Skip to main content

Leptin and Hypothalamic Amenorrhea

  • Chapter
Leptin and Reproduction

Abstract

Amenorrhea is characterized by the lack of regular menstrual periods. It may be classified as primary or secondary in nature. Primary amenorrhea is a delay in menarche beyond the age of 14, if no secondary sexual characteristics have developed, and beyond the age of 16, if secondary sexual characteristics have developed (Sakala, 1997). Secondary amenorrhea is diagnosed when menstruation has been absent for more than 3 months, if menses were previously regular; or 6 months, if menses were irregular (Constantini and Warren, 1994). The causes of amenorrhea among premenopausal women are numerous, among them are premature ovarian failure, past contraceptive use, androgen excess, intensive physical training, nutritional restriction, and stress.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abraham, S. F., Beumont, P. J. V., Fraser, I. S., and Llewellyn-Jones, D. (1982). Body weight, exercise and menstrual status among ballet dancers in training. Br. J. Obstet. Gynaecol., 89, 507–510.

    Article  PubMed  CAS  Google Scholar 

  • Al-Othman, F. N. and Warren, M. P. (1998). Exercise, the menstrual cycle, and reproduction. Infertil. Reprod. Med. Clin. North Am., 9, 667–687.

    Google Scholar 

  • Arnaud, C. D. (1996). Osteoporosis: using “bone markers” for diagnosis and monitoring. Geriatrics, 51, 24–30.

    PubMed  CAS  Google Scholar 

  • Bachrach, L. K., Katzman, D. K., Litt, I. F., Guido, D., and Marcus, R. (1991). Recovery from osteopenia in adolescent girls with anorexia nervosa. J. Clin. Endocrinol. Metab., 72, 602–606.

    Article  PubMed  CAS  Google Scholar 

  • Baker, D., Roberts, R., and Towell, T. (2000). Factors predictive of bone mineral density in eating-disordered women: a longitudinal study. Int. J. Eat. Disord., 27, 29–35.

    Article  PubMed  CAS  Google Scholar 

  • Barr, S. I. and McKay, H. A. (1998). Nutrition, exercise, and bone status in youth. Int. J. Sports Med., 8, 124–142.

    Article  CAS  Google Scholar 

  • Bass, S. L. and Myburgh, K. H. (2000). The role of exercise in the attainment of peak bone mass and bone strength. In M. P. Warren and N. W. Constantini (Eds.). Contemporary Endocrinology: Sports Endocrinology, Humana Press Inc., Totowa, NJ, pp. 253–280.

    Chapter  Google Scholar 

  • Beaumont, P. J. V., George, G. C. W., Pimstone, B. L., and Vinik, A. L. (1976). Body weight and pituitary response to hypothalamic releasing hormone in patients with anorexia nervosa. J. Clin. Endocrinol. Metab., 43, 487.

    Article  Google 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, 261–273.

    Article  PubMed  CAS  Google Scholar 

  • Biller, B. M. K., Saxe, V., Herzog, D. B., Rosenthal, D. I., Holzman, S., and Klibanski, A. (1989). Mechanisms of osteoporosis in adult and adolescent women with anorexia nervosa. J. Clin. Endocrinol. Metab., 68, 548–554.

    Article  PubMed  CAS  Google Scholar 

  • Biller, B. M. K., Schoenfeld, D., and Klibanski, A. (1993). Premenopausal osteopenia: effects of estrogen administration (Abstract#1616). Endocrine Society Annual Meeting, 75, 454.

    Google Scholar 

  • Boyar, R. M. and Bradlow, H. L. (1977). Studies of testosterone metabolism in anorexia nervosa. In R. Vigersky (Ed.). Anorexia Nervosa. New York: Raven Press, p. 271.

    Google Scholar 

  • Boyar, R. M., Hellman, L. D., Roffwarg, H., Katz, J., Zumoff, B., O’Connor, J., Bradlow, H. L., and Fukushima, D. K. (1977). Cortisol secretion and metabolism in anorexia nervosa. N. Engl. J. Med., 296, 190–193.

    Article  PubMed  CAS  Google Scholar 

  • Boyar, R. M., Katz, J., Finkelstein, J. W., Kapen, S., Weiner, H., Weitzman, E. D., and Hellman, L. D. (1974). Anorexia nervosa: immaturity of the 24-hour luteinizing hormone secretory pattern. N. Engl. J. Med., 291, 861–865.

    Article  PubMed  CAS  Google Scholar 

  • Bronson, F. H. and Manning, J. M. (1991). The energetic regulation of ovulation: a realistic role for body fat. Biol. Reprod., 44, 945–950.

    Article  PubMed  CAS  Google Scholar 

  • Brooks-Gunn, J., Warren, M. P., and Hamilton, L. H. (1987). The relation of eating problems and amenorrhea in ballet dancers. Med. Sci. Sports Exerc., 79(1), 41–44.

    Google Scholar 

  • Brotman, A. W. and Stern, T. A. (1985). Osteoporosis and pathological fractures in anorexia nervosa. Am. J. Psychiatry., 142, 495–496.

    PubMed  CAS  Google Scholar 

  • Bruni, V., Dei, M., Vicini, I., Beninato, L., and Magnani, L. (2000). Estrogen replacement therapy in the man agement of osteopenia related to eating disorders. Ann. N. Y. Acad. Sci., Abstract, 900, 416–421.

    Article  CAS  Google Scholar 

  • Burguera, B., Hofbauer, L., Thomas, T., Gori, F., Evans, G., Khosla, S., Riggs, B., and Turner, R. (2001). Leptin reduces ovariectomy-induced bone loss in rats. Endocrinology, 142, 3546–3553.

