Alzheimer Hastalığı Tedavisinde Endokrin Sistem Temelli Gelecek Vaat Eden Yaklaşımlar

Ancidoni A, Andreoletti M, Bacigalupo I, Bargagli A. Dementia in Refugees and Migrants: Epidemiology, Public Health Implications and Global Responses. 2025 [cited 2025 Jun 12]; Available from: https://www.research.ed.ac.uk/files/498648010/Calia2025DementiaInRefugees.pdf

Crous-Bou M, Minguillón C, Gramunt N, Molinuevo JL. Alzheimer’s disease prevention: From risk factors to early intervention. Alzheimers Res Ther [Internet]. 2017 Sep 12 [cited 2025 Jun 4];9(1). Available from: https://pubmed.ncbi.nlm.nih.gov/28899416/

Ciurea VA, Covache-Busuioc RA, Mohan AG, Costin HP, Voicu V. Alzheimer’s disease: 120 years of research and progress. J Med Life [Internet]. 2023 [cited 2025 Jun 4];2023(2):173–7. Available from: https://pubmed.ncbi.nlm.nih.gov/36937482/

Qiu C, Kivipelto M, Von Strauss E. Epidemiology of Alzheimer’s disease: Occurrence, determinants, and strategies toward intervention. Dialogues Clin Neurosci [Internet]. 2009 [cited 2025 Jun 4];11(2):111–28. Available from: https://pubmed.ncbi.nlm.nih.gov/19585947/

Spires-Jones TL, Hyman BT. The Intersection of Amyloid Beta and Tau at Synapses in Alzheimer’s Disease. Neuron [Internet]. 2014 May 21 [cited 2025 Jun 4];82(4):756–71. Available from: https://pubmed.ncbi.nlm.nih.gov/24853936/

2025 Alzheimer’s disease facts and figures. Alzheimer’s & Dementia [Internet]. 2025 Apr 29 [cited 2025 Jun 12];21(4):e70235. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC12040760/

Gustavsson A, Norton N, Fast T, Frölich L, Georges J, Holzapfel D, et al. Global estimates on the number of persons across the Alzheimer’s disease continuum. Alzheimer’s & Dementia [Internet]. 2023 Feb 1 [cited 2025 Jun 4];19(2):658–70. Available from: /doi/pdf/10.1002/alz.12694

Şen Metin F, Aksöz E. Alzheimer hastalığı tedavisinde aktif immünoterapi. In: Üçler N, editor. Çağdaş Nörolojik Hastalık Tedavileri. Ankara: BİDGE Yayınları; 2024. p. 46–74.

Kang C. Donanemab: First Approval. Drugs [Internet]. 2024 Oct 1 [cited 2025 Jun 4];84(10). Available from: https://pubmed.ncbi.nlm.nih.gov/39237715/

Pike CJ, Carroll JC, Rosario ER, Barron AM. Protective actions of sex steroid hormones in Alzheimer’s disease. Front Neuroendocrinol [Internet]. 2009 Jul [cited 2025 Jun 4];30(2):239–58. Available from: https://pubmed.ncbi.nlm.nih.gov/19427328/

Mosconi L, Rahman A, Diaz I, Wu X, Scheyer O, Hristov HW, et al. Increased Alzheimer’s risk during the menopause transition: A 3-year longitudinal brain imaging study. PLoS One [Internet]. 2018 Dec 1 [cited 2025 Jun 4];13(12). Available from: https://pubmed.ncbi.nlm.nih.gov/30540774/

Xiong J, Kang SS, Wang Z, Liu X, Kuo TC, Korkmaz F, et al. FSH blockade improves cognition in mice with Alzheimer’s disease. Nature [Internet]. 2022 Mar 17 [cited 2025 Jun 4];603(7901):470–6. Available from: https://pubmed.ncbi.nlm.nih.gov/35236988/

Molnár G, Kassai-Bazsa Z. Gonadotropin, ACTH, prolactin, sexual steroid and cortisol levels in postmenopausal women’s cerebrospinal fluid (CSF). Arch Gerontol Geriatr [Internet]. 1997 May [cited 2025 Jun 4];24(3):269–80. Available from: https://pubmed.ncbi.nlm.nih.gov/15374114/

Ryu V, Gumerova A, Korkmaz F, Kang SS, Katsel P, Miyashita S, et al. Brain atlas for glycoprotein hormone receptors at single-transcript level. Elife [Internet]. 2022 Sep 1 [cited 2025 Jun 4];11:e79612. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC9473692/

Gloaguen P, Crépieux P, Heitzler D, Poupon A, Reiter E. Mapping the follicle-stimulating hormone-induced signaling networks. Front Endocrinol (Lausanne) [Internet]. 2011 Oct 5 [cited 2025 Jun 4];2(OCT):13185. Available from: www.frontiersin.org

Simoni M, Gromoll J, Nieschlag E. The Follicle-Stimulating Hormone Receptor: Biochemistry, Molecular Biology, Physiology, and Pathophysiology*. Endocr Rev [Internet]. 1997 Dec 1 [cited 2025 Jun 11];18(6):739–73. Available from: https://pubmed.ncbi.nlm.nih.gov/9408742/

Das N, Kumar TR. Molecular regulation of follicle-stimulating hormone synthesis, secretion and action. J Mol Endocrinol [Internet]. 2018 Apr 1 [cited 2025 Jun 12];60(3):R131–55. Available from: https://pubmed.ncbi.nlm.nih.gov/29437880/

Sun L, Peng Y, Sharrow AC, Iqbal J, Zhang Z, Papachristou DJ, et al. FSH Directly Regulates Bone Mass. Cell [Internet]. 2006 Apr 21 [cited 2025 Jun 4];125(2):247–60. Available from: https://pubmed.ncbi.nlm.nih.gov/16630814/

Lei ZM, Rao C V. Neural actions of luteinizing hormone and human chorionic gonadotropin. Semin Reprod Med [Internet]. 2001 [cited 2025 Jun 4];19(1):103–9. Available from: https://pubmed.ncbi.nlm.nih.gov/11394198/

Lei ZM, Rao C V., Kornyei JL, Licht P, Hiatt ES. Novel expression of human chorionic gonadotropin/luteinizing hormone receptor gene in brain. Endocrinology [Internet]. 1993 [cited 2025 Jun 4];132(5):2262–70. Available from: https://pubmed.ncbi.nlm.nih.gov/8477671/

Short RA, O’brien PC, Graff-Radford NR. Elevated gonadotropin levels in patients with Alzheimer disease. Mayo Clin Proc [Internet]. 2001 Sep 1 [cited 2025 Jun 4];76(9):906–9. Available from: https://www.mayoclinicproceedings.org/action/showFullText?pii=S0025619611621095

Ge YJ, Xu W, Tan CC, Tan L. Blood-based biomarkers in hypothalamic-pituitary axes for the risk of dementia or cognitive decline: a systematic review and meta-analysis. Aging [Internet]. 2020 Oct 26 [cited 2025 Jun 11];12(20):20350–65. Available from: https://pubmed.ncbi.nlm.nih.gov/33104518/

Wilson AC, Clemente L, Liu T, Bowen RL, Meethal SV, Atwood CS. Reproductive hormones regulate the selective permeability of the blood-brain barrier. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease [Internet]. 2008 Jun 1 [cited 2025 Jun 4];1782(6):401–7. Available from: https://www.sciencedirect.com/science/article/pii/S0925443908000604?via%3Dihub

Andersen K, Launer LJ, Dewey ME, Letenneur L, Ott A, Copeland JRM, et al. Gender differences in the incidence of AD and vascular dementia: The EURODEM Studies. Neurology [Internet]. 1999 Dec 10 [cited 2025 Jun 4];53(9):1992–7. Available from: https://pubmed.ncbi.nlm.nih.gov/10599770/

Yaffe K, Sawaya G, Lieberburg I, Grady D. Estrogen therapy in postmenopausal women: Effects on cognitive function and dementia. JAMA [Internet]. 1998 Mar 4 [cited 2025 Jun 4];279(9):688–95. Available from: https://pubmed.ncbi.nlm.nih.gov/9496988/

Hogervorst E, Williams J, Budge M, Riedel W, Jolles J. The nature of the effect of female gonadal hormone replacement therapy on cognitive function in post-menopausal women: A meta-analysis. Neuroscience [Internet]. 2000 Nov 15 [cited 2025 Jun 4];101(3):485–512. Available from: https://pubmed.ncbi.nlm.nih.gov/11113299/

Shumaker SA, Legault C, Rapp SR, Thal L, Wallace RB, Ockene JK, et al. Estrogen Plus Progestin and the Incidence of Dementia and Mild Cognitive Impairment in Postmenopausal Women - The Women’s Health Initiative Memory Study: A Randomized Controlled Trial. J Am Med Assoc [Internet]. 2003 May 28 [cited 2025 Jun 4];289(20):2651–62. Available from: https://pubmed.ncbi.nlm.nih.gov/12771112/

Shumaker SA, Legault C, Kuller L, Rapp SR, Thal L, Lane DS, et al. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women’s Health Initiative Memory Study. JAMA [Internet]. 2004 Jun 23 [cited 2025 Jun 4];291(24):2947–58. Available from: https://pubmed.ncbi.nlm.nih.gov/15213206/

Rapp SR, Espeland MA, Shumaker SA, Henderson VW, Brunner RL, Manson JAE, et al. Effect of Estrogen Plus Progestin on Global Cognitive Function in Postmenopausal Women - The Women’s Health Initiative Memory Study: A Randomized Controlled Trial. JAMA [Internet]. 2003 May 28 [cited 2025 Jun 4];289(20):2663–72. Available from: https://pubmed.ncbi.nlm.nih.gov/12771113/

Coughlan GT, Rubinstein Z, Klinger H, Lopez KA, Hsieh S, Boyle R, et al. Associations between hormone therapy use and tau accumulation in brain regions vulnerable to Alzheimer’s disease. Sci Adv [Internet]. 2025 Mar 7 [cited 2025 Jun 4];11(10):eadt1288. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC11881894/

Whitmer RA, Quesenberry CP, Zhou J, Yaffe K. Timing of hormone therapy and dementia: The critical window theory revisited. Ann Neurol [Internet]. 2011 Jan [cited 2025 Jun 4];69(1):163–9. Available from: https://pubmed.ncbi.nlm.nih.gov/21280086/

Maki PM. Critical window hypothesis of hormone therapy and cognition: A scientific update on clinical studies. Menopause [Internet]. 2013 Jun [cited 2025 Jun 4];20(6):695–709. Available from: https://pubmed.ncbi.nlm.nih.gov/23715379/

Kling JM, Dowling NM, Bimonte-Nelson HA, Gleason CE, Kantarci K, Manson JE, et al. Impact of menopausal hormone formulations on pituitary-ovarian regulatory feedback. Am J Physiol Regul Integr Comp Physiol [Internet]. 2019 [cited 2025 Jun 4];317(6):R912. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC6957372/

Gregory CW, Bowen RL. Novel therapeutic strategies for Alzheimer’s disease based on the forgotten reproductive hormones. Cellular and Molecular Life Sciences [Internet]. 2005 Feb [cited 2025 Jun 4];62(3):313–9. Available from: https://pubmed.ncbi.nlm.nih.gov/15723167/

Wilson AC, Meethal SV, Bowen RL, Atwood CS. Leuprolide acetate: A drug of diverse clinical applications. Expert Opin Investig Drugs [Internet]. 2007 Nov [cited 2025 Jun 4];16(11):1851–63. Available from: https://pubmed.ncbi.nlm.nih.gov/17970643/

Bowen RL, Isley JP, Atkinson RL. An association of elevated serum gonadotropin concentrations and Alzheimer disease? J Neuroendocrinol [Internet]. 2000 [cited 2025 Jun 4];12(4):351–4. Available from: https://pubmed.ncbi.nlm.nih.gov/10718932/

Bowen RL, Verdile G, Liu T, Parlow AF, Perry G, Smith MA, et al. Luteinizing Hormone, a Reproductive Regulator That Modulates the Processing of Amyloid-β Precursor Protein and Amyloid-β Deposition. Journal of Biological Chemistry [Internet]. 2004 May 7 [cited 2025 Jun 4];279(19):20539–45. Available from: https://pubmed.ncbi.nlm.nih.gov/14871891/

Nuruddin S, Syverstad GHE, Lillehaug S, Leergaard TB, Nilsson LNG, Ropstad E, et al. Elevated mRNA-Levels of Gonadotropin-Releasing Hormone and Its Receptor in Plaque-Bearing Alzheimer’s Disease Transgenic Mice. PLoS One [Internet]. 2014 Aug 4 [cited 2025 Jun 4];9(8):e103607. Available from: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0103607

Rimon E, Sasson R, Dantes A, Land-Bracha A, Amsterdam A. Gonadotropin-induced gene regulation in human granulosa cells obtained from IVF patients: modulation of genes coding for growth factors and their receptors and genes involved in cancer and other diseases. Int J Oncol [Internet]. 2004 [cited 2025 Jun 4];24(5):1325–38. Available from: https://pubmed.ncbi.nlm.nih.gov/15067357/

Anukulthanakorn K, Malaivijitnond S, Kitahashi T, Jaroenporn S, Parhar I. Molecular events during the induction of neurodegeneration and memory loss in estrogen-deficient rats. Gen Comp Endocrinol [Internet]. 2013 Jan 5 [cited 2025 Jun 4];181(1):316–23. Available from: https://pubmed.ncbi.nlm.nih.gov/23036734/

Bowen RL, Perry G, Xiong C, Smith MA, Atwood CS. A clinical study of lupron depot in the treatment of women with Alzheimer’s disease: Preservation of cognitive function in patients taking an acetylcholinesterase inhibitor and treated with high dose lupron over 48 weeks. Journal of Alzheimer’s Disease [Internet]. 2015 [cited 2025 Jun 4];44(2):549–60. Available from: https://pubmed.ncbi.nlm.nih.gov/25310993/

Nerattini M, Rubino F, Jett S, Andy C, Boneu C, Zarate C, et al. Elevated gonadotropin levels are associated with increased biomarker risk of Alzheimer’s disease in midlife women. Frontiers in Dementia [Internet]. 2023 Nov 23 [cited 2025 Jun 4];2:1303256. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC11108587/

Bovenzi R, Schirinzi T, Conti M, Sancesario GM, Zenuni H, Simonetta C, et al. A biological characterization of patients with postmenopausal Parkinson’s disease. J Neurol [Internet]. 2024 Jun 1 [cited 2025 Jun 4];271(6):3610–5. Available from: https://pubmed.ncbi.nlm.nih.gov/38492015/

Thurston RC, Chang Y, Wu M, Harrison EM, Aizenstein HJ, Derby CA, et al. Reproductive hormones in relation to white matter hyperintensity volumes among midlife women. Alzheimer’s and Dementia [Internet]. 2024 Sep 1 [cited 2025 Jun 4];20(9). Available from: https://pubmed.ncbi.nlm.nih.gov/38948946/

Hu HY, Ou YN, Shen XN, Qu Y, Ma YH, Wang ZT, et al. White matter hyperintensities and risks of cognitive impairment and dementia: A systematic review and meta-analysis of 36 prospective studies. Neurosci Biobehav Rev [Internet]. 2021 Jan 1 [cited 2025 Jun 4];120:16–27. Available from: https://pubmed.ncbi.nlm.nih.gov/33188821/

Luetters C, Huang MH, Seeman T, Buckwalter G, Meyer PM, Avis NE, et al. Menopause transition stage and endogenous estradiol and follicle-stimulating hormone levels are not related to cognitive performance: Cross-sectional results from the Study of Women’s Health Across the Nation (SWAN). J Womens Health [Internet]. 2007 Apr 17 [cited 2025 Jun 12];16(3):331–44. Available from: /doi/pdf/10.1089/jwh.2006.0057?download=true

Oh DJ, Baek KH, Kang DW, Hong YJ, Jeong C. Association Between Serum Follicle-Stimulating Hormone Levels and Cognitive Function in Middle-Aged and Older Women. J Korean Med Sci [Internet]. 2025 Mar 4 [cited 2025 Jun 4];40(10). Available from: https://doi.org/10.3346/jkms.2025.40.e15

Rodrigues MA, Verdile G, Foster JK, Hogervorst E, Joesbury K, Dhaliwal S, et al. Gonadotropins and cognition in older women. Journal of Alzheimer’s Disease [Internet]. 2008 [cited 2025 Jun 4];13(3):267–74. Available from: https://www.researchgate.net/publication/5421889_Gonadotropins_and_Cognition_in_Older_Women

Xiong J, Kang SS, Wang M, Wang Z, Xia Y, Liao J, et al. FSH and ApoE4 contribute to Alzheimer’s disease-like pathogenesis via C/EBPβ/δ-secretase in female mice. Nat Commun [Internet]. 2023 Dec 1 [cited 2025 Jun 12];14(1). Available from: https://pubmed.ncbi.nlm.nih.gov/37852961/

Korkmaz F, Sims S, Sen F, Sultana F, Laurencin V, Cullen L, et al. Gene–dose-dependent reduction of Fshr expression improves spatial memory deficits in Alzheimer’s mice. Mol Psychiatry [Internet]. 2025 May 1 [cited 2025 Jun 4];30(5):2119–26. Available from: https://scholars.mssm.edu/en/publications/genedose-dependent-reduction-of-fshr-expression-improves-spatial-

Campbell WA, Lowther J, McKenzie I, Price WH. Serum gonadotrophins in Down’s syndrome. J Med Genet [Internet]. 1982 [cited 2025 Jun 4];19(2):98. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC1048836/

HESTNES A, STOVNER LJ, HUSØY, FØLLING I, FOUGNER KJ, SJAASTAD O. Hormonal and biochemical disturbances in Down’s syndrome. Journal of Intellectual Disability Research [Internet]. 1991 Jun 1 [cited 2025 Jun 4];35(3):179–93. Available from: /doi/pdf/10.1111/j.1365-2788.1991.tb01051.x

Schupf N, Kapell D, Nightingale B, Rodriguez A, Tycko B, Mayeux R. Earlier onset of Alzheimer’s disease in men with Down syndrome. Neurology. 1998;50(4):991–5.

Manfredi-Lozano M, Leysen V, Adamo M, Paiva I, Rovera R, Pignat JM, et al. GnRH replacement rescues cognition in Down syndrome. Science (1979) [Internet]. 2022 Sep 2 [cited 2025 Jun 4];377(6610). Available from: https://pubmed.ncbi.nlm.nih.gov/36048943/

Li C, Ling Y, Kuang H. Research progress on FSH-FSHR signaling in the pathogenesis of non-reproductive diseases. Front Cell Dev Biol. 2024 Nov 20;12:1506450.

