Does the environment affect menopause? A review of the effects of endocrine disrupting chemicals on menopause

References

• El Khoudary SR. Age at menopause onset and risk of cardiovascular disease around the world. Maturitas. 2020;141:33–38.
   PubMed Web of Science ®Google Scholar
• Nelson HD. Menopause. Lancet. 2008;371(9614):760–770.
   PubMed Web of Science ®Google Scholar
• Sowers MR, Eyvazzadeh AD, McConnell D, et al. Anti-mullerian hormone and inhibin B in the definition of ovarian aging and the menopause transition. J Clin Endocrinol Metab. 2008;93(9):3478–3483.
   PubMed Web of Science ®Google Scholar
• Xu X, Jones M, Mishra GD. Age at natural menopause and development of chronic conditions and multimorbidity: results from an Australian prospective cohort. Hum Reprod. 2020;35(1):203–211.
   PubMed Web of Science ®Google Scholar
• Faubion SS, Kuhle CL, Shuster LT, et al. Long-term health consequences of premature or early menopause and considerations for management. Climacteric. 2015;18(4):483–491.
   PubMed Web of Science ®Google Scholar
• La Merrill MA, Vandenberg LN, Smith MT, et al. Consensus on the key characteristics of endocrine-disrupting chemicals as a basis for hazard identification. Nat Rev Endocrinol. 2020;16(1):45–57.
   PubMed Web of Science ®Google Scholar
• Gore AC, Chappell VA, Fenton SE, et al. EDC-2: the Endocrine Society’s second scientific statement on endocrine-disrupting chemicals. Endocr Rev. 2015;36(6):E1–e150.
   PubMed Web of Science ®Google Scholar
• Rissman EF, Adli M. Minireview: transgenerational epigenetic inheritance: focus on endocrine disrupting compounds. Endocrinology. 2014;155(8):2770–2780.
   PubMed Web of Science ®Google Scholar
• World Health Organization. Human biomonitoring: facts and figures. Copenhagen, Denmark: WHO; 2015.
   Google Scholar
• Reed CE, Fenton SE. Exposure to diethylstilbestrol during sensitive life stages: a legacy of heritable health effects. Birth Defects Res C Embryo Today. 2013;99(2):134–146.
   PubMedGoogle Scholar
• Bae J, Park S, Kwon JW. Factors associated with menstrual cycle irregularity and menopause. BMC Womens Health. 2018;18(1):36.
   PubMedGoogle Scholar
• Basso CG, de Araújo-Ramos AT, Martino-Andrade AJ. Exposure to phthalates and female reproductive health: a literature review. Reprod Toxicol. 2022;109:61–79.
   PubMed Web of Science ®Google Scholar
• Heudorf U, Mersch-Sundermann V, Angerer J. Phthalates: toxicology and exposure. Int J Hyg Environ Health. 2007;210(5):623–634.
   PubMed Web of Science ®Google Scholar
• Bui TT, Giovanoulis G, Cousins AP, et al. Human exposure, hazard and risk of alternative plasticizers to phthalate esters. Sci Total Environ. 2016;541:451–467.
   PubMed Web of Science ®Google Scholar
• Grindler NM, Allsworth JE, Macones GA, et al. Persistent organic pollutants and early menopause in U.S. women. PLoS One. 2015;10(1):e0116057.
   PubMed Web of Science ®Google Scholar
• Long SE, Kahn LG, Trasande L, et al. Urinary phthalate metabolites and alternatives and serum sex steroid hormones among pre- and postmenopausal women from NHANES, 2013–16. Sci Total Environ. 2021;769:144560.
   PubMed Web of Science ®Google Scholar
• Ziv-Gal A, Gallicchio L, Chiang C, et al. Phthalate metabolite levels and menopausal hot flashes in midlife women. Reprod Toxicol. 2016;60:76–81.
   PubMed Web of Science ®Google Scholar
• Warner GR, Pacyga DC, Strakovsky RS, et al. Urinary phthalate metabolite concentrations and hot flashes in women from an urban convenience sample of midlife women. Environ Res. 2021;197:110891.
   PubMed Web of Science ®Google Scholar
• Edwards BJ, Li J. Endocrinology of menopause. Periodontol 2000. 2013;61(1):177–194.
