CoChat
Sign Up
Cited by 612Menopause: Health Impacts and TreatmentsEstrogen and related hormone effectsPhytoestrogen effects and research

Perimenopause as a neurological transition state

Open access
Brinton, Roberta D., Yao, Jia, Yin, Fei, Mack, Wendy J., Cadenas, Enrique·2015·Nature Reviews Endocrinology
DOI 10.1038/nrendo.2015.82PMC PMC9934205
Open this paper in CoChat — free account

Abstract

Perimenopause is a midlife transition state experienced by women that occurs in the context of a fully functioning neurological system and results in reproductive senescence. Although primarily viewed as a reproductive transition, the symptoms of perimenopause are largely neurological in nature. Neurological symptoms that emerge during perimenopause are indicative of disruption in multiple estrogen-regulated systems (including thermoregulation, sleep, circadian rhythms and sensory processing) and affect multiple domains of cognitive function. Estrogen is a master regulator that functions through a network of estrogen receptors to ensure that the brain effectively responds at rapid, intermediate and long timescales to regulate energy metabolism in the brain via coordinated signalling and transcriptional pathways. The estrogen receptor network becomes uncoupled from the bioenergetic system during the perimenopausal transition and, as a corollary, a hypometabolic state associated with neurological dysfunction can develop. For some women, this hypometabolic state might increase the risk of developing neurodegenerative diseases later in life. The perimenopausal transition might also represent a window of opportunity to prevent age-related neurological diseases. This Review considers the importance of neurological symptoms in perimenopause in the context of their relationship to the network of estrogen receptors that control metabolism in the brain.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/nrendo.2015.82

Cites

7 of 7 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Metabolomic techniques have uncovered metabolic abnormalities in AD, particularly those related to lipid metabolism, mitochondrial dysfunction, and inflammatory signaling.

    “These techniques have uncovered metabolic abnormalities in AD, particularly those related to lipid metabolism, mitochondrial dysfunction, and inflammatory signaling192,193.”

    From Artificial intelligence-driven multi-omics approaches in Alzheimer's disease: Progress, challenges, and future directions (2025) · cites this paper as [192]

    The Cognition section reports brain hypometabolism before Alzheimer disease diagnosis, supporting the general link between AD and metabolic abnormalities. The Estrogen and neural bioenergetics section discusses fatty-acid metabolism in the perimenopausal brain, but our copy does not say that metabolomic techniques uncovered the claimed combination of lipid, mitochondrial, and inflammatory abnormalities in AD. Page numbers were not available in the indexed passages. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 113

  1. [1]Brinton RD in Brockelhurst’s Textbook of Geriatric Medicine and Gerontology (eds Fillit H, Rockwood K & Young J) 163– 171 (Saunders, 2010).
  2. [2]Butler L & Santoro N The reproductive endocrinology of the menopausal transition. Steroids 76, 627– 635 (2011). 21419147 PMC3100375
  3. [3]Harlow SD Executive summary of the Stages of Reproductive Aging Workshop + 10: addressing the unfinished agenda of staging reproductive aging. Menopause 19, 387– 395, (2012). 22343510 PMC3340903
  4. [4]Greendale GA, Ishii S, Huang MH & Karlamangla AS Predicting the timeline to the final menstrual period: the study of women’s health across the nation. J. Clin. Endocrinol. Metab. 98, 1483– 1491 (2013). 23533245 PMC3615211
  5. [6]Brinton RD, Gore AC, Schmidt PJ & Morrison JH in Hormones, Brain and Behavior 2nd edn (eds Pfaff DW) 2199– 2222 (Elsevier, 2009).
  6. [7]Burger HG, Dudley EC, Robertson DM & Dennerstein L Hormonal changes in the menopause transition. Recent Prog. Horm. Res. 57, 257– 275 (2002). 12017547
  7. [8]Paus T, Keshavan M & Giedd JN Why do many psychiatric disorders emerge during adolescence? Nat. Rev. Neurosci. 9, 947– 957 (2008). 19002191 PMC2762785
  8. [9]Petricka JJ & Benfey PN Reconstructing regulatory network transitions. Trends Cell Biol. 21, 442– 451 (2011). 21632251 PMC3149721
  9. [10]Chen L, Liu R, Liu ZP, Li M & Aihara K Detecting early-warning signals for sudden deterioration of complex diseases by dynamical network biomarkers. Sci. Rep. 2, 342 (2012). 22461973 PMC3314989
  10. [11]Wilson RS, Leurgans SE, Boyle PA & Bennett DA Cognitive decline in prodromal Alzheimer disease and mild cognitive impairment. Arch. Neurol. 68, 351– 356 (2011). 21403020 PMC3100533
  11. [13]Santoro N & Sutton-Tyrrell K The SWAN song: Study of Women’s Health Across the Nation’s recurring themes. Obstet. Gynecol. Clin. North Am. 38, 417– 423 (2011). 21961710 PMC3185240
  12. [14]Burger H Nomenclature and endocrinology of menopause and perimenopause. Expert Rev. Neurother. 7 (11 Suppl.), S35– S43 (2007). 18039067
  13. [15]Genazzani AR Endocrinology of menopausal transition and its brain implications. CNS Spectr. 10, 449– 457 (2005). 15908899
  14. [16]Tepper PG Trajectory clustering of estradiol and follicle-stimulating hormone during the menopausal transition among women in the Study of Women’s Health across the Nation (SWAN). J. Clin. Endocrinol. Metab. 97, 2872– 2880 (2012). 22659249 PMC3410268
  15. [17]Bastian LA, Smith CM & Nanda K Is this woman perimenopausal? JAMA 289, 895– 902 (2003). 12588275
  16. [18]Avis NE Is there a menopausal syndrome? Menopausal status and symptoms across racial/ethnic groups. Soc. Sci. Med. 52, 345– 356 (2001). 11330770
  17. [20]Finch CE The menopause and aging, a comparative perspective. J. Steroid Biochem. Mol. Biol. 142, 132– 141 (2014). 23583565 PMC3773529
  18. [21]Walker ML, Gordon TP & Wilson ME Menstrual cycle characteristics of seasonally breeding rhesus monkeys. Biol. Reprod. 29, 841– 848 (1983). 6416317
  19. [22]Weiss G, Skurnick JH, Goldsmith LT, Santoro NF & Park SJ Menopause and hypothalamic-pituitary sensitivity to estrogen. JAMA 292, 2991– 2996 (2004). 15613667
  20. [23]Chen S, Nilsen J & Brinton RD Dose and temporal pattern of estrogen exposure determines neuroprotective outcome in hippocampal neurons: therapeutic implications. Endocrinology 147, 5303– 5313 (2006). 16916950
  21. [24]Mobbs CV Estradiol-induced adult anovulatory syndrome in female C57BL/6J mice: age-like neuroendocrine, but not ovarian, impairments. Biol. Reprod. 30, 556– 563 (1984). 6539132
  22. [25]Finch CE, Felicio LS, Mobbs CV & Nelson JF Ovarian and steroidal influences on neuroendocrine aging processes in female rodents. Endocr. Rev. 5, 467– 497 (1984). 6389107
  23. [26]Mobbs CV, Gee DM & Finch CE Reproductive senescence in female C57BL/6J mice: ovarian impairments and neuroendocrine impairments that are partially reversible and delayable by ovariectomy. Endocrinology 115, 1653– 1662 (1984). 6541567
  24. [27]Maki PM Objective hot flashes are negatively related to verbal memory performance in midlife women. Menopause 15, 848– 856 (2008). 18562950 PMC2756983
