Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Effects of hypogonadism on bone metabolism in female adolescents and young adults

Nature Reviews Endocrinology volume 8, pages 395–404 (2012)Cite this article

Subjects

Abstract

Gonadal steroids, including androgens and oestrogens, play a critical part in bone metabolism, and conditions associated with a deficiency of gonadal steroids can reduce BMD in adults and impair bone accrual in adolescents. In addition, other associated hormone alterations, for example, insulin-like growth factor 1 deficiency or high cortisol levels, can further exacerbate the effect of hypogonadism on bone metabolism, as can factors such as calcium and vitamin D deficiency, low body weight and exercise status. This Review discusses the effects of different hypogonadal states on bone metabolism in female adolescents and young adults, with particular emphasis on conditions associated with low energy availability, such as anorexia nervosa and athletic amenorrhoea, in which many factors other than hypogonadism affect bone. In contrast to most hypogonadal conditions, in which replacement of gonadal steroids is sufficient to normalize bone accrual rates and BMD, gonadal steroid replacement may not be sufficient to normalize bone metabolism in these states of energy deficit.

Key Points

  • Oestrogen primarily decreases bone resorption, whereas effects of testosterone on bone are mediated primarily through its aromatization to oestrogen; however, direct osteoanabolic effects have also been described

  • Hypogonadism is associated with low BMD and impaired bone microarchitecture, but its effect on bone may be compounded depending on the underlying etiology

  • In adolescent girls and young women, common causes of amenorrhoea include anorexia nervosa and athletic amenorrhoea, hypopituitarism, hyperprolactinaemia and ovarian failure (from autoimmune causes, gonadal dysgenesis, radiotherapy and chemotherapy)

  • Replacement of gonadal steroids is usually effective in improving BMD and bone structure; however, additional measures may be necessary when associated alterations in body composition and other hormones contribute to low BMD

  • In anorexia nervosa, causes of low BMD include not only hypogonadism, but also decreased lean mass, low insulin-like growth factor 1 and relatively high cortisol levels and alterations in energy-regulated hormones

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2: Factors contributing to impaired bone metabolism in female adolescents and young adults with anorexia nervosa (left) or athletic amenorrhoea (right).

Similar content being viewed by others

References

  1. Ackerman, K. E. et al. Bone microarchitecture is impaired in adolescent amenorrheic athletes compared with eumenorrheic athletes and nonathletic controls. J. Clin. Endocrinol. Metab. 96, 3123–3133 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Walsh, C. J. et al. Women with anorexia nervosa: finite element and trabecular structure analysis by using flat-panel volume CT. Radiology 257, 167–174 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Stein, E. M. et al. Abnormal microarchitecture and reduced stiffness at the radius and tibia in postmenopausal women with fractures. J. Bone Miner. Res. 25, 2572–2581 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Sornay-Rendu, E., Boutroy, S., Munoz, F. & Delmas, P. D. Alterations of cortical and trabecular architecture are associated with fractures in postmenopausal women, partially independent of decreased BMD measured by DXA: the OFELY study. J. Bone Miner. Res. 22, 425–433 (2007).

    Article  PubMed  Google Scholar 

  5. Misra, M. et al. Effects of anorexia nervosa on clinical, hematologic, biochemical, and bone density parameters in community-dwelling adolescent girls. Pediatrics 114, 1574–1583 (2004).

    Article  PubMed  Google Scholar 

  6. Ohlsson, C., Bengtsson, B. A., Isaksson, O. G., Andreassen, T. T. & Slootweg, M. C. Growth hormone and bone. Endocr. Rev. 19, 55–79 (1998).

    CAS  PubMed  Google Scholar 

  7. Rauch, F. Bone accrual in children: adding substance to surfaces. Pediatrics 119 (Suppl. 2), S137–S140 (2007).

    Article  PubMed  Google Scholar 

  8. Theintz, G. et al. Longitudinal monitoring of bone mass accumulation in healthy adolescents: evidence for a marked reduction after 16 years of age at the levels of lumbar spine and femoral neck in female subjects. J. Clin. Endocrinol. Metab. 75, 1060–1065 (1992).

    CAS  PubMed  Google Scholar 

  9. Harel, Z. et al. Bone mineral density in postmenarchal adolescent girls in the United States: associated biopsychosocial variables and bone turnover markers. J. Adolesc. Health 40, 44–53 (2007).

    Article  PubMed  Google Scholar 

  10. Sabatier, J. P. et al. Bone mineral acquisition during adolescence and early adulthood: a study in 574 healthy females 10–24 years of age. Osteoporos. Int. 6, 141–148 (1996).

    Article  CAS  PubMed  Google Scholar 

  11. Riggs, B. L., Khosla, S. & Melton, L. J. 3rd. Sex steroids and the construction and conservation of the adult skeleton. Endocr. Rev. 23, 279–302 (2002).

