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Timing hypothesis (menopausal hormone therapy)

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The timing hypothesis, gap hypothesis, gap theory, or critical window hypothesis for menopausal hormone therapy is a scientific theory that the benefits and risks of menopausal hormone therapy vary depending on the amount of time a woman has been in menopause upon initiation of treatment.[1][2][3][4][5] More specifically, it is thought that hormone therapy may be protective against coronary heart disease in women who initiate it in early menopause but may be harmful in women who start it in late menopause.[1][2][3][4] The timing hypothesis may also extend to risks of breast cancer[6][7][8][9] and dementia with hormone therapy.[10][11][12][13] It is thought that the increase in breast cancer risk may be greater in women who start hormone therapy in early menopause but may be lower or that even decreased risk of breast cancer may occur in women who start in late menopause.[6][7][8][9] The influence of hormone therapy on depressive symptoms may additionally be influenced by menopausal stage, with significant benefit seen in perimenopausal women but not in postmenopausal women.[14][15][16][17][18][19] The timing hypothesis is potentially able to resolve conflicting findings between large observational studies and randomized controlled trials on long-term health outcomes with menopausal hormone therapy.[1][2][4][8][9][20][21]

References

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  1. ^ a b c Clarkson TB, Meléndez GC, Appt SE (March 2013). "Timing hypothesis for postmenopausal hormone therapy: its origin, current status, and future". Menopause. 20 (3): 342–53. doi:10.1097/GME.0b013e3182843aad. PMID 23435033. S2CID 25966834.
  2. ^ a b c Choi SD, Steinberg EM, Lee HH, Naftolin F (February 2011). "The Timing Hypothesis remains a valid explanation of differential cardioprotective effects of menopausal hormone treatment". Menopause. 18 (2): 230–6. doi:10.1097/gme.0b013e3181e97344. PMID 21341398. S2CID 22951054.
  3. ^ a b Bassuk SS, Manson JE (May 2016). "The timing hypothesis: Do coronary risks of menopausal hormone therapy vary by age or time since menopause onset?". Metabolism. 65 (5): 794–803. doi:10.1016/j.metabol.2016.01.004. PMC 4834454. PMID 27085786.
  4. ^ a b c Hodis HN, Mack WJ (July 2014). "Hormone replacement therapy and the association with coronary heart disease and overall mortality: clinical application of the timing hypothesis". J Steroid Biochem Mol Biol. 142: 68–75. doi:10.1016/j.jsbmb.2013.06.011. PMID 23851166. S2CID 30838065.
  5. ^ Speth RC, D'Ambra M, Ji H, Sandberg K (December 2018). "A heartfelt message, estrogen replacement therapy: use it or lose it". Am J Physiol Heart Circ Physiol. 315 (6): H1765 – H1778. doi:10.1152/ajpheart.00041.2018. PMC 6336974. PMID 30216118.
  6. ^ a b Mueck AO, Seeger H (2015). "Estrogen as a new option for prevention and treatment of breast cancer – does this need a 'time gap'?". Climacteric. 18 (4): 444–7. doi:10.3109/13697137.2015.1041904. PMID 25958921. S2CID 26005779.
  7. ^ a b Coelingh Bennink HJ, Verhoeven C, Dutman AE, Thijssen J (January 2017). "The use of high-dose estrogens for the treatment of breast cancer". Maturitas. 95: 11–23. doi:10.1016/j.maturitas.2016.10.010. PMID 27889048.
  8. ^ a b c Chlebowski RT, Anderson GL (April 2015). "Menopausal hormone therapy and breast cancer mortality: clinical implications". Ther Adv Drug Saf. 6 (2): 45–56. doi:10.1177/2042098614568300. PMC 4406918. PMID 25922653.
  9. ^ a b c Prentice RL (November 2014). "Postmenopausal hormone therapy and the risks of coronary heart disease, breast cancer, and stroke". Semin Reprod Med. 32 (6): 419–25. doi:10.1055/s-0034-1384624. PMC 4212810. PMID 25321418.
  10. ^ Nerattini, Matilde; Jett, Steven; Andy, Caroline; Carlton, Caroline; Zarate, Camila; Boneu, Camila; Battista, Michael; Pahlajani, Silky; Loeb-Zeitlin, Susan; Havryulik, Yelena; Williams, Schantel; Christos, Paul; Fink, Matthew; Brinton, Roberta Diaz; Mosconi, Lisa (2023-10-23). "Systematic review and meta-analysis of the effects of menopause hormone therapy on risk of Alzheimer's disease and dementia". Frontiers in Aging Neuroscience. 15. Frontiers Media SA. doi:10.3389/fnagi.2023.1260427. ISSN 1663-4365. PMC 10625913. PMID 37937120.
  11. ^ Wu M, Li M, Yuan J, Liang S, Chen Z, Ye M, Ryan PM, Clark C, Tan SC, Rahmani J, Varkaneh HK, Bhagavathula AS (May 2020). "Postmenopausal hormone therapy and Alzheimer's disease, dementia, and Parkinson's disease: A systematic review and time-response meta-analysis". Pharmacol Res. 155: 104693. doi:10.1016/j.phrs.2020.104693. PMID 32057896. S2CID 211111795.
  12. ^ Maki PM (June 2013). "Critical window hypothesis of hormone therapy and cognition: a scientific update on clinical studies". Menopause. 20 (6): 695–709. doi:10.1097/GME.0b013e3182960cf8. PMC 3780981. PMID 23715379.
  13. ^ Henderson VW (July 2014). "Alzheimer's disease: review of hormone therapy trials and implications for treatment and prevention after menopause". J Steroid Biochem Mol Biol. 142: 99–106. doi:10.1016/j.jsbmb.2013.05.010. PMC 3830600. PMID 23727128.
  14. ^ Soares CN (June 2017). "Depression and Menopause: Current Knowledge and Clinical Recommendations for a Critical Window". Psychiatr Clin North Am. 40 (2): 239–254. doi:10.1016/j.psc.2017.01.007. PMID 28477650.
  15. ^ Rubinow DR, Johnson SL, Schmidt PJ, Girdler S, Gaynes B (August 2015). "Efficacy of Estradiol in Perimenopausal Depression: So Much Promise and So Few Answers". Depress Anxiety. 32 (8): 539–49. doi:10.1002/da.22391. PMC 6309886. PMID 26130315.
  16. ^ Gordon JL, Girdler SS (December 2014). "Hormone replacement therapy in the treatment of perimenopausal depression". Curr Psychiatry Rep. 16 (12): 517. doi:10.1007/s11920-014-0517-1. PMID 25308388. S2CID 23794180.
  17. ^ Toffol E, Heikinheimo O, Partonen T (May 2015). "Hormone therapy and mood in perimenopausal and postmenopausal women: a narrative review". Menopause. 22 (5): 564–78. doi:10.1097/GME.0000000000000323. PMID 25203891. S2CID 5830652.
  18. ^ Whedon JM, KizhakkeVeettil A, Rugo NA, Kieffer KA (January 2017). "Bioidentical Estrogen for Menopausal Depressive Symptoms: A Systematic Review and Meta-Analysis". J Womens Health (Larchmt). 26 (1): 18–28. doi:10.1089/jwh.2015.5628. PMID 27603786.
  19. ^ Santoro N (May 2020). "Does Hormone Therapy Protect the Heart? It Is a Stressful Question". J Clin Endocrinol Metab. 105 (5): e2080 – e2081. doi:10.1210/clinem/dgaa011. PMID 32215563. S2CID 214682856.
  20. ^ Prentice RL, Chlebowski RT, Stefanick ML, Manson JE, Langer RD, Pettinger M, Hendrix SL, Hubbell FA, Kooperberg C, Kuller LH, Lane DS, McTiernan A, O'Sullivan MJ, Rossouw JE, Anderson GL (June 2008). "Conjugated equine estrogens and breast cancer risk in the Women's Health Initiative clinical trial and observational study". Am J Epidemiol. 167 (12): 1407–15. doi:10.1093/aje/kwn090. PMC 2703736. PMID 18448442.
  21. ^ Prentice RL, Chlebowski RT, Stefanick ML, Manson JE, Pettinger M, Hendrix SL, Hubbell FA, Kooperberg C, Kuller LH, Lane DS, McTiernan A, Jo O'Sullivan M, Rossouw JE, Anderson GL (May 2008). "Estrogen plus progestin therapy and breast cancer in recently postmenopausal women". Am J Epidemiol. 167 (10): 1207–16. doi:10.1093/aje/kwn044. PMC 2670848. PMID 18372396.


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