   PubMedGoogle Scholar
• Hatcher KM, Smith RL, Chiang C, et al. Association of phthalate exposure and endogenous hormones with self-reported sleep disruptions: results from the Midlife Women’s Health Study. Menopause. 2020;27(11):1251–1264.
   PubMed Web of Science ®Google Scholar
• Hatcher KM, Smith RL, Li Z, et al. Preliminary findings reveal that phthalate exposure is associated with both subjective and objective measures of sleep in a small population of midlife women. Maturitas. 2022;157:62–65.
   PubMed Web of Science ®Google Scholar
• Brehm E, Rattan S, Gao L, et al. Prenatal exposure to di(2-ethylhexyl) phthalate causes long-term transgenerational effects on female reproduction in mice. Endocrinology. 2018;159(2):795–809.
   PubMed Web of Science ®Google Scholar
• Brehm E, Zhou C, Gao L, et al. Prenatal exposure to an environmentally relevant phthalate mixture accelerates biomarkers of reproductive aging in a multiple and transgenerational manner in female mice. Reprod Toxicol. 2020;98:260–268.
   PubMed Web of Science ®Google Scholar
• Wang JJ, Tian Y, Li MH, et al. Single-cell transcriptome dissection of the toxic impact of di (2-ethylhexyl) phthalate on primordial follicle assembly. Theranostics. 2021;11(10):4992–5009.
   PubMed Web of Science ®Google Scholar
• Chiang C, Lewis LR, Borkowski G, et al. Late-life consequences of short-term exposure to di(2-ethylhexyl) phthalate and diisononyl phthalate during adulthood in female mice. Reprod Toxicol. 2020;93:28–42.
   PubMed Web of Science ®Google Scholar
• Vandenberg LN, Hauser R, Marcus M, et al. Human exposure to bisphenol A (BPA). Reprod Toxicol. 2007;24(2):139–177.
   PubMed Web of Science ®Google Scholar
• Chen D, Kannan K, Tan H, et al. Bisphenol analogues other than BPA: environmental occurrence, human exposure, and toxicity-A review. Environ Sci Technol. 2016;50(11):5438–5453.
   PubMed Web of Science ®Google Scholar
• Ziv-Gal A, Flaws JA. Evidence for bisphenol A-induced female infertility: a review (2007–2016). Fertil Steril. 2016;106(4):827–856.
   PubMed Web of Science ®Google Scholar
• Cao Y, Qu X, Ming Z, et al. The correlation between exposure to BPA and the decrease of the ovarian reserve. Int J Clin Exp Pathol. 2018;11(7):3375–3382.
   PubMed Web of Science ®Google Scholar
• Souter I, Smith KW, Dimitriadis I, et al. The association of bisphenol-A urinary concentrations with antral follicle counts and other measures of ovarian reserve in women undergoing infertility treatments. Reprod Toxicol. 2013;42:224–231.
   PubMed Web of Science ®Google Scholar
• Nevoral J, Havránková J, Kolinko Y, et al. Exposure to alternative bisphenols BPS and BPF through breast milk: noxious heritage effect during nursing associated with idiopathic infertility. Toxicol Appl Pharmacol. 2021;413:115409.
   PubMed Web of Science ®Google Scholar
• De Silva AO, Armitage JM, Bruton TA, et al. PFAS exposure pathways for humans and wildlife: a synthesis of current knowledge and key gaps in understanding. Environ Toxicol Chem. 2021;40(3):631–657.
   PubMed Web of Science ®Google Scholar
• Sunderland EM, Hu XC, Dassuncao C, et al. A review of the pathways of human exposure to poly- and perfluoroalkyl substances (PFASs) and present understanding of health effects. J Expo Sci Environ Epidemiol. 2019;29(2):131–147.
   PubMed Web of Science ®Google Scholar
• Taylor KW, Hoffman K, Thayer KA, et al. Polyfluoroalkyl chemicals and menopause among women 20-65 years of age (NHANES). Environ Health Perspect. 2014;122(2):145–150.
   PubMed Web of Science ®Google Scholar
• Ding N, Harlow SD, Batterman S, et al. Longitudinal trends in perfluoroalkyl and polyfluoroalkyl substances among multiethnic midlife women from 1999 to 2011: the study of Women’s Health across the Nation. Environ Int. 2020;135:105381. Feb
   PubMed Web of Science ®Google Scholar
• Ding N, Harlow SD, Randolph JF, et al. Associations of perfluoroalkyl substances with incident natural menopause: the study of Women’s Health across the Nation. J Clin Endocrinol Metab. 2020;105(9):e3169–e3182.