    Article  PubMed  CAS  Google Scholar 

  • Cameron, J. L. (1989). Influence of nutrition on the hypothalamic-pituitary-gonadal axis in primates. In K. M. Pirke, W. Wuttke, and U. Schweiger (Eds.). The Menstrual Cycle and Its Disorders, Springer- Verlag, Heidelberg, pp. 66–78.

    Chapter  Google Scholar 

  • Cameron, J. L., Nosbisch, C., Helmreich, D. L., and Parfitt, D. B. (1990). Reversal of exercise-induced amenorrhea in female cynomolgus monkeys (Macaca fascicularis) by increasing food intake (Abstract #1042). Endocrine Society Annual Meeting, 72, 285.

    Google Scholar 

  • Carruth, B. R. and Skinner, J. D. (2000). Bone mineral status in adolescent girls: effects of eating disorders and exercise. J. Adolesc. Health., 26, 322–329.

    Article  PubMed  CAS  Google Scholar 

  • Cheung, C. C., Clifton, D. K., and Steiner, R. A. (1997). Proopiomelanocortin neurons are direct targets for leptin in the hypothalamus. Endocrinology, 138, 4489–4492.

    Article  PubMed  CAS  Google Scholar 

  • Cioffi, J., Shafer, A., and Zupancic, T. (1966). Novel B219/OB receptor isoforms: possible role of leptin in hematopoieses and reproduction. Nature Med., 2, 585–588.

    Google Scholar 

  • Constantini, N. W. and Warren, M. P. (1994). Physical activity, fitness, and reproductive health in women: clinical observations. In C. Bouchard, R. I. Shephard, and T. Stephens (Eds.). Physical Activity, Fitness, and Health: International Proceedings and Consensus Statement, Human Kinetics, Champaign, pp. 955–966.

    Google Scholar 

  • Couzinet, B., Young, J., Brailly, S., Le Bouc, Y., Chanson, P., and Schaison, G. (1999). Functional hypothalamic amenorrhoea: a partial and reversible gonadotrophin deficiency of nutritional origin. Clin. Endocrinol. (Oxf.), 50, 229–235.

    Article  CAS  Google Scholar 

  • Cumming, D. C. (1996). Exercise-associated amenorrhea, low bone density, and estrogen replacement therapy. Archives of Internal Medicine, 756(19), 2193–2195.

    Article  Google Scholar 

  • DeCree, C., Lewin, R., and Ostyn, M. (1988). Suitability of cyproterone acetate in the treatment of osteoporosis associated with athletic amenorrhea. Int. J. Sports Med., 9, 187–192.

    Article  CAS  Google Scholar 

  • Devlin, M. J., Walsh, B. T., Kral, J. G., Heymsfield, S. B., Pi-Sunyer, F. X., and Dantzic, S. (1990). Metabolic abnormalities in bulimia nervosa. Arch. Gen. Psychiatry 47, 144–148.

    Article  PubMed  CAS  Google Scholar 

  • Dhuper, S., Warren, M. P., Brooks-Gunn, J., and Fox, R. P. (1990). Effects of hormonal status on bone density in adolescent girls. J. Clin. Endocrinol. Metab., 71, 1083–1088.

    Article  PubMed  CAS  Google Scholar 

  • Ding, J. H., Sheckter, C. B., Drinkwater, B. L., Soules, M. R., and Bremner, W. J. (1988). High serum cortisol levels in exercise-associated amenorrhea. Ann. Intern. Med., 108, 530–534.

    PubMed  CAS  Google Scholar 

  • Drinkwater, B. L., Bruemner, B., and Chesnut, C. H., III (1990). Menstrual history as a determinant of current bone density in young athletes. JAMA, 263, 545–548.

    Article  PubMed  CAS  Google Scholar 

  • Drinkwater, B. L., Nilson, K., Chesnut, C. H., III, Bremner, W. J., Shainholtz, S., and Southworth, M. B. (1984). Bone mineral content of amenorrheic and eumenorrheic athletes. N. Engl. J. Med., 311(5), 277–281.

    Article  PubMed  CAS  Google Scholar 

  • Dubey, A. K., Cameron, J. L., Steiner, R. A., and Plant, T. M. (1986). Inhibition of gonadotropin secretion in castrated male rhesus monkeys (Macaca mulatta) induced by dietary restriction: analogy with the prepubertal hiatus of gonadotropin release. Endocrinology, 118, 518–525.

    Article  PubMed  CAS  Google Scholar 

  • Ducy, P., Amling, M., Takeda, S., Priemel, M., Schilling, A. F., Beil, F. T., Shen, J., Vinson, C., Rueger, J. M., and Karsenty, G. (2000). Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell, 100, 197–207.

    Article  PubMed  CAS  Google Scholar 

  • Falk, J. R. and Halmi, K. A. (1982). Amenorrhea in anorexia nervosa: examination of the critical body weight hypothesis. Biol. Psychiatry, 17, 799–806.

    PubMed  CAS  Google Scholar 

  • Feicht, C. B., Johnson, T. S., and Martin, B. J. (1978). Secondary amenorrhea in athletes. Lancet, 2, 1145–1146.

    Article  PubMed  CAS  Google Scholar 

  • Ferin, M., Jewelewicz, R., and Warren, M. P. (1993) The Menstrual Cycle. Oxford University Press, New York.

    Google Scholar 

  • 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, 1232–1236.

    Article  PubMed  CAS  Google Scholar 

  • Fohlin, L. (1975). Exercise, performance, and body dimensions in anorexia nervosa before and after rehabilitation. Acta. Med. Scand., 204, 61.

    Article  Google Scholar 

  • Fowler, P. B. S., Banim, S. O., and Ikram, H. (1972). Prolonged ankle reflex in anorexia nervosa. Lancet, 2, 307.