  25. [28]Maki PM Depressive symptoms are increased in the early perimenopausal stage in ethnically diverse human immunodeficiency virus-infected and human immunodeficiency virus-uninfected women. Menopause 19, 1215– 1223 (2012). 22872013 PMC3483358
  26. [29]Greendale GA Effects of the menopause transition and hormone use on cognitive performance in midlife women. Neurology 72, 1850– 1857 (2009). 19470968 PMC2690984
  27. [30]Greendale GA Menopause-associated symptoms and cognitive performance: results from the study of women’s health across the nation. Am. J. Epidemiol. 171, 1214– 1224 (2010). 20442205 PMC2915492
  28. [31]Rasgon N, Shelton S & Halbreich U Perimenopausal mental disorders: epidemiology and phenomenology. CNS Spectr. 10, 471– 478 (2005). 15908901
  29. [32]Schmidt PJ & Rubinow DR Reproductive ageing, sex steroids and depression. J. Br. Menopause Soc. 12, 178– 185 (2006). 17178020
  30. [33]Schmidt PJ & Rubinow DR Sex hormones and mood in the perimenopause. Ann. NY Acad. Sci. 1179, 70– 85 (2009). 19906233 PMC2891531
  31. [34]Weber MT, Rubin LH & Maki PM Cognition in perimenopause: the effect of transition stage. Menopause 20, 511– 517 (2013). 23615642 PMC3620712
  32. [35]Weber MT, Maki PM & McDermott MP Cognition and mood in perimenopause: a systematic review and meta-analysis. J. Steroid Biochem. Mol. Biol. 142, 90– 98 (2014). 23770320 PMC3830624
  33. [36]Freeman EW, Sammel MD & Lin H Temporal associations of hot flashes and depression in the transition to menopause. Menopause 16, 728– 734 (2009). 19188849 PMC2860597
  34. [37]Bromberger JT 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 67, 598– 607 (2010). 20530009 PMC3129620
  35. [38]Thurston RC, Santoro N & Matthews KA Adiposity and hot flashes in midlife women: a modifying role of age. J. Clin. Endocrinol. Metab. 96, E1588– E1595 (2011). 21778220 PMC3200246
  36. [39]Nelson HD Menopause. Lancet 371, 760– 770 (2008). 18313505
  37. [40]Usall J Suicide ideation across reproductive life cycle of women. Results from a European epidemiological study. J. Affect Disord. 116, 144– 147 (2009). 19155069
  38. [41]Genazzani AR, Gambacciani M & Simoncini T Menopause and aging, quality of life and sexuality. Climacteric 10, 88– 96 (2007). 17453857
  39. [43]Cray LA, Woods NF & Mitchell ES Identifying symptom clusters during the menopausal transition: observations from the Seattle Midlife Women’s Health Study. Climacteric 16, 539– 549 (2013). 23153001
  40. [44]Cray LA, Woods NF, Herting JR & Mitchell ES Symptom clusters during the late reproductive stage through the early postmenopause: observations from the Seattle Midlife Women’s Health Study. Menopause 19, 864– 869 (2012). 22643229 PMC4492115
  41. [45]Shughrue PJ, Lane MV & Merchenthaler I Comparative distribution of estrogen receptor-alpha and -beta mRNA in the rat central nervous system. J. Comp. Neurol. 388, 507– 525 (1997). 9388012
  42. [46]O’Dowd BF Discovery of three novel, G-protein-coupled receptor genes. Genomics 47, 310– 313 (1998). 9479505
  43. [47]Brinton RD Estrogen-induced plasticity from cells to circuits: predictions for cognitive function. Trends Pharmacol. Sci. 30, 212– 222 (2009). 19299024 PMC3167490
  44. [48]Nilsson S, Koehler KF & Gustafsson JA Development of subtype-selective estrogen receptor-based therapeutics. Nat. Rev. Drug Discov. 10, 778– 792 (2011). 21921919
  45. [50]Suzuki H Involvement of estrogen receptor β in maintenance of serotonergic neurons of the dorsal raphe. Mol. Psychiatry 18, 674– 680 (2013). 22665260
  46. [51]Brailoiu E Distribution and characterization of estrogen receptor G protein-coupled receptor 30 in the rat central nervous system. J. Endocrinol. 193, 311– 321 (2007). 17470522
  47. [52]Naugle MM G-protein coupled estrogen receptor, estrogen receptor α, and progesterone receptor immunohistochemistry in the hypothalamus of aging female rhesus macaques given long-term estradiol treatment. J. Exp. Zool. A Ecol. Genet. Physiol 321, 399– 414 (2014). 24862737 PMC4282650