    Article  CAS  PubMed  Google Scholar 

  12. Cara, J., Rosenfield, R. & Furlanetto, R. A longitudinal study of the relationship of plasma somatomedin-C concentration to the pubertal growth spurt. Am. J. Dis. Child. 141, 562–564 (1987).

    CAS  PubMed  Google Scholar 

  13. Misra, M., Cord, J., Prabhakaran, R., Miller, K. K. & Klibanski, A. Growth hormone suppression after an oral glucose load in children. J. Clin. Endocrinol. Metab. 92, 4623–4629 (2007).

    Article  CAS  PubMed  Google Scholar 

  14. Russell, M., Breggia, A., Mendes, N., Klibanski, A. & Misra, M. Growth hormone is positively associated with surrogate markers of bone turnover during puberty. Clin. Endocrinol. (Oxf.) 75, 482–488 (2011).

    Article  CAS  Google Scholar 

  15. Riggs, B. L. The mechanisms of estrogen regulation of bone resorption. J. Clin. Invest. 106, 1203–1204 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wang, Q. et al. Differential effects of sex hormones on peri- and endocortical bone surfaces in pubertal girls. J. Clin. Endocrinol. Metab. 91, 277–282 (2006).

    Article  CAS  PubMed  Google Scholar 

  17. Eastell, R. Role of oestrogen in the regulation of bone turnover at the menarche. J. Endocrinol. 185, 223–234 (2005).

    Article  CAS  PubMed  Google Scholar 

  18. Leder, B. Z., LeBlanc, K. M., Schoenfeld, D. A., Eastell, R. & Finkelstein, J. S. Differential effects of androgens and estrogens on bone turnover in normal men. J. Clin. Endocrinol. Metab. 88, 204–210 (2003).

    Article  CAS  PubMed  Google Scholar 

  19. Michael, H., Härkönen, P. L., Väänänen, H. K. & Hentunen, T. A. Estrogen and testosterone use different cellular pathways to inhibit osteoclastogenesis and bone resorption. J. Bone Miner. Res. 20, 2224–2232 (2005).

    Article  CAS  PubMed  Google Scholar 

  20. Falahati-Nini, A. et al. Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly men. J. Clin. Invest. 106, 1553–1560 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Gallagher, J. C., Riggs, B. L. & DeLuca, H. F. Effect of estrogen on calcium absorption and serum vitamin D metabolites in postmenopausal osteoporosis. J. Clin. Endocrinol. Metab. 51, 1359–1364 (1980).

    Article  CAS  PubMed  Google Scholar 

  22. Ash, S. L. & Goldin, B. R. Effects of age and estrogen on renal vitamin D metabolism in the female rat. Am. J. Clin. Nutr. 47, 694–699 (1988).

    Article  CAS  PubMed  Google Scholar 

  23. Hagenfeldt, Y., Linde, K., Sjöberg, H. E., Zumkeller, W. & Arver, S. Testosterone increases serum 1, 25-dihydroxyvitamin D and insulin-like growth factor-I in hypogonadal men. Int. J. Androl. 15, 93–102 (1992).

    Article  CAS  PubMed  Google Scholar 

  24. Wikström, A. M., Bay, K., Hero, M., Andersson, A. M. & Dunkel, L. Serum insulin-like factor 3 levels during puberty in healthy boys and boys with Klinefelter syndrome. J. Clin. Endocrinol. Metab. 91, 4705–4708 (2006).

    Article  CAS  PubMed  Google Scholar 

  25. Pepe, A. et al. INSL3 plays a role in the balance between bone formation and resorption. Ann. NY Acad. Sci. 1160, 219–220 (2009).

    Article  PubMed  Google Scholar 

  26. Ferlin, A. et al. Mutations in the insulin-like factor 3 receptor are associated with osteoporosis. J. Bone Miner. Res. 23, 683–693 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Foresta, C. et al. Bone mineral density and testicular failure: evidence for a role of vitamin D 25-hydroxylase in human testis. J. Clin. Endocrinol. Metab. 96, E646–E652 (2011).

    Article  CAS  PubMed  Google Scholar 

  28. Oury, F. et al. Endocrine regulation of male fertility by the skeleton. Cell 144, 796–809 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 3rd ed. revised: DSM-III-R (American Psychiatric Association, Washington DC, 1987).

  30. Grinspoon, S. et al. Prevalence and predictive factors for regional osteopenia in women with anorexia nervosa. Ann. Intern. Med. 133, 790–794 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Estour, B. et al. Hormonal profile heterogeneity and short-term physical risk in restrictive anorexia nervosa. J. Clin. Endocrinol. Metab. 95, 2203–2210 (2010).

