An Overview of the Extent and Nature of Menopause and Its Physiological Basis

Chapter
Part of the Nutrition and Health book series (NH)

Keypoints

  • Menopause is defined as the permanent cessation of menstruation due to depletion of the follicle pool.

  • The menstrual cycle and changes in the cyclic pattern until a complete stop are orchestrated by gonadotrophins, steroids, and inhibins.

  • The median age at natural menopause is around 50–51, for centuries and across populations.

  • Menopause is associated with vasomotor menopausal symptoms; of other symptoms such as incontinence, depressed feelings, and vaginal dryness it is not clear whether it is the menopause per se that causes these symptoms and complaints, or whether aging also plays a major role.

  • Early menopause is associated with increased risk of cardiovascular disease and osteoporosis and a decreased risk of breast cancer.

  • These effects are generally ascribed to estrogens, but for osteoporosis and breast cancer this is much more clear than for cardiovascular disease.

Keywords

Menopause Endocrinology Epidemiology Physiology Vasomotor menopausal symptoms 

Abbreviations

FMP

Final menstrual period

STRAW

Stages of reproductive aging workshop

LH

Luteinizing hormone

FSH

Follicle-stimulating hormone

GnRH

Gonadotrophin-releasing hormone

VMS

Vasomotor menopausal symptoms

CVD

Cardiovascular diseases

CHD

Coronary heart disease

HT

Hormone therapy

HERS

Heart and estrogen/progestin replacement study

WHI

Women’s Health Initiative trial

BMD

Bone mineral density

References

  1. 1.
    WHO Scientific Group on Research on the Menopause in the 1990s. Geneva, WHO: WHO Technical report series, Research on the menopause in the 1990s; 1996. Ref Type: Report. 866.Google Scholar
  2. 2.
    Peccei JS. A critique of the grandmother hypotheses: old and new. Am J Hum Biol. 2001;13:434–52.PubMedCrossRefGoogle Scholar
  3. 3.
    Hawkes K, O’Connell JF, Jones NG, Alvarez H, Charnov EL. Grandmothering, menopause, and the evolution of human life histories. Proc Natl Acad Sci USA. 1998;95:1336–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Kirkwood TB. Evolution of ageing. Nature. 1977;270:301–4.PubMedCrossRefGoogle Scholar
  5. 5.
    Walker ML, Herndon JG. Menopause in nonhuman primates? Biol Reprod. 2008;79:398–406.PubMedCrossRefGoogle Scholar
  6. 6.
    Walker ML, Anderson DC, Herndon JG, Walker LC. Ovarian aging in squirrel monkeys (Saimiri sciureus). Reproduction. 2009;138:793–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Treloar AE, Boynton RE, Behn BG. Variation of the human menstrual cycle through reproductive life. Int J Fertil. 1967;12:77–126.PubMedGoogle Scholar
  8. 8.
    Treloar AE. Menstrual cyclicity and the pre-menopause. Maturitas. 1981;3:249–64.PubMedCrossRefGoogle Scholar
  9. 9.
    Harlow SD, Gass M, Hall JE, Lobo R, Maki P, Rebar RW, et al. Executive summary of the stages of reproductive aging workshop  +  10: addressing the unfinished agenda of staging reproductive aging. Menopause. 2012;19(4):387–95.PubMedCrossRefGoogle Scholar
  10. 10.
    Baker TG. A quantitative and cytological study of germ cells in human ovaries. Proc R Soc Lond B Biol Sci. 1963;158:417–33.PubMedCrossRefGoogle Scholar
  11. 11.
    Block E. Quantitative morphological investigations of the follicular system in women; variations at different ages. Acta Anat (Basel). 1952;14:108–23.CrossRefGoogle Scholar
  12. 12.
    Richardson SJ, Senikas V, Nelson JF. Follicular depletion during the menopausal transition: evidence for accelerated loss and ultimate exhaustion. J Clin Endocrinol Metab. 1987;65:1231–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Faddy MJ, Gosden RG, Gougeon A, Richardson SJ, Nelson JF. Accelerated disappearance of ovarian follicles in mid-life: implications for forecasting menopause. Hum Reprod. 1992;7:1342–6.PubMedGoogle Scholar
  14. 14.
    Morabia A, Costanza MC. International variability in ages at menarche, first livebirth, and menopause. World Health Organization Collaborative Study of Neoplasia and Steroid Contraceptives. Am J Epidemiol. 1998;148:1195–205.PubMedCrossRefGoogle Scholar
  15. 15.
    Noord-Zaadstra BM, Looman CW, Alsbach H, Habbema JD, te Velde ER, Karbaat J. Delaying childbearing: effect of age on fecundity and outcome of pregnancy. BMJ. 1991;302:1361–5.PubMedCrossRefGoogle Scholar
  16. 16.
    Burger HG, Hale GE, Dennerstein L, Robertson DM. Cycle and hormone changes during perimenopause: the key role of ovarian function. Menopause. 2008;15:603–12.PubMedCrossRefGoogle Scholar
  17. 17.
    Burger H. The menopausal transition—endocrinology. J Sex Med. 2008;5:2266–73.PubMedGoogle Scholar
  18. 18.
    Burger HG, Dudley EC, Hopper JL, Shelley JM, Green A, Smith A, et al. The endocrinology of the menopausal transition: a cross-sectional study of a population-based sample. J Clin Endocrinol Metab. 1995;80:3537–45.PubMedCrossRefGoogle Scholar
  19. 19.
    Burger HG, Cahir N, Robertson DM, Groome NP, Dudley E, Green A, et al. Serum inhibins A and B fall differentially as FSH rises in perimenopausal women. Clin Endocrinol (Oxf). 1998;48:809–13.CrossRefGoogle Scholar
  20. 20.
    Welt CK, Adams JM, Sluss PM, Hall JE. Inhibin A and inhibin B responses to gonadotropin withdrawal depends on stage of follicle development. J Clin Endocrinol Metab. 1999;84:2163–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Burger HG, Hale GE, Robertson DM, 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. 2007;13:559–65.PubMedCrossRefGoogle Scholar
  22. 22.
    Sowers MR, Zheng H, McConnell D, Nan B, Harlow SD, Randolph Jr JF. Estradiol rates of change in relation to the final menstrual period in a population-based cohort of women. J Clin Endocrinol Metab. 2008;93:3847–52.PubMedCrossRefGoogle Scholar
  23. 23.
    Backman G. Die beschleunigte Entwicklung der Jugend. Verfrühte Menarche, verspätete Menopause, verlängerte Lebensdauer. Acta Anat (Basel). 1947;4:421–80.CrossRefGoogle Scholar
  24. 24.
    Tanner JM. Growth at adolescence: with a general consideration of the effects of hereditary and environmental factors upon growth and maturation from birth to maturity. Oxford: Blackwell Scientific Publications; 1962.Google Scholar
  25. 25.
    Amundsen DW, Diers CJ. The age of menopause in classical Greece and Rome. Hum Biol. 1970;42:79–86.PubMedGoogle Scholar
  26. 26.
    Amundsen DW, Diers CJ. The age of menopause in medieval Europe. Hum Biol. 1973;45:605–12.PubMedGoogle Scholar
  27. 27.
    Treloar AE. Menarche, menopause, and intervening fecundability. Hum Biol. 1974;46:89–107.PubMedGoogle Scholar
  28. 28.
    Flint M. Is there a secular trend in age of menopause? Maturitas. 1978;1:133–9.PubMedCrossRefGoogle Scholar
  29. 29.
    Flint MP. Secular trends in menopause age. J Psychosom Obstet Gynaecol. 1997;18:65–72.PubMedCrossRefGoogle Scholar
  30. 30.
    Frommer J. Changing age of the menopause. Br Med J. 1964;2:349–51.PubMedCrossRefGoogle Scholar
  31. 31.
    MacMahon B, Worcester J. Age at menopause, United States 1960–62. US Dept of Health, Education and Welfare, Public Health Service, National Center for Health Statistics, Series 11, Number 19. Washington, DC: US Government Printing Office; 1966.Google Scholar
  32. 32.
    McKinlay S, Jefferys M, Thompson B. An investigation of the age at menopause. J Biosoc Sci. 1972;4:161–73.PubMedCrossRefGoogle Scholar
  33. 33.
    van Asselt KM, Kok HS, van der Schouw YT, Grobbee DE, te Velde ER, Pearson PL, et al. Current smoking at menopause rather than duration determines the onset of natural menopause. Epidemiology. 2004;15:634–9.PubMedCrossRefGoogle Scholar
  34. 34.
    McKinlay SM, Bifano NL, McKinlay JB. Smoking and age at menopause in women. Ann Intern Med. 1985;103:350–6.PubMedCrossRefGoogle Scholar
  35. 35.
    Rodstrom K, Bengtsson C, Milsom I, Lissner L, Sundh V, Bjourkelund C. Evidence for a secular trend in menopausal age: a population study of women in Gothenburg. Menopause. 2003;10:538–43.PubMedCrossRefGoogle Scholar
  36. 36.
    Nichols HB, Trentham-Dietz A, Hampton JM, et al. From menarche to menopause: trends among US Women born from 1912 to 1969. Am J Epidemiol. 2006;164:1003–11.PubMedCrossRefGoogle Scholar
  37. 37.
    Kalichman L, Malkin I, Kobyliansky E. Time-related trends of age at menopause and reproductive period of women in a Chuvashian rural population. Menopause. 2007;14:135–40.PubMedCrossRefGoogle Scholar
  38. 38.
    Dratva J, Gomez Real F, Schindler C, Ackermann-Liebrich U, Gerbase MW, Probst-Hensch NM, et al. Is age at menopause increasing across Europe? Results on age at menopause and determinants from two population-based studies. Menopause. 2009;16:385–94.PubMedCrossRefGoogle Scholar
  39. 39.
    Pakarinen M, Raitanen J, Kaaja R, Luoto R. Secular trend in the menopausal age in Finland 1997–2007 and correlation with socioeconomic, reproductive and lifestyle factors. Maturitas. 2010;66:417–22.PubMedCrossRefGoogle Scholar
  40. 40.
    Stearns V, Ullmer L, Lopez JF, Smith Y, Isaacs C, Hayes D. Hot flushes. Lancet. 2002;360:1851–61.PubMedCrossRefGoogle Scholar
  41. 41.
    Freedman RR. Pathophysiology and treatment of menopausal hot flashes. Semin Reprod Med. 2005;23:117–25.PubMedCrossRefGoogle Scholar
  42. 42.
    Kronenberg F. Hot flashes: epidemiology and physiology. Ann N Y Acad Sci. 1990;592:52–86.PubMedCrossRefGoogle Scholar
  43. 43.
    Freedman RR, Krell W. Reduced thermoregulatory null zone in postmenopausal women with hot flashes. Am J Obstet Gynecol. 1999;181:66–70.PubMedCrossRefGoogle Scholar
  44. 44.
    Savage MV, Brengelmann GL. Control of skin blood flow in the neutral zone of human body temperature regulation. J Appl Physiol. 1996;80:1249–57.PubMedGoogle Scholar
  45. 45.
    Freedman RR. Physiology of hot flashes. Am J Hum Biol. 2001;13:453–64.PubMedCrossRefGoogle Scholar
  46. 46.
    Nelson HD. Commonly used types of postmenopausal estrogen for treatment of hot flashes: scientific review. JAMA. 2004;291:1610–20.PubMedCrossRefGoogle Scholar
  47. 47.
    Gast GC, Samsioe G, Grobbee DE, Nilsson PM, van der Schouw YT. Vasomotor symptoms, estradiol levels and cardiovascular risk profile in women. Maturitas. 2010;66:285–90.PubMedCrossRefGoogle Scholar
  48. 48.
    Deecher DC, Dorries K. Understanding the pathophysiology of vasomotor symptoms (hot flushes and night sweats) that occur in perimenopause, menopause, and postmenopause life stages. Arch Womens Ment Health. 2007;10:247–57.PubMedCrossRefGoogle Scholar
  49. 49.
    Freeman EW, Sammel MD, Lin H, et al. Symptoms associated with menopausal transition and reproductive hormones in midlife women. Obstet Gynecol. 2007;110:230–40.PubMedCrossRefGoogle Scholar
  50. 50.
    Politi MC, Schleinitz MD, Col NF. Revisiting the duration of vasomotor symptoms of menopause: a meta-analysis. J Gen Intern Med. 2008;23:1507–13.PubMedCrossRefGoogle Scholar
  51. 51.
    McKinlay SM, Jefferys M. The menopausal syndrome. Br J Prev Soc Med. 1974;28:108–15.PubMedGoogle Scholar
  52. 52.
    Freeman EW, Sherif K. Prevalence of hot flushes and night sweats around the world: a systematic review. Climacteric. 2007;10:197–214.PubMedCrossRefGoogle Scholar
  53. 53.
    Huang AJ, Grady D, Jacoby VL, Blackwell TL, Bauer DC, Sawaya GF. Persistent hot flushes in older postmenopausal women. Arch Intern Med. 2008;168:840–6.PubMedCrossRefGoogle Scholar
  54. 54.
    Bachmann GA. Vasomotor flushes in menopausal women. Am J Obstet Gynecol. 1999;180:S312–6.PubMedCrossRefGoogle Scholar
  55. 55.
    Nelson HD. Menopause. Lancet. 2008;371:760–70.PubMedCrossRefGoogle Scholar
  56. 56.
    Avis NE, Brockwell S, Colvin A. A universal menopausal syndrome? Am J Med. 2005;118(Suppl 12B):37–46.PubMedCrossRefGoogle Scholar
  57. 57.
    Greendale GA, Lee NP, Arriola ER. The menopause. Lancet. 1999;353:571–80.PubMedCrossRefGoogle Scholar
  58. 58.
    Dennerstein L, Dudley EC, Hopper JL, Guthrie JR, Burger HG. A prospective population-based study of menopausal symptoms. Obstet Gynecol. 2000;96:351–8.PubMedCrossRefGoogle Scholar
  59. 59.
    Avis NE, Brambilla D, McKinlay SM, Vass K. A longitudinal analysis of the association between menopause and depression. Results from the Massachusetts Women’s Health Study. Ann Epidemiol. 1994;4:214–20.PubMedCrossRefGoogle Scholar
  60. 60.
    Hunter MS. Psychological and somatic experience of the menopause: a prospective study [corrected]. Psychosom Med. 1990;52:357–67.PubMedGoogle Scholar
  61. 61.
    Witteman JC, Moerman CJ, Westendorp IC. Myth of the menopause paradox. Lancet. 1998;352:407.PubMedCrossRefGoogle Scholar
  62. 62.
    Kannel WB, Hjortland MC, McNamara PM, Gordon T. Menopause and the risk of cardiovascular disease: the Framingham study. Ann Intern Med. 1976;85:447–52.PubMedCrossRefGoogle Scholar
  63. 63.
    Colditz GA, Willett WC, Stampfer MJ, Rosner B, Speizer FE, Hennekens CH. Menopause and the risk of coronary heart disease in women. N Engl J Med. 1987;316:1105–10.PubMedCrossRefGoogle Scholar
  64. 64.