   PubMed Web of Science ®Google Scholar
• Knox SS, Jackson T, Javins B, et al. Implications of early menopause in women exposed to perfluorocarbons. J Clin Endocrinol Metab. 2011;96(6):1747–1753.
   PubMed Web of Science ®Google Scholar
• Ding N, Harlow SD, Randolph JF, Jr., et al. Perfluoroalkyl and polyfluoroalkyl substances (PFAS) and their effects on the ovary. Hum Reprod Update. 2020;26(5):724–752.
   PubMed Web of Science ®Google Scholar
• Dhingra R, Darrow LA, Klein M, et al. Perfluorooctanoic acid exposure and natural menopause: a longitudinal study in a community cohort. Environ Res. 2016;146:323–330. Apr
   PubMed Web of Science ®Google Scholar
• Björvang RD, Hassan J, Stefopoulou M, et al. Persistent organic pollutants and the size of ovarian reserve in reproductive-aged women. Environ Int. 2021;155:106589.
   PubMed Web of Science ®Google Scholar
• Dhingra R, Winquist A, Darrow LA, et al. A study of reverse causation: examining the associations of perfluorooctanoic acid serum levels with two outcomes. Environ Health Perspect. 2017;125(3):416–421.
   PubMed Web of Science ®Google Scholar
• Jain RB, Ducatman A. Serum concentrations of selected perfluoroalkyl substances for US females compared to males as they age. Sci Total Environ. 2022;842:156891.
   PubMed Web of Science ®Google Scholar
• Yang M, Lee Y, Gao L, et al. Perfluorooctanoic acid disrupts ovarian steroidogenesis and folliculogenesis in adult mice. Toxicol Sci. 2022;186(2):260–268.
   PubMed Web of Science ®Google Scholar
• Chow ET, Mahalingaiah S. Cosmetics use and age at menopause: is there a connection?. Fertil Steril. 2016;106(4):978–990.
   PubMed Web of Science ®Google Scholar
• Sandanger TM, Huber S, Moe MK, et al. Plasma concentrations of parabens in postmenopausal women and self-reported use of personal care products: the NOWAC postgenome study. J Expo Sci Environ Epidemiol. 2011;21(6):595–600.
   PubMed Web of Science ®Google Scholar
• Smith KW, Souter I, Dimitriadis I, et al. Urinary paraben concentrations and ovarian aging among women from a fertility center. Environ Health Perspect. 2013;121(11–12):1299–1305.
   PubMed Web of Science ®Google Scholar
• Li M, Zhou S, Wu Y, et al. Prenatal exposure to propylparaben at human-relevant doses accelerates ovarian aging in adult mice. Environ Pollut. 2021;285:117254.
   PubMed Web of Science ®Google Scholar
• Yan W, Li M, Guo Q, et al. Chronic exposure to propylparaben at the humanly relevant dose triggers ovarian aging in adult mice. Ecotoxicol Environ Saf. 2022;235:113432.
   PubMed Web of Science ®Google Scholar
• Neff AM, Laws MJ, Warner GR, et al. The effects of environmental contaminant exposure on reproductive aging and the menopause transition. Curr Environ Health Rep. 2022;9(1):53–79.
   PubMedGoogle Scholar
• Ding YC, Hurley S, Park JS, et al. Methylation biomarkers of polybrominated diphenyl ethers (PBDEs) and association with breast cancer risk at the time of menopause. Environ Int. 2021;156:106772.
   PubMed Web of Science ®Google Scholar
• Kummer V, Mašková J, Zralý Z, et al. Ovarian disorders in immature rats after postnatal exposure to environmental polycyclic aromatic hydrocarbons. J Appl Toxicol. 2013;33(2):90–99.
   PubMed Web of Science ®Google Scholar
• Lefevre PL, Wade M, Goodyer C, et al. A mixture reflecting polybrominated diphenyl ether (PBDE) profiles detected in human follicular fluid significantly affects steroidogenesis and induces oxidative stress in a female human granulosa cell line. Endocrinology. 2016;157(7):2698–2711.
   PubMed Web of Science ®Google Scholar
• Sun MH, Li XH, Xu Y, et al. Exposure to PBDE47 affects mouse oocyte quality via mitochondria dysfunction-induced oxidative stress and apoptosis. Ecotoxicol Environ Saf. 2020;198:110662.
   PubMed Web of Science ®Google Scholar
• Yu K, Zhang X, Tan X, et al. Multigenerational and transgenerational effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure on ovarian reserve and follicular development through AMH/AMHR2 pathway in adult female rats. Food Chem Toxicol. 2020;140:111309.
   PubMed Web of Science ®Google Scholar
• Faroon O, Ashizawa A, Wright S, et al. Toxicological profile for cadmium. Atlanta (GA): Agency for Toxic Substances and Disease Registry; 2015. [cited 2022 November 10]. Available from: https://wwwn.cdc.gov/TSP/ToxProfiles/ToxProfiles.aspx?id=48&tid=15
   Google Scholar
• Varga B, Zsolnai B, Paksy K, et al. Age dependent accumulation of cadmium in the human ovary. Reprod Toxicol. 1993;7(3):225–228.
   PubMed Web of Science ®Google Scholar
• Stoica A, Katzenellenbogen BS, Martin MB. Activation of estrogen receptor-alpha by the heavy metal cadmium. Mol Endocrinol. 2000;14(4):545–553.
   PubMed Web of Science ®Google Scholar
• Lee YM, Chung HW, Jeong K, et al. Association between cadmium and anti-Mullerian hormone in premenopausal women at particular ages. Ann Occup Environ Med. 2018;30:44.
   PubMed Web of Science ®Google Scholar
• Caini S, Bendinelli B, Masala G, et al. Predictors of erythrocyte cadmium levels in 454 adults in Florence, Italy. Sci Total Environ. 2018;644:37–44.
   PubMed Web of Science ®Google Scholar
• Järup L, Akesson A. Current status of cadmium as an environmental health problem. Toxicol Appl Pharmacol. 2009;238(3):201–208.
   PubMed Web of Science ®Google Scholar
• Nagata C, Konishi K, Goto Y, et al. Associations of urinary cadmium with circulating sex hormone levels in pre- and postmenopausal Japanese women. Environ Res. 2016;150:82–87.
   PubMed Web of Science ®Google Scholar
• Upson K, O’Brien KM, Hall JE, et al. Cadmium exposure and ovarian reserve in women aged 35–49 years: the impact on results from the creatinine adjustment approach used to correct for urinary dilution. Am J Epidemiol. 2021;190(1):116–124.
   PubMed Web of Science ®Google Scholar
• da Costa CS, Oliveira TF, Freitas-Lima LC, et al. Subacute cadmium exposure disrupts the hypothalamic-pituitary-gonadal axis, leading to polycystic ovarian syndrome and premature ovarian failure features in female rats. Environ Pollut. 2021;269:116154.
   PubMed Web of Science ®Google Scholar
• Cheng Y, Zhang J, Wu T, et al. Reproductive toxicity of acute Cd exposure in mouse: resulting in oocyte defects and decreased female fertility. Toxicol Appl Pharmacol. 2019;379:114684.
   PubMed Web of Science ®Google Scholar
• Weng S, Wang W, Li Y, et al. Continuous cadmium exposure from weaning to maturity induces downregulation of ovarian follicle development-related SCF/c-kit gene expression and the corresponding changes of DNA methylation/microRNA pattern. Toxicol Lett. 2014;225(3):367–377.
   PubMed Web of Science ®Google Scholar
• Meyer PA, Brown MJ, Falk H. Global approach to reducing lead exposure and poisoning. Mutat Res. 2008;659(1–2):166–175.
   PubMed Web of Science ®Google Scholar
• Eum KD, Weisskopf MG, Nie LH, et al. Cumulative lead exposure and age at menopause in the Nurses’ Health Study cohort. Environ Health Perspect. 2014;122(3):229–234. Mar
   PubMed Web of Science ®Google Scholar
• Levin R, Zilli Vieira CL, Rosenbaum MH, et al. The urban lead (Pb) burden in humans, animals and the natural environment. Environ Res. 2021;193:110377.
   PubMed Web of Science ®Google Scholar
• Rebeniak M, Wojciechowska-Mazurek M, Mania M, et al. Exposure to lead and cadmium released from ceramics and glassware intended to come into contact with food. Rocz Panstw Zakl Hig. 2014;65(4):301–309.
   PubMedGoogle Scholar
• Mendola P, Brett K, Dibari JN, et al. Menopause and lead body burden among US women aged 45-55, NHANES 1999-2010. Environ Res. 2013;121:110–113.
   PubMed Web of Science ®Google Scholar
• Chen C, Wang N, Zhai H, et al. Associations of blood lead levels with reproductive hormone levels in men and postmenopausal women: results from the SPECT-China study. Sci Rep. 2016;6:37809.
   PubMed Web of Science ®Google Scholar
• He Y, Wang L, Li X, et al. The effects of chronic lead exposure on the ovaries of female juvenile Japanese quails (Coturnix japonica): developmental delay, histopathological alterations, hormone release disruption and gene expression disorder. Ecotoxicol Environ Saf. 2020;205:111338.
   PubMed Web of Science ®Google Scholar
• Dumitrescu E, Cristina R, Muselin F. Reproductive biology study of dynamics of female sexual hormones: a 12-month exposure to lead acetate rat model. Turk J Biol. 2014;38(5):581–585.
   Web of Science ®Google Scholar
• Jiang X, Xing X, Zhang Y, et al. Lead exposure activates the Nrf2/Keap1 pathway, aggravates oxidative stress, and induces reproductive damage in female mice. Ecotoxicol Environ Saf. 2021;207:111231.
   PubMed Web of Science ®Google Scholar
• Feng Y, Yuan H, Wang W, et al. Co-exposure to polystyrene microplastics and lead aggravated ovarian toxicity in female mice via the PERK/eIF2α signaling pathway. Ecotoxicol Environ Saf. 2022;243:113966.
   PubMed Web of Science ®Google Scholar
• Özel Ş, Tokmak A, Aykut O, et al. Serum levels of phthalates and bisphenol-A in patients with primary ovarian insufficiency. Gynecol Endocrinol. 2019;35(4):364–367.
   PubMed Web of Science ®Google Scholar
• Cao M, Pan W, Shen X, et al. Urinary levels of phthalate metabolites in women associated with risk of premature ovarian failure and reproductive hormones. Chemosphere. 2020;242:125206.
   PubMed Web of Science ®Google Scholar
• Chiang C, Pacyga DC, Strakovsky RS, et al. Urinary phthalate metabolite concentrations and serum hormone levels in pre- and perimenopausal women from the Midlife Women’s Health Study. Environ Int. 2021;156:106633.
   PubMed Web of Science ®Google Scholar
• Sacha CR, Souter I, Williams PL, et al. Urinary phthalate metabolite concentrations are negatively associated with follicular fluid anti-müllerian hormone concentrations in women undergoing fertility treatment. Environ Int. 2021;157:106809.
   PubMed Web of Science ®Google Scholar
• Hu Y, Yuan DZ, Wu Y, et al. Bisphenol A initiates excessive premature activation of primordial follicles in mouse ovaries via the PTEN signaling pathway. Reprod Sci. 2018;25(4):609–620.
   PubMed Web of Science ®Google Scholar
• Ding N, Harlow SD, Randolph JF, et al. Perfluoroalkyl substances and incident natural menopause in midlife women: the mediating role of sex hormones. Am J Epidemiol. 2022;191(7):1212–1223.
   PubMed Web of Science ®Google Scholar
• Zhang S, Tan R, Pan R, et al. Association of perfluoroalkyl and polyfluoroalkyl substances with premature ovarian insufficiency in Chinese women. J Clin Endocrinol Metab. 2018;103(7):2543–2551.
   PubMed Web of Science ®Google Scholar
• Walker DM, Kermath BA, Woller MJ, et al. Disruption of reproductive aging in female and male rats by gestational exposure to estrogenic endocrine disruptors. Endocrinology. 2013;154(6):2129–2143.
   PubMed Web of Science ®Google Scholar
• Pan W, Ye X, Yin S, et al. Selected persistent organic pollutants associated with the risk of primary ovarian insufficiency in women. Environ Int. 2019;129:51–58.