    Article  CAS  PubMed  Google Scholar 

  32. Grinspoon, S. et al. 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, 3864–3870 (1996).

    CAS  PubMed  Google Scholar 

  33. Soyka, L. A. et al. Abnormal bone mineral accrual in adolescent girls with anorexia nervosa. J. Clin. Endocrinol. Metab. 87, 4177–4185 (2002).

    Article  CAS  PubMed  Google Scholar 

  34. Misra, M. et al. Weight gain and restoration of menses as predictors of bone mineral density change in adolescent girls with anorexia nervosa-1. J. Clin. Endocrinol. Metab. 93, 1231–1237 (2008).

    Article  CAS  PubMed  Google Scholar 

  35. Misra, M. et al. Bone metabolism in adolescent boys with anorexia nervosa. J. Clin. Endocrinol. Metab. 93, 3029–3036 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Misra, M. et al. Serum osteoprotegerin in adolescent girls with anorexia nervosa. J. Clin. Endocrinol. Metab. 88, 3816–3822 (2003).

    Article  CAS  PubMed  Google Scholar 

  37. Lawson, E. A. et al. Hormone predictors of abnormal bone microarchitecture in women with anorexia nervosa. Bone 46, 458–463 (2010).

    Article  CAS  PubMed  Google Scholar 

  38. Milos, G. et al. Cortical and trabecular bone density and structure in anorexia nervosa. Osteoporos. Int. 16, 783–790 (2005).

    Article  PubMed  Google Scholar 

  39. Bredella, M. A. et al. Distal radius in adolescent girls with anorexia nervosa: trabecular structure analysis with high-resolution flat-panel volume CT. Radiology 249, 938–946 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Vestergaard, P. et al. Fractures in patients with anorexia nervosa, bulimia nervosa, and other eating disorders—a nationwide register study. Int. J. Eat. Disord. 32, 301–308 (2002).

    Article  PubMed  Google Scholar 

  41. Lucas, A. R., Melton, L. J. 3rd, Crowson, C. S. & O'Fallon, W. M. Long-term fracture risk among women with anorexia nervosa: a population-based cohort study. Mayo Clin. Proc. 74, 972–977 (1999).

    Article  CAS  PubMed  Google Scholar 

  42. Miller, K. K. et al. Determinants of skeletal loss and recovery in anorexia nervosa. J. Clin. Endocrinol. Metab. 91, 2931–2937 (2006).

    Article  CAS  PubMed  Google Scholar 

  43. Misra, M. et al. Relationships between serum adipokines, insulin levels, and bone density in girls with anorexia nervosa. J. Clin. Endocrinol. Metab. 92, 2046–2052 (2007).

    Article  CAS  PubMed  Google Scholar 

  44. Misra, M. et al. Alterations in growth hormone secretory dynamics in adolescent girls with anorexia nervosa and effects on bone metabolism. J. Clin. Endocrinol. Metab. 88, 5615–5623 (2003).

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  46. Misra, M. et al. Alterations in cortisol secretory dynamics in adolescent girls with anorexia nervosa and effects on bone metabolism. J. Clin. Endocrinol. Metab. 89, 4972–4980 (2004).

    Article  CAS  PubMed  Google Scholar 

  47. Wojcik, M. H. et al. Reduced amylin levels are associated with low bone mineral density in women with anorexia nervosa. Bone 46, 796–800 (2010).

    Article  CAS  PubMed  Google Scholar 

  48. Misra, M. et al. Elevated peptide YY levels in adolescent girls with anorexia nervosa. J. Clin. Endocrinol. Metab. 91, 1027–1033 (2006).

    Article  CAS  PubMed  Google Scholar 

  49. Utz, A. L. et al. Peptide YY (PYY) levels and bone mineral density (BMD) in women with anorexia nervosa. Bone 43, 135–139 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Gordon, C. M. et al. Physiologic regulators of bone turnover in young women with anorexia nervosa. J. Pediatr. 141, 64–70 (2002).

    Article  CAS  PubMed  Google Scholar 

  51. Misra, M. et al. Physiologic estrogen replacement increases bone density in adolescent girls with anorexia nervosa. J. Bone Miner. Res. 26, 2430–2438 (2011).

    Article  CAS  PubMed  Google Scholar 

  52. Misra, M. et al. Nutrient intake in community-dwelling adolescent girls with anorexia nervosa and in healthy adolescents. Am. J. Clin. Nutr. 84, 698–706 (2006).

    Article  CAS  PubMed  Google Scholar 

  53. Haagensen, A. L., Feldman, H. A., Ringelheim, J. & Gordon, C. M. Low prevalence of vitamin D deficiency among adolescents with anorexia nervosa. Osteoporos. Int. 19, 289–294 (2008).

    Article  CAS  PubMed  Google Scholar 

  54. Golden, N. H. et al. The effect of estrogen-progestin treatment on bone mineral density in anorexia nervosa. J. Pediatr. Adolesc. Gynecol. 15, 135–143 (2002).

    Article  PubMed  Google Scholar 

  55. Strokosch, G. R., Friedman, A. J., Wu, S. C. & Kamin, M. Effects of an oral contraceptive (norgestimate/ethinyl estradiol) on bone mineral density in adolescent females with anorexia nervosa: a double-blind, placebo-controlled study. J. Adolesc. Health 39, 819–827 (2006).

    Article  PubMed  Google Scholar 

  56. Ho, K. K. & Weissberger, A. J. Impact of short-term estrogen administration on growth hormone secretion and action: distinct route-dependent effects on connective and bone tissue metabolism. J. Bone Miner. Res. 7, 821–827 (1992).

    Article  CAS  PubMed  Google Scholar 

  57. Weissberger, A. J., Ho, K. K. & Lazarus, L. Contrasting effects of oral and transdermal routes of estrogen replacement therapy on 24-hour growth hormone (GH) secretion, insulin-like growth factor I, and GH-binding protein in postmenopausal women. J. Clin. Endocrinol. Metab. 72, 374–381 (1991).

    Article  CAS  PubMed  Google Scholar 

  58. Miller, K. K. et al. Androgens in women with anorexia nervosa and normal-weight women with hypothalamic amenorrhea. J. Clin. Endocrinol. Metab. 92, 1334–1339 (2007).

    Article  CAS  PubMed  Google Scholar 

  59. Cuttler, L., Van Vliet, G., Conte, F. A., Kaplan, S. L. & Grumbach, M. M. Somatomedin-C levels in children and adolescents with gonadal dysgenesis: differences from age-matched normal females and effect of chronic estrogen replacement therapy. J. Clin. Endocrinol. Metab. 60, 1087–1092 (1985).

    Article  CAS  PubMed  Google Scholar 

  60. Nabhan, Z. M., Dimeglio, L. A., Qi, R., Perkins, S. M. & Eugster, E. A. Conjugated oral versus transdermal estrogen replacement in girls with Turner syndrome: a pilot comparative study. J. Clin. Endocrinol. Metab. 94, 2009–2014 (2009).

    Article  CAS  PubMed  Google Scholar 

  61. Taboada, M. et al. Pharmacokinetics and pharmacodynamics of oral and transdermal 17β estradiol in girls with turner syndrome. J. Clin. Endocrinol. Metab. 96, 3502–3510 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Fazeli, P. et al. Effects of recombinant human growth hormone in anorexia nervosa: a randomized, placebo-controlled study. J. Clin. Endocrinol. Metab. 95, 4889–4897 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Misra, M. et al. Effects of rhIGF-1 administration on surrogate markers of bone turnover in adolescents with anorexia nervosa. Bone 45, 493–498 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Grinspoon, S., Thomas, L., Miller, K., Herzog, D. & Klibanski, A. Effects of recombinant human IGF-I and oral contraceptive administration on bone density in anorexia nervosa. J. Clin. Endocrinol. Metab. 87, 2883–2891 (2002).

    Article  CAS  PubMed  Google Scholar 

  65. Gordon, C. M. et al. Effects of oral dehydroepiandrosterone on bone density in young women with anorexia nervosa: a randomized trial. J. Clin. Endocrinol. Metab. 87, 4935–4941 (2002).

    Article  CAS  PubMed  Google Scholar 

  66. Golden, N. H. et al. Alendronate for the treatment of osteopenia in anorexia nervosa: a randomized, double-blind, placebo-controlled trial. J. Clin. Endocrinol. Metab. 90, 3179–3185 (2005).

    Article  CAS  PubMed  Google Scholar 

  67. Miller, K. K. et al. Effects of risedronate and low-dose transdermal testosterone on bone mineral density in women with anorexia nervosa: a randomized, placebo-controlled study. J. Clin. Endocrinol. Metab. 96, 2081–2088 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Nichols, J. F., Rauh, M. J., Lawson, M. J., Ji, M. & Barkai, H. S. Prevalence of the female athlete triad syndrome among high school athletes. Arch. Pediatr. Adolesc. Med. 160, 137–142 (2006).

    Article  PubMed  Google Scholar 

  69. Loucks, A. B. & Horvath, S. M. Athletic amenorrhea: a review. Med. Sci. Sports Exerc. 17, 56–72 (1985).

    CAS  PubMed  Google Scholar 

  70. Otis, C. L. Exercise-associated amenorrhea. Clin. Sports Med. 11, 351–362 (1992).

    CAS  PubMed  Google Scholar 

  71. Shangold, M., Rebar, R. W., Wentz, A. C. & Schiff, I. Evaluation and management of menstrual dysfunction in athletes. JAMA 263, 1665–1669 (1990).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  73. Robinson, T. L. et al. Gymnasts exhibit higher bone mass than runners despite similar prevalence of amenorrhea and oligomenorrhea. J. Bone Miner. Res. 10, 26–35 (1995).

