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The right weight: Body fat, menarche, and fertility
452
EDITORIAL COMMENTS
REFERENCES 1. Schiffman SS, Sattely-Miller EA, Zimmerman IA, et al. Taste perception of monosodium glutamate (MSG) in foods in young and elderly subjects. Physiol Behav 1994;56:265 2. Yamaguchi S. Basic properties of umami and effects on humans. Physiol Behav 1991;49:833 3. Bellisle F, Monneuse MO, Chabert M, et al. Monosodium glutamate as a palatability enhancer in the European diet. Physiol Behav 1991;49:869 4. Taliaferro PJ. Monosodium glutamate and the Chinese Restaurant Syndrome: a review of food additive safety. J Env Health 1995;57:8 5. Raiten DJ, Talbot JM, Fisher KD. Analysis of adverse reactions to monosodium glutamate (MSG). Prepared by Life Sciences Research Office, Federation of American Societies for Experimental Biology, 9650 Rockville Pike, Bethesda, Maryland 20814-3998 for Center for Food Safety and Applied Nutrition, Food and Drug Administration, Department of Health and Human Services, Washington, DC 20204 under FDA Contract No 223-92~2185 6. Stone B, Bachorik L. FASEB issues final report on MSG. FDA Talk Paper, August 11, 1995 7. JECFA (the Joint F A t / W H O Expert Committee on Food Additives). L-Glutamic acid and its ammonium, calcium, monosodium and potassium salts. Toxicological evaluation of certain food additives. WHO Food Additive Series 1988;22:97 8. SCF (Scientific Committee for Foods), Commission of the European Communities Food Science and Techniques Reports of the Scientific Committee for Food. Twenty-fifth series, EUR13416 EN, Luxembourg: Office of Official Publications of the European Communities, 1991
9. Kenney RA, Tidball CS. Human susceptibility to oral monosodium L-glutamate. Am J Clin Nutr 1972;25:140 10. Kenney, RA. Placebo-controlled studies of human reaction to oral monosodium L-glutamate. In: Filer LJ Jr., Garattini S, Kate MR, et al., eds. Glutamic acid: advances in biochemistry and physiology. New York: Raven Press, 1979:363 11. Kenney RA. Chinese restaurant syndrome [letter]. Lancet 1980; 1:311 12. Kenney RA. The Chinese restaurant syndrome: an anecdote revisited. Fd Chem Toxic 1986;24:351 13. Allen DH, Delohery J, Baker G. Monosodium L-glutamate-induced asthma. J Allergy Clin Immunol 1987;80:530 14. Germano P, Cohen SG, Hibbard V, et al. Assessment of bronchial hyperreactivity by methacholine challenge (MTC) in asthmatics before and after monosodium glutamate (MSG) administration. J Allergy Clin Immunol 1993;91:340 15. Germano P, Cohen SG, Hahn B, et al: An evaluation of clinical reactions to monosodium glutamate (MSG) in asthmatics using a blinded, placebo-controlled challenge. J Allergy Clin Immunol 1991;87:177 16. Schwartzstein RM, Kelleher M, Weinberger SE, et al. Airway effects of monosodium glutamate in subjects with chronic stable asthma. J Asthma 1987;24:167 17. Manning ME, Stevenson DD, Mathison DA. Reactions to aspirin and other nonsteroidal anti-inflammatory drugs. Anaphylax Anaphylac React 1992; 12:611 18. Fernstrom JD, Cameron JL, Fernstrom MH, et al. Short-term neuroendocrine effects of a large oral dose of monosodium glutamate in fasting male subjects. J Clin Endocrinol Metab 1996; 81:184
The Right Weight: Body Fat, Menarche, and Fertility Many well-trained athletes, ballet dancers, and women who diet excessively have primary or secondary amenorrhea. Menarche may be delayed until as late as age 19 or 20 y. Women who train moderately or who are regaining weight into the normal range may have a menstrual cycle that appears to be normal but actually has a shortened luteal phase or is anovulatory. These disruptions of reproductive ability are usually reversible, after varying periods of time, after weight gain, decreasing athletic activity, or both. Secondary amenorrhea occurs in dieting women when weight loss is in the range of 10-15% of normal weight for height, which is equivalent to a loss of about one third of body fat. These data suggested that a minimum level of body fat (i.e., stored, easily mobilized energy) is necessary for the onset and maintenance of regular ovulatory menstrual cycles. Obesity also is associated with amenorrhea. Too much fat and too little fat are therefore both associated with the disruption of reproductive ability of women.