    Article  PubMed  CAS  Google Scholar 

  • Fritz, M. A. and 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, 647–689.

    Article  PubMed  CAS  Google Scholar 

  • Genazzani, A. R., Petraglia, F., Bernardi, F., Casarosa, E., Salvestroni, C., Tonetti, A., Nappi, R. E., Luisi, S., Palumbo, M., Purdy, R. H., and Luisi, M. (1998). Circulating levels of allopregnanolone in humans: gender, age, and endocrine influences. J. Clin. Endocrinol. Metab., 83, 2099–2103.

    Article  PubMed  CAS  Google Scholar 

  • Gibson, J. H., Mitchell, A., Reeve, J., and Harries, M. G. (1999). Treatment of reduced bone mineral density in athletic amenorrhea: a pilot study. Osteoporos. Int., 10, 284–289.

    Article  PubMed  CAS  Google Scholar 

  • Glass, A. R., Deuster, P. A., Kyle, S. B., Yahiro, J. A., Vigersky, R. A., and Schoomaker, E. B.(1987). Amenorrhea in Olympic marathon runners. Fertility and Sterility, 48, 740–745.

    PubMed  CAS  Google Scholar 

  • Gold, P., Gwirtsman, H., Avgerinos, P., Nieman, L., Gallucci, W., Kaye, W., Jimerson, D., Ebert, M., Rittmaster, R., Loriaux, L., and Chrousos, G. (1986). Abnormal hypothalamic-pituitary-adrenal function in anorexia nervosa. N. Engl. J. Med., 314, 1335–1342.

    Article  PubMed  CAS  Google Scholar 

  • Goulding, A. and Taylor, R. W. (1998). Plasma leptin values in relation to bone mass and density and to dynamic biochemical markers of bone resorption and formation in postmenopausal women. Calcif. Tissue Int., 63, 456–458.

    Article  PubMed  CAS  Google Scholar 

  • Grinspoon, S., Miller, K. K., and Coyle, C. (1999). Severity of osteopenia in estrogen-deficient women with anorexia nervosa and hypothalamic amenorrhea. J. Clin. Endcrinol. Metab., Abstract, 68, 402–411.

    Google Scholar 

  • Grinspoon, S., Thomas, E., Pitts, S., Gross, E., Mickley, D., Miller, K., Herzog, D., and Klibanski, A. (2000). Prevalence and predictive factors for regional osteopenia in women with anorexia nervosa. Ann. Intern. Med., 133, 790–794.

    PubMed  CAS  Google Scholar 

  • Hartman, D., Crisp, A., Rooney, B., Rackow, C., Atkinson, R., and Patel, S. (1999). Bone density of women who have recovered from anorexia nervosa. Int. J. Eat. Dis., Abstract, 28(1), 107–112.

    Article  Google Scholar 

  • Hay, P., Delahunt, J. W., Hall, A., Mitchell, A. W., Harper, G., and Salmond, C. (1992). Predictors of osteopenia in premenopausal women with anorexia nervosa. Calcif. Tissue Int., 50, 498–501.

    Article  PubMed  CAS  Google Scholar 

  • Helmreich, D. L., Mattern, L. G., and Cameron, J. L. (1993). Lack of a role of the hypothalamic-pituitaryadrenal axis in the fasting-induced suppression of luteinizing hormone secretion in adult male rhesus monkeys (Macaca mulatta). Endocrinology, 132, 2427–2437.

    CAS  Google Scholar 

  • Hergenroeder, A. C., O’Brian Smith, 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, 1017–1025.

    Article  PubMed  CAS  Google Scholar 

  • Hoggard, N., Hunter, L., Duncan, J. S., Williams, L. M., Trayhurn, P., and Mercer, J. G. (1997). Leptin and leptin receptor mRNA and protein expression in the murine fetus and placenta. Proc. Natl. Acod. Sci. USA, 94, 11073–11078.

    Article  CAS  Google Scholar 

  • Hotta, I., Shebasoki, K., Masuda, A., Imaki, T., Hiroshi, D., Ling, N., and Shizume, K. (1986) The responses of plasma adrenocorticotropin and cortisol to corticotropin releasing hormone (CRH) and cerebrospinal fluid immunoreactive CRH in anorexia nervosa patients. J. Clin. Endocrinol. Metab., 62, 319–324.

    Article  PubMed  CAS  Google Scholar 

  • Jonnavithula, S., Warren, M. P., Fox, R. P., and Lazaro, M. I. (1993). Bone density is compromised in amenorrheic women despite return of menses: a 2-year study. Obstet. Gynecol., 81, 669–674.

    PubMed  CAS  Google Scholar 

  • Kanders, B., Dempster, D. W., and Lindsay, R. (1988). Interaction of calcium nutrition and physical activity on bone mass in young women. J. Bone Miner. Res., 3(2), 145–149.

    Article  PubMed  CAS  Google Scholar 

  • Katz, J. L., Boyar, R. M., Roffwarg, H., Hellman, L., and Weiner, H. (1978). Weight and circadian luteinizing hormone secretory pattern in anorexia nervosa. Psychosom. Med., 40, 549–567.

    PubMed  CAS  Google Scholar 

  • Kaufman, B. A., Warren, M. P., Dominguez, J. E., Wang, J., Heymsfield, S. B., and Pierson, R. N. (2002). Bone density and amenorrhea in ballet dancers are related to a decreased resting metabolic rate and lower leptin levels. J. Clin. Endocrinol. Metab. 2002; 87(6): 2777–2783.

    Article  CAS  Google Scholar 

  • Khan, K. M., Warren, M. P., Stiehl, A., McKay, H. A., and Wark, J. D. (1999). Bone mineral density in active and retired ballet dancers. J. Dance Med. Sci., 3, 15–23.

    Google Scholar 

  • Kiyohara, K., Tamai, H., Takaichi, Y., Nakagawa, T., and Kumagai, L. F. (1989). Decreased thyroidal triiodothyronine secretion in patients with anorexia nervosa: influence of weight recovery. Am. J. Clin. Nutr., 50, 161–112.

    Google Scholar 

  • Klibanski, A., Biller, B. M. K., Schoenfeld, D. A., Herzog, D. B., and Saxe, V. C. (1995). The effects of estrogen administration on trabecular bone loss in young women with anorexia nervosa. J. Clin. Endocrinol. Metab., 80, 898–904.

    Article  PubMed  CAS  Google Scholar 

  • Kohmura, H., Miyake, A., Aono, T., and Tanizawa, O. (1986). Recovery of reproductive function in patients with anorexia nervosa: a 10-year follow up study. Eur. J. Obstet. Gynecol. Reprod. Biol. 22, 293–296.

    Article  PubMed  CAS  Google Scholar 

  • Kopp, W., Blum, W. F., von Prittwitz, S., Ziegler, A., Lubbert, H., Emons, G., Herzog, W., Herpertz, S., Deter, H. C, Remschmidt, H., and Hebebrand, J. (1997). Low leptin levels predict amenorrhea in underweight and eating disordered females. Mol. Psychiatry, 2, 335–340.

    Article  PubMed  CAS  Google Scholar 

  • Kreipe, R. E. (1992). Bones of today, bones of tomorrow (editorial). Am. J. Dis. Child, 146, 22–25.

    PubMed  CAS  Google Scholar 

  • Kreipe, R. E. and Forbes, G. B. (1990). Osteoporosis: a “new morbidity” for dieting female adolescents? Pediatrics 86, 478–480.

    PubMed  CAS  Google Scholar 

  • Kreipe, R. E., Churchill, B. H., and Strauss, J. (1989a). Long-term outcome of adolescents with anorexia nervosa. Am. J. Dis. Child, 143, 1322–1327.

    PubMed  CAS  Google Scholar 

  • Kreipe, R. E., Hicks, D. G., Rosier, R. N., and Puzas, J. E. (1993). Preliminary findings on the effects of sex hormones on bone metabolism in anorexia nervosa. J. Adolesc. Health, 14, 319–324.

    Article  PubMed  CAS  Google Scholar 

  • Kreipe, R. E., Strauss, J., Hodgeman, C. H., and Ryan, R. M. (1989b). Menstrual cycle abnormalities and subclinical eating disorders: a preliminary report. Psychosom. Med., 51, 81–86.

    PubMed  CAS  Google Scholar 

  • Laughlin, G. A. (1999). The role of nutrition in the etiology of functional hypothalamic amenorrhea. Curr. Opin. Endocrinol. Diabetes, 6, 38–43.

    Article  Google Scholar 

  • Laughlin, G. A. and Yen, S. S. C. (1997). Hypoleptinemia in women athletes: absence of a diurnal rhythm with amenorrhea. J. Clin. Endocrinol. Metab., 82, 318–321.

    Article  PubMed  CAS  Google Scholar 

  • Laughlin, G. A., Dominguez, C. E., and Yen, S. S. C. (1998). Nutritional and endocrine-metabolic aberrations in women with functional hypothalamic amenorrhea. J. Clin. Endcrinol. Metab., 83, 25–32.

    Article  CAS  Google Scholar 

  • Legradi, G., Emerson, C. H., Ahima, R. S., Flier, J. S., and 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, 2569–2576.

    Article  PubMed  CAS  Google Scholar 

  • Legradi, G., Emerson, C. H., Ahima, R. S., Rand, W. M., Flier, J. S., and Lechan, R. M. (1998). Arcuate nucleus ablation prevents fasting-induced suppression of proTRH mRNA in the hypothalamic paraventricular nucleus. Neuroendocrinology, 68, 89–97.

    Article  PubMed  CAS  Google Scholar 

  • Leibel, R. L., Rosenbaum, M., and Hirsch, J. (1995). Changes in energy expenditure resulting from altered body weight. N. Engl. J. Med., 332, 621–628.

    Article  PubMed  CAS  Google Scholar 

  • Lindberg, J. S., Fears, W. B., Hunt, M. M., Powell, M. R., Boll, D., and Wade, C. E. (1984). Exercise-induced amenorrhea and bone density. Ann. Intern. Med., 101, 647–648.

    PubMed  CAS  Google Scholar 

  • Lindsay, R., Cosman, F., Herrington, B. S., and Himmelstein, S. (1992). Bone mass and body composition in normal women. J. Bone Miner. Res., 7, 55–63.

    Article  PubMed  CAS  Google Scholar 

  • Liu, C, Grossman, A., Bain, S., Strchan, M., Puermner, D., Bailey, C, Humes, J., Lenox, J., Yamamoto, G., Sprugel, K., Kuijper, J., Weigle, S., Dumam, D., and Moore, E. (1997). Leptin stimulates cortical bone formation in obese (ob/ob) mice. J. Bone. Miner. Res., 12, S115.

    Article  Google Scholar 

  • Liu, J. H. (1998). Anovulation of CNS Origin. In B. R. Carr and R. E. Blackwell (Eds.). Textbook of Reproductive Medicine, Appleton and Lange, Stamford, CT, pp. 309–322.

    Google Scholar 

  • Lloyd, S. J., Triantafyllou, S. J., Baker, E. R., Houts, P. S., Whiteside, J. A., Kalenak, A., and Stumpf, P. (1986). Women athletes with menstrual irregularity have increased musculoskeletal injuries. Med. Sci. Sports Exert., 18(4), 374–379.

    CAS  Google Scholar 

  • Locke, R. J. and Warren, M. P. (2000). How to prevent bone loss in women with hypothalamic amenorrhea. Womens Health Primary Care, 3, 210–21S.

    Google Scholar 

  • Loucks, A. B. and Heath, E. M. (1994). Induction of low-T3 syndrome in exercising women occurs at a threshold of energy availability. Am. J. Physiol., 266, R817–R823.

    PubMed  CAS  Google Scholar 

  • Loucks, A. B., Brown, R., King, K., Thuma, J. R., and Verdun, M. (1995). A combined regimen of moderate dietary restriction and exercise training alters luteinizing hormone pulsatility in regularly menstruating young women. Endocrine Society Annual Meeting, Washington DC (June 14–17), Abstract, 558–558.

    Google Scholar 

  • Loucks, A. B., Mortola, J. F., Girton, L., and Yen, S. S. C. (1989). Alterations in the hypothalamic-pituitaryovarian and the hypothalamic-pituitary-adrenal axes in athletic women. J. Clin. Endocrinol. Metab., 68, 402–411.

    Article  PubMed  CAS  Google Scholar 

  • Macut, D., Micic, D., Pralong, F. P., Bischof, P., and Campana, A. (1998). Is there a role for leptin in human reproduction? Gynecol. Endocrinol., 12, 321–326.

    Article  PubMed  CAS  Google Scholar 

  • Maffei, M., Halaas, J., Ravussin, E., Pratley, R. E., Lee, G. H., Zhang, Y., Fei, H., Kim, S., Lallone, R., and Ranganathan, S. (1995). Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat. Med., 1, 1155–1161.

    Article  PubMed  CAS  Google Scholar 

  • Manolagas, S. C., and Jilka, R. L. (1995). Bone marrow, cytokines, and bone remodeling: Emerging insights into the pathophysiology of osteoporosis. N. Eng. J. Med., 332(5):305–311.

    Article  CAS  Google Scholar 

  • Marcus, R., Cann, C. E., Madvig, P., Minkoff, J., Goddard, M., Bayer, M., Martin, M. C., Gaudiani, L., Haskell, W., and Genant, H. K. (1985). Menstrual function and bone mass in elite women distance runners. Ann. Intern. Med., 102, 158–163.

    PubMed  CAS  Google Scholar 

  • Masuda, A., Shibasaki, T., Hotta, M., Yamauchi, N., Ling, N., Demura, H., and Shizume, K. (1990). Insulininduced hypoglycemia, L-dopa and arginine stimulate GH secretion through different mechanisms in man. Regul. Pept., 31, 53–64.

    Article  PubMed  CAS  Google Scholar 

  • Mecklenburg, R. S., Loriaux, D. L., and Thompson, R. H. (1974). Hypothalamic dysfunction in patients with anorexia nervosa. Medicine, 53, 147.

    Article  PubMed  CAS  Google Scholar 

  • Miller, K. K. and Klibanski, A. (1999). Amenorrheic bone loss. J. Clin. Endocrinol. Metab., 84, 1775–1783.

    Article  PubMed  CAS  Google Scholar 

  • Miller, K. K., Parulekar, M. S., Schoenfeld, E., Anderson, E., Hubbard, J., Klibanski, A., and Grinspoon, S. K. (1998). Decreased leptin levels in normal weight women with hypothalamic amenorrhea: the effects of body composition and nutritional insults. J. Clin. Endocrinol. Metab., 83, 2309–2312.

    Article  PubMed  CAS  Google Scholar 

  • Moshang, T., Jr. and Utiger, R. D. (1977). Low triiodothyronine euthyroidism in anorexia nervosa. In R. Vigersky (Ed.) Anorexia Nervosa. New York: Raven Press, p. 263.

    Google Scholar 

  • Moshang, T., Jr., Parks, J. S., Baker, L., Vaidya, V., Utiger, R. D., Bongiovanni, A. M., and Snyder, P. J. (1975). Low serum triiodothyronine in patients with anorexia nervosa. J. Clin. Endocrinol. Metab., 40, 470–473.

    Article  PubMed  Google Scholar 

  • Myerson, M., Gutin, B., Warren, M. P., May, M., Contento, I., Lee, M., Pierson, R. N., and Pi-Sunyer, F. X. (1987). Energy balance of amenorrhea and eumenorrheic runners. Med. Sci. Sports. Exert., Abstract, 19, S37.

    Article  Google Scholar 

  • Myerson, M., Gutin, B., Warren, M. P., May, M., Contento, I., Lee, M., Pi-Sunyer, F. X., Pierson, R. N., and Brooks-Gunn, J. (1991). Resting metabolic rate and energy balance in amenorrheic and eumenorrheic runners. Med. Sci. Sports. Exerc., 23(1), 15–22.

    PubMed  CAS  Google Scholar 

  • Nappi, R. E., Petraglia, F., Genazzani, A. D., D’Ambrogio, G., Zara, C., and Genazzani, A. R. (1993). Hypothalamic amenorrhea: evidence for a central derangement of hypothalamic-pituitary-adrenal cortex axis activity. Fertil. Steril., 59, 571–576.

    PubMed  CAS  Google Scholar 

  • Newman, M. M. and Halmi, K. A. (1988). The endocrinology of anorexia nervosa and bulimia nervosa. Neurol. Clin., 6, 195–212.

    PubMed  CAS  Google Scholar 

  • Newman, M. M., Halmi, K. A., and Marchi, P. (1987). Relationship of clinical factors to caloric requirements in subtypes of eating disorders. Biol. Psychiatry., 22, 1253–1263.

    Article  PubMed  CAS  Google Scholar 

  • Ogueh, O., Sooranna, S., Nicolaides, K. H., and Johnson, M. R. (2000). The relationship between leptin concentration and bone metabolism in the human fetus. J. Clin. Endocrinol. Metab., 85, 1997–1999.

    Article  PubMed  CAS  Google Scholar 

  • Okano, H., Mizunuma, H., Soda, M. Matsui, H., Honjo, S., and Ibuki, Y. (1995). Effects of exercise and amenorrhea on bone mineral density in teenage runners. Endocrine Journal, 42, 271–276.

    Article  PubMed  CAS  Google Scholar 

  • Olson, B. R., Cartledge, T., Sebring, N., Defensor, R., and Nieman, L. (1995). Short-term fasting affects luteinizing hormone secretory dynamics but not reproductive function in normal-weight sedentary women. J. Clin. Endocrinol. Metab, 80, 1187–1193.

    Article  PubMed  CAS  Google Scholar 

  • Ott, S. M. (1990). Editorial: attainment of peak bone mass. J. Clin. Endocrinol. Metab., 71, 1082A–1082C.

    Article  PubMed  CAS  Google Scholar 

  • Pettersson, F., Fries, H., and Nillius, S. J. (1973). Epidemiology of secondary amenorrhea: incidence and prevalence rates. Am. J. Obstet. Gynecol., 7, 80–86.

    Google Scholar 

  • Pettersson, U., Stalnacke, B., Ahlenius, G., Henriksson-Larsen, K., and Lorentzon, R. (1999). Low bone mass density at multiple skeletal sites, including the appendicular skeleton in amenorrheic runners. Calcif. Tissue Int., 64, 117–125.

    Article  PubMed  CAS  Google Scholar 

  • Pirke, K. M., Pahl, J., Schweiger, U., and Warnhoff, M. (1985). Metabolic and endocrine indices of starvation in bulimia: a comparison with anorexia nervosa. Psychiatry. Res., 15, 33–39.

    Article  PubMed  CAS  Google Scholar 

  • Platte, P., Pirke, K. M., Trimborn, P., Pietsch, K., Krieg, J. C., and Fichter, M. M. (1994). Resting metabolic rate and total energy expenditure in acute and weight recovered patients with anorexia nervosa and in healthy young women. Int. J. Eating. Disord., 16, 45–52.

    Article  CAS  Google Scholar 

  • Ponzo, O. J., Szwarcfarb, B., Rondina, D., Carbone, S., Reynoso, R., Scacchi, P., and Moguilevsky, J. A. (2001). Changes in the sensitivity of gonadotrophin axis to leptin during sexual maturation in female rats. Neuroendocrinol. Lett., 22, 427–431.

    PubMed  CAS  Google Scholar 

  • Powers, P. S. (1999). Osteoporosis and eating disorders. J. Pediatr. Adolesc. Gynecol., 12, 51–57.

    Article  PubMed  CAS  Google Scholar 

  • Prior, J. C. and Vigna, Y. M. (1985). Gonadal steroids in athletic women: contraception, complications and performance. Sports Med., 2, 287–295.

    Article  PubMed  CAS  Google Scholar 

  • Prior, J. C, Vigna, Y. M., Schechter, M. T., and Burgess, A. E. (1990). Spinal bone loss and ovulatory disturbances. N. Engl. J. Med., 323, 1221–1227.

    Article  PubMed  CAS  Google Scholar 

  • Rauch, F., Blum, W. F., Klein, K., Allolio, B., and Schonau, E. (1998). Does leptin have an effect on bone in adult women? Calcif. Tissue Int., 63, 453–455.

    Article  PubMed  CAS  Google Scholar 

  • Reseland, J. E., Syversen, U., Bakke, I., Qvigstad, G., Eide, L. G., Hjertner, O., Gordeladze, J. O., and Drevon, C. A. (2001). Leptin is expressed in and secreted from primary cultures of human osteoblasts and promotes bone mineralization. J. Bone Miner. Res., 16, 1426–1433.

    Article  PubMed  CAS  Google Scholar 

  • Riggs, B. L. and Eastell, R. (1986). Exercise, hypogonadism and osteopenia. JAMA, 256, 392–393.

    Article  PubMed  CAS  Google Scholar 

  • Rigotti, N. A., Neer, R. M., Skates, S. J., Herzog, D. B., and Nussbaum, S. R. (1991). The clinical course of osteoporosis in anorexia nervosa: a longitudinal study of cortical bone mass. JAMA, 265, 1133–1138.

    Article  PubMed  CAS  Google Scholar 

  • Rigotti, N. A., Nussbaum, S. R., Herzog, D. B., and Neer, R. M. (1984). Osteoporosis in women with anorexia nervosa. N. Engl. J. Med, 311, 1601–1606.

    Article  PubMed  CAS  Google Scholar 

  • Robinson, E., Bachrach, L. K., and Katzman, D. K. (2000). Use of hormone replacement therapy to reduce the risk of osteopenia in adolescent girls with anorexia nervosa. J. Adolesc. Health, 26, 343–348.

    Article  PubMed  CAS  Google Scholar 

  • Roth, J. C., Kelch, R. P., Kaplan, S. L., and Grumbach, M. M. (1972). FSH and LH response to luteinizing hormone-releasing factor in prepubertal and pubertal children, adult males and patients with hypogonadotropic and hypergonadotropic hypogonadism. J. Clin. Endocrinol. Metab., 35, 926–930.

    Article  PubMed  CAS  Google Scholar 

  • Rutherford, O. M. (1993). Spine and total body bone mineral density in amenorrheic endurance athletes. J. Appl. Physiol., 74, 2904–2908.

    PubMed  CAS  Google Scholar 

  • Sakala, E. P. (1997). Obstetrics & Gynecology. Williams & Wilkins, Baltimore, 266–272.

    Google Scholar 

  • Salisbury, J. J. and Mitchell, J. E. (1991). Bone mineral density and anorexia nervosa in women. Am. J. Psychiatry, 148, 768–774.

    PubMed  CAS  Google Scholar 

  • Salisbury, J. J., Levine, A. S., Crow, S. J., and Mitchell, J. E. (1995). Refeeding, metabolic rate, and weight gain in anorexia nervosa: a review. Int. J. Eating Disord., 17, 337–345.

    Article  CAS  Google Scholar 

  • Sanborn, C. F., Martin, B. J., and Wagner, W. W., Jr. (1982) Is athletic amenorrhea specific to runners? Am. J. Obstet. Gynecol., 143, 859–861.

    PubMed  CAS  Google Scholar 

  • Schreihofer, D. A., Amico, J. A., and Cameron, J. L. (1993). Reversal of fasting-induced suppression of luteinizing hormone (LH) secretion in male rhesus monkeys by intragastric nutrient infusion: evidence for rapid stimulation of LH by nutritional signals. Endocrinology, 132, 1890–1897.

    Article  PubMed  CAS  Google Scholar 

  • Schweiger, U. (1991). Menstrual function and luteal-phase deficiency in relation to weight changes and dieting. Clin. Obstet. Gynecol., 34(1), 191–197.

    Article  PubMed  CAS  Google Scholar 

  • Shangold, M. M., and Levine, H. S. The effect of marathon training upon menstrual function. Am. J. Obstet. Gynecol., 143, 862–869.

    Google Scholar 

  • Singh, K. B. (1981). Menstrual disorders in college students. Am. J. Obstet. Gynecol., 1210, 299–302.

    Google Scholar 

  • Smith, E. L. and Gilligan, C. (1994). Bone Concerns. In M. M. Shangold and G. Mirkin (Eds.). Women and Exercise: Physiology and Sports Medicine, F. A. Davis Company, Philadelphia, pp. 89–101.

    Google Scholar 

  • Soules, M. R., Steiner, R. A., Clifton, D. K., and Bremner, W. J. (1984). Abnormal patterns of pulsatile luteinizing hormone in women with luteal phase deficiency. Obstet. Gynecol., 63, 626–629.

    PubMed  CAS  Google Scholar 

  • Soyka, L. A., Grinspoon, S., Levitsky, L. L., Herzog, D. B., and Klibanski, A. (1999). The effects of anorexia nervosa on bone metabolism in female adolescents. J. Clin. Endcrinol. Metab., Abstract, 84(12), 4489–4496.

    Article  CAS  Google Scholar 

  • Steen, S. N., Oppliger, R. A., and Brownell, K. D. (1988). Metabolic effects of repeated weight loss and regain in adolescent wrestlers. JAMA, 260, 47–50.

    Article  PubMed  CAS  Google Scholar 

  • Steppan, C. M., Crawford, D. T., Chidsey-Frink, K. L., Ke, H., and Swick, A. G. (2000). Leptin is a potent stimulator of bone growth in ob/ob mice. Regul. Pept., 92, 73–78.

    Article  PubMed  CAS  Google Scholar 

  • Steppan, C. M., Chidsey-Frink, K. L., Crawford, D. T., et al. (1998). Leptin administration causes bone growth in ob/ob mice. The Endocrine Society, 80th Annual Meeting, New Orleans, LA, Abstract.

    Google Scholar 

  • Tezuka, M., Irahara, M., Ogura, K., Kiyokawa, M., Tamura, T., Matsuzaki, T., Yasui, T., and Aono, T. (2002). Effects of leptin on gonadotropin secretion in juvenile female rat pituitary cells. Eur. J. Endocrinol., 146, 261–266.

    Article  PubMed  CAS  Google Scholar 

  • Thomas, T., Gori, F., Burguera, B., et al. (1998). Leptin acts on human marrow stromal precursor cells to enhance osteoblast differentiation and to inhibit adipocyte differentiation: a potential mechanism for increased bone mass in obesity. The Endocrine Society, 80th Annual Meeting, New Orleans, LA, Abstract.

    Google Scholar 

  • Thong, F. S., McLean, C., and Graham, T. E. (2000). Plasma leptin in female athletes: relationship with body fat, reproductive, nutritional, and endocrine factors. J. Appl. Physiol., 88, 2037–2044.

    PubMed  CAS  Google Scholar 

  • Tsafriri, A., Dekel, N., and Bar-Ami, S. (1982). The role of oocyte maturation inhibitor in follicular regulation of oocyte maturation. J. Reprod. Eertil., 64, 541–551.

    Article  CAS  Google Scholar 

  • Tuschl, R. J., Platte, P., Laessle, R. G., Stichler, W., and Pirke, K. M. (1990). Energy expenditure and every day eating behavior in healthy young women. Am. J. Clin. Nutr., 52, 81–86.

    PubMed  CAS  Google Scholar 

  • van Binsbergen, C. J. M., Coelingh Bennink, H. J. T., Odink, J., Haspels. A. A., and 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, 705–711.

    Article  PubMed  Google Scholar 

  • Vigersky, R. A., Andersen, A. E., Thompson, R. H., and Loriaux, D. L. (1977). Hypothalamic dysfunction in secondary amenorrhea associated with simple weight loss. N. Engl. J. Med., 297, 1141–1145.

    Article  PubMed  CAS  Google Scholar 

  • Walsh, B. T., Katz, J. L., Levin, J., Kream, J., Fukushima, D. K., Hellman, L. D., Weiner, H., and Zumoff, B. (1978). Adrenal activity in anorexia nervosa. Psychosom. Med., 40, 499–506.

    PubMed  CAS  Google Scholar 

  • Warren, M. P. (1980). The effects of exercise on pubertal progression and reproductive function in girls. J. Clin. Endocrinol. Metab., 57(5), 1150–1157.

    Article  Google Scholar 

  • Warren, M. P. (1983). The effects of undernutrition on reproductive function in the human. Endocr. Rev., 4, 363–377.

    Article  PubMed  CAS  Google Scholar 

  • Warren, M. P. (1999). Health issues for women athletes: exercise-induced amenorrhea [see comments]. J. Clin. Endocrinol. Metab., 84, 1,892–1,896.

    Article  Google Scholar 

  • Warren, M. P. and Shangold, M. M. (1997). Sports Gynecology: Problems and Care of the Athletic Female. Blackwell Science, Cambridge, MA.

    Google Scholar 

  • Warren, M. P. and Vande Wiele, R. L. (1973). Clinical and metabolic features of anorexia nervosa. Am. J. Obstet. Gynecol., 777(3), 435–449.

    Google Scholar 

  • Warren, M. P., Fox, R. P., DeRogatis, A. J., and Hamilton, W. G. (1994a). Osteopenia in hypothalamic amenorrhea: a 3-year longitudinal study. The Endocrine Society Annual Meeting, Anaheim, California, Abstract.

    Google Scholar 

  • Warren, M. P., Brooks-Gunn, J., Hamilton, L. H., Warren, L. F., and Hamilton, W. G. (1986). Scoliosis and fractures in young ballet dancers: relation to delayed menarche and secondary amenorrhea. N. Engl. J. Med., 314, 1348–1353.

    Article  PubMed  CAS  Google Scholar 

  • Warren, M. P., Jewelewicz, R., Dyrenfurth, I., Ans, R., Khalaf, S., and Vande 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, 601–611.

    Article  PubMed  CAS  Google Scholar 

  • Warren, M. P., Brooks-Gunn, J., Fox, R. P., Lancelot, C, Newman, D., and Hamilton, W. G. (1991). Lack of bone accretion and amenorrhea: evidence for a relative osteopenia in weight bearing bones. J. Clin. Endocrinol. Metab., 72, 847–853.

    Article  PubMed  CAS  Google Scholar 

  • Warren, M. P., Holderness, C. C., Lesobre, V., Tzen, R., Vossoughian, F., and Brooks-Gunn, J. (1994b). Hypothalamic amenorrhea and hidden nutritional insults. J. Soc. Gynecol. Invest., 1, 84–88.

    CAS  Google Scholar 

  • Warren, M. P., Voussoughian, F., Geer, E. B., Hyle, E. P., Adberg, C. L., and Ramos, R. H. (1999). Functional hypothalamic amenorrhea: hypoleptinemia and disordered eating. J. Clin. Endocrinol. Metab., 84, 873–877.

    Article  PubMed  CAS  Google Scholar 

  • Warren, M. P., Brooks-Gunn, J., Fox, R. P., Holderness, C. C., Hyle, E. P., and Hamilton, W. G. (2002). Osteopenia in exercise associated amenorrhea using ballet dancers as a model: a longitudinal study. J. Clin. Endocrinol. Metab., 87(1): 3162–3168.

    Article  PubMed  CAS  Google Scholar 

  • Williams, N. I., Helmreich, D. L., Parfitt, D. B., Caston-Balderrama, A., and Cameron, J. L. (2001). Evidence for a causal role of low energy availability in the induction of menstrual cycle disturbances during strenuous exercise training. J. Clin. Endocrinol. Metab., 86, 5184–5193.

    Article  PubMed  CAS  Google Scholar 

  • Wilson, G. T. and Walsh, B. T. (1991). Eating disorders in the DSM-IV. J. Abnorm. Psychol., 100(3), 362–365.

    Article  PubMed  CAS  Google Scholar 

  • Wolman, R. L., Clark, P., McNally, E., Harries, M., and Reeve, J. (1990). Menstrual state and exercise as determinants of spinal trabecular bone density in female athletes. Brit. Med. J., 301, 516–518.

    Article  PubMed  CAS  Google Scholar 

  • Yamauchi, M., Sugimoto, T., Yamaguchi, T., Nakaoka, D., Kanzawa, M., Yano, S., Ozuru, R., Sugishita, T., and Chihara, K. (2001). Plasma leptin concentrations are associated with bone mineral density and the presence of vertebral fractures in postmenopausal women. Clin. Endocrinol. (Oxf), 55, 341–347.

    Article  CAS  Google Scholar 

  • Zanker, C. L. (1999). Bone metabolism in exercise associated amenorrhoea: the importance of nutrition. Br. J. Sports Med., 33, 228–229.

    Article  PubMed  CAS  Google Scholar 

  • Zanker, C. L. and Swaine, I. L. (1998a). Bone turnover in amenorrhoeic and eumenorrhoeic distance runners. Scand. J. Med. Sci. Sports, 8, 20–26.

    Article  PubMed  CAS  Google Scholar 

  • Zanker, C. L. and Swaine, I. L. (1998b). The relationship between bone turnover, oestradiol, and energy balance in women distance runners. Br. J. Sports Med., 32, 167–171.

    Article  PubMed  CAS  Google Scholar 

  • Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., and Friedman, J. M. (1994). Positional cloning of the mouse obese gene and its human homologue. Nature, 372, 425–432.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer Science+Business Media New York

About this chapter

Cite this chapter

Warren, M.P., Dominguez, J.E. (2003). Leptin and Hypothalamic Amenorrhea. In: Henson, M.C., Castracane, V.D. (eds) Leptin and Reproduction. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0157-2_19

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-0157-2_19

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-4946-4

  • Online ISBN: 978-1-4615-0157-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics