Skip to main content Accessibility help
×
Hostname: page-component-78c5997874-xbtfd Total loading time: 0 Render date: 2024-11-17T18:12:36.998Z Has data issue: false hasContentIssue false

39 - Nutritional amenorrhoea: long-term sequelae

from Part III - Management of specific disorders

Published online by Cambridge University Press:  04 May 2010

Joanna L. Fried
Affiliation:
Columbia Presbyterian Medical Center, New York, USA
Russalind Ramos
Affiliation:
Columbia Presbyterian Medical Center, New York, USA
Michelle P. Warren
Affiliation:
Columbia Presbyterian Medical Center, New York, USA
Adam H. Balen
Affiliation:
Leeds Teaching Hospitals, University Trust
Sarah M. Creighton
Affiliation:
University College London Hospitals
Melanie C. Davies
Affiliation:
University College London
Jane MacDougall
Affiliation:
Addenbrooke's Hospital, Cambridge
Richard Stanhope
Affiliation:
Great Ormond Street Hospital
Get access

Summary

Introduction

The amenorrhoea associated with energy deficit or nutritional imbalance has far-reaching long-term effects, including reduced bone density, stress fractures, osteopenia, osteoporosis, and infertility. This can be illustrated by referring to EG, a 54-year-old woman. She is a former professional ballet dancer who has performed on stages all over the world. Today, she relies on a walker in order to get from place to place. After a lifelong struggle with anorexia nervosa, she suffers from severe osteoporosis. She has suffered numerous fractures in the last 20 years and today her bone mineral density (BMD) is comparable to that of an 80-year-old woman. This is an extreme, though not uncommon, result of long-term nutritionally induced amenorrhoea.

Figure 39.1 shows the BMD scans for three women: a normal 25-year-old woman with regular periods; a 25-year-old woman who has had amenorrhoea for 5 years and has 30% lower total bone mass than most women her age; and a woman in her thirties with a 15 year history of amenorrhoea and osteoporotic bones.

There are a number of different environmental stressors thought to be associated with hypothalamic amenorrhoea (HA). Reproductive function may be affected by weight loss, exercise, nutritional deprivation or emotional stress. Recent research suggests that it may be an adaptive response to chronic low energy intake, and that metabolic factors may mediate reproductive adaptations in response to nutritional insults.

Type
Chapter
Information
Paediatric and Adolescent Gynaecology
A Multidisciplinary Approach
, pp. 522 - 532
Publisher: Cambridge University Press
Print publication year: 2004

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abraham, S F, Beumont, P J V, Fraser, I S, Llewellyn-Jones, D (1982). Body weight, exercise and menstrual status among ballet dancers in training. Br J Obstet Gynaecol 89, 507–510CrossRefGoogle ScholarPubMed
Al-Othman, F NWarren, M P (1998). Exercise, the menstrual cycle, and reproduction. Infertil Reprod Med Clin North Am 9, 667–687Google Scholar
Arnaud, C D (1996). Osteoporosis: Using ‘bone markers’ for diagnosis and monitoring. Geriatrics 51, 24–30Google ScholarPubMed
Bachrach, L K, Katzman, D K, Litt, I F, Guido, D, Marcus, R (1991). Recovery from osteopenia in adolescent girls with anorexia nervosa. J Clin Endocrinol Metab 72, 602–606CrossRefGoogle ScholarPubMed
Barash, I A, Cheung, C, Weigle, D S et al. (1996). Leptin is a metabolic signal to the reproductive system. Endocrinology 137, 3144–3147CrossRefGoogle ScholarPubMed
Barr, S I, McKay, H A (1998). Nutrition, exercise, and bone status in youth. Int J Sports Med 8, 124–142Google ScholarPubMed
Bass S L, Myburgh K H (2000). The role of exercise in the attainment of peak bone mass and bone strength. In Contemporary Endocrinology: Sports Endocrinology, Warren M P, Constantini N W, eds., pp. 253–280. Humana Press, Totowa, NJ
Beaumont, P J V, George, G C W, Pimstone, B L, Vinik, A L (1976). Body weight and pituitary response to hypothalamic releasing hormone in patients with anorexia nervosa. J Clin Endocrinol Metab 43, 487CrossRefGoogle Scholar
Bennell, K L, Malcolm, S A, Wark, J D et al. (1997). Skeletal effects of menstrual disturbances in athletes. Scand J Med Sci Sports 7, 261–273CrossRefGoogle ScholarPubMed
Biller, B M K, Saxe, V, Herzog, D B, Rosenthal, D I, Holzman, S, Klibanski, A (1989). Mechanisms of osteoporosis in adult and adolescent women with anorexia nervosa. J Clin Endocrinol Metab 68, 548–554CrossRefGoogle ScholarPubMed
Boyar R M, Bradlow H L (1977). Studies of testosterone metabolism in anorexia nervosa. In Anorexia Nervosa, Vigersky R, ed., p. 271. Raven Press, New York
Boyar, R M, Hellman, L D, Roffwarg, H et al. (1977). Cortisol secretion and metabolism in anorexia nervosa. N Engl J Med 296, 190–193CrossRefGoogle ScholarPubMed
Brooks-Gunn, J, Warren, M P, Hamilton, L H (1987). The relation of eating problems and amenorrhea in ballet dancers. Med Sci Sports Exerc 19, 41–44CrossRefGoogle ScholarPubMed
Brotman, A W, Stern, T A (1985). Osteoporosis and pathological fractures in anorexia nervosa. Am J Psychiatry 142, 495–496Google ScholarPubMed
Bruni, V, Dei, M, Vicini, I, Beninato, L, Magnani, L (2000). Estrogen replacement therapy in the management of osteopenia related to eating disorders. Ann N Y Acad Sci 900, 416–421CrossRefGoogle ScholarPubMed
Bulik, C M, Sullivan, P F, Fear, J L, Pickering, A, Dawn, A, McCullin, M (1999). Fertility and reproduction in women with anorexia nervosa: a controlled study. J Clin Psychiatry 60, 130–135CrossRefGoogle ScholarPubMed
Cann, C E, Martin, M C, Genant, H K, Jaffe, R B (1984). Decreased spinal mineral content in amenorrheic women. J Am Med Assoc 251, 626–629CrossRefGoogle ScholarPubMed
Cheung, C C, Clifton, D K, Steiner, R A (1997). Proopiomelanocortin neurons are direct targets for leptin in the hypothalamus. Endocrinology 138, 4489–4492CrossRefGoogle ScholarPubMed
Constantini N W, Warren M P (1994). Physical activity, fitness, and reproductive health in women: clinical observations. In Physical Activity, Fitness, and Health: International Proceedings and Consensus Statement Bouchard C, Shephard R J, Stephens T, eds., pp. 955–966. Human Kinetics, Champaign
Conti, J, Abraham, S, Taylor, A (1998). Eating behavior and pregnancy outcome. J Psychosom Res 44, 465–477CrossRefGoogle ScholarPubMed
Couzinet, B, Young, J, Brailly, S, Bouc, Y, Chanson, P, Schaison, G (1999). Functional hypothalamic amenorrhoea: a partial and reversible gonadotrophin deficiency of nutritional origin. Clin Endocrinol 50, 229–235CrossRefGoogle ScholarPubMed
Dhuper, S, Warren, M P, Brooks-Gunn, J, Fox, R P (1990). Effects of hormonal status on bone density in adolescent girls. J Clin Endocrinol Metab 71, 1083–1088CrossRefGoogle Scholar
Ding, J H, Sheckter, C B, Drinkwater, B L, Soules, M R, Bremner, W J (1988). High serum cortisol levels in exercise-associated amenorrhea. Ann Intern Med 108, 530–534CrossRefGoogle ScholarPubMed
Drinkwater, B L, Nilson, K, Chesnut, C H, III, Bremner, W J, Shainholtz, S, Southworth, M B (1984). Bone mineral content of amenorrheic and eumenorrheic athletes. N Eng J Med 311, 277-281CrossRefGoogle ScholarPubMed
Ducy, P, Amling, M, Takeda, S et al. (2000). Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell 100, 197–207CrossRefGoogle ScholarPubMed
Falk, J R, Halmi, K A (1982). Amenorrhea in anorexia nervosa: examination of the critical body weight hypothesis. Biol Psychiatry 17, 799–806Google ScholarPubMed
Ferin M, Jewelewicz R, Warren M P (1993). The Menstrual Cycle, Oxford University Press, New York
Fisher, E C, Nelson, M E, Frontera, W R et al. (1986). Bone mineral content and levels of gonadotropins and estrogen in amenorrheic running women. J Clin Endocrinol Metab 62, 1232–1236CrossRefGoogle ScholarPubMed
Fohlin, L (1975). Exercise, performance, and body dimensions in anorexia nervosa before and after rehabilitation. Acta Med Scand 204, 61CrossRefGoogle Scholar
Fowler, P B S, Banim, S O, Ikram, H (1972). Prolonged ankle reflex in anorexia nervosa. Lancet , 307CrossRefGoogle Scholar
Franko, D L, Walton, B E (1993). Pregnancy and eating disorders: a review and clinical implications. Int J Eat Disord 13, 41–473.0.CO;2-L>CrossRefGoogle ScholarPubMed
Fritz, M A, Speroff, L (1983). Current concepts of the endocrine characteristics of normal menstrual function: the key to diagnosis and management of menstrual disorders. Clin Obstet Gynecol 26, 647–689CrossRefGoogle ScholarPubMed
Genazzani, A R, Petraglia, F, Bernardi, F et al. (1998). Circulating levels of allopregnanolone in humans: gender, age, and endocrine influences. J Clin Endocrinol Metab 83, 2099–2103CrossRefGoogle ScholarPubMed
Gibson, J H, Mitchell, A, Reeve, J, Harries, M G (1999). Treatment of reduced bone mineral density in athletic amenorrhea: a pilot study. Osteoporos Int 10, 284–289CrossRefGoogle ScholarPubMed
Gordon, C M, Grace, E, Emans, S J, Goodman, E, Crawford, M H, Leboff, M S (1999). Changes in bone turnover markers and menstrual function after short-term oral DHEA in young women with anorexia nervosa. J Bone Min Res 14, 136–145CrossRefGoogle ScholarPubMed
Grinspoon, S, Baum, H, Lee, K, Anderson, E, Herzog, D, Klibanski, A (1996). Effects of short-term recombinant human insulin-like growth factor I administration on bone turnover in osteopenic women with anorexia nervosa. J Clin Endocrinol Metab 81, 3864–3870Google Scholar
Grinspoon, S, Miller, K K, Coyle, C (1999). Severity of osteopenia in estrogen-deficient women with anorexia nervosa and hypothalamic amenorrhea. J Clin Endcrinol Metab 68, 402–411Google Scholar
Hamann, A, Matthaei, S (1996). Regulation of energy balance by leptin. Exp Clin Endocrinol Diabetes 104, 293–300CrossRefGoogle ScholarPubMed
Hartman, D, Crisp, A, Rooney, B, Rackow, C, Atkinson, R, Patel, S (1999). Bone density of women who have recovered from anorexia nervosa. Int J Eat Disord 28, 107–1123.0.CO;2-M>CrossRefGoogle Scholar
Hay, P, Delahunt, J W, Hall, A, Mitchell, A W, Harper, G, Salmond, C (1992). Predictors of osteopenia in premenopausal women with anorexia nervosa. Calcif Tissue Int 50, 498–501CrossRefGoogle ScholarPubMed
Hergenroeder, A C, Smith, O'Brian E, Shypailo, R et al. (1997). Bone mineral changes in young women with hypothalamic amenorrhea treated with oral contraceptives, medroxyprogesterone, or placebo over 12 months. Am J Obstet Gynecol 176, 1017–1025CrossRefGoogle ScholarPubMed
Jonnavithula, S, Warren, M P, Fox, R P, Lazaro, M I (1993). Bone density is compromised in amenorrheic women despite return of menses: A 2-year study. Obstet Gynecol 81, 669–674Google ScholarPubMed
Kanders, B, Dempster, D W, Lindsay, R (1988). Interaction of calcium nutrition and physical activity on bone mass in young women. J Bone Miner Res 3, 145–149CrossRefGoogle Scholar
Katz, J L, Boyar, R M, Roffwarg, H, Hellman, L, Weiner, H (1978). Weight and circadian luteinizing hormone secretory pattern in anorexia nervosa. Psychosom Med 40, 549–567CrossRefGoogle ScholarPubMed
Kaufman, B A, Warren, M P, Dominguez, J L, Wang, J, Heymsfield, S B, Pierson, R N (2002). Bone density and amenorrhea in ballet dancers is related to a decreased resting metabolic rate. J Clin Endocrinol Metab 87, 2777–2783CrossRefGoogle ScholarPubMed
Khan, K M, Warren, M P, Stiehl, A, McKay, H A, Wark, J D (1999). Bone mineral density in active and retired ballet dancers. J Dance Med Science 3, 15–23Google Scholar
Kiyohara, K, Tamai, H, Takaichi, Y, Nakagawa, T, Kumagai, L F (1989). Decreased thyroidal triiodothyronine secretion in patients with anorexia nervosa: influence of weight recovery. Am J Clin Nutrit 50, 767–772CrossRefGoogle ScholarPubMed
Klibanski, A, Biller, B M K, Schoenfeld, D A, Herzog, D B, Saxe, V C (1995). The effects of estrogen administration on trabecular bone loss in young women with anorexia nervosa. J Clin Endocrinol Metab 80, 898–904Google ScholarPubMed
Kohmura, H, Miyake, A, Aono, T, Tanizawa, O (1986). Recovery of reproductive function in patients with anorexia nervosa: A 10-year follow up study. Eur J Obstet Gynaecol Reprod Biol 22, 293–296CrossRefGoogle ScholarPubMed
Kopp, W, Blum, W F, Prittwitz, S et al. (1997). Low leptin levels predict amenorrhea in underweight and eating disordered females. Mol Psychiatry 2, 335–340CrossRefGoogle ScholarPubMed
Kreipe, R E (1992). Bones of today, bones of tomorrow. [Editorial]. Am J Dis Child 146, 22–25Google Scholar
Kreipe, R E, Forbes, G B (1990). Osteoporosis: a ‘new morbidity’ for dieting female adolescents?Pediatrics 86, 478–480Google Scholar
Kreipe, R E, Churchill, B H, Strauss, J (1989a). Long-term outcome of adolescents with anorexia nervosa. Am J Dis Child 143, 1322–1327Google Scholar
Kreipe, R E, Strauss, J, Hodgeman, C H, Ryan, R M (1989b). Menstrual cycle abnormalities and subclinical eating disorders: a preliminary report. Psychosom Med 51, 81–86CrossRefGoogle Scholar
Kreipe, R E, Hicks, D G, Rosier, R N, Puzas, J E (1993). Preliminary findings on the effects of sex hormones on bone metabolism in anorexia nervosa. J Adolesc Health 14, 319–324CrossRefGoogle Scholar
Laughlin, G A (1999). The role of nutrition in the etiology of functional hypothalamic amenorrhea. Curr Opin Endocr Diabetes 6, 38–43CrossRefGoogle Scholar
Laughlin, G A, Yen, S S C (1996). Nutritional and endocrine: metabolic aberrations in amenorrheic athletes. J Clin Endocrinol Metab 81, 4301–4309Google ScholarPubMed
Laughlin, G A, Yen, S S C (1997). Hypoleptinemia in women athletes: absence of a diurnal rhythm with amenorrhea. J Clin Endocrinol Metab 82, 318–321CrossRefGoogle ScholarPubMed
Laughlin, G A, Dominguez, C E, Yen, S S C (1998). Nutritional and endocrine-metabolic aberrations in women with functional hypothalamic amenorrhea. J Clin Endcrinol Metab 83, 25–32Google ScholarPubMed
Legradi, G, Emerson, C H, Ahima, R S, Flier, J S, Lechan, R M (1997). Leptin prevents fasting-induced suppression of prothyrotropin-releasing hormone messenger ribonucleic acid in neurons of the hypothalamic paraventricular nucleus. Endocrinology 138, 2569–2576CrossRefGoogle ScholarPubMed
Legradi, G, Emerson, C H, Ahima, R S, Rand, W M, Flier, J S, Lechan, R M (1998). Arcuate nucleus ablation prevents fasting-induced suppression of proTRH mRNA in the hypothalamic paraventricular nucleus. Neuroendocrinology 68, 89–97CrossRefGoogle ScholarPubMed
Leibel, R L, Rosenbaum, M, Hirsch, J (1995). Changes in energy expenditure resulting from altered body weight. N Engl J Med 333, 343–347Google Scholar
Lindberg, J S, Fears, W B, Hunt, M M, Powell, M R, Boll, D, Wade, C E (1984). Exercise-induced amenorrhea and bone density. Ann Intern Med 101, 647–648CrossRefGoogle ScholarPubMed
Lloyd, S J, Triantafyllou, S J, Baker, E R et al. (1986). Women athletes with menstrual irregularity have increased musculoskeletal injuries. Med Sci Sports Exerc 18, 374–379CrossRefGoogle ScholarPubMed
Locke, R J, Warren, M P (2000). How to prevent bone loss in women with hypothalamic amenorrhea. Womens Health Primary Care 3, 270–278Google Scholar
Loucks, A B, Heath, E M (1994). Induction of low-T3 syndrome in exercising women occurs at a threshold of energy availability. Am J Physiol 266, R817–R823Google Scholar
Loucks, A B, Mortola, J F, Girton, L, Yen, S S C (1989). Alterations in the hypothalamic—pituitary—ovarian and the hypothalamic—pituitary—adrenal axes in athletic women. J Clin Endocrinol Metab 68, 402–411CrossRefGoogle ScholarPubMed
Loucks A B, Brown R, King K, Thuma J R, Verdun M (1995). A combined regimen of moderate dietary restriction and exercise training alters luteinizing hormone pulsatility in regularly menstruating young women. In Proceedings of the 77th Endocrine Society Annual Meeting Washington DC, pp. 558–558
Macut, D, Micic, D, Pralong, F P, Bischof, P, Campana, A (1998). Is there a role for leptin in human reproduction?Gynecol Endocrinol 12, 321–326CrossRefGoogle Scholar
Maffei, M, Halaas, J, Ravussin, E et al. (1995). Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med 1, 1155–1161CrossRefGoogle ScholarPubMed
Marcus, R, Cann, C E, Madvig, P et al. (1985). Menstrual function and bone mass in elite women distance runners. Ann Intern Med 102, 158–163CrossRefGoogle ScholarPubMed
Mecklenburg, R S, Loriaux, D L, Thompson, R H (1974). Hypothalamic dysfunction in patients with anorexia nervosa. Medicine 53, 147CrossRefGoogle ScholarPubMed
Miller, K K, Parulekar, M S, Schoenfeld, E et al. (1998). Decreased leptin levels in normal weight women with hypothalamic amenorrhea: the effects of body composition and nutritional insults. J Clin Endocrinol Metab 83, 2309–2312Google Scholar
Miller K K, Klibanski A, Grinspoon S K (2001). Androgen deficiency in women with anorexia nervosa. In Proceedings of the 83rd Endocrine Society Annual Meeting, pp. 394–394
Moshang T Jr, Utiger R D (1977). Low triiodothyronine euthyroidism in anorexia nervosa. In Anorexia Nervosa Vigersky R, ed., p. 263. Raven Press, New York
Myerson, M, Gutin, B, Warren, M P et al. (1987). Energy balance of amenorrhea and eumenorrheic runners. Med Sci Sports Exer 19(Suppl.), S37CrossRefGoogle Scholar
Myerson, M, Gutin, B, Warren, M P et al. (1991). Resting metabolic rate and energy balance in amenorrheic and eumenorrheic runners. Med Sci Sports Exer 23, 15–22CrossRefGoogle ScholarPubMed
Nagatani, S, Guthikonda, P, Thompson, R C, Tsukamura, H, Maeda, K I, Foster, D L (1998). Evidence for GnRH regulation by leptin: leptin administration prevents reduced pulsatile LH secretion during fasting. Neuroendocrinology 67, 370–376CrossRefGoogle ScholarPubMed
Newman, M M, Halmi, K A (1988). The endocrinology of anorexia nervosa and bulimia nervosa. Neurol Clin 6, 195–212Google ScholarPubMed
Ott, S M (1990). Editorial: Attainment of peak bone mass. J Clin Endocrinol Metab, 71, 1082A–1082CGoogle ScholarPubMed
Pettersson, F, Fries, H, Nillius, S J (1973). Epidemiology of secondary amenorrhea: Incidence and prevalence rates. Am J Obstet Gynecol 7, 80–86CrossRefGoogle Scholar
Pettersson, U, Stalnacke, B, Ahlenius, G, Henriksson-Larsen, K, Lorentzon, R (1999). Low bone mass density at multiple skeletal sites, including the appendicular skeleton in amenorrheic runners. Calcif Tissue Int 64, 117–125CrossRefGoogle ScholarPubMed
Pirke, K M, Fichter, M M, Chlond, C et al. (1987). Disturbances of the menstrual cycle in bulimia nervosa. Clin Endocrinol 27, 245–251CrossRefGoogle ScholarPubMed
Prior, J C, Vigna, Y M, Schechter, M T, Burgess, A E (1990). Spinal bone loss and ovulatory disturbances. N Engl J Med 323, 1221–1227CrossRefGoogle ScholarPubMed
Riggs, B L, Eastell, R (1986). Exercise, hypogonadism and osteopenia. J Am Med Assoc 256, 392–393CrossRefGoogle ScholarPubMed
Rigotti, N A, Nussbaum, S R, Herzog, D B, Neer, R M (1984). Osteoporosis in women with anorexia nervosa. N Engl J Med 311, 1601–1606CrossRefGoogle ScholarPubMed
Rigotti, N A, Neer, R M, Skates, S J, Herzog, D B, Nussbaum, S R (1991). The clinical course of osteoporosis in anorexia nervosa: A longitudinal study of cortical bone mass. J Am Med Assoc 265, 1133–1138CrossRefGoogle ScholarPubMed
Rutherford, O M (1993). Spine and total body bone mineral density in amenorrheic endurance athletes. J Applied Physiol 74, 2904–2908CrossRefGoogle ScholarPubMed
Salisbury, J J, Mitchell, J E (1991). Bone mineral density and anorexia nervosa in women. Am J Psychiatry 148, 768–774Google ScholarPubMed
Salisbury, J J, Levine, A S, Crow, S J, Mitchell, J E (1995). Refeeding, metabolic rate, and weight gain in anorexia nervosa: a review. Int J Eat Disord 17, 337–3453.0.CO;2-Q>CrossRefGoogle ScholarPubMed
Schweiger, U (1991). Menstrual function and luteal-phase deficiency in relation to weight changes and dieting. Clin Obstet Gynecol 34, 191–197CrossRefGoogle ScholarPubMed
Schweiger, U, Laessle, R, Pfister, H et al. (1987). Diet-induced menstrual irregularities: effects of age and weight loss. Fertil Steril 48, 746–751CrossRefGoogle ScholarPubMed
Schweiger, U, Tuschl, R J, Platte, P, Broocks, A, Laessle, R G, Pirke, K M (1992). Everyday eating behavior and menstrual function in young women. Fertil Steril 57, 771–775CrossRefGoogle ScholarPubMed
Singh, K B (1981). Menstrual disorders in college students. Am J Obstet Gynecol 1210, 299–302CrossRefGoogle Scholar
Smith E L, Gilligan C (1994). Bone Concerns. In Women and Exercise: Physiology and Sports Medicine, Shangold M M, Mirkin G, eds., pp. 89–101. F. A. Davis, Philadelphia, PA
Soyka, L A, Grinspoon, S, Levitsky, L L, Herzog, D B, Klibanski, A (1999). The effects of anorexia nervosa on bone metabolism in female adolescents. J Clin Endcrinol Metab 84, 4489–4496Google Scholar
Tsafriri, A, Dekel, N, Bar-Ami, S (1982). The role of oocyte maturation inhibitor in follicular regulation of oocyte maturation. J Reprod Fertil 64, 541–551CrossRefGoogle ScholarPubMed
Tuschl, R J, Platte, P, Laessle, R G, Stichler, W, Pirke, K M (1990). Energy expenditure and every day eating behavior in healthy young women. Am J Clin Nutrit 52, 81–86CrossRefGoogle Scholar
Binsbergen, C J M, Bennink, Coelingh H J T, Odink, J, Haspels, A A, Koppeschaar, H P F (1990). A comparative and longitudinal study on endocrine changes related to ovarian function in patients with anorexia nervosa. J Clin Endocrinol Metab 71, 705–711CrossRefGoogle ScholarPubMed
Vigersky, R A, Andersen, A E, Thompson, R H, Loriaux, D L (1977). Hypothalamic dysfunction in secondary amenorrhea associated with simple weight loss. N Engl J Med 297, 1141–1145CrossRefGoogle ScholarPubMed
Warren, M P (1980). The effects of exercise on pubertal progression and reproductive function in girls. J Clin Endocrinol Metab 51, 1150–1157CrossRefGoogle ScholarPubMed
Warren, M P (1983). The effects of undernutrition on reproductive function in the human. Endocr Rev 4, 363–377CrossRefGoogle ScholarPubMed
Warren M P, Shangold M M (1997). Sports gynecology: Problems and Care of the Athletic Female, Blackwell Science, Cambridge, MA
Warren, M P, Wiele, R L (1973). Clinical and metabolic features of anorexia nervosa. Am J Obstet Gynecol 117, 435–449CrossRefGoogle ScholarPubMed
Warren, M P, Jewelewicz, R, Dyrenfurth, I, Ans, R, Khalaf, S, Wiele, R L (1975). The significance of weight loss in the evaluation of pituitary response to LH-RH in women with secondary amenorrhea. J Clin Endocrinol Metab 40, 601–611CrossRefGoogle ScholarPubMed
Warren, M P, Brooks-Gunn, J, Hamilton, L H, Warren, L F, Hamilton, W G (1986). Scoliosis and fractures in young ballet dancers: Relation to delayed menarche and secondary amenorrhea. N Engl J Med 314, 1348–1353CrossRefGoogle ScholarPubMed
Warren, M P, Brooks-Gunn, J, Fox, R P et al. (1991). Lack of bone accretion and amenorrhea: Evidence for a relative osteopenia in weight bearing bones. J Clin Endocrinol Metab 72, 847–853CrossRefGoogle ScholarPubMed
Warren, M P, Holderness, C C, Lesobre, V, Tzen, R, Vossoughian, F, Brooks-Gunn, J (1994). Hypothalamic amenorrhea and hidden nutritional insults. J Soc Gynecol Invest 1, 84–88CrossRefGoogle ScholarPubMed
Warren, M P, Voussoughian, F, Geer, E B, Hyle, E P, Adberg, C L, Ramos, R H (1999). Functional hypothalamic amenorrhea: hypoleptinemia and disordered eating. J Clin Endocrinol Metab 84, 873–877CrossRefGoogle ScholarPubMed
Warren, M P, Brooks-Gunn, J, Fox, R P et al. (2002). Osteopenia in exercise-induced amenorrhea using ballet dancers as a model: a longitudinal study. J Clin Endocrinol Metab 87, 3162–3168CrossRefGoogle Scholar
Wolman, R L, Clark, P, McNally, E, Harries, M, Reeve, J (1990). Menstrual state and exercise as determinants of spinal trabecular bone density in female athletes. Br Med J 301, 516–518CrossRefGoogle ScholarPubMed
Zanker, C L (1999). Bone metabolism in exercise associated amenorrhoea: the importance of nutrition. Br J Sports Med 33, 228–229Google ScholarPubMed
Zanker, C L, Swaine, I L (1998a). Bone turnover in amenorrhoeic and eumenorrhoeic distance runners. Scand J Med Sci Sports 8, 20–26CrossRefGoogle Scholar
Zanker, C L, Swaine, I L (1998b). The relationship between bone turnover, oestradiol, and energy balance in women distance runners. Br J Sports Med 32, 167–171CrossRefGoogle Scholar
Zhang, Y, Proenca, R, Maffei, M, Barone, M, Leopold, L, Friedman, J M (1994). Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425–432CrossRefGoogle ScholarPubMed
Zucker, L M, Zucker, T F (1961). Fatty, a new mutation in the rat. J Hered 52, 275–278CrossRefGoogle Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×