* total water...percent is the fatness index.
I have proposed that these associations are causal and that the high percentage of body fat ( 2 6 - 2 8 % ) in the mature woman at the completion of growth may influence reproduction directly. The main function of the 16 kg of stored female fat, which is equivalent to 144,000 calories, may be to provide the energy for a pregnancy, which requires about 50,000 calories over and above normal metabolic requirements. Lactation requires from about 500-1000 calories per day; in premodem times, lactation was an essential part of reproduction. Infant survival is correlated with birth weight, and birth weight is correlated with the prepregnancy weight of the mother and, independently, her weight gain during pregnancy. A particular minimum ratio of fat-to-lean body mass is normally necessary for menarche and the maintenance of normal ovulatory cycles. These critical minimum weights for height are predicted from a fatness index,* total water as percent of body weight. Nomograms were published giving these pre-
EDITORIAL COMMENTS dicted weights, ~and they are now used clinically in the evaluation of nutritional amenorrhea and the restoration of fertility in underweight women. Four mechanisms are known on the influence of body fat on reproduction. First, adipose tissue converts androgens to estrogen by aromatization. A third of the circulating estrogen in premenopausal women is from this conversion. It is the main source of estrogen in postmenopausal women. Second, body weight, hence fatness, influences the direction of estrogen metabolism to more potent or less potent forms. Leaner women make more of the less potent forms (catechol estrogens). Third, obese women and young overweight girls have a diminished capacity to bind sex-hormone binding globulin. This results in an elevated percentage of free serum estradiol. Finally, adipose tissue can store steroid hormones. An indirect mechanism may be providing signals to the hypothalamus of abnormal control of temperature and changes in energy metabolism that accompany excessive leanness in women. The hypothalamus controls reproduction and food intake, temperature, water intake, and the emotions. Weight loss and excessive leanness is correlated with hypothalamic dysfunction resulting in abnormal gonadotropin secretion: there is an ageinappropriate secretory pattern resembling that of prepubertal children. The responses to gonadotropin releasing hormone are reduced in direct correlation with the amount of weight loss. A study of the long-term reproductive health of 2622 former college athletes compared with 2766 nonathletes showed that the former athletes had a significantly lower lifetime occurrence of breast cancer and cancers of the reproductive system than
453 the nonathletes. Over 82% of the former athletes began their training in high school or earlier. Their training was moderate and regular. Long term, the athletes may have had lower levels of estrogen because they were leaner and more of the estrogen was metabolized to the nonpotent form. Using magnetic resonance imaging for direct quantification of body fat showed that athletes who did not differ in body weight with nonathletes actually had 30-40% less fat than did the nonathletes. Muscles are heavy (80% water), so the body weight of an athlete does not necessarily indicate her (or his) body composition. Athletes had a more sensitive insulin response to a glucose tolerance test than controls. The insulin area under the curve of athletes and controls was significantly related to their total fat/total volume percentage, determined by magnetic resonance imaging. In accord with these relations on fatness and fertility are the recent findings on the "obese" gene that adipose tissue produces a protein hormone, leptin, that has receptors in the hypothalamus. Leptin controls appetite and energy metabolism and thus acts as a "lipostat," regulating body fat storage.
ROSE E. FRISCH, PI-ID Associate Professor of Population Sciences Emeritus Harvard School of Public Health Boston, Massachusetts, USA REFERENCE 1. Frisch RE, McArthurJW. Menstrualcycles: Fatness as a determinant of minimum weight for height necessary for their maintenance or onset. Science. 185, 949-951, 1974.
EDITORIAL COMMENTS
REFERENCES 1. Schiffman SS, Sattely-Miller EA, Zimmerman IA, et al. Taste perception of monosodium glutamate (MSG) in foods in young and elderly subjects. Physiol Behav 1994;56:265 2. Yamaguchi S. Basic properties of umami and effects on humans. Physiol Behav 1991;49:833 3. Bellisle F, Monneuse MO, Chabert M, et al. Monosodium glutamate as a palatability enhancer in the European diet. Physiol Behav 1991;49:869 4. Taliaferro PJ. Monosodium glutamate and the Chinese Restaurant Syndrome: a review of food additive safety. J Env Health 1995;57:8 5. Raiten DJ, Talbot JM, Fisher KD. Analysis of adverse reactions to monosodium glutamate (MSG). Prepared by Life Sciences Research Office, Federation of American Societies for Experimental Biology, 9650 Rockville Pike, Bethesda, Maryland 20814-3998 for Center for Food Safety and Applied Nutrition, Food and Drug Administration, Department of Health and Human Services, Washington, DC 20204 under FDA Contract No 223-92~2185 6. Stone B, Bachorik L. FASEB issues final report on MSG. FDA Talk Paper, August 11, 1995 7. JECFA (the Joint F A t / W H O Expert Committee on Food Additives). L-Glutamic acid and its ammonium, calcium, monosodium and potassium salts. Toxicological evaluation of certain food additives. WHO Food Additive Series 1988;22:97 8. SCF (Scientific Committee for Foods), Commission of the European Communities Food Science and Techniques Reports of the Scientific Committee for Food. Twenty-fifth series, EUR13416 EN, Luxembourg: Office of Official Publications of the European Communities, 1991
9. Kenney RA, Tidball CS. Human susceptibility to oral monosodium L-glutamate. Am J Clin Nutr 1972;25:140 10. Kenney, RA. Placebo-controlled studies of human reaction to oral monosodium L-glutamate. In: Filer LJ Jr., Garattini S, Kate MR, et al., eds. Glutamic acid: advances in biochemistry and physiology. New York: Raven Press, 1979:363 11. Kenney RA. Chinese restaurant syndrome [letter]. Lancet 1980; 1:311 12. Kenney RA. The Chinese restaurant syndrome: an anecdote revisited. Fd Chem Toxic 1986;24:351 13. Allen DH, Delohery J, Baker G. Monosodium L-glutamate-induced asthma. J Allergy Clin Immunol 1987;80:530 14. Germano P, Cohen SG, Hibbard V, et al. Assessment of bronchial hyperreactivity by methacholine challenge (MTC) in asthmatics before and after monosodium glutamate (MSG) administration. J Allergy Clin Immunol 1993;91:340 15. Germano P, Cohen SG, Hahn B, et al: An evaluation of clinical reactions to monosodium glutamate (MSG) in asthmatics using a blinded, placebo-controlled challenge. J Allergy Clin Immunol 1991;87:177 16. Schwartzstein RM, Kelleher M, Weinberger SE, et al. Airway effects of monosodium glutamate in subjects with chronic stable asthma. J Asthma 1987;24:167 17. Manning ME, Stevenson DD, Mathison DA. Reactions to aspirin and other nonsteroidal anti-inflammatory drugs. Anaphylax Anaphylac React 1992; 12:611 18. Fernstrom JD, Cameron JL, Fernstrom MH, et al. Short-term neuroendocrine effects of a large oral dose of monosodium glutamate in fasting male subjects. J Clin Endocrinol Metab 1996; 81:184
The Right Weight: Body Fat, Menarche, and Fertility Many well-trained athletes, ballet dancers, and women who diet excessively have primary or secondary amenorrhea. Menarche may be delayed until as late as age 19 or 20 y. Women who train moderately or who are regaining weight into the normal range may have a menstrual cycle that appears to be normal but actually has a shortened luteal phase or is anovulatory. These disruptions of reproductive ability are usually reversible, after varying periods of time, after weight gain, decreasing athletic activity, or both. Secondary amenorrhea occurs in dieting women when weight loss is in the range of 10-15% of normal weight for height, which is equivalent to a loss of about one third of body fat. These data suggested that a minimum level of body fat (i.e., stored, easily mobilized energy) is necessary for the onset and maintenance of regular ovulatory menstrual cycles. Obesity also is associated with amenorrhea. Too much fat and too little fat are therefore both associated with the disruption of reproductive ability of women.
* total water...percent is the fatness index.
I have proposed that these associations are causal and that the high percentage of body fat ( 2 6 - 2 8 % ) in the mature woman at the completion of growth may influence reproduction directly. The main function of the 16 kg of stored female fat, which is equivalent to 144,000 calories, may be to provide the energy for a pregnancy, which requires about 50,000 calories over and above normal metabolic requirements. Lactation requires from about 500-1000 calories per day; in premodem times, lactation was an essential part of reproduction. Infant survival is correlated with birth weight, and birth weight is correlated with the prepregnancy weight of the mother and, independently, her weight gain during pregnancy. A particular minimum ratio of fat-to-lean body mass is normally necessary for menarche and the maintenance of normal ovulatory cycles. These critical minimum weights for height are predicted from a fatness index,* total water as percent of body weight. Nomograms were published giving these pre-
EDITORIAL COMMENTS dicted weights, ~and they are now used clinically in the evaluation of nutritional amenorrhea and the restoration of fertility in underweight women. Four mechanisms are known on the influence of body fat on reproduction. First, adipose tissue converts androgens to estrogen by aromatization. A third of the circulating estrogen in premenopausal women is from this conversion. It is the main source of estrogen in postmenopausal women. Second, body weight, hence fatness, influences the direction of estrogen metabolism to more potent or less potent forms. Leaner women make more of the less potent forms (catechol estrogens). Third, obese women and young overweight girls have a diminished capacity to bind sex-hormone binding globulin. This results in an elevated percentage of free serum estradiol. Finally, adipose tissue can store steroid hormones. An indirect mechanism may be providing signals to the hypothalamus of abnormal control of temperature and changes in energy metabolism that accompany excessive leanness in women. The hypothalamus controls reproduction and food intake, temperature, water intake, and the emotions. Weight loss and excessive leanness is correlated with hypothalamic dysfunction resulting in abnormal gonadotropin secretion: there is an ageinappropriate secretory pattern resembling that of prepubertal children. The responses to gonadotropin releasing hormone are reduced in direct correlation with the amount of weight loss. A study of the long-term reproductive health of 2622 former college athletes compared with 2766 nonathletes showed that the former athletes had a significantly lower lifetime occurrence of breast cancer and cancers of the reproductive system than
453 the nonathletes. Over 82% of the former athletes began their training in high school or earlier. Their training was moderate and regular. Long term, the athletes may have had lower levels of estrogen because they were leaner and more of the estrogen was metabolized to the nonpotent form. Using magnetic resonance imaging for direct quantification of body fat showed that athletes who did not differ in body weight with nonathletes actually had 30-40% less fat than did the nonathletes. Muscles are heavy (80% water), so the body weight of an athlete does not necessarily indicate her (or his) body composition. Athletes had a more sensitive insulin response to a glucose tolerance test than controls. The insulin area under the curve of athletes and controls was significantly related to their total fat/total volume percentage, determined by magnetic resonance imaging. In accord with these relations on fatness and fertility are the recent findings on the "obese" gene that adipose tissue produces a protein hormone, leptin, that has receptors in the hypothalamus. Leptin controls appetite and energy metabolism and thus acts as a "lipostat," regulating body fat storage.
ROSE E. FRISCH, PI-ID Associate Professor of Population Sciences Emeritus Harvard School of Public Health Boston, Massachusetts, USA REFERENCE 1. Frisch RE, McArthurJW. Menstrualcycles: Fatness as a determinant of minimum weight for height necessary for their maintenance or onset. Science. 185, 949-951, 1974.