    Article  CAS  PubMed  Google Scholar 

  74. Christo, K. et al. Bone metabolism in adolescent athletes with amenorrhea, athletes with eumenorrhea, and control subjects. Pediatrics 121, 1127–1136 (2008).

    Article  PubMed  Google Scholar 

  75. Cobb, K. et al. Disordered eating, menstrual irregularity, and bone mineral density in female runners. Med. Sci. Sports Exerc. 35, 711–719 (2003).

    Article  PubMed  Google Scholar 

  76. Ihle, R. & Loucks, A. B. Dose-response relationships between energy availability and bone turnover in young exercising women. J. Bone Miner. Res. 19, 1231–1240 (2004).

    Article  PubMed  Google Scholar 

  77. Russell, M. et al. Peptide YY in adolescent athletes with amenorrhea, eumenorrheic athletes and non-athletic controls. Bone 45, 104–109 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Castelo-Branco, C. et al. Bone mineral density in young, hypothalamic oligoamenorrheic women treated with oral contraceptives. J. Reprod. Med. 46, 875–879 (2001).

    CAS  PubMed  Google Scholar 

  79. Hergenroeder, A. C. et al. 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 (1997).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  81. Burr, D. B. et al. Exercise and oral contraceptive use suppress the normal age-related increase in bone mass and strength of the femoral neck in women 18–31 years of age. Bone 27, 855–863 (2000).

    Article  CAS  PubMed  Google Scholar 

  82. Hartard, M. et al. Age at first oral contraceptive use as a major determinant of vertebral bone mass in female endurance athletes. Bone 35, 836–841 (2004).

    Article  CAS  PubMed  Google Scholar 

  83. Nattiv, A. et al. American College of Sports Medicine position stand. The female athlete triad. Med. Sci. Sports Exerc. 39, 1867–1882 (2007).

    Article  PubMed  Google Scholar 

  84. Ishizaka, K., Suzuki, M., Kageyama, Y., Kihara, K. & Yoshida, K. Bone mineral density in hypogonadal men remains low after long-term testosterone replacement. Asian J. Androl. 4, 117–121 (2002).

    CAS  PubMed  Google Scholar 

  85. Legrand, E. et al. Trabecular bone microarchitecture is related to the number of risk factors and etiology in osteoporotic men. Microsc. Res. Tech. 70, 952–959 (2007).

    Article  PubMed  Google Scholar 

  86. Lubushitzky, R. et al. Quantitative bone SPECT in young males with delayed puberty and hypogonadism: implications for treatment of low bone mineral density. J. Nucl. Med. 39, 104–107 (1998).

    CAS  PubMed  Google Scholar 

  87. Okinaga, H., Matsuno, A. & Okazaki, R. High risk of osteopenia and bone derangement in postsurgical patients with craniopharyngiomas, pituitary adenomas and other parasellar lesions. Endocr. J. 52, 751–756 (2005).

    Article  PubMed  Google Scholar 

  88. Mazziotti, G. et al. Effect of gonadal status on bone mineral density and radiological spinal deformities in adult patients with growth hormone deficiency. Pituitary 11, 55–61 (2008).

    Article  CAS  PubMed  Google Scholar 

  89. Wüster, C. et al. The influence of growth hormone deficiency, growth hormone replacement therapy, and other aspects of hypopituitarism on fracture rate and bone mineral density. J. Bone Miner. Res. 16, 398–405 (2001).

    Article  PubMed  Google Scholar 

  90. Kosowicz, J., El Ali, Z., Ziemnicka, K. & Sowinski, J. Abnormalities in bone mineral density distribution and bone scintigraphy in patients with childhood onset hypopituitarism. J. Clin. Densitom. 10, 332–339 (2007).

    Article  PubMed  Google Scholar 

  91. Miller, K. K. et al. Effects of testosterone replacement in androgen-deficient women with hypopituitarism: a randomized, double-blind, placebo-controlled study. J. Clin. Endocrinol. Metab. 91, 1683–1690 (2006).

    Article  CAS  PubMed  Google Scholar 

  92. Ragnarsson, O., Nyström, H. F. & Johannsson, G. Glucocorticoid replacement therapy is independently associated with reduced bone mineral density in women with hypopituitarism. Clin. Endocrinol. (Oxf.) 76, 246–252 (2012).

    Article  CAS  Google Scholar 

  93. Colao, A. et al. Prolactinomas in adolescents: persistent bone loss after 2 years of prolactin normalization. Clin. Endocrinol. (Oxf.) 52, 319–327 (2000).

    Article  CAS  Google Scholar 

  94. Galli-Tsinopoulou, A., Nousia-Arvanitakis, S., Mitsiakos, G., Karamouzis, M. & Dimitriadis, A. Osteopenia in children and adolescents with hyperprolactinemia. J. Pediatr. Endocrinol. Metab. 13, 439–441 (2000).

    CAS  PubMed  Google Scholar 

  95. Ciccarelli, E. et al. Vertebral bone density in non-amenorrhoeic hyperprolactinaemic women. Clin. Endocrinol. (Oxf.) 28, 1–6 (1988).

    Article  CAS  Google Scholar 

  96. Klibanski, A., Biller, B. M., Rosenthal, D. I., Schoenfeld, D. A. & Saxe, V. Effects of prolactin and estrogen deficiency in amenorrheic bone loss. J. Clin. Endocrinol. Metab. 67, 124–130 (1988).

    Article  CAS  PubMed  Google Scholar 

  97. Naliato, E. C., Farias, M. L. & Violante, A. H. Prolactinomas and bone mineral density in men [Portuguese]. Arq. Bras. Endocrinol. Metabol. 49, 183–195 (2005).

    Article  PubMed  Google Scholar 

  98. Naliato, E. C. et al. Bone density in women with prolactinoma treated with dopamine agonists. Pituitary 11, 21–28 (2008).

    Article  CAS  PubMed  Google Scholar 

  99. Seriwatanachai, D. et al. Prolactin directly enhances bone turnover by raising osteoblast-expressed receptor activator of nuclear factor κB ligand/osteoprotegerin ratio. Bone 42, 535–546 (2008).

    Article  CAS  PubMed  Google Scholar 

  100. Klibanski, A. & Greenspan, S. L. Increase in bone mass after treatment of hyperprolactinemic amenorrhea. N. Engl. J. Med. 315, 542–546 (1986).

    Article  CAS  PubMed  Google Scholar 

  101. Schlaff, W. D., Carson, S. A., Luciano, A., Ross, D. & Bergqvist, A. Subcutaneous injection of depot medroxyprogesterone acetate compared with leuprolide acetate in the treatment of endometriosis-associated pain. Fertil. Steril. 85, 314–325 (2006).

    Article  CAS  PubMed  Google Scholar 

  102. Hornstein, M. D., Surrey, E. S., Weisberg, G. W. & Casino, L. A. Leuprolide acetate depot and hormonal add-back in endometriosis: a 12-month study. Lupron Add-Back Study Group. Obstet. Gynecol. 91, 16–24 (1998).

    Article  CAS  PubMed  Google Scholar 

  103. Mitwally, M. F., Gotlieb, L. & Casper, R. F. Prevention of bone loss and hypoestrogenic symptoms by estrogen and interrupted progestogen add-back in long-term GnRH-agonist down-regulated patients with endometriosis and premenstrual syndrome. Menopause 9, 236–241 (2002).

    Article  PubMed  Google Scholar 

  104. Ripps, B. A., VanGilder, K., Minhas, B., Welford, M. & Mamish, Z. Alendronate for the prevention of bone mineral loss during gonadotropin-releasing hormone agonist therapy. J. Reprod. Med. 48, 761–766 (2003).

    CAS  PubMed  Google Scholar 

  105. Cromer, B. A. et al. Depot medroxyprogesterone acetate, oral contraceptives and bone mineral density in a cohort of adolescent girls. J. Adolesc. Health 35, 434–441 (2004).

    Article  PubMed  Google Scholar 

  106. Scholes, D., LaCroix, A. Z., Ichikawa, L. E., Barlow, W. E. & Ott, S. M. Change in bone mineral density among adolescent women using and discontinuing depot medroxyprogesterone acetate contraception. Arch. Pediatr. Adolesc. Med. 159, 139–144 (2005).

    Article  PubMed  Google Scholar 

  107. Walsh, J. S., Eastell, R. & Peel, N. F. Effects of Depot medroxyprogesterone acetate on bone density and bone metabolism before and after peak bone mass: a case-control study. J. Clin. Endocrinol. Metab. 93, 1317–1323 (2008).

    Article  CAS  PubMed  Google Scholar 

  108. Cromer, B. A. et al. Bone mineral density in adolescent females using injectable or oral contraceptives: a 24-month prospective study. Fertil. Steril. 90, 2060–2067 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  109. Kaunitz, A. M., Miller, P. D., Rice, V. M., Ross, D. & McClung, M. R. Bone mineral density in women aged 25–35 years receiving depot medroxyprogesterone acetate: recovery following discontinuation. Contraception 74, 90–99 (2006).

    Article  CAS  PubMed  Google Scholar 

  110. Kaunitz, A. M., Arias, R. & McClung, M. Bone density recovery after depot medroxyprogesterone acetate injectable contraception use. Contraception 77, 67–76 (2008).

    Article  CAS  PubMed  Google Scholar 

  111. Popat, V. B. et al. Bone mineral density in estrogen-deficient young women. J. Clin. Endocrinol. Metab. 94, 2277–2283 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Uygur, D. et al. Bone loss in young women with premature ovarian failure. Arch. Gynecol. Obstet. 273, 17–19 (2005).

    Article  PubMed  Google Scholar 

  113. Leite-Silva, P., Bedone, A., Pinto-Neto, A. M., Costa, J. V. & Costa-Paiva, L. Factors associated with bone density in young women with karyotypically normal spontaneous premature ovarian failure. Arch. Gynecol. Obstet. 280, 177–181 (2009).

    Article  PubMed  Google Scholar 

  114. Allen, E. G. et al. Examination of reproductive aging milestones among women who carry the FMR1 premutation. Hum. Reprod. 22, 2142–2152 (2007).

    Article  CAS  PubMed  Google Scholar 

  115. Bakalov, V. K. et al. Selective reduction in cortical bone mineral density in turner syndrome independent of ovarian hormone deficiency. J. Clin. Endocrinol. Metab. 88, 5717–5722 (2003).

    Article  CAS  PubMed  Google Scholar 

  116. Costa, A. M. et al. Bone mineralization in Turner syndrome: a transverse study of the determinant factors in 58 patients. J. Bone Miner. Metab. 20, 294–297 (2002).

    Article  CAS  PubMed  Google Scholar 

  117. Gravholt, C. H. et al. Marked disproportionality in bone size and mineral, and distinct abnormalities in bone markers and calcitropic hormones in adult turner syndrome: a cross-sectional study. J. Clin. Endocrinol. Metab. 87, 2798–2808 (2002).

    Article  CAS  PubMed  Google Scholar 

  118. Bakalov, V. K. et al. Bone mineral density and fractures in Turner syndrome. Am. J. Med. 115, 259–264 (2003).

    Article  PubMed  Google Scholar 

  119. Holroyd, C. R. et al. Reduced cortical bone density with normal trabecular bone density in girls with Turner syndrome. Osteoporos. Int. 21, 2093–2099 (2010).

    Article  CAS  PubMed  Google Scholar 

  120. Buzi, F. et al. Serum osteoprotegerin and receptor activator of nuclear factors κB (RANKL) concentrations in normal children and in children with pubertal precocity, Turner's syndrome and rheumatoid arthritis. Clin. Endocrinol. (Oxf.) 60, 87–91 (2004).

    Article  CAS  Google Scholar 

  121. Gravholt, C. H. et al. Increased fracture rates in Turner's syndrome: a nationwide questionnaire survey. Clin. Endocrinol. (Oxf.) 59, 89–96 (2003).

    Article  Google Scholar 

  122. Nissen, N. et al. Disproportional geometry of the proximal femur in patients with Turner syndrome: a cross-sectional study. Clin. Endocrinol. (Oxf.) 67, 897–903 (2007).

    Article  CAS  Google Scholar 

  123. Landin-Wilhelmsen, K., Bryman, I., Windh, M. & Wilhelmsen, L. Osteoporosis and fractures in Turner syndrome-importance of growth promoting and oestrogen therapy. Clin. Endocrinol. (Oxf.) 51, 497–502 (1999).

    Article  CAS  Google Scholar 

  124. Högler, W. et al. Importance of estrogen on bone health in turner syndrome: a cross-sectional and longitudinal study using dual-energy x-ray absorptiometry. J. Clin. Endocrinol. Metab. 89, 193–199 (2004).

    Article  CAS  PubMed  Google Scholar 

  125. Sass, T. C. et al. A longitudinal study on bone mineral density until adulthood in girls with Turner's syndrome participating in a growth hormone injection frequency-response trial. Clin. Endocrinol. (Oxf.) 52, 531–536 (2000).

    Article  CAS  Google Scholar 

  126. Molina, J. R., Barton, D. L. & Loprinzi, C. L. Chemotherapy-induced ovarian failure: manifestations and management. Drug Saf. 28, 401–416 (2005).

    Article  CAS  PubMed  Google Scholar 

  127. Hadji, P., Ziller, M., Maskow, C., Albert, U. & Kalder, M. The influence of chemotherapy on bone mineral density, quantitative ultrasonometry and bone turnover in pre-menopausal women with breast cancer. Eur. J. Cancer 45, 3205–3212 (2009).

    Article  CAS  PubMed  Google Scholar 

  128. Saarto, T., Blomqvist, C., Rissanen, P., Auvinen, A. & Elomaa, I. Haematological toxicity: a marker of adjuvant chemotherapy efficacy in stage II and III breast cancer. Br. J. Cancer 75, 301–305 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Bruning, P. F. et al. Bone mineral density after adjuvant chemotherapy for premenopausal breast cancer. Br. J. Cancer 61, 308–310 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Headley, J. A., Theriault, R. L., LeBlanc, A. D., Vassilopoulou-Sellin, R. & Hortobagyi, G. N. Pilot study of bone mineral density in breast cancer patients treated with adjuvant chemotherapy. Cancer Invest. 16, 6–11 (1998).

    Article  CAS  PubMed  Google Scholar 

  131. Powles, T. J. et al. Oral clodronate and reduction in loss of bone mineral density in women with operable primary breast cancer. J. Natl Cancer Inst. 90, 704–708 (1998).

    Article  CAS  PubMed  Google Scholar 

  132. Tham, Y. L. et al. The adherence to practice guidelines in the assessment of bone health in women with chemotherapy-induced menopause. J. Support. Oncol. 4, 295–298 (2006).

    PubMed  Google Scholar 

  133. Davies, J. H., Evans, B. A., Jenney, M. E. & Gregory, J. W. In vitro effects of combination chemotherapy on osteoblasts: implications for osteopenia in childhood malignancy. Bone 31, 319–326 (2002).

    Article  CAS  PubMed  Google Scholar 

  134. Vehmanen, L., Elomaa, I., Blomqvist, C. & Saarto, T. Tamoxifen treatment after adjuvant chemotherapy has opposite effects on bone mineral density in premenopausal patients depending on menstrual status. J. Clin. Oncol. 24, 675–680 (2006).

    Article  CAS  PubMed  Google Scholar 

  135. Pereyra Pacheco, B. et al. Use of GnRH analogs for functional protection of the ovary and preservation of fertility during cancer treatment in adolescents: a preliminary report. Gynecol. Oncol. 81, 391–397 (2001).

    Article  CAS  PubMed  Google Scholar 

  136. Blumenfeld, Z., Dann, E., Avivi, I., Epelbaum, R. & Rowe, J. M. Fertility after treatment for Hodgkin's disease. Ann. Oncol. 13 (Suppl. 1), 138–147 (2002).

    Article  PubMed  Google Scholar 

  137. Mardesic, T. et al. Protocol combining GnRH agonists and GnRH antagonists for rapid suppression and prevention of gonadal damage during cytotoxic therapy. Eur. J. Gynaecol. Oncol. 25, 90–92 (2004).

    CAS  PubMed  Google Scholar 

  138. Recchia, F. et al. Goserelin as ovarian protection in the adjuvant treatment of premenopausal breast cancer: a phase II pilot study. Anticancer Drugs 13, 417–424 (2002).

    Article  CAS  PubMed  Google Scholar 

  139. Gnant, M. et al. Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 5-year follow-up of the ABCSG-12 bone-mineral density substudy. Lancet Oncol. 9, 840–849 (2008).

    Article  CAS  PubMed  Google Scholar 

  140. Gnant, M. F. et al. Zoledronic acid prevents cancer treatment-induced bone loss in premenopausal women receiving adjuvant endocrine therapy for hormone-responsive breast cancer: a report from the Austrian Breast and Colorectal Cancer Study Group. J. Clin. Oncol. 25, 820–828 (2007).

    Article  CAS  PubMed  Google Scholar 

  141. Cumber, P. M. & Whittaker, J. A. Ovarian failure after total body irradiation. BMJ 300, 464 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Kondo, H. et al. Total-body irradiation of postpubertal mice with 137Cs acutely compromises the microarchitecture of cancellous bone and increases osteoclasts. Radiat. Res. 171, 283–289 (2009).

    Article  CAS  PubMed  Google Scholar 

  143. Bakker, B. et al. Pubertal development and growth after total-body irradiation and bone marrow transplantation for haematological malignancies. Eur. J. Pediatr. 159, 31–37 (2000).

    Article  CAS  PubMed  Google Scholar 

  144. Sarafoglou, K., Boulad, F., Gillio, A. & Sklar, C. Gonadal function after bone marrow transplantation for acute leukemia during childhood. J. Pediatr. 130, 210–216 (1997).

    Article  CAS  PubMed  Google Scholar 

  145. Castelo-Branco, C. et al. The effect of hormone replacement therapy on bone mass in patients with ovarian failure due to bone marrow transplantation. Maturitas 23, 307–312 (1996).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The author's work is supported in part by grant 1 R01 HD060827-01A1.

Author information

Authors and Affiliations

  1. Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, BUL 457, 55 Fruit Street, Boston, 02114, MA, USA

    Madhusmita Misra

Authors
  1. Madhusmita Misra
    View author publications

    You can also search for this author in PubMed Google Scholar

Ethics declarations

Competing interests

The author declares no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Misra, M. Effects of hypogonadism on bone metabolism in female adolescents and young adults. Nat Rev Endocrinol 8, 395–404 (2012). https://doi.org/10.1038/nrendo.2011.238

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrendo.2011.238

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing