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  • Primer
  • Published:

Menopause

Abstract

Menopause is an inevitable component of ageing and encompasses the loss of ovarian reproductive function, either occurring spontaneously or secondary to other conditions. It is not yet possible to accurately predict the onset of menopause, especially early menopause, to give women improved control of their fertility. The decline in ovarian oestrogen production at menopause can cause physical symptoms that may be debilitating, including hot flushes and night sweats, urogenital atrophy, sexual dysfunction, mood changes, bone loss, and metabolic changes that predispose to cardiovascular disease and diabetes. The individual experience of the menopause transition varies widely. Important influential factors include the age at which menopause occurs, personal health and wellbeing, and each woman's environment and culture. Management options range from lifestyle assessment and intervention through to hormonal and non-hormonal pharmacotherapy, each of which has specific benefits and risks. Decisions about therapy for perimenopausal and postmenopausal women depend on symptomatology, health status, immediate and long-term health risks, personal life expectations, and the availability and cost of therapies. More effective and safe therapies for the management of menopausal symptoms need to be developed, particularly for women who have absolute contraindications to hormone therapy. For an illustrated summary of this Primer, visit: http://go.nature.com/BjvJVX

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Figure 1: Regulation of menstrual cycles.
Figure 2: The stages of reproductive ageing in women.
Figure 3: Menopausal loss of ovarian function.
Figure 4: Pathogenesis of postmenopausal osteoporosis.
Figure 5: Consequences of menopause on the cardiovascular system.

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References

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

    Article  CAS  PubMed  Google Scholar 

  2. Harlow, S. D. et al. Executive summary of the Stages of Reproductive Aging Workshop + 10: addressing the unfinished agenda of staging reproductive aging. Menopause 19, 387–395 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Harlow, S. et al. Executive summary of the Stages of Reproductive Aging Workshop + 10: addressing the unfinished agenda of staging reproductive aging. Fertil. Steril. 97, 843–851 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Harlow, S. D. et al. Executive summary of the Stages of Reproductive Aging Workshop + 10: addressing the unfinished agenda of staging reproductive aging. Climacteric 15, 105–114 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Harlow, S. D. et al. Executive summary of the Stages of Reproductive Aging Workshop + 10: addressing the unfinished agenda of staging reproductive aging. J. Clin. Endocrinol. Metabolism 97, 1159–1168 (2012).

    Article  CAS  Google Scholar 

  6. Jane, F. M. & Davis, S. R. A practitioner's toolkit for managing the menopause. Climacteric 17, 1–16 (2014).

    Article  Google Scholar 

  7. Tom, S. E. & Mishra, G. D. Current Topics in Menopause: a Life Course Approach to Reproductive Aging (Bentham Science Publishers Ltd., 2013).

    Google Scholar 

  8. Schoenaker, D. A., Jackson, C. A., Rowlands, J. V. & Mishra, G. D. Socioeconomic position, lifestyle factors and age at natural menopause: a systematic review and meta-analyses of studies across six continents. Int. J. Epidemiol. 43, 1542–1562 (2014). This paper provides a global perspective of factors associated with age at menopause.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Dratva, J. et al. Is age at menopause increasing across Europe? Results on age at menopause and determinants from two population-based studies. Menopause 16, 385–394 (2009).

    Article  PubMed  Google Scholar 

  10. Flint, M. P. Secular trends in menopause age. J. Psychosomat. Obstetr. Gynaecol. 18, 65–72 (1997).

    Article  CAS  Google Scholar 

  11. Flint, M. Is there a secular trend in age of menopause? Maturitas 1, 133–139 (1978).

    Article  CAS  PubMed  Google Scholar 

  12. Nichols, H. B. et al. From menarche to menopause: trends among US Women born from 1912 to 1969. Am. J. Epidemiol. 164, 1003–1011 (2006).

    Article  PubMed  Google Scholar 

  13. Rodstrom, K. et al. Evidence for a secular trend in menopausal age: a population study of women in Gothenburg. Menopause 10, 538–543 (2003).

    Article  PubMed  Google Scholar 

  14. McKinlay, S. M., Brambilla, D. J. & Posner, J. G. The normal menopause transition. Maturitas 61, 4–16 (2008).

    Article  PubMed  Google Scholar 

  15. Mishra, G. D. & Dobson, A. J. Using longitudinal profiles to characterize women's symptoms through midlife: results from a large prospective study. Menopause 19, 549–555 (2012).

    Article  PubMed  Google Scholar 

  16. Gartoulla, P., Islam, M. R., Bell, R. J. & Davis, S. R. Prevalence of menopausal symptoms in Australian women at midlife: a systematic review. Climacteric 17, 529–539 (2014).

    Article  CAS  PubMed  Google Scholar 

  17. Mishra, G. & Kuh, D. Perceived change in quality of life during the menopause. Social Sci. Med. 62, 93–102 (2006).

    Article  Google Scholar 

  18. Utian, W. H. Psychosocial and socioeconomic burden of vasomotor symptoms in menopause: a comprehensive review. Health Qual. Life Outcomes 3, 47 (2005).

  19. Thurston, R. C. & Joffe, H. Vasomotor symptoms and menopause: findings from the Study of Women's Health across the Nation. Obstetr. Gynecol. Clin. North Amer. 38, 489–501 (2011).

    Article  Google Scholar 

  20. Gold, E. B. et al. Longitudinal analysis of the association between vasomotor symptoms and race/ethnicity across the menopausal transition: study of women's health across the nation. Am. J. Publ. Health 96, 1226–1235 (2006).

    Article  Google Scholar 

  21. Freeman, E. W. et al. Association of anti-mullerian hormone levels with obesity in late reproductive-age women. Fertil. Steril. 87, 101–106 (2007).

    Article  CAS  PubMed  Google Scholar 

  22. Islam, M. R., Gartoulla, P., Bell, R. J., Fradkin, P. & Davis, S. R. Prevalence of menopausal symptoms in Asian midlife women: a systematic review. Climacteric 1–42 (2014).

  23. Mishra, G. D. & Kuh, D. Health symptoms during midlife in relation to menopausal transition: British prospective cohort study. BMJ 344, e402 (2012). This paper demonstrates the various trajectories of symptoms associated with menopause.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Colditz, G. A. et al. Menopause and the risk of coronary heart disease in women. N. Engl. J. Med. 316, 1105–1110 (1987).

    Article  CAS  PubMed  Google Scholar 

  25. Anasti, J. N., Kalantaridou, S. N., Kimzey, L. M., Defensor, R. A. & Nelson, L. M. Bone loss in young women with karyotypically normal spontaneous premature ovarian failure. Obstet. Gynecol. 91, 12–15 (1998).

    Article  CAS  PubMed  Google Scholar 

  26. Kalantaridou, S. N., Davis, S. R. & Nelson, L. M. Premature ovarian failure. Endocrinol. Metabolism Clin. North Amer. 27, 989–1006 (1998).

    Article  CAS  Google Scholar 

  27. Kok, H. S. et al. Heart disease risk determines menopausal age rather than the reverse. J. Am. College Cardiol. 47, 1976–1983 (2006).

    Article  Google Scholar 

  28. Ossewaarde, M. E. et al. Age at menopause, cause-specific mortality and total life expectancy. Epidemiology 16, 556–562 (2005).

    Article  PubMed  Google Scholar 

  29. Mondul, A. M., Rodriguez, C., Jacobs, E. J. & Calle, E. E. Age at natural menopause and cause-specific mortality. Am. J. Epidemiol. 162, 1089–1097 (2005).

    Article  PubMed  Google Scholar 

  30. Kok, H. S., van, A. K. M., van, d. S. Y. T., Peeters, P. H. & Wijmenga, C. Genetic studies to identify genes underlying menopausal age. Hum. Reprod. Update 11, 483–493 (2005).

    Article  CAS  PubMed  Google Scholar 

  31. van Asselt, K. M. et al. Heritability of menopausal age in mothers and daughters. Fertil. Steril. 82, 1348–1351 (2004).

    Article  PubMed  Google Scholar 

  32. Murabito, J. M., Yang, O., Fox, C., Wilson, P. W. & Cupples, L. A. Heritability of age at natural menopause in the Framingham Heart Study. J. Clin. Endocrinol. Metab. 90, 3427–3430 (2005).

    Article  CAS  PubMed  Google Scholar 

  33. Torgerson, D. J., Thomas, R. E. & Reid, D. M. Mothers and daughters menopausal ages: is there a link? . Eur. J. Obstet. Gynecol. Reprod. Biol. 74, 63–66 (1997).

    Article  CAS  PubMed  Google Scholar 

  34. Cramer, D. W., Xu, H. & Harlow, B. L. Family history as a predictor of early menopause. Fertil. Steril. 64, 740–745 (1995).

    Article  CAS  PubMed  Google Scholar 

  35. de, B. J. P. et al. The role of genetic factors in age at natural menopause. Hum. Reprod. 16, 2014–2018 (2001).

    Article  Google Scholar 

  36. Mishra, G., Hardy, R. & Kuh, D. Are the effects of risk factors for timing of menopause modified by age? Results from a British birth cohort study. Menopause 14, 717–724 (2007).

    PubMed  Google Scholar 

  37. Voorhuis, M., Onland-Moret, N. C., van der Schouw, Y. T., Fauser, B. C. & Broekmans, F. J. Human studies on genetics of the age at natural menopause: a systematic review. Hum. Reprod. Update 16, 364–377 (2010).

    Article  CAS  PubMed  Google Scholar 

  38. van Asselt, K. M. et al. Linkage analysis of extremely discordant and concordant sibling pairs identifies quantitative trait loci influencing variation in human menopausal age. Am. J. Hum. Genet. 74, 444–453 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Murabito, J. M., Yang, Q., Fox, C. S. & Cupples, L. A. Genome-wide linkage analysis to age at natural menopause in a community-based sample: the Framingham Heart Study. Fertil. Steril. 84, 1674–1679 (2005).

    Article  CAS  PubMed  Google Scholar 

  40. Lin, W. T. et al. Comparison of age at natural menopause in BRCA1/2 mutation carriers with a non-clinic based sample of women in northern California. Cancer 119, 1652–1659 (2013).

    Article  CAS  PubMed  Google Scholar 

  41. Watkins, W. J. et al. An investigation into FOXE1 polyalanine tract length in premature ovarian failure. Mol. Hum. Reprod. 12, 145–149 (2006).

    Article  CAS  PubMed  Google Scholar 

  42. Chand, A. L., Ponnampalam, A. P., Harris, S. E., Winship, I. M. & Shelling, A. N. Mutational analysis of BMP15and GDF9 as candidate genes for premature ovarian failure. Fertil. Steril. 86, 1009–1012 (2006).

    Article  CAS  PubMed  Google Scholar 

  43. Ferrarini, E. et al. Clinical characteristics and genetic analysis in women with premature ovarian insufficiency. Maturitas 74, 61–67 (2013). This is a comprehensive summary of primary ovarian insufficiency.

    Article  CAS  PubMed  Google Scholar 

  44. Cramer, D. W., Harlow, B. L., Barbieri, R. L. & Ng, W. G. Galactose-1-phosphate uridyl transferase activity associated with age at menopause and reproductive history. Fertil. Steril. 51, 609–615 (1989).

    Article  CAS  PubMed  Google Scholar 

  45. Kaufman, F. R., Devgan, S. & Donnell, G. N. Results of a survey of carrier women for the galactosemia gene. Fertil. Steril. 60, 727–728 (1993).

    Article  CAS  PubMed  Google Scholar 

  46. Nelson, L. M. Clinical practice. Primary ovarian insufficiency. N. Engl. J. Med. 360, 606–614 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. He, C. et al. Genome-wide association studies identify loci associated with age at menarche and age at natural menopause. Nat. Genet. 41, 724–728 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Stolk, L. et al. Loci at chromosomes 13, 19 and 20 influence age at natural menopause. Nat. Genet. 41, 645–647 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Elks, C. E. et al. Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies. Nat. Genet. 42, 1077–1085 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Stolk, L. et al. Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways. Nat. Genet. 44, 260–268 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Nejat, E. J. & Chervenak, J. L. The continuum of ovarian aging and clinicopathologies associated with the menopausal transition. Maturitas 66, 187–190 (2010).

    Article  PubMed  Google Scholar 

  52. Broekmans, F. J., Soules, M. R. & Fauser, B. C. Ovarian aging: mechanisms and clinical consequences. Endocr. Rev. 30, 465–493 (2009).

    Article  CAS  PubMed  Google Scholar 

  53. Burger, H. G., Hale, G. E., Robertson, D. M. & Dennerstein, L. A review of hormonal changes during the menopausal transition: focus on findings from the Melbourne Women's Midlife Health Project. Hum. Reprod. Update 13, 559–565 (2007).

    Article  CAS  PubMed  Google Scholar 

  54. Wise, P. M. Neuroendocrine modulation of the “menopause”: insights into the aging brain. Am. J. Physiol. 277, E965–E970 (1999).

    Article  CAS  PubMed  Google Scholar 

  55. Downs, J. L. & Wise, P. M. The role of the brain in female reproductive aging. Mol. Cell Endocrinol. 299, 32–38 (2009).

    Article  CAS  PubMed  Google Scholar 

  56. Butler, L. & Santoro, N. The reproductive endocrinology of the menopausal transition. Steroids 76, 627–635 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Santoro, N. et al. Impaired folliculogenesis and ovulation in older reproductive aged women. J. Clin. Endocrinol. Metab. 88, 5502–5509 (2003).

    Article  CAS  PubMed  Google Scholar 

  58. Archer, D. F. et al. Menopausal hot flushes and night sweats: where are we now?. Climacteric 14, 515–528 (2011).

    Article  CAS  PubMed  Google Scholar 

  59. Freeman, E. W., Sammel, M. D., Lin, H., Liu, Z. & Gracia, C. R. Duration of menopausal hot flushes and associated risk factors. Obstet. Gynecol. 117, 1095–1104 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  60. Gjelsvik, B., Rosvold, E. O., Straand, J., Dalen, I. & Hunskaar, S. Symptom prevalence during menopause and factors associated with symptoms and menopausal age. Results from the Norwegian Hordaland Women's Cohort study. Maturitas 70, 383–390 (2011).

    Article  PubMed  Google Scholar 

  61. Richard-Davis, G. & Wellons, M. Racial and ethnic differences in the physiology and clinical symptoms of menopause. Semin. Reprod. Med. 31, 380–386 (2013).

    Article  PubMed  Google Scholar 

  62. Duffy, O. K., Iversen, L., Aucott, L. & Hannaford, P. C. Factors associated with resilience or vulnerability to hot flushes and night sweats during the menopausal transition. Menopause 20, 383–392 (2013).

    PubMed  Google Scholar 

  63. Zervas, I. M. et al. Additive effect of depressed mood and vasomotor symptoms on postmenopausal insomnia. Menopause 16, 837–842 (2009).

    Article  PubMed  Google Scholar 

  64. Al-Safi, Z. A. & Santoro, N. Menopausal hormone therapy and menopausal symptoms. Fertil. Steril. 101, 905–915 (2014).

    Article  CAS  PubMed  Google Scholar 

  65. Vivian-Taylor, J. & Hickey, M. Menopause and depression: is there a link? Maturitas 79, 142–146 (2014).

    Article  PubMed  Google Scholar 

  66. Bay-Jensen, A. C. et al. Role of hormones in cartilage and joint metabolism: understanding an unhealthy metabolic phenotype in osteoarthritis. Menopause 20, 578–586 (2013).

    PubMed  Google Scholar 

  67. Blumel, J. E. et al. Menopause could be involved in the pathogenesis of muscle and joint aches in mid-aged women. Maturitas 75, 94–100 (2013).

    Article  PubMed  Google Scholar 

  68. Nappi, R. E. & Kokot-Kierepa, M. Vaginal Health: Insights, Views and Attitudes (VIVA) - results from an international survey. Climacteric 15, 36–44 (2012).

    Article  CAS  PubMed  Google Scholar 

  69. Portman, D. J. & Gass, M. L. Genitourinary syndrome of menopause: new terminology for vulvovaginal atrophy from the International Society for the Study of Women's Sexual Health and The North American Menopause Society. Menopause 21, 1063–1068 (2014).

    Article  PubMed  Google Scholar 

  70. Nappi, R. E. & Palacios, S. Impact of vulvovaginal atrophy on sexual health and quality of life at postmenopause. Climacteric 17, 3–9 (2014).

    Article  CAS  PubMed  Google Scholar 

  71. Avis, N. E. et al. Longitudinal changes in sexual functioning as women transition through menopause: results from the Study of Women's Health Across the Nation. Menopause 16, 442–452 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  72. Boyle, W. J., Simonet, W. S. & Lacey, D. L. Osteoclast differentiation and activation. Nature 423, 337–342 (2003).

    Article  CAS  PubMed  Google Scholar 

  73. Tella, S. H. & Gallagher, J. C. Prevention and treatment of postmenopausal osteoporosis. J. Steroid Biochem. Mol. Biol. 142, 155–170 (2014).

    Article  CAS  PubMed  Google Scholar 

  74. Khosla, S. Pathogenesis of age-related bone loss in humans. J. Gerontol. A Biol. Sci. Med. Sci. 68, 1226–1235 (2013). This paper illustrates the mechanisms of postmenopausal bone loss.

    Article  CAS  PubMed  Google Scholar 

  75. Clarke, B. L. & Khosla, S. Physiology of bone loss. Radiol Clin. North Am. 48, 483–495 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  76. Sapir-Koren, R. & Livshits, G. Is interaction between age-dependent decline in mechanical stimulation and osteocyte-estrogen receptor levels the culprit for postmenopausal-impaired bone formation? Osteoporos. Int. 24, 1771–1789 (2013).

    CAS  Google Scholar 

  77. Shuster, L. T., Rhodes, D. J., Gostout, B. S., Grossardt, B. R. & Rocca, W. A. Premature menopause or early menopause: long-term health consequences. Maturitas 65, 161–166 (2010).

    Article  PubMed  Google Scholar 

  78. Davis, S. R. et al. Understanding weight gain at menopause. Climacteric 15, 419–429 (2012).

    Article  CAS  PubMed  Google Scholar 

  79. Tchernof, A. & Despres, J. P. Pathophysiology of human visceral obesity: an update. Physiol. Rev. 93, 359–404 (2013).

    Article  CAS  PubMed  Google Scholar 

  80. Barton, M. Cholesterol and atherosclerosis: modulation by oestrogen. Curr. Opin. Lipidol 24, 214–220 (2013).

    Article  CAS  PubMed  Google Scholar 

  81. Chedraui, P. et al. Angiogenesis, inflammation and endothelial function in postmenopausal women screened for the metabolic syndrome. Maturitas 77, 370–374 (2014).

    Article  CAS  PubMed  Google Scholar 

  82. Chedraui, P. et al. Circulating leptin, resistin, adiponectin, visfatin, adipsin and ghrelin levels and insulin resistance in postmenopausal women with and without the metabolic syndrome. Maturitas 79, 86–90 (2014).

    Article  CAS  PubMed  Google Scholar 

  83. Hage, F. G. & Oparil, S. Ovarian hormones and vascular disease. Curr. Opin. Cardiol 28, 411–416 (2013). This paper describes the mechanisms of vasoprotection by endogenous oestrogens and the development of cardiovascular disease in menopause.

    PubMed  Google Scholar 

  84. Abramson, B. L. & Melvin, R. G. Cardiovascular risk in women: focus on hypertension. Can. J. Cardiol 30, 553–559 (2014).

    Article  PubMed  Google Scholar 

  85. El Khoudary, S. R. et al. Progression rates of carotid intima-media thickness and adventitial diameter during the menopausal transition. Menopause 20, 8–14 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  86. Hildreth, K. L., Kohrt, W. M. & Moreau, K. L. Oxidative stress contributes to large elastic arterial stiffening across the stages of the menopausal transition. Menopause 21, 624–632 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  87. Moreau, K. L., Hildreth, K. L., Meditz, A. L., Deane, K. D. & Kohrt, W. M. Endothelial function is impaired across the stages of the menopause transition in healthy women. J. Clin. Endocrinol. Metab. 97, 4692–4700 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Stamatelopoulos, K. S. et al. Recently postmenopausal women have the same prevalence of subclinical carotid atherosclerosis as age and traditional risk factor matched men. Atherosclerosis 221, 508–513 (2012).

    Article  CAS  PubMed  Google Scholar 

  89. Lobo, R. A. et al. Prevention of diseases after menopause. Climacteric 17, 540–556 (2014).

    Article  CAS  PubMed  Google Scholar 

  90. Lisabeth, L. & Bushnell, C. Stroke risk in women: the role of menopause and hormone therapy. Lancet Neurol. 11, 82–91 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  91. Rocca, W. A., Grossardt, B. R., Miller, V. M., Shuster, L. T. & Brown, R. D. Jr. Premature menopause or early menopause and risk of ischemic stroke. Menopause 19, 272–277 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  92. De Vos, M., Devroey, P. & Fauser, B. C. Primary ovarian insufficiency. Lancet 376, 911–921 (2010).

    Article  PubMed  Google Scholar 

  93. Wellons, M., Ouyang, P., Schreiner, P. J., Herrington, D. M. & Vaidya, D. Early menopause predicts future coronary heart disease and stroke: the Multi-Ethnic Study of Atherosclerosis. Menopause 19, 1081–1087 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  94. Luine, V. N. Estradiol and cognitive function: past, present and future. Horm. Behav. 66, 602–618 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Silva, I. & Naftolin, F. Brain health and cognitive and mood disorders in ageing women. Best Pract. Res. Clin. Obstet. Gynaecol. 27, 661–672 (2013).

    Article  PubMed  Google Scholar 

  96. Weber, M. T., Maki, P. M. & McDermott, M. P. Cognition and mood in perimenopause: a systematic review and meta-analysis. J. Steroid Biochem. Mol. Biol. 142, 90–98 (2014).

    Article  CAS  PubMed  Google Scholar 

  97. de Villiers, T. J. et al. Updated 2013 International Menopause Society recommendations on menopausal hormone therapy and preventive strategies for midlife health. Climacteric 16, 316–337 (2013).

    Article  CAS  PubMed  Google Scholar 

  98. Henderson, V. W. Action of estrogens in the aging brain: dementia and cognitive aging. Biochim. Biophys. Acta 1800, 1077–1083 (2010).

    Article  CAS  PubMed  Google Scholar 

  99. Hardy, R. & Kuh, D. Does early growth influence timing of the menopause? Evidence from a British birth cohort. Hum. Reprod. 17, 2474–2479 (2002).

    Article  CAS  PubMed  Google Scholar 

  100. Elias, S. G., van Noord, P. A., Peeters, P. H., den Tonkelaar, T. I. & Grobbee, D. E. Childhood exposure to the 1944–1945 Dutch famine and subsequent female reproductive function. Hum. Reprod. 20, 2483–2488 (2005).

    Article  PubMed  Google Scholar 

  101. Mishra, G. D., Cooper, R., Tom, S. E. & Kuh, D. Early life circumstances and their impact on menarche and menopause. Women's Health 5, 175–190 (2009).

  102. Hardy, R., Mishra, G. & Kuh, D. in Menopause, Postmenopause and Aging. (eds Purdie, D. W. et al.) 11–19 (Royal Society of Medicine Press Ltd London, 2005).

    Google Scholar 

  103. Do, K. A. et al. Predictive factors of age at menopause in a large Australian twin study. Hum. Biol. 70, 1073–1091 (1998).

    CAS  PubMed  Google Scholar 

  104. Shinberg, D. S. An event history analysis of age at last menstrual period: correlates of natural and surgical menopause among midlife Wisconsin women. Social Sci. Med. 46, 1381–1396 (1998).

    Article  CAS  Google Scholar 

  105. Torgerson, D. J., Avenell, A., Russell, I. T. & Reid, D. M. Factors associated with onset of menopause in women aged 45–49. Maturitas 19, 83–92 (1994).

    Article  CAS  PubMed  Google Scholar 

  106. Wise, L. A., Krieger, N., Zierler, S. & Harlow, B. L. Lifetime socioeconomic position in relation to onset of perimenopause. J. Epidemiol. Commun. Health 56, 851–860 (2002).

    Article  CAS  Google Scholar 

  107. Castelo-Branco, C. et al. Age at menopause in Latin America. Menopause 13, 706–712 (2006).

    Article  PubMed  Google Scholar 

  108. Bromberger, J. T. et al. Prospective study of the determinants of age at menopause. Am. J. Epidemiol. 145, 124–133 (1997).

    Article  CAS  PubMed  Google Scholar 

  109. Hardy, R., Kuh, D. & Wadsworth, M. Smoking, body mass index, socioeconomic status and the menopausal transition in a British national cohort. Int. J. Epidemiol. 29, 845–851 (2000).

    Article  CAS  PubMed  Google Scholar 

  110. van Asselt, K. M. et al. Current smoking at menopause rather than duration determines the onset of natural menopause. Epidemiology 15, 634–639 (2004).

    Article  PubMed  Google Scholar 

  111. Discigil, G., Gemalmaz, A., Tekin, N. & Basak, O. Profile of menopausal women in west Anatolian rural region sample. Maturitas 55, 247–254 (2006).

    Article  PubMed  Google Scholar 

  112. Hardy, R. & Kuh, D. Reproductive characteristics and the age at inception of the perimenopause in a British National Cohort. Am. J. Epidemiol. 149, 612–620 (1999).

    Article  CAS  PubMed  Google Scholar 

  113. Gold, E. B. et al. Factors related to age at natural menopause: longitudinal analyses. Am. J. Epidemiol. 178, 70–83 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  114. McKinlay, S. M., Bifano, N. L. & McKinlay, J. B. Smoking and age at menopause in women. Ann. Intern. Med. 103, 350–356 (1985).

    Article  CAS  PubMed  Google Scholar 

  115. Mikkelesen, T. F., Graff-Iverseon, S., Sundby, J. & Bjertness, E. Early menopause, association with tobacco smoking, coffee consumption and other lifestyle factors: a cross-sectional study. BMC Public Health 7, 149–167 (2007).

    Article  Google Scholar 

  116. Mark-Kappeler, C. J., Hoyer, P. B. & Devine, P. J. Xenobiotic effects on ovarian preantral follicles. Biol. Reprod. 85, 871–883 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Plante, B. J., Cooper, G. S., Baird, D. D. & Steiner, A. Z. The impact of smoking on antimullerian hormone levels in women aged 38 to 50 years. Maturitas 17, 571–576 (2010).

    Google Scholar 

  118. Luoto, R., Laprio, J. & Uutela, A. Age at natural menopause and sociodemographic status in Finland. Am. J. Epidemiol. 139, 64–76 (1994).

    Article  CAS  PubMed  Google Scholar 

  119. Lawlor, D. A., Ebrahim, S. & Smith, G. D. The association of socio-economic position across the life course and age at menopause: teh British Women's Heart and Health Study. BJOG 110, 1078–1087 (2003).

    Article  PubMed  Google Scholar 

  120. Schoenbaum, E. E. et al. HIV infection, drug use, and onset of natural menopause. Clin. Infect. Dis. 41, 1517–1524 (2005).

    Article  PubMed  Google Scholar 

  121. van Noord, P. A., Dubas, J. S., Dorland, M., Boersma, H. & te Velde, E. Age at natural menopause in a population-based screening cohort: the role of menarche, fecundity, and lifestyle factors. Fertil. Steril. 68, 95–102 (1997).

    Article  CAS  PubMed  Google Scholar 

  122. Akahoshi, M. et al. The effects of body mass index on age at menopause. International journal of obesity and related metabolic disorders. Int. J. Obes. Relat. Metab. Disord. 26, 961–968 (2002).

    Article  CAS  PubMed  Google Scholar 

  123. Sammel, M. D., Freeman, E. W., Liu, Z., Lin, H. & Guo, W. Factors that influence entry into stages of the menopausal transition. Menopause 16, 1218–1227 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  124. Aydin, Z. D. Determinants of age at natural menopause in the Isparta Menopause and Health Study: premenopausal body mass index gain rate and episodic weight loss. Menopause 17, 494–505 (2010).

    PubMed  Google Scholar 

  125. Sowers, M. R. et al. Genetic polymorphisms and obesity influence estradiol decline during the menopause. Clin. Endocrinol. (Oxf.) 74, 618–623 (2011).

    Article  CAS  Google Scholar 

  126. Cohen, L. S., Soares, C. N., Vitonis, A. F., Otto, M. W. & Harlow, B. L. Risk for new onset of depression during the menopausal transition: the Harvard study of moods and cycles. Arch. Gen. Psychiatry 63, 385–390 (2006). This is the first work to find that new-onset depression is specifically associated with the late menopause transition.

    Article  PubMed  Google Scholar 

  127. Bromberger, J. T. et al. Depressive symptoms during the menopausal transition: the Study of Women's Health Across the Nation (SWAN). J. Affect Disord. 103, 267–272 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  128. Pastore, L. M., Carter, R. A., Hulka, B. S. & Wells, E. Self-reported urogenital symptoms in postmenopausal women: Women's Health Initiative. Maturitas 49, 292–303 (2004).

    Article  PubMed  Google Scholar 

  129. Freeman, E. W., Sammel, M. D. & Sanders, R. J. Risk of long-term hot flashes after natural menopause: evidence from the Penn Ovarian Aging Study cohort. Menopause 21, 924–932 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  130. Politi, M. C., Schleinitz, M. D. & Col, N. F. Revisiting the duration of vasomotor symptoms of menopause: a meta-analysis. J. Gen. Intern. Med. 23, 1507–1513 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  131. Col, N. F., Guthrie, J. R., Politi, M. & Dennerstein, L. Duration of vasomotor symptoms in middle-aged women: a longitudinal study. Menopause 16, 453–457 (2009).

    Article  PubMed  Google Scholar 

  132. Kravitz, H. M. & Joffe, H. Sleep during the perimenopause: a SWAN story. Obstet. Gynecol. Clin. North Am. 38, 567–586 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  133. Freeman, E. W., Sammel, M. D., Lin, H. & Nelson, D. B. Associations of hormones and menopausal status with depressed mood in women with no history of depression. Arch. Gen. Psychiatry 63, 375–382 (2006).

    Article  CAS  PubMed  Google Scholar 

  134. Wallace, R. B., Sherman, B. M., Bean, J. A., Treloar, A. E. & Schlabaugh, L. Probability of menopause with increasing duration of amenorrhea in middle-aged women. Am. J. Obstet. Gynecol. 135, 1021–1024 (1979).

    Article  CAS  PubMed  Google Scholar 

  135. Burger, H. G., Dudley, E. C., Cui, J., Dennerstein, L. & Hopper, J. L. A prospective longitudinal study of serum testosterone, dehydroepiandrosterone sulfate, and sex hormone-binding globulin levels through the menopause transition. J. Clin. Endocrinol. Metab. 85, 2832–2838 (2000).

    CAS  PubMed  Google Scholar 

  136. Metcalf, M. G., D.Onald, R. A. & Livesey, J. H. Pituitary-ovarian function before, during and after the menopause: a longitudinal study. Clin. Endocrinol. (Oxf.) 17, 489–494 (1982).

    Article  CAS  Google Scholar 

  137. Davison, S. L., Bell, R., Donath, S., Montalto, J. G. & Davis, S. R. Androgen levels in adult females: changes with age, menopause, and oophorectomy. J. Clin. Endocrinol. Metab. 90, 3847–3853 (2005).

    Article  CAS  PubMed  Google Scholar 

  138. Modi, D., Bhartiya, D. & Puri, C. Developmental expressionand cellular distribution of Mullerian inhibiting substance in the primate ovary. Reproduction 132, 443–453 (2006).

    Article  CAS  PubMed  Google Scholar 

  139. Sowers, M. R. et al. Anti-mullerian hormone and inhibin B in the defintion of ovarian aging and the menopause transition. J. Clin. Endocrinol. Metab. 93, 3478–3483 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Santoro, N. et al. Helping midlife women predict the onset of the final menses, SWAN, the Study of Women's Health Across the Nation. Menopause 14, 415–424 (2007).

    Article  PubMed  Google Scholar 

  141. Freeman, E. W., Sammel, M. D., Lin, H., Boorman, D. W. & Gracia, C. R. Contribution of the rate of change of antimullerian hormone in estimating time to menopause for late reproductive-age women. Fertil. Steril. 98, 1254–1259 (2012). This is the first work to examine the value of serial AMH levels in predicting menopause.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. La Marca, A. et al. Anti-Mullerian hormone-based prediction model for a live birth in assisted reproduction. Reprod. Biomed. Online 22, 341–349 (2011).

    Article  CAS  PubMed  Google Scholar 

  143. Hansen, K. R., Craig, L. B., Zavy, M. T., Klein, N. A. & Soules, M. R. Ovarian primordial and nongrowing follicle counts according to the Stages of Reproductive Aging Workshop (STRAW) staging system. Menopause 19, 164–171 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  144. Crandall, C. J. et al. Osteoporosis screening in postmenopausal women 50 to 64 years old: comparison of US Preventive Services Task Force strategy and two traditional strategies in the Women's Health Initiative. J. Bone Miner. Res. 29, 1661–1666 (2014).

    Article  PubMed  Google Scholar 

  145. Sowers, M. R. et al. Amount of bone loss in relation to time around the final menstrual period and follicle-stimulating hormone staging of the transmenopause. J. Clin. Endocrinol. Metabolism 95, 2155–2162 (2010).

    Article  CAS  Google Scholar 

  146. Hawker, G. et al. A clinical decision rule to enhance targeted bone mineral density testing in healthy mid-life women. Osteoporos Int. 23, 1931–1938 (2012).

    Article  CAS  PubMed  Google Scholar 

  147. Lim, L. S., Hoeksema, L. J. & Sherin, K. Screening for osteoporosis in the adult U. S. population: ACPM position statement on preventive practice. Am. J. Prev. Med. 36, 366–375 (2009).

    Article  PubMed  Google Scholar 

  148. Davis, S. R., Tan, A. & Bell, R. J. Targeted assessment of fracture risk in women at midlife. Osteoporos. Int.http://dx.doi.org/10.1007/s00198-015-3046-9 (2015). This paper offers a clinical approach to pre-screening women at midlife using bone densitometry.

  149. Lenders, J. W. et al. Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 99, 1915–1942 (2014).

    Article  CAS  PubMed  Google Scholar 

  150. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders 5th edn (American Psychiatric Association, 2013).

  151. Bromberger, J. T. et al. Persistent mood symptoms in a multiethnic community cohort of pre- and perimenopausal women. Am. J. Epidemiol. 158, 347–356 (2003).

    Article  PubMed  Google Scholar 

  152. Morse, C. A., Dudley, E., Guthrie, J. & Dennerstein, L. Relationships between premenstrual complaints and perimenopausal experiences. J. Psychosom. Obstet. Gynaecol. 19, 182–191 (1998).

    Article  CAS  PubMed  Google Scholar 

  153. Holte, A. & Mikkelsen, A. The menopausal syndrome: a factor analytic replication. Maturitas 13, 193–203 (1991).

    Article  CAS  PubMed  Google Scholar 

  154. Tehrani, F. R., Solaymani-Dodaran, M., Tohidi, M., Gohari, M. R. & Azizi, F. Modeling age at menopause using serum concentration of anti-mullerian hormone. J. Clin. Endocrinol. Metab. 98, 729–735 (2013).

    Article  CAS  PubMed  Google Scholar 

  155. Dewailly, D. et al. The physiology and clinical utility of anti-Mullerian hormone in women. Hum. Reprod. Update 20, 370–385 (2014).

    Article  PubMed  Google Scholar 

  156. Tran, N. D., Cedars, M. I. & Rosen, M. P. The role of anti-mullerian hormone (AMH) in assessing ovarian reserve. J. Clin. Endocrinol. Metab. 96, 3609–3614 (2011).

    Article  CAS  PubMed  Google Scholar 

  157. Sullivan, S. D., Welt, C. & Sherman, S. FMR1 and the continuum of primary ovarian insufficiency. Semin. Reprod. Med. 29, 299–307 (2011).

    Article  PubMed  Google Scholar 

  158. Spath, M. A. et al. Intra-individual stability over time of standardized anti-Mullerian hormone in FMR1 premutation carriers. Hum. Reprod. 26, 2185–2191 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Richardson, S. J., Senikas, V. & Nelson, J. F. Follicular depletion during the menopausal transition: evidence for accelerated loss and ultimate exhaustion. J. Clin. Endocrinol. Metab. 65, 1231–1237 (1987).

    Article  CAS  PubMed  Google Scholar 

  160. Woods, D. C., White, Y. A. & Tilly, J. L. Purification of oogonial stem cells from adult mouse and human ovaries: an assessment of the literature and a view toward the future. Reprod. Sci. 20, 7–15 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  161. Hanna, C. B. & Hennebold, J. D. Ovarian germline stem cells: an unlimited source of oocytes? Fertil. Steril. 101, 20–30 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  162. Yuan, J. et al. No evidence for neo-oogenesis may link to ovarian senescence in adult monkey. Stem Cells 31, 2538–2550 (2013).

    Article  CAS  PubMed  Google Scholar 

  163. de Villiers, T. J. et al. Global Consensus Statement on menopausal hormone therapy. Maturitas 74, 391–392 (2013).

    Article  CAS  PubMed  Google Scholar 

  164. Furness, S., Roberts, H., Marjoribanks, J. & Lethaby, A. Hormone therapy in postmenopausal women and risk of endometrial hyperplasia. Cochrane Database Syst. Rev. 8, CD000402 (2012).

  165. Hall, E., Frey, B. N. & Soares, C. N. Non-hormonal treatment strategies for vasomotor symptoms: a critical review. Drugs 71, 287–304 (2011).

    Article  CAS  PubMed  Google Scholar 

  166. Borrelli, F. & Ernst, E. Alternative and complementary therapies for the menopause. Maturitas 66, 333–343 (2010). This is a comprehensive systematic review of alternative and complementary medicine for menopausal symptoms.

    Article  PubMed  Google Scholar 

  167. Dunn, J. F., Nisula, B. C. & Rodboard, D. Transport of steroid hormones. Binding of 21 endogenous steroids to both testosterone-binding globulin and cortico-steroid-binding globulin in human plasma. J. Clin. Endocrinol. Metab. 53, 58–68 (1981).

    Article  CAS  PubMed  Google Scholar 

  168. Raisz, L. G. et al. Comparison of the effects of estrogen alone and estrogen plus androgen on biochemical markers of bone form and resorption in postmenopausal women. J. Clin. Endocrinol. Metab. 81, 37–43 (1995).

    Google Scholar 

  169. Olie, V. et al. Hormone therapy and recurrence of venous thromboembolism among postmenopausal women. Menopause 18, 488–493 (2011).

    Article  PubMed  Google Scholar 

  170. Hoibraaten, E. et al. Increased risk of recurrent venous thromboembolism during hormone replacement therapy —results of the randomized, double-blind, placebo-controlled estrogen in venous thromboembolism trial (EVTET). Thromb. Haemost. 84, 961–967 (2000).

    Article  CAS  PubMed  Google Scholar 

  171. Liu, B. et al. Gallbladder disease and use of transdermal versus oral hormone replacement therapy in postmenopausal women: prospective cohort study. BMJ 337, a386 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  172. Constantine, G., Graham, S., Portman, D. J., Rosen, R. C. & Kingsberg, S. A. Female sexual function improved with ospemifene in postmenopausal women with vulvar and vaginal atrophy: results of a randomized, placebo-controlled trial. Climacterichttp://dx.doi.org/10.3109/13697137.2014.954996 (2014).

  173. Wurz, G. T., Soe, L. H. & DeGregorio, M. W. Ospemifene, vulvovaginal atrophy, and breast cancer. Maturitas 74, 220–225 (2013).

    Article  CAS  PubMed  Google Scholar 

  174. Pinkerton, J. V. et al. Evaluation of the efficacy and safety of bazedoxifene/conjugated estrogens for secondary outcomes including vasomotor symptoms in postmenopausal women by years since menopause in the Selective Estrogens, Menopause and Response to Therapy (SMART) trials. J. Womens Health (Larchmt) 23, 18–28 (2014).

    Article  Google Scholar 

  175. Wierman, M. E. et al. Androgen therapy in women: a reappraisal: an endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 99, 3489–3510 (2014).

    Article  CAS  PubMed  Google Scholar 

  176. Davis, S. R. Cardiovascular and cancer safety of testosterone in women. Curr. Opin. Endocrinol. Diabetes Obes 18, 198–203 (2011).

    Article  CAS  PubMed  Google Scholar 

  177. Santen, R. J. Vaginal administration of estradiol: effects of dose, preparation and timing on plasma estradiol levels. Climacteric 17, 1–14 (2014).

    Google Scholar 

  178. Grodstein, F., Manson, J. E., Stampfer, M. J. & Rexrode, K. Postmenopausal hormone therapy and stroke: role of time since menopause and age at initiation of hormone therapy. Arch. Intern. Med. 168, 861–866 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. American College of Obstetricians and Gynecologists. ACOG committee opinion no. 556: Postmenopausal estrogen therapy: route of administration and risk of venous thromboembolism. Obstet. Gynecol. 121, 887–890 (2013).

  180. Canonico, M. et al. Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study. Circulation 115, 840–845 (2007).

    Article  CAS  PubMed  Google Scholar 

  181. Fournier, A. et al. Risks of endometrial cancer associated with different hormone replacement therapies in the E3N cohort, 1992–2008. Am. J. Epidemiol. 180, 508–517 (2014).

    Article  PubMed  Google Scholar 

  182. Manson, J. E. et al. Algorithm and mobile app for menopausal symptom management and hormonal/non-hormonal therapy decision making: a clinical decision-support tool from The North American Menopause Society. Menopause 22, 247–253 (2014).

    Article  Google Scholar 

  183. Chin, J., Konje, J. C. & Hickey, M. Levonorgestrel intrauterine system for endometrial protection in women with breast cancer on adjuvant tamoxifen. Cochrane Database Syst. Rev. 4, CD007245 (2009).

    Google Scholar 

  184. Wan, Y. L. & Holland, C. The efficacy of levonorgestrel intrauterine systems for endometrial protection: a systematic review. Climacteric 14, 622–632 (2011).

    Article  CAS  PubMed  Google Scholar 

  185. Stearns, V. et al. Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine. J. Natl Cancer Inst. 95, 1758–1764 (2003).

    Article  CAS  PubMed  Google Scholar 

  186. Lethaby, A. et al. Phytoestrogens for menopausal vasomotor symptoms. Cochrane Database Syst. Rev. 12, CD001395 (2013).

    Google Scholar 

  187. Rada, G. et al. Non-hormonal interventions for hot flushes in women with a history of breast cancer. Cochrane Database Syst. Rev. 9, CD004923 (2010).

    Google Scholar 

  188. Leach, M. J. & Moore, V. Black cohosh (Cimicifugaspp.) for menopausal symptoms. Cochrane Database Syst. Rev. 9, CD007244 (2012).

    Google Scholar 

  189. Laakmann, E., Grajecki, D., Doege, K., zu Eulenburg, C. & Buhling, K. J. Efficacy of Cimicifuga racemosa, Hypericum perforatum and Agnus castus in the treatment of climacteric complaints: a systematic review. Gynecol. Endocrinol. 28, 703–709 (2012).

    Article  PubMed  Google Scholar 

  190. Walega, D. R., Rubin, L. H., Banuvar, S., Shulman, L. P. & Maki, P. M. Effects of stellate ganglion block on vasomotor symptoms: findings from a randomized controlled clinical trial in postmenopausal women. Menopause 21, 807–814 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  191. Sinha, A. & Ewies, A. A. Non-hormonal topical treatment of vulvovaginal atrophy: an up-to-date overview. Climacteric 16, 305–312 (2013).

    Article  CAS  PubMed  Google Scholar 

  192. Gartoulla, P., Worsley, R., Bell, R. J. & Davis, S. R. Moderate-severe vasomotor and sexual symptoms remain problematic for 60–65 year old women. Menopausehttp://dx.doi.org/10.1097/GME.0000000000000383 (2014).

  193. Elavsky, S., Gonzales, J. U., Proctor, D. N., Williams, N. & Henderson, V. W. Effects of physical activity on vasomotor symptoms: examination using objective and subjective measures. Menopause 19, 1095–1103 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  194. Daley, A. et al. The effectiveness of exercise as treatment for vasomotor menopausal symptoms: randomised controlled trial. BJOG 122, 565–575 (2015). This is a randomized trial in primary care that examines the effects of exercise on symptoms of menopause. It shows no effect, thus questioning the recommendation of exercise by healthcare providers as a first-line therapy.

    Article  CAS  PubMed  Google Scholar 

  195. Babatunde, O. O., Forsyth, J. J. & Gidlow, C. J. A meta-analysis of brief high-impact exercises for enhancing bone health in premenopausal women. Osteoporos Int. 23, 109–119 (2012).

    Article  CAS  PubMed  Google Scholar 

  196. Martyn- St James, M. & Carroll, S. A meta-analysis of impact exercise on postmenopausal bone loss: the case for mixed loading exercise programmes. Br. J. Sports Med. 43, 898–908 (2009).

    Article  Google Scholar 

  197. Tucker, L. A., Fosson, E., Bailey, B. W. & Lecheminant, J. D. Is the dose response relationship between body mass and hip bone mineral density in women influenced by diet, physical activity, or menopause? Am. J. Health Promot. 28, 325–327 (2013).

    Article  PubMed  Google Scholar 

  198. Newton, K. M. et al. Efficacy of yoga for vasomotor symptoms: a randomized controlled trial. Menopause 21, 339–346 (2014).

    PubMed  PubMed Central  Google Scholar 

  199. Portman, D. J., Bachmann, G. A. & Simon, J. A. Ospemifene, a novel selective estrogen receptor modulator for treating dyspareunia associated with postmenopausal vulvar and vaginal atrophy. Menopause 20, 623–630 (2013).

    Article  PubMed  Google Scholar 

  200. Avis, N. E. et al. Change in health-related quality of life over the menopausal transition in a multiethnic cohort of middle-aged women: Study of Women's Health Across the Nation. Menopause 16, 860–869 (2009). This paper discusses the impact of menopause on HRQoL.

    Article  PubMed  PubMed Central  Google Scholar 

  201. Zollner, Y. F., Acquadro, C. & Schaefer, M. Literature review of instruments to assess health-related quality of life during and after menopause. Qual. Life Res. 14, 309–327 (2005).

    Article  CAS  PubMed  Google Scholar 

  202. Salpeter, S. R., Buckley, N. S., Liu, H. & Salpeter, E. E. The cost-effectiveness of hormone therapy in younger and older postmenopausal women. Am. J. Med. 122, 42–52.e2 (2009). This paper reinforces the importance of QoL at a community level.

    Article  PubMed  Google Scholar 

  203. Utian, W. H. & Woods, N. F. Impact of hormone therapy on quality of life after menopause. Menopause 20, 1098–1105 (2013).

    Article  PubMed  Google Scholar 

  204. Archer, D. F. et al. Long-term safety of drospirenone-estradiol for hormone therapy: a randomized, double-blind, multicenter trial. Menopause 12, 716–727 (2005).

    Article  PubMed  Google Scholar 

  205. Al-Akoum, M. et al. Effects of Hypericum perforatum (St. John's wort) on hot flashes and quality of life in perimenopausal women: a randomized pilot trial. Menopause 16, 307–314 (2009).

    Article  PubMed  Google Scholar 

  206. Kalay, A. E., Demir, B., Haberal, A., Kalay, M. & Kandemir, O. Efficacy of citalopram on climacteric symptoms. Menopause 14, 223–229 (2007).

    Article  PubMed  Google Scholar 

  207. Somunkiran, A., Erel, C. T., Demirci, F. & Senturk, M. L. The effect of tibolone versus 17β-estradiol on climacteric symptoms in women with surgical menopause: a randomized, cross-over study. Maturitas 56, 61–68 (2007).

    Article  CAS  PubMed  Google Scholar 

  208. Utian, W. et al. Bazedoxifene/conjugated estrogens and quality of life in postmenopausal women. Maturitas 63, 329–335 (2009).

    Article  CAS  PubMed  Google Scholar 

  209. Wiklund, I. K., Mattsson, L. A., Lindgren, R. & Limoni, C. Effects of a standardized ginseng extract on quality of life and physiological parameters in symptomatic postmenopausal women: a double-blind, placebo-controlled trial. Swedish Alternative . Med. Group. Int. J. Clin. Pharmacol. Res. 19, 89–99 (1999).

    CAS  Google Scholar 

  210. Hays, J. et al. Effects of estrogen plus progestin on health-related quality of life. N. Engl. J. Med. 348, 1839–1854 (2003).

    Article  CAS  PubMed  Google Scholar 

  211. Brunner, R. L. et al. Effects of conjugated equine estrogen on health-related quality of life in postmenopausal women with hysterectomy: results from the Women's Health Initiative randomized clinical trial. Arch. Internal Med. 165, 1976–1986 (2005).

    Article  CAS  Google Scholar 

  212. Hlatky, M. A., Boothroyd, D., Vittinghoff, E., Sharp, P. & Whooley, M. A. Quality-of-life and depressive symptoms in postmenopausal women after receiving hormone therapy: results from the Heart and Estrogen/Progestin Replacement Study (HERS) trial. JAMA 287, 591–597 (2002).

    Article  CAS  PubMed  Google Scholar 

  213. Ylikangas, S., Sintonen, H. & Heikkinen, J. Decade-long use of continuous combined hormone replacement therapy is associated with better health-related quality of life in postmenopausal women, as measured by the generic 15D instrument. J. Br. Menopause Soc. 11, 145–151 (2005).

    Article  PubMed  Google Scholar 

  214. Zeleke, B. M., Davis, S. R., Fradkin, P. & Bell, R. J. Vasomotor symptoms and urogenital atrophy in older women: a systematic review. Climacterichttp://dx.doi.org/10.3109/13697137.2014.978754 (2014).

  215. Rossouw, J. et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative Randomised Controlled Trial. JAMA 288, 321–333 (2002).

    Article  CAS  PubMed  Google Scholar 

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Introduction (S.R.D.); Epidemiology (G.D.M.); Mechanisms and pathophysiology (T.S. and I.L.); Diagnosis, screening and prevention (N.S. and S.R.D.); Management (M.R., L.P. and S.R.D.); Quality of life (M.L.); Outlook (S.R.D.); and overview of Primer (S.R.D.).

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Correspondence to Susan R. Davis.

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S.R.D. has received an honorarium from Abbott Pharmaceuticals for one presentation and is an investigator for Trimel Pharmaceuticals and Lawley Pharmaceuticals; all other authors declare no competing interests.

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Davis, S., Lambrinoudaki, I., Lumsden, M. et al. Menopause. Nat Rev Dis Primers 1, 15004 (2015). https://doi.org/10.1038/nrdp.2015.4

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