  48. [53]McEwen BS, Akama KT, Spencer-Segal JL, Milner TA and Waters EM Estrogen effects on the brain: actions beyond the hypothalamus via novel mechanisms. Behav. Neurosci. 126, 4– 16 (2012). 22289042 PMC3480182
  49. [54]Bethea CL, Mirkes SJ, Su A & Michelson D Effects of oral estrogen, raloxifene and arzoxifene on gene expression in serotonin neurons of macaques. Psychoneuroendocrinology 27, 431– 445 (2002). 11911997
  50. [55]Maki PM The timing of estrogen therapy after ovariectomy--implications for neurocognitive function. Nat. Clin. Pract. Endocrinol. Metab. 4, 494– 495 (2008). 18648334
  51. [56]Brinton RD The healthy cell bias of estrogen action: mitochondrial bioenergetics and neurological implications. Trends Neurosci. 31, 529– 537 (2008). 18774188 PMC10124615
  52. [57]Rocca WA, Grossardt BR & Shuster LT Oophorectomy, estrogen, and dementia: a 2014 update. Mol. Cell. Endocrinol. 389, 7– 12 (2014). 24508665 PMC4040304
  53. [58]Brinton RD Progesterone receptors: form and function in brain. Front. Neuroendocrinol. 29, 313– 339 (2008). 18374402 PMC2398769
  54. [59]Zhao L Continuous versus cyclic progesterone exposure differentially regulates hippocampal gene expression and functional profiles. PLoS ONE 7, e31267 (2012). 22393359 PMC3290616
  55. [60]Rasgon NL Prospective randomized trial to assess effects of continuing hormone therapy on cerebral function in postmenopausal women at risk for dementia. PLoS ONE 9, e89095 (2014). 24622517 PMC3951184
  56. [61]Rettberg JR, Yao J & Brinton RD Estrogen: a master regulator of bioenergetic systems in the brain and body. Front. Neuroendocrinol. 35, 8– 30 (2014). 23994581 PMC4024050
  57. [62]Tiano JP & Mauvais-Jarvis F Importance of estrogen receptors to preserve functional β-cell mass in diabetes. Nat. Rev. Endocrinol. 8, 342– 351 (2012). 22330739
  58. [63]Ruiz-Palmero I, Hernando M, Garcia-Segura LM & Arevalo MA G protein-coupled estrogen receptor is required for the neuritogenic mechanism of 17β-estradiol in developing hippocampal neurons. Mol. Cell. Endocrinol. 372, 105– 115 (2013). 23545157
  59. [64]Levin ER Extranuclear estrogen receptor’s roles in physiology: lessons from mouse models. Am. J. Physiol. Endocrinol. Metab 307, E133– E140 (2014). 24895281 PMC4101634
  60. [65]Mannella P & Brinton RD Estrogen receptor protein interaction with phosphatidylinositol 3-kinase leads to activation of phosphorylated Akt and extracellular signal-regulated kinase 1/2 in the same population of cortical neurons: a unified mechanism of estrogen action. J. Neurosci. 26, 9439– 9447 (2006). 16971528 PMC6674594
  61. [66]Scharfman HE & Maclusky NJ Similarities between actions of estrogen and BDNF in the hippocampus: coincidence or clue? Trends Neurosci. 28, 79– 85 (2005). 15667930
  62. [67]Simpkins JW, Yi KD, Yang SH & Dykens JA Mitochondrial mechanisms of estrogen neuroprotection. Biochim. Biophys. Acta 1800, 1113– 1120 (2010). 19931595 PMC2889195
  63. [68]Milner TA Ultrastructural localization of estrogen receptor β immunoreactivity in the rat hippocampal formation. J. Comp. Neurol. 491, 81– 95 (2005). 16127691
  64. [69]Irwin RW Selective estrogen receptor modulators differentially potentiate brain mitochondrial function. J. Neuroendocrinol. 24, 236– 248 (2012). 22070562 PMC3264398
  65. [70]Arnold S, Victor MB & Beyer C Estrogen and the regulation of mitochondrial structure and function in the brain. J. Steroid Biochem. Mol. Biol. 131, 2– 9 (2012). 22326731
  66. [71]Nilsen J, Irwin RW, Gallaher TK & Brinton RD Estradiol in vivo regulation of brain mitochondrial proteome. J. Neurosci. 27, 14069– 14077 (2007). 18094246 PMC6673510
  67. [72]Heldring N Estrogen receptors: how do they signal and what are their targets. Physiol. Rev. 87, 905– 931 (2007). 17615392
  68. [73]NCBI AceView. Homo sapiens gene ESR1, encoding estrogen receptor 1 [ online], http://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?db=human&term=ESR1 (2010).
  69. [74]NCBI AceView. Homo sapiens complex locus ESR2, encoding estrogen receptor 2 (ER beta). [ online], http://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?db=human&term=ESR2 (2010).
  70. [75]Ishunina TA & Swaab DF Age-dependent ERα MB1 splice variant expression in discrete areas of the human brain. Neurobiol. Aging 29, 1177– 1189 (2008). 17368651
  71. [76]Chung WC Detection and localization of an estrogen receptor beta splice variant protein (ERβ2) in the adult female rat forebrain and midbrain regions. J. Comp. Neurol. 505, 249– 267 (2007). 17879269
  72. [77]Wang JM A dominant negative ERβ splice variant determines the effectiveness of early or late estrogen therapy after ovariectomy in rats. PLoS ONE 7, e33493 (2012). 22428062 PMC3302771
  73. [78]Zhang QG C terminus of Hsc70-interacting protein (CHIP)-mediated degradation of hippocampal estrogen receptor-α and the critical period hypothesis of estrogen neuroprotection. Proc. Natl Acad. Sci. USA 108, E617– E624 (2011). 21808025 PMC3167560
  74. [79]Frick KM Epigenetics, estradiol and hippocampal memory consolidation. J. Neuroendocrinol. 25, 1151– 1162 (2013). 24028406 PMC3943552
  75. [80]Fortress AM & Frick KM Epigenetic regulation of estrogen-dependent memory. Front. Neuroendocrinol. 35, 530– 549 (2014). 24878494 PMC4174980
  76. [82]Zhang X Regulation of estrogen receptor α by histone methyltransferase SMYD2-mediated protein methylation. Proc. Natl Acad. Sci. USA 110, 17284– 17289 (2013). 24101509 PMC3808627
  77. [83]Lomniczi A Epigenetic control of female puberty. Nat. Neurosci. 16, 281– 289, (2013). 23354331 PMC3581714
  78. [84]McCarthy MM A piece in the puzzle of puberty. Nat. Neurosci. 16, 251– 253 (2013). 23434974
  79. [85]Mendez P, Wandosell F & Garcia-Segura LM Cross-talk between estrogen receptors and insulin-like growth factor-I receptor in the brain: cellular and molecular mechanisms. Front. Neuroendocrinol. 27, 391– 403 (2006). 17049974
  80. [86]Ding F, Yao J, Rettberg JR, Chen S & Brinton RD Early decline in glucose transport and metabolism precedes shift to ketogenic system in female aging and Alzheimer’s mouse brain: implication for bioenergetic intervention. PLoS ONE 8, e79977 (2013). 24244584 PMC3823655
  81. [87]Yao J, Hamilton RT, Cadenas E & Brinton RD Decline in mitochondrial bioenergetics and shift to ketogenic profile in brain during reproductive senescence. Biochim. Biophys. Acta 1800, 1121– 1126 (2010). 20538040 PMC3200365
  82. [88]Yao J Ovarian hormone loss induces bioenergetic deficits and mitochondrial beta-amyloid. Neurobiol. Aging 33, 1507– 1521 (2012). 21514693 PMC3181273
  83. [89]Yin F The perimenopausal aging transition in the female rat brain: decline in bioenergetic systems and synaptic plasticity. Neurobiol. Aging 10.1016/j.neurobiolaging.2015.03.013. PMC4416218 25921624 · DOI
  84. [90]Zhao L, Mao Z, Chen S, Schneider LS & Brinton RD Early intervention with an estrogen receptor β-selective phytestrogenic formulation prolongs survival, improves spatial recognition memory, and slows progression of amyloid pathology in a female mouse model of Alzheimer’s disease. J. Alzheimers Dis. 37, 403– 419 (2013). 23948892 PMC4197935
  85. [91]Hara Y Presynaptic mitochondrial morphology in monkey prefrontal cortex correlates with working memory and is improved with estrogen treatment. Proc. Natl Acad. Sci. USA 111, 486– 491 (2014). 24297907 PMC3890848
  86. [92]Cahill GF Jr. Fuel metabolism in starvation. Annu. Rev. Nutr. 26, 1– 22 (2006). 16848698
  87. [93]Yao J, Rettberg JR, Klosinski LP, Cadenas E & Brinton RD Shift in brain metabolism in late onset Alzheimer’s disease: implications for biomarkers and therapeutic interventions. Mol. Aspects Med. 32, 247– 257 (2011). 22024249 PMC3658304
  88. [94]Yao J Mitochondrial bioenergetic deficit precedes Alzheimer’s pathology in female mouse model of Alzheimer’s disease. Proc. Natl Acad. Sci. USA 106, 14670– 14675 (2009). 19667196 PMC2732886
  89. [95]Rasgon NL Estrogen use and brain metabolic change in postmenopausal women. Neurobiol. Aging 26, 229– 235 (2005). 15582750
  90. [96]Maki PM & Resnick SM Longitudinal effects of estrogen replacement therapy on PET cerebral blood flow and cognition. Neurobiol. Aging 21, 373– 383 (2000). 10867223
  91. [97]Rasgon NL, Kenna HA, Geist C, Small G & Silverman D Cerebral metabolic patterns in untreated postmenopausal women with major depressive disorder. Psychiatry Res. 164, 77– 80 (2008). 18707852
  92. [98]Santoro N Symptoms of menopause: hot flushes. Clin. Obstet. Gynecol. 51, 539– 548 (2008). 18677148
  93. [99]Freedman RR Menopausal hot flashes: mechanisms, endocrinology, treatment. J. Steroid Biochem. Mol. Biol. 142, 115– 120 (2014). 24012626 PMC4612529
  94. [100]Maki PM Minireview: effects of different HT formulations on cognition. Endocrinology 153, 3564– 3570 (2012). 22673228
  95. [101]Avis NE Change in health-related quality of life over the menopausal transition in a multiethnic cohort of middle-aged women: Study of Women’s Health Across the Nation. Menopause 16, 860– 869 (2009). 19436224 PMC2743857
  96. [102]Freedman RR, Benton MD, Genik RJ 2nd & Graydon, F. X. Cortical activation during menopausal hot flashes. Fertil. Steril. 85, 674– 678 (2006). 16500337
  97. [103]Simpkins JW, Katovich MJ & Millard WJ Glucose modulation of skin temperature responses during morphine withdrawal in the rat. Psychopharmacology (Berl.) 102, 213– 220 (1990). 2274603
  98. [104]Thurston RC Vasomotor symptoms and insulin resistance in the study of women’s health across the nation. J. Clin. Endocrinol. Metab. 97, 3487– 3494 (2012). 22851488 PMC3462945
  99. [105]Thurston RC, Chang Y, Mancuso P & Matthews KA Adipokines, adiposity, and vasomotor symptoms during the menopause transition: findings from the Study of Women’s Health Across the Nation. Fertil. Steril. 100, 793– 800 (2013). 23755948 PMC3759568
  100. [106]Campbell IG Evaluation of the association of menopausal status with delta and beta EEG activity during sleep. Sleep 34, 1561– 1568 (2011). 22043127 PMC3198211
  101. [107]Kravitz HM & Joffe H Sleep during the perimenopause: a SWAN story. Obstet. Gynecol. Clin. North Am. 38, 567– 586 (2011). 21961720 PMC3185248
  102. [108]Wilson ME Age differentially influences estrogen receptor-α (ERα) and estrogen receptor-β (ERβ) gene expression in specific regions of the rat brain. Mech. Ageing Dev. 123, 593– 601 (2002). 11850023
  103. [110]Ju YE, Lucey BP & Holtzman DM Sleep and Alzheimer disease pathology-—a bidirectional relationship. Nat. Rev. Neurol 10, 115– 119 (2014). 24366271 PMC3979317
  104. [111]Kenna H Fasting plasma insulin and the default mode network in women at risk for Alzheimer’s disease. Neurobiol. Aging 34, 641– 649 (2013). 22770543 PMC4769033
  105. [112]Yee LT, Roe K & Courtney SM Selective involvement of superior frontal cortex during working memory for shapes. J. Neurophysiol. 103, 557– 563 (2010). 19923241 PMC2807238
  106. [113]Maki PM Perimenopausal use of hormone therapy is associated with enhanced memory and hippocampal function later in life. Brain Res. 1379, 232– 243 (2011). 21078303 PMC3046212
  107. [114]Rasgon NL Insulin resistance and medial prefrontal gyrus metabolism in women receiving hormone therapy. Psychiatry Res. 223, 28– 36 (2014). 24819305
  108. [115]Mosconi L Declining brain glucose metabolism in normal individuals with a maternal history of Alzheimer disease. Neurology 72, 513– 520 (2009). 19005175 PMC2677512
  109. [116]Rasgon NL Insulin resistance and hippocampal volume in women at risk for Alzheimer’s disease. Neurobiol. Aging 32, 1942– 1948 (2011). 20031276 PMC2891925
  110. [117]Mosconi L Brain imaging of cognitively normal individuals with 2 parents affected by late-onset AD. Neurology 82, 752– 760 (2014). 24523481 PMC3945651
  111. [118]Ryan J Estrogen receptor α gene variants and major depressive episodes. J. Affect Disord. 136, 1222– 1226 (2012). 22051074
  112. [119]Yaffe K The epidemiology of Alzheimer’s disease: laying the foundation for drug design, conduct, and analysis of clinical trials. Alzheimers Dement. 8, 237– 242 (2012). 22546356
  113. [120]Norton S, Matthews FE, Barnes DE, Yaffe K & Brayne C Potential for primary prevention of Alzheimer’s disease: an analysis of population-based data. Lancet Neurol. 13, 788– 794 (2014). 25030513

Cited by

Sorted by citations

Authors
Brinton, R. D., Yao, J., Yin, F., Mack, W. J., & Cadenas, E.
Affiliations
University of Southern California (US)
Corresponding author
Brinton, Roberta D.
ORCID
Venue
Nature Reviews Endocrinology
Publisher
Springer Science and Business Media LLC
Published
2015-05-26
Volume
11
Issue
7
Pages
393-405
ISSN
  • 1759-5029 (ISSN-L)
  • 1759-5037
DOI
10.1038/nrendo.2015.82
PMC
PMC9934205
OpenAlex
W1913092771
Cited by
612
References
7
Citations by year
2026: 101 · 2025: 117 · 2024: 98 · 2023: 67 · 2022: 48 · 2021: 45 · 2020: 40 · 2019: 27 · 2018: 35 · 2017: 13 · 2016: 19 · 2015: 2
FWCI
3.48
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Reviews Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute on Aging (R01AG032236, P01AG026572)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Phytoestrogen effects and research
Keywords
perimenopause, estrogen deficiency, estrogen receptor, brain energy metabolism, hypometabolism, neurological symptoms, cognitive function, thermoregulation, sleep, circadian rhythm, sensory processing, neurodegenerative disease risk, reproductive aging, middle-aged women
MeSH terms
Affect, Anxiety, Arousal, Attention, Brain, Cognition, Eating, Estrogens, Female, Humans, Learning, Memory, Receptors, Estrogen, Perimenopause, Executive Function

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review