    Rivera CM, Grossardt BR, Rhodes DJ, et al. Increased cardiovascular mortality after early bilateral oophorectomy. Menopause. 2009;16:15–23.PubMedCrossRefGoogle Scholar
  65. 65.
    Parker WH, Jacoby V, Shoupe D, Rocca W. Effect of bilateral oophorectomy on women’s long-term health. Womens Health (Lond Engl). 2009;5:565–76.CrossRefGoogle Scholar
  66. 66.
    van der Schouw YT, van der Graaf Y, Steyerberg EW, Eijkemans JC, Banga JD. Age at menopause as a risk factor for cardiovascular mortality. Lancet. 1996;347:714–8.PubMedCrossRefGoogle Scholar
  67. 67.
    de Kleijn MJ, van der Schouw YT, Verbeek AL, Peeters PH, Banga JD, van der Graaf Y. Endogenous estrogen exposure and cardiovascular mortality risk in postmenopausal women. Am J Epidemiol. 2002;155:339–45.PubMedCrossRefGoogle Scholar
  68. 68.
    Atsma F, Bartelink ML, Grobbee DE, van der Schouw YT. Postmenopausal status and early menopause as independent risk factors for cardiovascular disease: a meta-analysis. Menopause. 2006;13:265–79.PubMedCrossRefGoogle Scholar
  69. 69.
    Baer HJ, Glynn RJ, Hu FB, Hankinson SE, Willett WC, Colditz GA, et al. Risk factors for mortality in the nurses’ health study: a competing risks analysis. Am J Epidemiol. 2011;173:319–29.PubMedCrossRefGoogle Scholar
  70. 70.
    Bairey Merz CN, Johnson BD, Sharaf BL, Bittner V, Berga SL, Braunstein GD, et al. Hypoestrogenemia of hypothalamic origin and coronary artery disease in premenopausal women: a report from the NHLBI-sponsored WISE study. J Am Coll Cardiol. 2003;41:413–9.PubMedCrossRefGoogle Scholar
  71. 71.
    Barrett-Connor E, Goodman-Gruen D. Prospective study of endogenous sex hormones and fatal cardiovascular disease in postmenopausal women. BMJ. 1995;311:1193–6.PubMedCrossRefGoogle Scholar
  72. 72.
    Rexrode KM, Manson JE, Lee IM, et al. Sex hormone levels and risk of cardiovascular events in postmenopausal women. Circulation. 2003;108(14):1688–93.PubMedCrossRefGoogle Scholar
  73. 73.
    Chen Y, Zeleniuch-Jacquotte A, Arslan AA, Wojcik O, Toniolo P, Shore RE, et al. Endogenous hormones and coronary heart disease in postmenopausal women. Atherosclerosis. 2011;216:414–9.PubMedCrossRefGoogle Scholar
  74. 74.
    Stampfer MJ, Colditz GA. Estrogen replacement therapy and coronary heart disease: a quantitative assessment of the epidemiologic evidence. Prev Med. 1991;20:47–63.PubMedCrossRefGoogle Scholar
  75. 75.
    Grodstein F, Stampfer M. The epidemiology of coronary heart disease and estrogen replacement in postmenopausal women. Prog Cardiovasc Dis. 1995;38:199–210.PubMedCrossRefGoogle Scholar
  76. 76.
    Grodstein F, Manson JE, Colditz GA, Willett WC, Speizer FE, Stampfer MJ. A prospective, observational study of postmenopausal hormone therapy and primary prevention of cardiovascular disease. Ann Intern Med. 2000;133:933–41.PubMedCrossRefGoogle Scholar
  77. 77.
    Grodstein F, Manson JE, Stampfer MJ. Postmenopausal hormone use and secondary prevention of coronary events in the nurses’ health study. a prospective, observational study. Ann Intern Med. 2001;135:1–8.PubMedCrossRefGoogle Scholar
  78. 78.
    Farquhar C, Marjoribanks J, Lethaby A, Suckling JA, Lamberts Q. Long term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev. 2009;CD004143.Google Scholar
  79. 79.
    Rossouw JE, Prentice RL, Manson JE, Wu L, Barad D, Barnabei VM, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA. 2007;297:1465–77.PubMedCrossRefGoogle Scholar
  80. 80.
    Lindh-Astrand L, Brynhildsen J, Hoffman M, Hammar M. Vasomotor symptoms usually reappear after cessation of postmenopausal hormone therapy: a Swedish population-based study. Menopause. 2009;16(6):1213–7.PubMedCrossRefGoogle Scholar
  81. 81.
    Burger HG. WHI risks: any relevance to menopause management? Maturitas. 2007;57:6–10.PubMedCrossRefGoogle Scholar
  82. 82.
    van der Schouw YT, Grobbee DE. Menopausal complaints, oestrogens, and heart disease risk: an explanation for discrepant findings on the benefits of post-menopausal hormone therapy. Eur Heart J. 2005;26:1358–61.PubMedCrossRefGoogle Scholar
  83. 83.
    Gast GC, Grobbee DE, Pop VJ, Keyzer JJ, Wijnands-van Gent CJ, Samsioe GN, et al. Menopausal complaints are associated with cardiovascular risk factors. Hypertension. 2008;51:1492–8.PubMedCrossRefGoogle Scholar
  84. 84.
    Gast GC, Pop VJ, Samsioe G, Grobbee DE, Nilsson PM, Keyzer JJ, et al. Vasomotor menopausal symptoms are associated with increased risk of coronary heart disease. Menopause. 2011;18:51.Google Scholar
  85. 85.
    Tuomikoski P, Mikkola TS, Hamalainen E, Tikkanen MJ, Turpeinen U, Ylikorkala O. Biochemical markers for cardiovascular disease in recently postmenopausal women with or without hot flashes. Menopause. 2010;17:151.CrossRefGoogle Scholar
  86. 86.
    Svartberg J, von MD, Kritz-Silverstein D, Barrett-Connor E. Vasomotor symptoms and mortality: the Rancho Bernardo Study. Menopause. 2009;16:888–91.PubMedCrossRefGoogle Scholar
  87. 87.
    Allison MA, Manson JE, Aragaki A, et al. Vasomotor symptoms and coronary artery calcium in postmenopausal women. Menopause. 2010;17:1145.CrossRefGoogle Scholar
  88. 88.
    Allison MA, Manson JE. The complex interplay of vasomotor symptoms, hormone therapy, and cardiovascular risk. Menopause. 2009;16:619–20.PubMedCrossRefGoogle Scholar
  89. 89.
    Gast GC, Pop VJ, Samsioe GN, Grobbee DE, Nilsson PM, Keyzer JJ, et al. Hormone therapy and coronary heart disease risk by vasomotor menopausal symptoms. Maturitas. 2011;70:373–8.PubMedCrossRefGoogle Scholar
  90. 90.
    Block JE, Smith R, Glueer CC, Steiger P, Ettinger B, Genant HK. Models of spinal trabecular bone loss as determined by quantitative computed tomography. J Bone Miner Res. 1989;4:249–57.PubMedCrossRefGoogle Scholar
  91. 91.
    Gudmundsdottir H, Jonsdottir B, Kristinsson S, Johannesson A, Goodenough D, Sigurdsson G. Vertebral bone density in Icelandic women using quantitative computed tomography without an external reference phantom. Osteoporos Int. 1993;3:84–9.PubMedCrossRefGoogle Scholar
  92. 92.
    Seifert-Klauss V, Link T, Heumann C, Luppa P, Haseitl M, Laakmann J, et al. Influence of pattern of menopausal transition on the amount of trabecular bone loss. Results from a 6-year prospective longitudinal study. Maturitas. 2006;55:317–24.PubMedCrossRefGoogle Scholar
  93. 93.
    Prior JC, Vigna YM, Wark JD, Eyre DR, Lentle BC, Li DK, et al. Premenopausal ovariectomy-related bone loss: a randomized, double-blind, one-year trial of conjugated estrogen or medroxyprogesterone acetate. J Bone Miner Res. 1997;12:1851–63.PubMedCrossRefGoogle Scholar
  94. 94.
    Genant HK, Cann CE, Ettinger B, Gordan GS. Quantitative computed tomography of vertebral spongiosa: a sensitive method for detecting early bone loss after oophorectomy. Ann Intern Med. 1982;97:699–705.PubMedCrossRefGoogle Scholar
  95. 95.
    Gallagher JC. Effect of early menopause on bone mineral density and fractures. Menopause. 2007;14:567–71.PubMedCrossRefGoogle Scholar
  96. 96.
    Weiss NS, Ure CL, Ballard JH, Williams AR, Daling JR. Decreased risk of fractures of the hip and lower forearm with postmenopausal use of estrogen. N Engl J Med. 1980;303:1195–8.PubMedCrossRefGoogle Scholar
  97. 97.
    Grady D, Rubin SM, Petitti DB, et al. Hormone therapy to prevent disease and prolong life in postmenopausal women. Ann Intern Med. 1992;117:1016–37.PubMedCrossRefGoogle Scholar
  98. 98.
    Cauley JA, Seeley DG, Ensrud K, Ettinger B, Black D, Cummings SR. Estrogen replacement therapy and fractures in older women. Study of Osteoporotic Fractures Research Group. Ann Intern Med. 1995;122:9–16.PubMedCrossRefGoogle Scholar
  99. 99.
    Wells G, Tugwell P, Shea B, Guyatt G, Peterson J, Zytaruk N, et al. Meta-analyses of therapies for postmenopausal osteoporosis. V. Meta-analysis of the efficacy of hormone replacement therapy in treating and preventing osteoporosis in postmenopausal women. Endocr Rev. 2002;23:529–39.PubMedCrossRefGoogle Scholar
  100. 100.
    Torgerson DJ, Bell-Syer SE. Hormone replacement therapy and prevention of nonvertebral fractures: a meta-analysis of randomized trials. JAMA. 2001;285:2891–7.PubMedCrossRefGoogle Scholar
  101. 101.
    Nelson HD, Humphrey LL, Nygren P, Teutsch SM, Allan JD. Postmenopausal hormone replacement therapy: scientific review. JAMA. 2002;288:872–81.PubMedCrossRefGoogle Scholar
  102. 102.
    Heiss G, Wallace R, Anderson GL, Aragaki A, Beresford SA, Brzyski R, et al. Health risks and benefits 3 years after stopping randomized treatment with estrogen and progestin. JAMA. 2008;299:1036–45.PubMedCrossRefGoogle Scholar
  103. 103.
    Pike MC, Krailo MD, Henderson BE, Casagrande JT, Hoel DG. “Hormonal” risk factors, “breast tissue age” and the age-incidence of breast cancer. Nature. 1983;303:767–70.PubMedCrossRefGoogle Scholar
  104. 104.
    Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Collaborative Group on Hormonal Factors in Breast Cancer. Lancet. 1997;350:1047–59.Google Scholar
  105. 105.
    Persson I. Estrogens in the causation of breast, endometrial and ovarian cancers—evidence and hypotheses from epidemiological findings. J Steroid Biochem Mol Biol. 2000;74:357–64.PubMedCrossRefGoogle Scholar
  106. 106.
    Klinkert ER. Clinical significance and management of poor response in IVF. Ref Type: Thesis/Dissertation: Utrecht University; 2005.Google Scholar
  107. 107.
    Lambalk CB, van Disseldorp J, de Koning CH, Broekmans FJ. Testing ovarian reserve to predict age at menopause. Maturitas. 2009;63:280–91.PubMedCrossRefGoogle Scholar
  108. 108.
    Ferrell RJ, Sowers M. Longitudinal, epidemiologic studies of female reproductive aging. Ann N Y Acad Sci. 2010;1204:188–97.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Julius Center for Health Sciences and Primary CareUniversity Medical Center UtrechtUtrechtThe Netherlands

Personalised recommendations