Michailidis M, Moraitou D, Tata DA, Kalinderi K, Papamitsou T, Papaliagkas V. Alzheimer’s Disease as Type 3 Diabetes: Common Pathophysiological Mechanisms between Alzheimer’s Disease and Type 2 Diabetes. Int J Mol Sci [Internet]. 2022 Mar 1 [cited 2025 Jun 4];23(5). Available from: https://pubmed.ncbi.nlm.nih.gov/35269827/

Ancidoni A, Andreoletti M, Bacigalupo I, Bargagli A. Dementia in Refugees and Migrants: Epidemiology, Public Health Implications and Global Responses. 2025 [cited 2025 Jun 12]; Available from: https://www.research.ed.ac.uk/files/498648010/Calia2025DementiaInRefugees.pdf

Crous-Bou M, Minguillón C, Gramunt N, Molinuevo JL. Alzheimer’s disease prevention: From risk factors to early intervention. Alzheimers Res Ther [Internet]. 2017 Sep 12 [cited 2025 Jun 4];9(1). Available from: https://pubmed.ncbi.nlm.nih.gov/28899416/

Ciurea VA, Covache-Busuioc RA, Mohan AG, Costin HP, Voicu V. Alzheimer’s disease: 120 years of research and progress. J Med Life [Internet]. 2023 [cited 2025 Jun 4];2023(2):173–7. Available from: https://pubmed.ncbi.nlm.nih.gov/36937482/

Qiu C, Kivipelto M, Von Strauss E. Epidemiology of Alzheimer’s disease: Occurrence, determinants, and strategies toward intervention. Dialogues Clin Neurosci [Internet]. 2009 [cited 2025 Jun 4];11(2):111–28. Available from: https://pubmed.ncbi.nlm.nih.gov/19585947/

Spires-Jones TL, Hyman BT. The Intersection of Amyloid Beta and Tau at Synapses in Alzheimer’s Disease. Neuron [Internet]. 2014 May 21 [cited 2025 Jun 4];82(4):756–71. Available from: https://pubmed.ncbi.nlm.nih.gov/24853936/

2025 Alzheimer’s disease facts and figures. Alzheimer’s & Dementia [Internet]. 2025 Apr 29 [cited 2025 Jun 12];21(4):e70235. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC12040760/

Gustavsson A, Norton N, Fast T, Frölich L, Georges J, Holzapfel D, et al. Global estimates on the number of persons across the Alzheimer’s disease continuum. Alzheimer’s & Dementia [Internet]. 2023 Feb 1 [cited 2025 Jun 4];19(2):658–70. Available from: /doi/pdf/10.1002/alz.12694

Şen Metin F, Aksöz E. Alzheimer hastalığı tedavisinde aktif immünoterapi. In: Üçler N, editor. Çağdaş Nörolojik Hastalık Tedavileri. Ankara: BİDGE Yayınları; 2024. p. 46–74.

Kang C. Donanemab: First Approval. Drugs [Internet]. 2024 Oct 1 [cited 2025 Jun 4];84(10). Available from: https://pubmed.ncbi.nlm.nih.gov/39237715/

Pike CJ, Carroll JC, Rosario ER, Barron AM. Protective actions of sex steroid hormones in Alzheimer’s disease. Front Neuroendocrinol [Internet]. 2009 Jul [cited 2025 Jun 4];30(2):239–58. Available from: https://pubmed.ncbi.nlm.nih.gov/19427328/

Mosconi L, Rahman A, Diaz I, Wu X, Scheyer O, Hristov HW, et al. Increased Alzheimer’s risk during the menopause transition: A 3-year longitudinal brain imaging study. PLoS One [Internet]. 2018 Dec 1 [cited 2025 Jun 4];13(12). Available from: https://pubmed.ncbi.nlm.nih.gov/30540774/

Xiong J, Kang SS, Wang Z, Liu X, Kuo TC, Korkmaz F, et al. FSH blockade improves cognition in mice with Alzheimer’s disease. Nature [Internet]. 2022 Mar 17 [cited 2025 Jun 4];603(7901):470–6. Available from: https://pubmed.ncbi.nlm.nih.gov/35236988/

Molnár G, Kassai-Bazsa Z. Gonadotropin, ACTH, prolactin, sexual steroid and cortisol levels in postmenopausal women’s cerebrospinal fluid (CSF). Arch Gerontol Geriatr [Internet]. 1997 May [cited 2025 Jun 4];24(3):269–80. Available from: https://pubmed.ncbi.nlm.nih.gov/15374114/

Ryu V, Gumerova A, Korkmaz F, Kang SS, Katsel P, Miyashita S, et al. Brain atlas for glycoprotein hormone receptors at single-transcript level. Elife [Internet]. 2022 Sep 1 [cited 2025 Jun 4];11:e79612. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC9473692/

Gloaguen P, Crépieux P, Heitzler D, Poupon A, Reiter E. Mapping the follicle-stimulating hormone-induced signaling networks. Front Endocrinol (Lausanne) [Internet]. 2011 Oct 5 [cited 2025 Jun 4];2(OCT):13185. Available from: www.frontiersin.org

Simoni M, Gromoll J, Nieschlag E. The Follicle-Stimulating Hormone Receptor: Biochemistry, Molecular Biology, Physiology, and Pathophysiology*. Endocr Rev [Internet]. 1997 Dec 1 [cited 2025 Jun 11];18(6):739–73. Available from: https://pubmed.ncbi.nlm.nih.gov/9408742/

Das N, Kumar TR. Molecular regulation of follicle-stimulating hormone synthesis, secretion and action. J Mol Endocrinol [Internet]. 2018 Apr 1 [cited 2025 Jun 12];60(3):R131–55. Available from: https://pubmed.ncbi.nlm.nih.gov/29437880/

Sun L, Peng Y, Sharrow AC, Iqbal J, Zhang Z, Papachristou DJ, et al. FSH Directly Regulates Bone Mass. Cell [Internet]. 2006 Apr 21 [cited 2025 Jun 4];125(2):247–60. Available from: https://pubmed.ncbi.nlm.nih.gov/16630814/

Lei ZM, Rao C V. Neural actions of luteinizing hormone and human chorionic gonadotropin. Semin Reprod Med [Internet]. 2001 [cited 2025 Jun 4];19(1):103–9. Available from: https://pubmed.ncbi.nlm.nih.gov/11394198/

Lei ZM, Rao C V., Kornyei JL, Licht P, Hiatt ES. Novel expression of human chorionic gonadotropin/luteinizing hormone receptor gene in brain. Endocrinology [Internet]. 1993 [cited 2025 Jun 4];132(5):2262–70. Available from: https://pubmed.ncbi.nlm.nih.gov/8477671/

Short RA, O’brien PC, Graff-Radford NR. Elevated gonadotropin levels in patients with Alzheimer disease. Mayo Clin Proc [Internet]. 2001 Sep 1 [cited 2025 Jun 4];76(9):906–9. Available from: https://www.mayoclinicproceedings.org/action/showFullText?pii=S0025619611621095

Ge YJ, Xu W, Tan CC, Tan L. Blood-based biomarkers in hypothalamic-pituitary axes for the risk of dementia or cognitive decline: a systematic review and meta-analysis. Aging [Internet]. 2020 Oct 26 [cited 2025 Jun 11];12(20):20350–65. Available from: https://pubmed.ncbi.nlm.nih.gov/33104518/

Wilson AC, Clemente L, Liu T, Bowen RL, Meethal SV, Atwood CS. Reproductive hormones regulate the selective permeability of the blood-brain barrier. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease [Internet]. 2008 Jun 1 [cited 2025 Jun 4];1782(6):401–7. Available from: https://www.sciencedirect.com/science/article/pii/S0925443908000604?via%3Dihub

Andersen K, Launer LJ, Dewey ME, Letenneur L, Ott A, Copeland JRM, et al. Gender differences in the incidence of AD and vascular dementia: The EURODEM Studies. Neurology [Internet]. 1999 Dec 10 [cited 2025 Jun 4];53(9):1992–7. Available from: https://pubmed.ncbi.nlm.nih.gov/10599770/

Yaffe K, Sawaya G, Lieberburg I, Grady D. Estrogen therapy in postmenopausal women: Effects on cognitive function and dementia. JAMA [Internet]. 1998 Mar 4 [cited 2025 Jun 4];279(9):688–95. Available from: https://pubmed.ncbi.nlm.nih.gov/9496988/

Hogervorst E, Williams J, Budge M, Riedel W, Jolles J. The nature of the effect of female gonadal hormone replacement therapy on cognitive function in post-menopausal women: A meta-analysis. Neuroscience [Internet]. 2000 Nov 15 [cited 2025 Jun 4];101(3):485–512. Available from: https://pubmed.ncbi.nlm.nih.gov/11113299/

Shumaker SA, Legault C, Rapp SR, Thal L, Wallace RB, Ockene JK, et al. Estrogen Plus Progestin and the Incidence of Dementia and Mild Cognitive Impairment in Postmenopausal Women - The Women’s Health Initiative Memory Study: A Randomized Controlled Trial. J Am Med Assoc [Internet]. 2003 May 28 [cited 2025 Jun 4];289(20):2651–62. Available from: https://pubmed.ncbi.nlm.nih.gov/12771112/

Shumaker SA, Legault C, Kuller L, Rapp SR, Thal L, Lane DS, et al. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women’s Health Initiative Memory Study. JAMA [Internet]. 2004 Jun 23 [cited 2025 Jun 4];291(24):2947–58. Available from: https://pubmed.ncbi.nlm.nih.gov/15213206/

Rapp SR, Espeland MA, Shumaker SA, Henderson VW, Brunner RL, Manson JAE, et al. Effect of Estrogen Plus Progestin on Global Cognitive Function in Postmenopausal Women - The Women’s Health Initiative Memory Study: A Randomized Controlled Trial. JAMA [Internet]. 2003 May 28 [cited 2025 Jun 4];289(20):2663–72. Available from: https://pubmed.ncbi.nlm.nih.gov/12771113/

Coughlan GT, Rubinstein Z, Klinger H, Lopez KA, Hsieh S, Boyle R, et al. Associations between hormone therapy use and tau accumulation in brain regions vulnerable to Alzheimer’s disease. Sci Adv [Internet]. 2025 Mar 7 [cited 2025 Jun 4];11(10):eadt1288. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC11881894/

Whitmer RA, Quesenberry CP, Zhou J, Yaffe K. Timing of hormone therapy and dementia: The critical window theory revisited. Ann Neurol [Internet]. 2011 Jan [cited 2025 Jun 4];69(1):163–9. Available from: https://pubmed.ncbi.nlm.nih.gov/21280086/

Maki PM. Critical window hypothesis of hormone therapy and cognition: A scientific update on clinical studies. Menopause [Internet]. 2013 Jun [cited 2025 Jun 4];20(6):695–709. Available from: https://pubmed.ncbi.nlm.nih.gov/23715379/

Kling JM, Dowling NM, Bimonte-Nelson HA, Gleason CE, Kantarci K, Manson JE, et al. Impact of menopausal hormone formulations on pituitary-ovarian regulatory feedback. Am J Physiol Regul Integr Comp Physiol [Internet]. 2019 [cited 2025 Jun 4];317(6):R912. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC6957372/

Gregory CW, Bowen RL. Novel therapeutic strategies for Alzheimer’s disease based on the forgotten reproductive hormones. Cellular and Molecular Life Sciences [Internet]. 2005 Feb [cited 2025 Jun 4];62(3):313–9. Available from: https://pubmed.ncbi.nlm.nih.gov/15723167/

Wilson AC, Meethal SV, Bowen RL, Atwood CS. Leuprolide acetate: A drug of diverse clinical applications. Expert Opin Investig Drugs [Internet]. 2007 Nov [cited 2025 Jun 4];16(11):1851–63. Available from: https://pubmed.ncbi.nlm.nih.gov/17970643/

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