1 t 9 years. MENSTRUAL CYCLES Ten percent f the wmen in grup A had secndary amenrrhea; 89% f the wmen in grup B had secndary amenrrhea (Table 3). In this study, 62% f the infertile wmen had a temperature elevatin f less than 10 days fllwing the biphasic shift. These wmen gave a histry f regular, predictable menstrual cycles, but an analysis f the BBT recrd revealed that the lu- teal phase, as determined by the biphasic shift, was less than 10 days; the maximal temperature elevatin was reached 4 t 5 days, rather than the usual 48 hurs, fllwing vulatin. When the suggestin f weight cntrl practice as the etilgy f infertility was made, mst f the wmen in grup A were highly mtivated t participate in a weight-gaining regimen; 26 f the wmen gained t near IBW. Twenty-tw (84%) resumed nrmal vulatry menstrual cycles, tw (8%) had a shrt temperature elevatin phase after weight gain, and tw (8%) had irregular cycles. Three wmen (10%) did nt accept the diagnsis and did nt return fr fllw-up care. The 22 wmen wh established nrmal cycles nted increased abdminal blating, a perceptible increase in breast size, and a sense f lethargy just befre menses. Althugh circulating prgesterne cncentratins were nt measured in this study, these subjective changes were presumed t be due t increased prgesterne secretin fllwing vulatin. Unlike the wmen with unexplained infertility, the wmen with menstrual disrders were nt mtivated t gain weight. When the suggestin f weight cntrl practice as the etilgy f men- 99CYCLE1--1l9POOS LL 97 W a:: ::J 98 \i 97x a.. 99 :E xxx x x xx x DAYS Figure 1 Basal bdy temperature recrds f five cnsecutive cycles fllwing the return f menses in a wman with secndary amenrrhea f 4 years' duratin. She weighed 107 punds when she entered the study. Menstruatin resumed at 119 punds. Presumed vulatin is nted by the arrw. Nte the prgressive lengthening f the menstrual phase (X) and the luteal phase. Nte the prgressive shrtening f the cycle. Vl. 37, N.3, March 1982 Bates et ai. Reprductive failure in wmen 375

4 OLH.FSH X! SEM 0... <85 N= ::: :x: 3 en N= N=17 >94 N=9 O..."--'--_..L...L..._..L...&..._..L--'-_ < >94 N=6 N=12 N=17 N=9 Figure 2 (A), Serum LH and FSH cncentratins in 44 wmen at varius percentages f IBW befre weight gain. (B), Serum LH:FSH rati in these wmen befre weight gain. strual dysfunctin was made t the wmen in grup B, eight wmen (44%) did nt accept the diagnsis and did nt return fr fllw-up care; ten wmen gained t near IBW; and ne wman (10%) had persistent amenrrhea after weight gain. (An example f the prgressive changes in the BBT with weight gain in ne wman with menstrual dysfunctin is presented in Figure 1.) SERUM GONADOTROPINS Serum gnadtrpins were measured in 44 wmen befre initiatin f a weight-gaining regimen (Fig. 2). In the wmen wh weighed belw 85% fibw, bth serum FSH and LH cncentra- 376 Bates et al. Reprductive failure in wmen A. B. tins were lw, but within the limits f nrmal; the LH:FSH rati was 1.3. In the wmen weighing between 85% and 89% f IBW, the gnadtrpin values were in the nrmal range; the LH:FSH rati was 2.4. In the wmen weighing between 90% and 94% fibw, the serum cncentratin f LH (50.9 miulml) greatly exceeded the prevulatry nrmal range t the extent that the LH:FSH rati in this grup was 4.6. In the wmen wh exceeded 94% f IBW, serum LH was als elevated (39.2 miulml), resulting in a LH:FSH rati f 3.5. The serum LH cncentratin and LH:FSH rati f the grup with 90% t 94% f IBW were significantly higher (P < 0.01) than thse f wmen weighing less than 90% f IBW. Hwever, in the grup greater than 94% f IBW, the serum LH cncentratin and LH:FSH rati were significantly higher (P < 0.01) than nly the grup less than 85% f IBW. WEIGHT GAIN AND REPRODUCTIVE OUTCOME Twenty-six infertile wmen restred their weight t greater than 95% f IBW. Nineteen wmen (73%) cnceived spntaneusly; fur f these wmen (21%) abrted in the first trimester (Table 4). One f the wmen wh abrted cnceived a secnd time and had an uncmplicated pregnancy. The data fr percentage f IBW befre weight gain and at cnceptin in the 19 wmen wh cnceived are presented in Figure 3. The mean weight gain fr this grup was nly 8.2 punds. DISCUSSION Frisch and Revelle! prpsed that menarche is related t the attainment f a critical bdy weight (bdy fat) independent f height; heavy girls experience menarche earlier than light girls f a similar height. They suggested that this critical weight is cupled with a change in metablic rate and is assciated with a decrease in the sensitiv- Table 4. Reprductive Outcme in Wmen with Reprductive Failure Resulting frm Weight Cntrl Practice Did nt Weight Preg- Abrtin return gain" nancy Grup A: Infertil- 3 (10%) 8.2 ± (73%) 4 (21%) ity (n = 29) Grup B: Men- 8 (44%) 9.8 ± 1.3 strual disrder (n = 18) amean ± standard errr f the mean. lb Fertility and Sterility

5 I- ::J: LLJ 80 >- 0 0 (Xl -' LLJ e N=19 N=19 PRIOR TO CONCEPTION AT CONCEPTION X "± SEM Figure 3 Percentage f ideal bdy weight in 19 wmen befre weight gain and at cnceptin. The difference is statistically significant (P < 0.01). ity f the hypthalamic-pituitary axis t circulating hrmnes. Nrmally, girls gain weight between ages 16 and 18 years; this weight gain. must be stabilized in rder t maintain nrmal menstrual cycles. Frisch and McArthur3 reprted that weight lss causes lss f menstrual functin and that weight gain restres menstrual functin. Wentz,8 in a study f 24 wmen with primary and secndary amenrrhea, reprted that simple weight lss is assciated with menstrual dysfunctin when ver 30% f bdy fat (cinciding with 10% t 15% f bdy weight) is lst. Others have reprted a relatinship between vluntary weight lss and amenrrhea.9, 10 An unexpected finding in this study was the frequent ccurrence f a temperature elevatin f less than 10 days fllwing presumed vulatin in wmen belw predicted IBW. As these wmen gained weight t greater than 95% f IBW, the temperature elevatin fllwing the biphasic shift exceeded 11 days. We did nt measure circulating prgesterne cncentratins r btain endmetrial samples during the luteal phase f the menstrual cycle in any f ur subjects; therefre, we cannt claim that these wmen had a luteal phase defect in assciatin with weight cntrl practice as a cause f their infertility. Hwever, we speculate that a luteal phase defect, as first described by Jnes,l1 may be assciated with weight cntrl practice. In this investigatin, we fund that the gnadtrpin rati (LH:FSH) was assciated with the percentage f IBW. This is nt surprising, since Byar et al.12 measured plasma LH and FSH cncentratins at 20-minute intervals fr 24 hurs in Vl. 37, N.3, March 1982 nine wmen with anrexia nervsa and fund age-inapprpriate gnadtrpin secretry patterns resembling thse fund in prepubertal children. Katz et al.13 fund that wmen with anrexia nervsa wh gain weight and reestablish nrmal menses prgress back thrugh a gnadtrpin secretry pattern resembling the physilgic events that ccur at puberty. Interestingly, Katz fund that as weight gain apprachd 90% f IBW, the secretin f LH began t increase during sleep. This is cnsistent with the percentage f IBW at which we bserved an increase in serum LH cncentratin in the present study. The elevated LH:FSH rati in thse wmen weighing between 90% and 94% fibw raises the pssibility f plycystic varian disease in this grup. We did nt measure adrenal r varian andrgens in these wmen; therefre, we cannt cmment further n this pssibility. Hwever, the pregnancy rate in this grup fllwing weight gain was n different frm that f the ther subjects in the study. Vigersky et al.14 reprted that mean basal plasma FSH levels in wmen with simple weight lss were lwer than nrmal early-fllicular-phase values but were higher than values fund in anrexia nervsa. They fund basal LH levels indistinguishable frm thse in nrmal wmen but significantly higher than thse fund in patients with anrexia nervsa. Several investigatrs l5-19 have reprted that wmen wh are severely underweight are unrespnsive t an infusin f luteinizing hrmne-releasing hrmne. McArthur et al.,20 in a study f nine wmen with nutritinal amenrrhea, fund a lw plasma LH befre refeeding. As these wmen gained weight, plasma LH increased, and when a mean weight f 96.6% fibw was reached, these wmen began t menstruate (three wmen cnceived). Weight cntrl t maintain a fashinable bdy image. is a cmmn practice in Western sciety. Testimny t this is the frequency f articles n weight cntrl and exercise prgrams in wmen's magazines, the ppularity f jgging and distance running, and the prjectin f a slender bdy habitus by the fashin industry. Even thugh a slender bdy is cnsidered desirable, the practice f weight cntrl may be an unrecgnized cause f reprductive failure. It was ften difficult fr us t make a diagnsis f infertility r menstrual dysfunctin resulting frm weight cntrl practice in many wmen in this study because these wmen appeared "nrmal"; they met the expectatins f the bdy image mst desired in mdem sciety. Bates et ai. Reprductive failure in wmen 377

