{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T06:23:13Z","timestamp":1772778193682,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Lower urinary tract symptoms (LUTSs), particularly nocturia and urgency, often intensify during the menopause transition and may worsen with caffeine intake and cold exposure. This review aims to synthesize evidence relevant to a hypothesized caffeine\u2013cold interaction in transitional menopause, focusing on water homeostasis and the estrogen\u2013transient receptor potential melastatin 8 (TRPM8) cold-sensory axis, and to propose potentially actionable, nutrition-centered intervention candidates for future testing. Methods: Structured narrative review of PubMed, Embase, Web of Science, and citation tracking (inception\u2013January 2026). Evidence was mapped into a mechanistic framework distinguishing established from hypothesis-generating links; no formal systematic-review study selection or meta-analysis was performed. Results: Caffeine can increase urine output via renal mechanisms (adenosine receptor antagonism and natriuresis) and may lower bladder sensory thresholds. Because half-life is long and variable, afternoon intake can extend into sleep, potentially increasing awakenings and nocturnal voids. Human studies link colder indoor environments to nocturia\/overactive bladder, and passive pre-bedtime heating is associated with fewer nocturnal voids. We propose that repeated nighttime cold may amplify caffeine-related diuresis and may shift urine production toward the night, while estradiol decline may heighten TRPM8-mediated cold sensory gain, potentially contributing to urgency\/frequency flares. A testable 2 \u00d7 2 cold \u00d7 caffeine framework can operationalize dose, timing, and metabolism, pairing voiding diaries and bedroom temperature sensing with copeptin profiling. Conclusions: Transitional menopause may represent a susceptibility window in which endocrine instability and estradiol decline could plausibly increase sensitivity to indoor cold exposure and caffeine intake, potentially contributing to nocturia and urgency. The hypothesis label \u2018dual hormone suppression\u2019 (attenuated nocturnal AVP signal plus estradiol decline) may provide a mechanistic substrate for cold-exacerbated nocturnal polyuria, while an estrogen\u2013TRPM8 axis may amplify cold-evoked urgency. Potentially actionable candidates include chronobiological caffeine timing\/management and low-burden thermal strategies; nevertheless, menopause-stage-specific epidemiologic and clinical evidence for a caffeine \u00d7 cold interaction remains limited and several mechanistic links are extrapolated, so prospective diary- and biomarker-enabled studies and controlled trials are needed to validate mechanisms and refine cold-sensitive endotypes.<\/jats:p>","DOI":"10.3390\/nu18050825","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T16:17:31Z","timestamp":1772641051000},"page":"825","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dietary Caffeine, Cold Exposure, and the Estrogen\u2013TRPM8 Axis: A Nutri-Environmental Model for Lower Urinary Tract Symptoms in the Menopause Transition: A Narrative Review"],"prefix":"10.3390","volume":"18","author":[{"given":"Dong Hee","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeong Jun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, CHA Bundang Medical Centre, CHA University School of Medicine, Seongnam 13496, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1097\/gme.0b013e31824d8f40","article-title":"Executive summary of the Stages of Reproductive Aging Workshop + 10: Addressing the unfinished agenda of staging reproductive aging","volume":"19","author":"Harlow","year":"2012","journal-title":"Menopause"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4038","DOI":"10.1016\/j.cell.2023.08.016","article-title":"Menopause-Biology, consequences, supportive care, and therapeutic options","volume":"186","author":"Davis","year":"2023","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1097\/GME.0000000000001424","article-title":"The menopause transition and women\u2019s health at midlife: A progress report from the Study of Women\u2019s Health Across the Nation (SWAN)","volume":"26","author":"Greendale","year":"2019","journal-title":"Menopause"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1097\/AOG.0b013e3181bb531a","article-title":"Association between menopausal transition stages and developing urinary incontinence","volume":"114","author":"Waetjen","year":"2009","journal-title":"Obstet. Gynecol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1089\/jwh.2015.5370","article-title":"Bladder Symptoms in the Early Menopausal Transition","volume":"25","author":"Jones","year":"2016","journal-title":"J. Women\u2019s Health"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1097\/GME.0000000000002541","article-title":"Association of menopausal status and hormone use with bladder health and lower urinary tract symptoms in US women: Results from the RISE FOR HEALTH study","volume":"32","author":"Vaughan","year":"2025","journal-title":"Menopause"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.maturitas.2014.07.013","article-title":"Genitourinary syndrome of menopause: New terminology for vulvovaginal atrophy from the International Society for the Study of Women\u2019s Sexual Health and the North American Menopause Society","volume":"79","author":"Portman","year":"2014","journal-title":"Maturitas"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"The NAMS 2020 GSM Position Statement Editorial Panel (2020). The 2020 genitourinary syndrome of menopause position statement of The North American Menopause Society. Menopause, 27, 976\u2013992.","DOI":"10.1097\/GME.0000000000001609"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1097\/JU.0000000000000309","article-title":"Diagnosis and Treatment of Overactive Bladder (Non-Neurogenic) in Adults: AUA\/SUFU Guideline Amendment 2019","volume":"202","author":"Lightner","year":"2019","journal-title":"J. Urol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1002\/nau.23917","article-title":"International Continence Society (ICS) report on the terminology for nocturia and nocturnal lower urinary tract function","volume":"38","author":"Hashim","year":"2019","journal-title":"Neurourol. Urodyn."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"114869","DOI":"10.1016\/j.enpol.2025.114869","article-title":"Who is \u201cenergy poor\u201d in the EU?","volume":"208","author":"Maier","year":"2026","journal-title":"Energy Policy"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"102294","DOI":"10.1016\/j.healthplace.2020.102294","article-title":"Energy poverty and health: Trends in the European Union before and during the economic crisis, 2007\u20132016","volume":"67","author":"Oliveras","year":"2021","journal-title":"Health Place"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"110869","DOI":"10.1016\/j.enpol.2019.07.005","article-title":"Structural energy poverty vulnerability and excess winter mortality in the European Union: Exploring the association between structural determinants and health","volume":"133","author":"Recalde","year":"2019","journal-title":"Energy Policy"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Temple, J.L., Bernard, C., Lipshultz, S.E., Czachor, J.D., Westphal, J.A., and Mestre, M.A. (2017). The Safety of Ingested Caffeine: A Comprehensive Review. Front. Psychiatry, 8.","DOI":"10.3389\/fpsyt.2017.00080"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"334","DOI":"10.5213\/inj.1938078.039","article-title":"Seasonal Variation of Overactive Bladder Symptoms in Female Patients","volume":"23","author":"Tae","year":"2019","journal-title":"Int. Neurourol. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1111\/bju.13325","article-title":"Indoor cold exposure and nocturia: A cross-sectional analysis of the HEIJO-KYO study","volume":"117","author":"Saeki","year":"2016","journal-title":"BJU Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.urology.2020.08.020","article-title":"Impact of Cold Indoor Temperatures on Overactive Bladder: A Nationwide Epidemiological Study in Japan","volume":"145","author":"Ishimaru","year":"2020","journal-title":"Urology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"398","DOI":"10.2188\/jea.JE20210471","article-title":"Association Between Before-bedtime Passive Body Heating and Nocturia During the Cold Season Among Older Adults","volume":"33","author":"Tai","year":"2023","journal-title":"J. Epidemiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"F1472","DOI":"10.1152\/ajprenal.00430.2005","article-title":"Genetic AVP deficiency abolishes cold-induced diuresis but does not attenuate cold-induced hypertension","volume":"290","author":"Sun","year":"2006","journal-title":"Am. J. Physiol.-Ren. Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1046\/j.1365-201X.1998.0314f.x","article-title":"The role of antidiuretic hormone in cold-induced diuresis in the anaesthetized rat","volume":"162","author":"Broman","year":"1998","journal-title":"Acta Physiol. Scand."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e250100","DOI":"10.1530\/EC-25-0100","article-title":"Coffee intake and the vasopressin system: An epidemiological and experimental study","volume":"14","author":"Schill","year":"2025","journal-title":"Endocr. Connect."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"F1409","DOI":"10.1152\/ajprenal.00129.2015","article-title":"Caffeine-induced diuresis and natriuresis is independent of renal tubular NHE3","volume":"308","author":"Fenton","year":"2015","journal-title":"Am. J. Physiol.-Ren. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"14","DOI":"10.4103\/0974-7796.75862","article-title":"Effect of caffeine on bladder function in patients with overactive bladder symptoms","volume":"3","author":"Lohsiriwat","year":"2011","journal-title":"Urol. Ann."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"23","DOI":"10.5213\/inj.2346014.007","article-title":"Effectiveness of Fluid and Caffeine Modifications on Symptoms in Adults With Overactive Bladder: A Systematic Review","volume":"27","author":"Park","year":"2023","journal-title":"Int. Neurourol. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1016\/j.juro.2011.01.003","article-title":"Caffeine intake, and the risk of stress, urgency and mixed urinary incontinence","volume":"185","author":"Jura","year":"2011","journal-title":"J. Urol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"F797","DOI":"10.1152\/ajprenal.00403.2003","article-title":"Downregulation of renal vasopressin V2 receptor and aquaporin-2 expression parallels age-associated defects in urine concentration","volume":"287","author":"Tian","year":"2004","journal-title":"Am. J. Physiol.-Ren. Physiol."},{"key":"ref_27","first-page":"F400","article-title":"Dehydration reverses vasopressin antagonist-induced diuresis and aquaporin-2 downregulation in rats","volume":"275","author":"Marples","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.eururo.2015.03.037","article-title":"Essential role of transient receptor potential M8 (TRPM8) in a model of acute cold-induced urinary urgency","volume":"68","author":"Uvin","year":"2015","journal-title":"Eur. Urol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.1016\/j.juro.2012.10.014","article-title":"The relationship between alpha1-adrenergic receptors and TRPM8 channels in detrusor overactivity induced by cold stress in ovariectomized rats","volume":"189","author":"Noguchi","year":"2013","journal-title":"J. Urol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Mukerji, G., Yiangou, Y., Corcoran, S.L., Selmer, I.S., Smith, G.D., Benham, C.D., Bountra, C., Agarwal, S.K., and Anand, P. (2006). Cool and menthol receptor TRPM8 in human urinary bladder disorders and clinical correlations. BMC Urol., 6.","DOI":"10.1186\/1471-2490-6-6"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"F803","DOI":"10.1152\/ajprenal.90269.2008","article-title":"AMTB, a TRPM8 channel blocker: Evidence in rats for activity in overactive bladder and painful bladder syndrome","volume":"295","author":"Lashinger","year":"2008","journal-title":"Am. J. Physiol.-Ren. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"eaav9334","DOI":"10.1126\/science.aav9334","article-title":"Structural basis of cooling agent and lipid sensing by the cold-activated TRPM8 channel","volume":"363","author":"Yin","year":"2019","journal-title":"Science"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1538\/expanim.17-0028","article-title":"Effects of beta-estradiol on cold-sensitive receptor channel TRPM8 in ovariectomized rats","volume":"66","author":"Kubo","year":"2017","journal-title":"Exp. Anim."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1074\/mcp.RA117.000290","article-title":"Proteomic Analysis of Urothelium of Rats with Detrusor Overactivity Induced by Bladder Outlet Obstruction","volume":"17","author":"Park","year":"2018","journal-title":"Mol. Cell. Proteom."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.eururo.2009.03.080","article-title":"Nocturia frequency, bother, and quality of life: How often is too often? A population-based study in Finland","volume":"57","author":"Tikkinen","year":"2010","journal-title":"Eur. Urol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"S86","DOI":"10.1016\/j.juro.2012.11.033","article-title":"The prevalence and causes of nocturia","volume":"189","author":"Bosch","year":"2013","journal-title":"J. Urol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.smrv.2010.03.002","article-title":"The effect of nocturia on sleep","volume":"15","author":"Bliwise","year":"2011","journal-title":"Sleep Med. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e01283-01214","DOI":"10.1128\/mBio.01283-14","article-title":"The female urinary microbiome: A comparison of women with and without urgency urinary incontinence","volume":"5","author":"Pearce","year":"2014","journal-title":"mBio"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Thomas-White, K., Taege, S., Limeira, R., Brincat, C., Joyce, C., Hilt, E.E., Mac-Daniel, L., Radek, K.A., Brubaker, L., and Mueller, E.R. (2020). Vaginal estrogen therapy is associated with increased Lactobacillus in the urine of postmenopausal women with overactive bladder symptoms. Am. J. Obstet. Gynecol., 223.","DOI":"10.1016\/j.ajog.2020.08.006"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1007\/s00192-019-04175-6","article-title":"Urinary metabolomics predict the severity of overactive bladder syndrome in an aging female population","volume":"31","author":"Mossa","year":"2020","journal-title":"Int. Urogynecol. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"afac024","DOI":"10.1093\/ageing\/afac024","article-title":"Considerations for integrated cognitive behavioural treatment for older adults with coexisting nocturia and insomnia","volume":"51","author":"Vaughan","year":"2022","journal-title":"Age Ageing"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1097\/JU.0000000000000459","article-title":"The Impact of Nocturia on Falls and Fractures: A Systematic Review and Meta-Analysis","volume":"203","author":"Pesonen","year":"2020","journal-title":"J. Urol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1111\/j.1742-1241.2009.02326.x","article-title":"The association of nocturia with incident falls in an elderly community-dwelling cohort","volume":"64","author":"Vaughan","year":"2010","journal-title":"Int. J. Clin. Pract."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1111\/bju.13718","article-title":"Low-dose desmopressin combined with serum sodium monitoring can prevent clinically significant hyponatraemia in patients treated for nocturia","volume":"119","author":"Juul","year":"2017","journal-title":"BJU Int."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Kim, S., Jo, C.H., and Kim, G.H. (2021). The Role of Vasopressin V2 Receptor in Drug-Induced Hyponatremia. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.797039"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"100592","DOI":"10.1016\/j.cont.2023.100592","article-title":"Systematic review and meta-analysis of randomized control trials addressing efficacy and safety of desmopressin for females with nocturia","volume":"6","author":"Alsahabi","year":"2023","journal-title":"Continence"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/5\/825\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T05:18:38Z","timestamp":1772774318000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/5\/825"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,3]]},"references-count":46,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["nu18050825"],"URL":"https:\/\/doi.org\/10.3390\/nu18050825","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,3]]}}}