   PubMed Web of Science ®Google Scholar
• Baldridge MG, Marks GT, Rawlins RG, et al. Very low-dose (femtomolar) 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) disrupts steroidogenic enzyme mRNAs and steroid secretion by human luteinizing granulosa cells. Reprod Toxicol. 2015;52:57–61.
   PubMed Web of Science ®Google Scholar
• Feng Y, Hu Q, Meng G, et al. Simulating long-term occupational exposure to decabrominated diphenyl ether using C57BL/6 mice: biodistribution and pathology. Chemosphere. 2015;128:118–124.
   PubMed Web of Science ®Google Scholar
• Talsness CE, Kuriyama SN, Sterner-Kock A, et al. In utero and lactational exposures to low doses of polybrominated diphenyl ether-47 alter the reproductive system and thyroid gland of female rat offspring. Environ Health Perspect. 2008;116(3):308–314.
   PubMed Web of Science ®Google Scholar
• Farr SL, Cai J, Savitz DA, et al. Pesticide exposure and timing of menopause: the Agricultural Health Study. Am J Epidemiol. 2006;163(8):731–742.
   PubMed Web of Science ®Google Scholar
• Björvang RD, Hallberg I, Pikki A, et al. Follicular fluid and blood levels of persistent organic pollutants and reproductive outcomes among women undergoing assisted reproductive technologies. Environ Res. 2022;208:112626.
   PubMed Web of Science ®Google Scholar
• Huang Y, Guo J, Lv N, et al. Associations of urinary polycyclic aromatic hydrocarbons with age at natural menopause in U.S. women aged 35–65, NHANES 2003–2012. Environ Pollut. 2018;243(Pt B):1878–1886.
   PubMedGoogle Scholar
• Ye X, Pan W, Li C, et al. Exposure to polycyclic aromatic hydrocarbons and risk for premature ovarian failure and reproductive hormones imbalance. J Environ Sci (China). 2020;91:1–9.
   PubMedGoogle Scholar
• Luderer U, Meier MJ, Lawson GW, et al. In utero exposure to benzo[a]pyrene induces ovarian mutations at doses that deplete ovarian follicles in mice. Environ Mol Mutagen. 2019;60(5):410–420.
   PubMed Web of Science ®Google Scholar
• Archibong AE, Ramesh A, Inyang F, et al. Endocrine disruptive actions of inhaled benzo(a)pyrene on ovarian function and fetal survival in fisher F-344 adult rats. Reprod Toxicol. 2012;34(4):635–643.
   PubMed Web of Science ®Google Scholar
• Pan W, Ye X, Zhu Z, et al. Urinary cadmium concentrations and risk of primary ovarian insufficiency in women: a case-control study. Environ Geochem Health. 2021;43(5):2025–2035.
   PubMed Web of Science ®Google Scholar
• Caini S, Bendinelli B, Masala G, et al. Determinants of erythrocyte lead levels in 454 adults in Florence, Italy. Int J Environ Res Public Health. 2019;16(3):425.
   PubMed Web of Science ®Google Scholar
• What you can do about EDCs: The Endocrine Society; [cited 2023 January 3]. Available from: https://www.endocrine.org/topics/edc/what-you-can-do.
   Google Scholar
• Endocrine disrupting chemicals (EDCs): A global health concern: The Endocrine Society; [cited 2023 January 2]. Available from: https://www.endocrine.org/-/media/endocrine/files/advocacy/documents/edcs-factsheet.pdf.
   Google Scholar
• Sessa F, Polito R, Monda V, et al. Effects of a plastic-free lifestyle on urinary bisphenol a levels in school-aged children of Southern Italy: a pilot study. Front Public Health. 2021;9:626070.
   PubMed Web of Science ®Google Scholar
• Yang T, Doherty J, Zhao B, et al. Effectiveness of commercial and homemade washing agents in removing pesticide residues on and in apples. J Agric Food Chem. 2017;65(44):9744–9752.
   PubMed Web of Science ®Google Scholar
• Álvarez-Muñoz D, Rodríguez-Mozaz S, Maulvault AL, et al. Occurrence of pharmaceuticals and endocrine disrupting compounds in macroalgaes, bivalves, and fish from coastal areas in Europe. Environ Res. 2015;143(Pt B):56–64.
   PubMedGoogle Scholar