6 Yet they were belw predicted mw fr height, and each subject carefully cntrlled her calric intake. Participatin in a weight-gaining prgram was anathema fr mst f the wmen in this study. As they gained weight, the added weight (fat) was depsited in the thighs, hips, and t sme extent, arund the lwer abdmen. They cmplained f becming bese and unattractive. Many wanted t initiate an exercise prgram t redistribute the fat, but we discuraged any prgram that wuld reduce bdy fat. It is well established that weight lss f greater than 15% f mw is assciated with amenrrhea and a hst f ther metablic changes. Hwever, we find that even smaller changes in bdy weight (i.e., reductins f 5% t 10%) are assciated with subtle alteratins in the menstrual cycle and reprductive failure. When bdy weight is restred t within 5% f IBW in wmen wh practice weight cntrl, menstrual cycles lengthen and fertility is restred in a significant majrity. We cnclude that the practice f weight cntrl may be a cause f unexplained infertility and menstrual dysfunctin in therwise healthy wmen. Acknwledgments. We are grateful t Pam Fryer, Denise Schreiber, and Margaret Taylr fr excellent editrial assistance in preparing the manuscript. REFERENCES 1. Frisch RE, Revelle R: Height and weight at menarche and a hypthesis f critical bdy weights and adlescent events. Science 169:397, Frisch RE: In The Cntrl f the Onset f Puberty, Edited by M Grumbach, G Grave, F Mayer. New Yrk, Wiley, 1974, p Frisch RE, McArthur JW: Menstrual cycles: fatness as a determinant f minimum weight fr height necessary fr their maintenance r nset. Science 185:949, Drssman DA, Ontjes DA, Heizer WD: Anrexia nervsa. Gastrenterlgy 77:1115, Feighner JP, Rbins E, Guze SB, Wdruff RA Jr, Winkur G, Munz R: Diagnstic criteria fr use in psychiatric research. Arch Gen Psychiatry 26:57, Marshall J: Thermal changes in the nrmal menstrual cycle. Br Med J 1:102, Edwards AL: Experimental design in psychlgical research. New Yrk, Hlt, Rinehart, and Winstn, 1950, p Wentz AC: Bdy weight and amenrrhea. Obstet Gynecl 56:482, Graham RL, Grimes DL, Gambrell RD: Amenrrhea secndary t vluntary weight lss. Suth Med J 72:1259, Knuth UA, Hull MGR, Jacbs HS: Amenrrhea and lss f weight. Br J Obstet Gynaecl 84:801, Jnes GES: Sme newer aspects f management finfertility. JAMA 141:1123, Byar RM, Katz J, Finkelstein JW, Kapen S, Weiner H, Weitzman ED, Hellman L: Anrexia nervsa: immaturity f the 24-hur luteinizing hrmne secretry pattern. N Engl J Med 291:861, Katz JL, Byar R, Rffwarg H, Hellman L, Weiner H: Weight and circadian luteinizing hrmne secretry pattern in anrexia nervsa. Psychsmatic Med 40:549, Vigersky RA, Andersen AE, Thmpsn RH, Lriaux DL: Hypthalamic dysfunctin in secndary amenrrhea assciated with simple weight lss. N Engl J Med 297:1141, Jeuniewic N, Brwn GM, Garfinkle PE, Mldfsky H: Hypthalamic functin as related t bdy weight and bdy fat in anrexia nervsa. Psychsmatic Med 40:187, Warren MP, Jewelewicz R, Dyrenfurth I, Ans R, KhalafS, Vande Wiele RL: The significance f weight lss in the evaluatin f pituitary respnse t LH-RH in wmen with secndary amenrrhea. J Clin Endcrinl Metab 40:601, Vigersky RA, Lriaux DL, Andersen AE, Mecklenburg RS, Vaitukaitis JL: Delayed pituitary hrmne respnse t LRF and TRF in patients with anrexia nervsa and with secndary amenrrhea assciated with simple weight lss. J Clin Endcrinl Metab 43:893, Sherman BM, Halmi KA, Zamudi R: LH and FSH respnse t gnadtrpin-releasing hrmne in anrexia nervsa: effect f nutritinal rehabilitatin. J Clin Endcrinl Metab 41:135, Beumnt PJV, Gerge GCW, Pimstne BL, Vinik AI: Bdy weight and the pituitary respnse t hypthalamic releasing hrmnes in patients with anrexia nervsa. J Clin Endcrinl Metab 43:487, McArthur JW, O'Lughlin KM, Beitins IZ, Jhnsn L, Hurihan J, Alns C: Endcrine studies during the refeeding f yung wmen with nutritinal amenrrhea and infertility. May Clin Prc 51:607, Bates et ai. Reprductive failure in wmen Fertility and Sterility