Skip to main content
SpringerLink
Log in

Neuroendocrine Changes of the Menopausal Transition

  • Chapter
  • First Online:
Book cover Sex Steroids' Effects on Brain, Heart and Vessels

Part of the book series: ISGE Series ((ISGE))

  • 721 Accesses

Abstract

During menopausal transition, the ovaries are depleted of follicles, oestradiol and inhibin B production falls, and ovulation and menstruation no longer occur. The loss of ovarian sensitivity to follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and the loss of negative feedback of oestradiol and inhibin B on the hypothalamic–pituitary unit result in increased production and release of gonadotropin release hormone (GnRH), FSH and LH. Increased FSH levels are particularly specific to postmenopause. Modifications of gonadotropins, oestradiol (E2), alterations in the function of noradrenergic and serotoninergic pathways and opioid tone in the hypothalamus cause the onset of vasomotor symptoms and consequent sleep disruption. Thermoregulatory dysfunction might be a result of a maladaptation of the brain to kisspeptin, neurokinin B and dynorphin (KNDy) neuron hypertrophy, which project to the preoptic thermoregulatory area. Mood, cognitive functions and neuroendocrine activity, which are closely related to the impairment of GABAergic, opioid and neurosteroid neurotransmitter milieu in the central nervous system (CNS), occur with climacteric period and during ageing. Failure of the main target of neurosteroids, the GABA-A receptor, to adapt to changes in levels of allopregnanolone over the course of the menopausal transition might lead to depressive symptoms, mood and cognitive dysfunctions.

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

Access this chapter

Log in via an institution
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
Hardcover Book
USD 99.99
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. Wise PM. Neuroendocrine modulation of the “menopause”: insights into the aging brain. Am J Phys. 1999;277(6 Pt 1):E965–70.

    CAS  Google Scholar 

  2. Downs JL, Wise PM. The role of the brain in female reproductive aging. Mol Cell Endocrinol. 2009;299(1):32–8.

    Article  CAS  Google Scholar 

  3. Butler L, Santoro N. The reproductive endocrinology of the menopausal transition. Steroids. 2011;76(7):627–35.

    Article  CAS  Google Scholar 

  4. Santoro N, Isaac B, Neal-Perry G, et al. Impaired folliculogenesis and ovulation in older reproductive aged women. J Clin Endocrinol Metab. 2003;88(11):5502–9.

    Article  CAS  Google Scholar 

  5. Woods NF, Mitchell ES. Symptoms during the perimenopause: prevalence, severity, trajectory, and significance in women’s lives. Am J Med. 2005;118(Suppl 12B):14–24.

    Article  Google Scholar 

  6. Woods NF, Smith-DiJulio K, Percival DB, Tao EY, Mariella A, Mitchell S. Depressed mood during the menopausal transition and early postmenopause: observations from the Seattle Midlife Women’s Health Study. Menopause. 2008;15(2):223–32.

    Article  Google Scholar 

  7. Weber MT, Maki PM, McDermott MP. Cognition and mood in perimenopause: a systematic review and meta-analysis. J Steroid Biochem Mol Biol. 2014;142:90–8.

    Article  CAS  Google Scholar 

  8. Bromberger JT, Schott LL, Kravitz HM, et al. Longitudinal change in reproductive hormones and depressive symptoms across the menopausal transition: results from the Study of Women’s Health Across the Nation (SWAN). Arch Gen Psychiatry. 2010;67(6):598–607.

    Article  CAS  Google Scholar 

  9. Bromberger JT, Schott L, Kravitz HM, Joffe H. Risk factors for major depression during midlife among a community sample of women with and without prior major depression: are they the same or different? Psychol Med. 2015;45(8):1653–64.

    Article  CAS  Google Scholar 

  10. Fogle RH, Stanczyk FZ, Zhang X, Paulson RJ. Ovarian androgen production in postmenopausal women. J Clin Endocrinol Metab. 2007;92(8):3040–3.

    Article  CAS  Google Scholar 

  11. Freedman RR. Hot flashes: behavioral treatments, mechanisms, and relation to sleep. Am J Med. 2005;118(Suppl 12B):124–30.

    Article  Google Scholar 

  12. McConnell DS, Stanczyk FZ, Sowers MR, Randolph JFJ, Lasley BL. Menopausal transition stage-specific changes in circulating adrenal androgens. Menopause. 2012;19(6):658–63.

    Article  Google Scholar 

  13. Rossmanith WG, Ruebberdt W. What causes hot flushes? The neuroendocrine origin of vasomotor symptoms in the menopause. Gynecol Endocrinol. 2009;25(5):303–14.

    Article  Google Scholar 

  14. Boulant JA. Role of the preoptic-anterior hypothalamus in thermoregulation and fever. Clin Infect Dis. 2000;31(Suppl 5):S157–61.

    Article  Google Scholar 

  15. Woods NF, Carr MC, Tao EY, Taylor HJ, Mitchell ES. Increased urinary cortisol levels during the menopausal transition. Menopause. 2006;13(2):212–21.

    Article  Google Scholar 

  16. Hale GE, Hitchcock CL, Williams LA, Vigna YM, Prior JC. Cyclicity of breast tenderness and night-time vasomotor symptoms in mid-life women: information collected using the Daily Perimenopause Diary. Climacteric. 2003;6(2):128–39.

    Article  CAS  Google Scholar 

  17. Gordon JL, Rubinow DR, Thurston RC, Paulson J, Schmidt PJ, Girdler SS. Cardiovascular, hemodynamic, neuroendocrine, and inflammatory markers in women with and without vasomotor symptoms. Menopause. 2016;23(11):1189–98.

    Article  Google Scholar 

  18. Freeman EW, Sammel MD, Lin H, et al. Symptoms associated with menopausal transition and reproductive hormones in midlife women. Obstet Gynecol. 2007;110(2 Pt 1):230–40.

    Article  Google Scholar 

  19. Pines A. Circadian rhythm and menopause. Climacteric. 2016;19(6):551–2.

    Article  CAS  Google Scholar 

  20. Andersen ML, Bittencourt LR, Antunes IB, Tufik S. Effects of progesterone on sleep: a possible pharmacological treatment for sleep-breathing disorders? Curr Med Chem. 2006;13(29):3575–82.

    Article  CAS  Google Scholar 

  21. Short RA, Bowen RL, O’Brien PC, Graff-Radford NR. Elevated gonadotropin levels in patients with Alzheimer disease. Mayo Clin Proc. 2001;76(9):906–9.

    Article  CAS  Google Scholar 

  22. Wober C, Brannath W, Schmidt K, et al. Prospective analysis of factors related to migraine attacks: the PAMINA study. Cephalalgia. 2007;27(4):304–14.

    Article  CAS  Google Scholar 

  23. 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(3):214–20.

    Article  CAS  Google Scholar 

  24. Freeman EW, Sammel MD, Boorman DW, Zhang R. Longitudinal pattern of depressive symptoms around natural menopause. JAMA Psychiat. 2014;71(1):36–43.

    Article  Google Scholar 

  25. Gordon JL, Girdler SS, Meltzer-Brody SE, et al. Ovarian hormone fluctuation, neurosteroids, and HPA axis dysregulation in perimenopausal depression: a novel heuristic model. Am J Psychiatry. 2015;172(3):227–36.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Obstetrics and Gynecology, Department of Experimental and Clinical Medicine, University of Pisa, Pisa, Italy

    Andrea Giannini, Marta Caretto & Tommaso Simoncini

Authors
  1. Andrea Giannini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marta Caretto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tommaso Simoncini
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tommaso Simoncini .

Editor information

Editors and Affiliations

  1. Center for Innovation in Brain Sciencies-Department of Pharmacology and Neurology, College of Medicine, University of Arizona, Tucson, AZ, USA

    Roberta Diaz Brinton

  2. International School for Gynecological and Reproductive Endocrinology, International Society of Gynecological Endocrinology, Locarno, Switzerland

    Andrea R. Genazzani

  3. Department of Clinical and Experimental Medicine, Division of Obstetrics and Gynecology, University of Pisa, Pisa, Italy

    Tommaso Simoncini

  4. National Heart and Lung Institute, Imperial College London, London, UK

    John C. Stevenson

Rights and permissions

Reprints and permissions

Copyright information

© 2019 International Society of Gynecological Endocrinology

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Giannini, A., Caretto, M., Simoncini, T. (2019). Neuroendocrine Changes of the Menopausal Transition. In: Brinton, R., Genazzani, A., Simoncini, T., Stevenson, J. (eds) Sex Steroids' Effects on Brain, Heart and Vessels. ISGE Series. Springer, Cham. https://doi.org/10.1007/978-3-030-11355-1_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-11355-1_1

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-11354-4

  • Online ISBN: 978-3-030-11355-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation