Skip to main content

Menopause: The Concepts and the Biological Background

  • Chapter
  • First Online:
Menopause

Abstract

The exhaustion of the follicular endowment in the ovary defines the biological basis of menopause. The clinical implications are the loss of menses and fertility. Menopause is preceded by a series of clinical phases, reflected in the Staging of Reproductive Aging Workshop (STRAW). STRAW includes the different reproductive stages, with the clinically impacting menopausal transition and the end of the reproductive life, represented by the late post-menopausal period. Epidemiological studies show that the age at menopause, globally considered at around 50 years, undergoes significant differences across the world regions. High socio-economic conditions may prolong the age at menopause, but other variables are at work. The hormonal background of each stage has been well described. The prediction of the age at menopause, however, remains uncertain.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 129.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Strauss JF III, Williams CJ. The ovarian life cycle. In: Strauss III JF, Barbieri RL, editors. Yen & Jaffe’s reproductive endocrinology. Philadelphia: Elsevier Saunders; 2014. p. 157–91.

    Chapter  Google Scholar 

  2. WHO Scientific Group on Research on the Menopause in the 1990s. WHO Technical Report Series. WHO: Geneva. 1996. http://apps.who.int/iris/bitstream/10665/41841/1/WHO_TRS_866.pdf. Accessed 22 Dec 2016.

  3. Menopause: diagnosis and management (NICE Guideline 23). https://www.nice.org.uk/guidance/ng23. Accessed 22 Dec 2016.

  4. Soules MR, Sherman S, Parrott E, Rebar R, Santoro N, Utian W, et al. Executive summary: stages of reproductive aging workshop (STRAW). Fertil Steril. 2001;76:874–8.

    Article  CAS  PubMed  Google Scholar 

  5. Harlow S, 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. Fertil Steril. 2012;97:843–51.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Shadyab AH, Macera CA, Shaffer RA, Jain S, Gallo LC, Gass ML, et al. Ages at menarche and menopause and reproductive lifespan as predictors of exceptional longevity in women: the Women’s Health Initiative. Menopause. 2017;24:35–44.

    Article  PubMed  Google Scholar 

  7. Muka T, Oliver-Williams C, Kunutsor S, Laven JS, Fauser BC, Chowdhury R, et al. Association of age at onset of menopause and time since onset of menopause with cardiovascular outcomes, intermediate vascular traits, and all-cause mortality: a systematic review and meta-analysis. JAMA Cardiol. 2016;1:767–76.

    Article  PubMed  Google Scholar 

  8. Schoenaker DA, Jackson CA, Rowlands JV, Mishra GD. Socioeconomic position, lifestyle factors and age at natural menopause: a systematic review and meta-analyses of studies across six continents. Int J Epidemiol. 2014;43:1542–62.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Dratva J, Gómez 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.

    Article  PubMed  Google Scholar 

  10. McKinlay SM, Brambilla DJ, Posner JG. The normal menopause transition. Maturitas. 2008;61:4–16.

    Article  PubMed  Google Scholar 

  11. Treloar AE, Boynton RE, Behn BG, Brown BW. Variation of the human menstrual cycle through reproductive life. Int J Fertil. 1967;12(1 Pt 2):77–126.

    CAS  PubMed  Google Scholar 

  12. Hallberg L, Högdahl AM, Nilsson L, Rybo G. Menstrual blood loss—a population study. Variation at different ages and attempts to define normality. Acta Obstet Gynecol Scand. 1966;45:320–51.

    Article  CAS  PubMed  Google Scholar 

  13. Murabito JM, Yang Q, Fox C, Wilson PW, Cupples LA. Heritability of age at natural menopause in the Framingham Heart Study. J Clin Endocrinol Metab. 2005;90:3427–30.

    Article  CAS  PubMed  Google Scholar 

  14. Day FR, Ruth KS, Thompson DJ, Lunetta KL, Pervjakova N, Chasman DI, et al. Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair. Nat Genet. 2015;47:1294–303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Laven JS, Visser JA, Uitterlinden AG, Vermeij WP, Hoeijmakers JH. Menopause: genome stability as new paradigm. Maturitas. 2016;92:15–23.

    Article  CAS  PubMed  Google Scholar 

  16. Oboni JB, Marques-Vidal P, Bastardot F, Vollenweider P, Waeber G. Impact of smoking on fertility and age of menopause: a population-based assessment. BMJ Open. 2016;6:e012015.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Henderson K, Bernstein L, Henderson B, Kolonel L, Pike MC. Predictors of the timing of natural menopause in the Multiethnic Cohort Study. Am J Epidemiol. 2008;167:1287–94.

    Article  PubMed  Google Scholar 

  18. Morris DH, Jones ME, Schoemaker MJ, McFadden E, Ashworth A, Swerdlow AJ. Body mass index, exercise, and other lifestyle factors in relation to age at natural menopause: analyses from the breakthrough generations study. Am J Epidemiol. 2012;175:998–1005.

    Article  PubMed  Google Scholar 

  19. Mattison DR, Thorgeirsson SS. Smoking and industrial pollution, and their effects on menopause and ovarian cancer. Lancet. 1978;1(8057):187–9.

    Article  CAS  PubMed  Google Scholar 

  20. Pelosi E, Simonsick E, Forabosco A, Garcia-Ortiz JE, Schlessinger D. Dynamics of the ovarian reserve and impact of genetic and epidemiological factors on age of menopause. Biol Reprod. 2015;92:130.

    Article  PubMed  PubMed Central  Google Scholar 

  21. McKinlay SM, Brambilla DJ, Posner JG. The normal menopause transition. Maturitas. 1992;14:103–15.

    Article  CAS  PubMed  Google Scholar 

  22. Willett W, Stampfer MJ, Bain C, Lipnick R, Speizer FE, Rosner B, et al. Cigarette smoking, relative weight, and menopause. Am J Epidemiol. 1983;117:651–8.

    Article  CAS  PubMed  Google Scholar 

  23. Aydin ZD. Determinants of age at natural menopause in the Isparta Menopause and Health Study: premenopausal body mass index gain rate and episodic weight loss. Menopause. 2010;17:494–505.

    PubMed  Google Scholar 

  24. Hardy R, Kuh D. Does early growth influence timing of the menopause? Evidence from a British birth cohort. Hum Reprod. 2002;17:2474–9.

    Article  CAS  PubMed  Google Scholar 

  25. Gold EB, Crawford SL, Avis NE, Crandall CJ, Matthews KA, Waetjen LE, et al. Factors related to age at natural menopause: longitudinal analyses from SWAN. Am J Epidemiol. 2013;178:70–83.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Mishra GD, Cooper R, Tom SE, Kuh D. Early life circumstances and their impact on menarche and menopause. Womens Health (Lond). 2009;5:175–90.

    Article  Google Scholar 

  27. Mishra GD, Pandeya N, Dobson AJ, Chung HF, Anderson D, Kuh D, et al. Early menarche, nulliparity and the risk for premature and early natural menopause. Hum Reprod. 2017;32(3):679–86.

    PubMed  Google Scholar 

  28. Depmann M, Broer SL, van der Schouw YT, Tehrani FR, Eijkemans MJ, Mol BW, et al. Can we predict age at natural menopause using ovarian reserve tests or mother’s age at menopause? A systematic literature review. Menopause. 2016;23:224–32.

    Article  PubMed  Google Scholar 

  29. White YA, Woods DC, Takai Y, Ishihara O, Seki H, Tilly JL. Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women. Nat Med. 2012;18:413–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. McGee EA, Raj RS. Regulators of ovarian preantral follicle development. Semin Reprod Med. 2015;33:179–84.

    Article  CAS  PubMed  Google Scholar 

  31. Durlinger AL, Kramer P, Karels B, de Jong FH, Uilenbroek JT, Grootegoed JA, et al. Control of primordial follicle recruitment by anti-Müllerian hormone in the mouse ovary. Endocrinology. 1999;140:5789–96.

    Article  CAS  PubMed  Google Scholar 

  32. Hall JE. Endocrinology of the menopause. Endocrinol Metab Clin N Am. 2015;44:485–96.

    Article  Google Scholar 

  33. Gougeon A. Dynamics of follicular growth in the human: a model from preliminary results. Hum Reprod. 1986;1:81–7.

    Article  CAS  PubMed  Google Scholar 

  34. Groome NP, Illingworth PJ, O’Brien M, Pai R, Rodger FE, Mather JP, et al. Measurement of dimeric inhibin B throughout the human menstrual cycle. J Clin Endocrinol Metab. 1996;81:1401–5.

    CAS  PubMed  Google Scholar 

  35. Klein NA, Illingworth PJ, Groome NP, McNeilly AS, Battaglia DE, Soules MR. Decreased inhibin B secretion is associated with the monotropic FSH rise in older, ovulatory women: a study of serum and follicular fluid levels of dimeric inhibin A and B in spontaneous menstrual cycles. J Clin Endocrinol Metab. 1996;81:2742–5.

    CAS  PubMed  Google Scholar 

  36. Klein NA, Battaglia DE, Clifton DK, Bremner WJ, Soules MR. The gonadotropin secretion pattern in normal women of advanced reproductive age in relation to the monotropic FSH rise. J Soc Gynecol Investig. 1996;3:27–32.

    Article  CAS  PubMed  Google Scholar 

  37. Soules MR, Battaglia DE, Klein NA. Inhibin and reproductive aging in women. Maturitas. 1998;30:193–204.

    Article  CAS  PubMed  Google Scholar 

  38. Shaw ND, Srouji SS, Welt CK, Cox KH, Fox JH, Adams JA, et al. Compensatory increase in ovarian aromatase in older regularly cycling women. J Clin Endocrinol Metab. 2015;100:3539–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Downs JL, Wise PM. The role of the brain in female reproductive aging. Mol Cell Endocrinol. 2009;299:32–8.

    Article  CAS  PubMed  Google Scholar 

  40. Cano A, Gimeno F, Fuente T, Parrilla JJ, Abad L. The positive feedback of estradiol on gonadotropin secretion in women with perimenopausal dysfunctional uterine bleeding. Eur J Obstet Gynecol Reprod Biol. 1986;22:353–8.

    Article  CAS  PubMed  Google Scholar 

  41. Gill S, Lavoie HB, Bo-Abbas Y, Hall JE. Negative feedback effects of gonadal steroids are preserved with aging in postmenopausal women. J Clin Endocrinol Metab. 2002;87:2297–302.

    Article  CAS  PubMed  Google Scholar 

  42. Randolph JF Jr, Zheng H, Sowers MR, Crandall C, Crawford S, Gold EB, et al. Change in follicle-stimulating hormone and estradiol across the menopausal transition: effect of age at the final menstrual period. J Clin Endocrinol Metab. 2011;96:746–54.

    Article  CAS  PubMed  Google Scholar 

  43. Fogle RH, Stanczyk FZ, Zhang X, Paulson RJ. Ovarian androgen production in postmenopausal women. J Clin Endocrinol Metab. 2007;92:3040–3.

    Article  CAS  PubMed  Google Scholar 

  44. Shifren JL, Braunstein GD, Simon JA, Casson PR, Buster JE, Redmond GP, et al. Transdermal testosterone treatment in women with impaired sexual function after oophorectomy. N Engl J Med. 2000;343:682–8.

    Article  CAS  PubMed  Google Scholar 

  45. Shifren JL, Davis SR, Moreau M, Waldbaum A, Bouchard C, DeRogatis L, et al. Testosterone patch for the treatment of hypoactive sexual desire disorder in naturally menopausal women: results from the INTIMATE NM1 Study. Menopause. 2006;13:770–9.

    Article  PubMed  Google Scholar 

  46. Labrie F. All sex steroids are made intracellularly in peripheral tissues by the mechanisms of intracrinology after menopause. J Steroid Biochem Mol Biol. 2015;145:133–8.

    Article  CAS  PubMed  Google Scholar 

  47. Labrie F, Bélanger A, Pelletier G, Martel C, Archer DF, Utian WH. Science of intracrinology in postmenopausal women. Menopause. 2017;24(6):702–12.

    Article  PubMed  Google Scholar 

  48. McNamara KM, Sasano H. The intracrinology of breast cancer. J Steroid Biochem Mol Biol. 2015;145:172–8.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Antonio Cano .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Cano, A. (2017). Menopause: The Concepts and the Biological Background. In: Cano, A. (eds) Menopause. Springer, Cham. https://doi.org/10.1007/978-3-319-59318-0_2

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-59318-0_2

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-59317-3

  • Online ISBN: 978-3-319-59318-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics