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:

Influence of menopause on diabetes and diabetes risk

Nature Reviews Endocrinology volume 5, pages 553–558 (2009)Cite this article

Abstract

Many postmenopausal women live with diabetes mellitus; however, little information is available about how the changes that occur around the time of menopause might uniquely affect management of diabetes mellitus in this population. Although the weight gain that commonly occurs during the menopausal transition is largely attributable to aging rather than the transition itself, changes in body composition have been independently associated with menopausal status. These changes in body composition have, in turn, been associated with alterations in insulin sensitivity and glucose metabolism in postmenopausal women. Hormone therapy seems to have neutral or beneficial effects on the adverse changes in body composition associated with menopause. Whether menopausal status independently influences diabetes risk remains controversial. Nevertheless, consistent findings from large clinical trials suggest that postmenopausal hormone therapy decreases the risk of developing diabetes mellitus. Similarly, many studies suggest that postmenopausal hormone therapy has neutral or beneficial effects on glycemic control among women already diagnosed as having diabetes mellitus. Future studies are needed to elucidate the mechanisms that underlie these relationships and to determine how these observations should influence recommendations for the care of postmenopausal women with diabetes mellitus.

Key Points

  • Menopause has been associated with changes in body composition, which in turn have been linked to adverse changes in insulin sensitivity and glucose metabolism

  • Hormone therapy seems to have neutral or beneficial effects on the adverse changes in body composition associated with menopause

  • Whether menopausal status independently influences diabetes risk remains controversial

  • Some evidence suggests that postmenopausal hormone therapy decreases the risk of developing diabetes mellitus

  • Postmenopausal hormone therapy has neutral or beneficial effects on glycemic control among women already diagnosed as having diabetes mellitus

  • Further studies are needed to determine how these observations will affect clinical practice; in the meantime, postmenopausal hormone therapy should not be prescribed for the purpose of diabetes prevention

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

Similar content being viewed by others

References

  1. Department of Health and Human Services Centers for Disease Control and Prevention. National diabetes fact sheet 2007 [online], (2008).

  2. Day, J. C. National Population Projections. US Census Bureau: Population Profile of the United States [online], (2009).

    Google Scholar 

  3. Legato, M. J. et al. Gender-specific care of the patient with diabetes: review and recommendations. Gend. Med. 3, 131–158 (2006).

    Article  Google Scholar 

  4. Soules, M. R. et al. Executive summary: Stages of Reproductive Aging Workshop (STRAW). Fertil. Steril. 76, 874–878 (2001).

    Article  CAS  Google Scholar 

  5. Gold, E. B. et al. Factors associated with age at natural menopause in a multiethnic sample of midlife women. Am. J. Epidemiol. 153, 865–874 (2001).

    Article  CAS  Google Scholar 

  6. Nelson, H. D. Menopause. Lancet 371, 760–770 (2008).

    Article  Google Scholar 

  7. Bulun, S. E. & Adashi, E. Y. in Williams Textbook of Endocrinology Edn 10 (eds Larsen, P. R. et al.) 587–664 (Saunders, Philadelphia, 2003).

    Google Scholar 

  8. Dougherty, P. & Pastors, J. G. Women & diabetes. Menopause. What to expect, how to cope. Diabetes Self Manag. 24, 84–87 (2007).

    PubMed  Google Scholar 

  9. Salonia, A. et al. Sexual function and endocrine profile in fertile women with type 1 diabetes. Diabetes Care 29, 312–316 (2006).

    Article  Google Scholar 

  10. Jackson, S. L., Scholes, D., Boyko, E. J., Abraham, L. & Fihn, S. D. Urinary incontinence and diabetes in postmenopausal women. Diabetes Care 28, 1730–1738 (2005).

    Article  Google Scholar 

  11. Dorman, J. S. et al. Menopause in type 1 diabetic women: is it premature? Diabetes 50, 1857–1862 (2001).

    Article  CAS  Google Scholar 

  12. Strotmeyer, E. S., Steenkiste, A. R., Foley, T. P. Jr, Berga, S. L. & Dorman, J. S. Menstrual cycle differences between women with type 1 diabetes and women without diabetes. Diabetes Care 26, 1016–1021 (2003).

    Article  Google Scholar 

  13. Malacara, J. M., Huerta, R., Rivera, B., Esparza, S. & Fajardo, M. E. Menopause in normal and uncomplicated NIDDM women: physical and emotional symptoms and hormone profile. Maturitas 28, 35–45 (1997).

    Article  CAS  Google Scholar 

  14. López-López, R., Huerta, R. & Malacara, J. M. Age at menopause in women with type 2 diabetes mellitus. Menopause 6, 174–178 (1999).

    PubMed  Google Scholar 

  15. Eisenbarth, G. S. & Gottlieb, P. A. Autoimmune polyendocrine syndromes. N. Engl. J. Med. 350, 2068–2079 (2004).

    Article  CAS  Google Scholar 

  16. Janssen, I., Powell, L. H., Crasford, S., Lasley, B. & Sutton-Tyrell, K. Menopause and the metabolic syndrome: the study of women's health across the nation. Arch. Intern. Med. 168, 1568–1575 (2008).

    Article  CAS  Google Scholar 

  17. Shaw, L. J. et al. Postmenopausal women with a history of irregular menses and elevated androgen measurements at high risk for worsening cardiovascular event-free survival: results from the National Institutes of Health–National Heart, Lung, and Blood Institute sponsored women's ischemia syndrome evaluation. J. Clin. Endocrinol. Metab. 93, 1276–1284 (2008).

    Article  CAS  Google Scholar 

  18. Korytkowski, M. T. et al. Does androgen excess contribute to the cardiovascular risk profile in postmenopausal women with type 2 diabetes? Metabolism 54, 1626–1631 (2005).

    Article  CAS  Google Scholar 

  19. Carr, M. C. The emergence of the metabolic syndrome with menopause. J. Clin. Endocrinol. Metab. 88, 2404–2411 (2003).

    Article  CAS  Google Scholar 

  20. Douchi, T. et al. The effect of menopause on regional and total body lean mass. Maturitas 29, 247–252 (1998).

    Article  CAS  Google Scholar 

  21. Guo, S. S., Zeller, C., Chumlea, W. C. & Siervogel, R. M. Aging, body composition, and lifestyle: the FELS longitudinal study. Am. J. Clin. Nutr. 70, 405–411 (1999).

    Article  CAS  Google Scholar 

  22. Ley, C. J., Lees, B. & Stevenson, J. C. Sex- and menopause-associated changes in body-fat distribution. Am. J. Clin. Nutr. 55, 950–954 (1992).

    Article  CAS  Google Scholar 

  23. Panotopoulos, G., Ruiz, J. C., Raison, J., Guy-Grand, B. & Basdevant, A. Menopause, fat and lean distribution in obese women. Maturitas 25, 11–19 (1996).

    Article  CAS  Google Scholar 

  24. Sowers, M. et al. Changes in body composition in women over six years at midlife: ovarian and chronological aging. J. Clin. Endocrinol. Metab. 92, 895–901 (2007).

    Article  CAS  Google Scholar 

  25. Sternfeld, B., Bhat, A. K., Wang, H., Sharp, T. & Quesenberry, C. P. Jr. Menopause, physical activity, and body composition/fat distribution in midlife women. Med. Sci. Sports Exerc. 37, 1195–1202 (2005).

    Article  Google Scholar 

  26. Svendsen, O. L., Hassager, C. & Christiansen, C. Age- and menopause-associated variations in body composition and fat distribution in healthy women as measured by dual-energy X-ray absorptiometry. Metabolism 44, 369–373 (1995).

    Article  CAS  Google Scholar 

  27. Trémollieres, F. A., Pouilles, J. M. & Ribot, C. A. Relative influence of age and menopause on total and regional body composition changes in postmenopausal women. Am. J. Obstet. Gynecol. 175, 1594–1600 (1996).

    Article  Google Scholar 

  28. Wang, Q., Hassager, C., Ravn, P., Wang, S. & Christiansen, C. Total and regional body-composition changes in early postmenopausal women: age-related or menopause-related? Am. J. Clin. Nutr. 60, 843–848 (1994).

    Article  CAS  Google Scholar 

  29. Iribarren, C., Darbinian, J. A., Lo, J. C., Fireman, B. H. & Go, A. S. Value of the sagittal abdominal diameter in coronary heart disease risk assessment: cohort study in a large, multiethnic population. Am. J. Epidemiol. 164, 1150–1159 (2006).

    Article  Google Scholar 

  30. Rexrode, K. M. et al. Abdominal adiposity and coronary heart disease in women. JAMA 280, 1843–1848 (1998).

    Article  CAS  Google Scholar 

  31. Soriguer, F. et al. Type 2 diabetes mellitus and other cardiovascular risk factors are no more common during menopause: longitudinal study. Menopause 16, 817–821 (2009).

    Article  Google Scholar 

  32. Kritz-Silverstein, D. & Barrett-Connor, E. Long-term postmenopausal hormone use, obesity and fat distribution in older women. JAMA 275, 46–49 (1996).

    Article  CAS  Google Scholar 

  33. Sites, C. K. et al. The effect of hormone replacement therapy on body composition, body fat distribution, and insulin sensitivity in menopausal women: a randomized, double-blind, placebo-controlled trial. J. Clin. Endocrinol. Metab. 90, 2701–2707 (2005).

    Article  CAS  Google Scholar 

  34. Kanaya, A. M. et al. Glycemic effects of postmenopausal hormone therapy: the Heart and Estrogen/Progestin Replacement Study. A randomized, double-blind, placebo-controlled trial. Ann. Intern. Med. 138, 1–9 (2003).

    Article  CAS  Google Scholar 

  35. Espeland, M. A. et al. Effect of postmenopausal hormone therapy on body weight and waist and hip girths. Postmenopausal Estrogen–Progestin Interventions study investigators. J. Clin. Endocrinol. Metab. 82, 1549–1556 (1997).

    CAS  PubMed  Google Scholar 

  36. Haarbo, J., Marslew, U., Gotfredsen, A. & Christiansen, C. Postmenopausal hormone replacement therapy prevents central distribution of body fat after menopause. Metabolism 40, 1323–1326 (1991).

    Article  CAS  Google Scholar 

  37. Salpeter, S. R. et al. Meta-analysis: effect of hormone-replacement therapy on components of the metabolic syndrome in postmenopausal women. Diabetes Obes. Metab. 8, 538–554 (2006).

    Article  CAS  Google Scholar 

  38. Samaras, K., Hayward, C. S., Sullivan, D., Kelly, R. P. & Campbell, L. V. Effects of postmenopausal hormone replacement therapy on central abdominal fat, glycemic control, lipid metabolism, and vascular factors in type 2 diabetes: a prospective study. Diabetes Care 22, 1401–1407 (1999).

    Article  CAS  Google Scholar 

  39. Progetto Menopausa Italia Study Group. Determinants of body mass index in women around menopause attending menopause clinics in Italy. Climacteric 6, 67–74 (2003).

  40. Kuller, L. H., Simkin-Silverman, L. R., Wing, R. R., Meilahn, E. N. & Ives, D. G. Women's Healthy Lifestyle Project: a randomized clinical trial. Circulation 103, 32–37 (2001).

    Article  CAS  Google Scholar 

  41. Muscelli, E. et al. The effect of menopause on carotid artery remodeling, insulin sensitivity, and plasma adiponectin in healthy women. Am. J. Hypertens. 4, 364–370 (2009).

    Article  Google Scholar 

  42. Després, J. P. & Lemieux, I. Abdominal obesity and metabolic syndrome. Nature 444, 881–887 (2006).

    Article  Google Scholar 

  43. Barrett-Connor, E. et al. Factors associated with glucose and insulin levels in healthy postmenopausal women. Diabetes Care 19, 333–340 (1996).

    Article  CAS  Google Scholar 

  44. Sites, C. K. et al. Relation of regional fat distribution to insulin sensitivity in postmenopausal women. Fertil. Steril. 73, 61–65 (2000).

    Article  CAS  Google Scholar 

  45. Campbell, A. J., Busby, W. J., Horwath, C. C. & Robertson, M. C. Relation of age, exercise, anthropometric measurements, and diet with glucose and insulin levels in a population aged 70 years and over. Am. J. Epidemiol. 138, 688–696 (1993).

    Article  CAS  Google Scholar 

  46. Cuff, D. J. et al. Effective exercise modality to reduce insulin resistance in women with type 2 diabetes. Diabetes Care 26, 2977–2982 (2003).

    Article  Google Scholar 

  47. Golden, S. H. et al. Endogenous sex hormones and glucose tolerance status in postmenopausal women. J. Clin. Endocrinol. Metab. 92, 1289–1295 (2007).

    Article  CAS  Google Scholar 

  48. Oh, J. Y., Barrett-Connor, E., Wedick, N. M., Wingard, D. L. & Rancho Bernardo Study Investigators. Endogenous sex hormones and the development of type 2 diabetes in older men and women: the Rancho Bernardo study. Diabetes Care 25, 55–60 (2002).

    Article  CAS  Google Scholar 

  49. Stefanick, M. L. Estrogens and progestins: background and history, trends in use, and guidelines and regimens approved by the US Food and Drug Administration. Am. J. Med. 118 (Suppl. 12B), 64–73 (2005).

    Article  Google Scholar 

  50. Manson, J. E. et al. A prospective study of postmenopausal estrogen therapy and subsequent incidence of non-insulin-dependent diabetes mellitus. Ann. Epidemiol. 2, 665–673 (1992).

    Article  CAS  Google Scholar 

  51. Margolis, K. L. et al. Effect of oestrogen plus progestin on the incidence of diabetes in postmenopausal women: results from the Women's Health Initiative hormone trial. Diabetologia 47, 1175–1187 (2004).

    Article  CAS  Google Scholar 

  52. Rossi, R., Origliani, G. & Modena, M. G. Transdermal 17β-estradiol and risk of developing type 2 diabetes in a population of healthy, nonobese postmenopausal women. Diabetes Care 27, 645–649 (2004).

    Article  CAS  Google Scholar 

  53. Gabal, L. L., Goodman-Gruen, D. & Barrett-Connor, E. The effect of postmenopausal estrogen therapy on the risk of non-insulin-dependent diabetes mellitus. Am. J. Public Health 87, 443–445 (1997).

    Article  CAS  Google Scholar 

  54. Bonds, D. E. et al. The effect of conjugated equine oestrogen on diabetes incidence: the Women's Health Initiative randomised trial. Diabetologia 49, 459–468 (2006).

    Article  CAS  Google Scholar 

  55. Espeland, M. A. et al. Effect of postmenopausal hormone therapy on glucose and insulin concentrations. PEPI Investigators. Postmenopausal Estrogen/Progestin Interventions. Diabetes Care 21, 1589–1595 (1998).

    Article  CAS  Google Scholar 

  56. Smith, N. L. et al. Fasting and 2-hour postchallenge serum glucose measures and risk of incident cardiovascular events in the elderly: the Cardiovascular Health Study. Arch. Intern. Med. 162, 209–216 (2002).

    Article  Google Scholar 

  57. Keating, N. L., Cleary, P. D., Rossi, A. S., Zaslavsky, A. M. & Ayanian, J. Z. Use of hormone replacement therapy by postmenopausal women in the United States. Ann. Intern. Med. 130, 545–553 (1999).

    Article  CAS  Google Scholar 

  58. Ferrara, A. et al. Hormone replacement therapy is associated with better glycemic control in women with type 2 diabetes: the Northern California Kaiser Permanente diabetes registry. Diabetes Care 24, 1144–1150 (2001).

    Article  CAS  Google Scholar 

  59. Crespo, C. J. et al. Hormone replacement therapy and its relationship to lipid and glucose metabolism in diabetic and nondiabetic postmenopausal women: results from the Third National Health and Nutrition Examination Survey (NHANES III). Diabetes Care 25, 1675–1680 (2002).

    Article  CAS  Google Scholar 

  60. Friday, K. E., Dong, C. & Fontenot, R. U. Conjugated equine estrogen improves glycemic control and blood lipoproteins in postmenopausal women with type 2 diabetes. J. Clin. Endocrinol. Metab. 86, 48–52 (2001).

    CAS  PubMed  Google Scholar 

  61. Andersson, B. et al. Estrogen replacement therapy decreases hyperandrogenicity and improves glucose homeostasis and plasma lipids in postmenopausal women with noninsulin-dependent diabetes mellitus. J. Clin. Endocrinol. Metab. 82, 638–643 (1997).

    CAS  PubMed  Google Scholar 

  62. Brussaard, H. E., Gevers Leuven, J. A., Frölich, M., Kluft, C. & Krans, H. M. Short-term oestrogen replacement therapy improves insulin resistance, lipids and fibrinolysis in postmenopausal women with NIDDM. Diabetologia 40, 843–849 (1997).

    Article  CAS  Google Scholar 

  63. Manwaring, P., Morfis, L., Diamond, T. & Howes, L. G. The effects of hormone replacement therapy on plasma lipids in type II diabetes. Maturitas 34, 239–247 (2000).

    Article  CAS  Google Scholar 

  64. Manning, P. J., Allum, A., Jones, S., Sutherland, W. H. & Williams, S. M. The effect of hormone replacement therapy on cardiovascular risk factors in type 2 diabetes: a randomized controlled trial. Arch. Intern. Med. 161, 1772–1776 (2001).

    Article  CAS  Google Scholar 

  65. Mosnier-Pudar, H., Faguer, B., Guyenne, T. T. & Tchobroutsky, G. Effects of deprivation and replacement by percutaneous 17β estradiol and oral progesterone on blood pressure and metabolic parameters in menopause patients with non-insulin-dependent diabetes [French]. Arch. Mal Coeur Vaiss. 84, 1111–1115 (1991).

    CAS  PubMed  Google Scholar 

  66. Perera, M. et al. The effects of transdermal estradiol in combination with oral norethisterone on lipoproteins, coagulation, and endothelial markers in postmenopausal women with type 2 diabetes: a randomized, placebo-controlled study. J. Clin. Endocrinol. Metab. 86, 1140–1143 (2001).

    Article  CAS  Google Scholar 

  67. Cornu, C. et al. Postmenopause hormone treatment in women with NIDDM or impaired glucose tolerance: the MEDIA randomized clinical trial. Maturitas 37, 95–104 (2000).

    Article  CAS  Google Scholar 

  68. Rossouw, J. E. et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA 288, 321–333 (2002).

    Article  CAS  Google Scholar 

  69. Anderson, G. L. et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA 291, 1701–1712 (2004).

    Article  CAS  Google Scholar 

  70. Mosca, L. et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 115, 1481–1501 (2007).

    Article  Google Scholar 

  71. Nelson, H. D. et al. Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis. JAMA 295, 2057–2071 (2006).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank Zainab Abdul-Rahim (Brigham and Women's Hospital, Boston, MA, USA) for assistance with manuscript preparation.

Author information

Authors and Affiliations

  1. Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University, Chicago, IL, USA

    Emily D. Szmuilowicz

  2. Division of Endocrinology and Metabolism, University of California, San Diego, CA, USA

    Cynthia A. Stuenkel

  3. Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA

    Ellen W. Seely

Authors
  1. Emily D. Szmuilowicz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cynthia A. Stuenkel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ellen W. Seely
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ellen W. Seely.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Szmuilowicz, E., Stuenkel, C. & Seely, E. Influence of menopause on diabetes and diabetes risk. Nat Rev Endocrinol 5, 553–558 (2009). https://doi.org/10.1038/nrendo.2009.166

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrendo.2009.166

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