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  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id specific-use="scielo-v3" pub-id-type="publisher-id">nrBDjqnNvXLZrj7xj8gzVGM</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2026000501401</article-id>
      <article-id pub-id-type="other">01401</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20250737</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigo de Revis&#227;o</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>A Silenciosa Transi&#231;&#227;o da Menopausa: A Interse&#231;&#227;o entre Gl&#226;ndulas Salivares, Condi&#231;&#227;o da Cavidade Oral e Sa&#250;de Cardiovascular</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Louren&#231;o</surname>
            <given-names>Silvia Vanessa</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
          <role>Concep&#231;&#227;o e desenho da pesquisa</role>
          <role>Obten&#231;&#227;o de dados e An&#225;lise e interpreta&#231;&#227;o dos dados</role>
          <role>Obten&#231;&#227;o de financiamento</role>
          <role>Reda&#231;&#227;o do manuscrito e Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante</role>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-5328-0937</contrib-id>
          <name>
            <surname>Florezi</surname>
            <given-names>Giovanna Piacenza</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
          <xref ref-type="corresp" rid="c1"/>
          <role>Obten&#231;&#227;o de dados e An&#225;lise e interpreta&#231;&#227;o dos dados</role>
          <role>Reda&#231;&#227;o do manuscrito e Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Pelissari</surname>
            <given-names>Cibele</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
          <role>Reda&#231;&#227;o do manuscrito e Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Hojaij</surname>
            <given-names>Flavio Carneiro</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <role>Reda&#231;&#227;o do manuscrito e Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Otoch</surname>
            <given-names>Jos&#233; Pinhata</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <role>Obten&#231;&#227;o de financiamento</role>
          <role>Reda&#231;&#227;o do manuscrito e Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ramires</surname>
            <given-names>Jos&#233; Antonio Franchini</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">
            <sup>3</sup>
          </xref>
          <role>Concep&#231;&#227;o e desenho da pesquisa</role>
          <role>Obten&#231;&#227;o de dados e An&#225;lise e interpreta&#231;&#227;o dos dados</role>
          <role>Obten&#231;&#227;o de financiamento</role>
          <role>Reda&#231;&#227;o do manuscrito e Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante</role>
        </contrib>
        <aff id="aff1">
          <label>1</label>
          <institution content-type="orgname">Universidade de S&#227;o Paulo</institution>
          <institution content-type="orgdiv1">Faculdade de Medicina</institution>
          <institution content-type="orgdiv2">Departamento de Cirurgia</institution>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Departamento de Cirurgia, Faculdade de Medicina, Universidade de S&#227;o Paulo, S&#227;o Paulo, SP &#8211; Brasil</institution>
        </aff>
        <aff id="aff2">
          <label>2</label>
          <institution content-type="orgname">Universidade de S&#227;o Paulo</institution>
          <institution content-type="orgdiv1">Instituto de Medicina Tropical</institution>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Instituto de Medicina Tropical, Universidade de S&#227;o Paulo, S&#227;o Paulo, SP &#8211; Brasil</institution>
        </aff>
        <aff id="aff3">
          <label>3</label>
          <institution content-type="orgname">Universidade de S&#227;o Paulo</institution>
          <institution content-type="orgdiv1">Instituto do Cora&#231;&#227;o do Hospital das Cl&#237;nicas</institution>
          <institution content-type="orgdiv2">Departamento Cardiopulmonar</institution>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Departamento Cardiopulmonar, Instituto do Cora&#231;&#227;o do Hospital das Cl&#237;nicas da Faculdade de Medicina da Universidade de S&#227;o Paulo, S&#227;o Paulo, SP &#8211; Brasil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c1"><label>Correspond&#234;ncia:</label><bold>Giovanna P. Florezi</bold> &#8226; Faculdade de Medicina da Universidade de S&#227;o Paulo - Av. Dr. Arnaldo, 455. CEP <postal-code>01246-903</postal-code>, S&#227;o Paulo, SP - Brasil Email: <email>giovanna.florezi@usp.br</email> </corresp>
        <fn fn-type="coi-statement">
          <label>Potencial Conflito de Interesse</label>
          <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
        </fn>
        <fn fn-type="edited-by">
          <label>Editor respons&#225;vel pela revis&#227;o:</label>
          <p>Gl&#225;ucia Maria Moraes de Oliveira</p>
        </fn>
      </author-notes>
      <pub-date date-type="pub" publication-format="electronic">
        <day>22</day>
        <month>06</month>
        <year>2026</year>
      </pub-date>
      <pub-date date-type="collection" publication-format="electronic">
        <month>05</month>
        <year>2026</year>
      </pub-date>
      <volume>123</volume>
      <issue>5</issue>
      <elocation-id>e20250737</elocation-id>
      <history>
        <date date-type="received">
          <day>28</day>
          <month>10</month>
          <year>2025</year>
        </date>
        <date date-type="rev-recd">
          <day>19</day>
          <month>12</month>
          <year>2025</year>
        </date>
        <date date-type="accepted">
          <day>19</day>
          <month>12</month>
          <year>2025</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
          <license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License</license-p>
        </license>
      </permissions>
      <abstract>
        <title>Resumo</title>
        <sec>
          <title>Fundamento:</title>
          <p>A menopausa representa uma importante transi&#231;&#227;o biol&#243;gica na vida da mulher, definida pela cessa&#231;&#227;o da fun&#231;&#227;o ovariana e por uma redu&#231;&#227;o acentuada dos n&#237;veis de estrog&#234;nio. Embora suas consequ&#234;ncias sist&#234;micas, incluindo osteoporose e aumento do risco cardiovascular, estejam bem estabelecidas, seu impacto na sa&#250;de oral permanece insuficientemente reconhecido tanto por profissionais m&#233;dicos quanto odontol&#243;gicos.</p>
        </sec>
        <sec>
          <title>Objetivo:</title>
          <p>Examinar a influ&#234;ncia da menopausa na sa&#250;de oral das mulheres, enfatizando os principais mecanismos fisiopatol&#243;gicos, as manifesta&#231;&#245;es cl&#237;nicas e as estrat&#233;gias interdisciplinares de preven&#231;&#227;o e manejo.</p>
        </sec>
        <sec>
          <title>M&#233;todos:</title>
          <p>Foi realizada uma revis&#227;o narrativa utilizando artigos recuperados da base de dados PubMed, publicados entre 2000 e 2025. Foram utilizados os seguintes descritores: "menopause", "oral health", "hormonal changes", "cardiovascular disease", "xerostomia", "salivary glands", "periodontitis" e "postmenopausal women".</p>
        </sec>
        <sec>
          <title>Resultados:</title>
          <p>As altera&#231;&#245;es hormonais durante a menopausa est&#227;o associadas a diversas manifesta&#231;&#245;es orais, incluindo xerostomia, s&#237;ndrome da ard&#234;ncia bucal, doen&#231;a periodontal e altera&#231;&#245;es do paladar. A defici&#234;ncia de estrog&#234;nio parece contribuir para a redu&#231;&#227;o do fluxo salivar, atrofia da mucosa e aumento da resposta inflamat&#243;ria nos tecidos periodontais. Evid&#234;ncias emergentes tamb&#233;m sugerem uma associa&#231;&#227;o entre a sa&#250;de oral na menopausa e a doen&#231;a cardiovascular, entre outras condi&#231;&#245;es sist&#234;micas. No entanto, persistem lacunas importantes no conhecimento quanto ao manejo cl&#237;nico e ao cuidado interdisciplinar de mulheres na menopausa.</p>
        </sec>
        <sec>
          <title>Conclus&#227;o:</title>
          <p>A sa&#250;de oral durante a menopausa reflete uma intera&#231;&#227;o complexa de fatores hormonais, sist&#234;micos e comportamentais. Diante do aumento da expectativa de vida em todo o mundo, programas de educa&#231;&#227;o e pesquisa em sa&#250;de oral devem priorizar esse tema. O fortalecimento da conscientiza&#231;&#227;o e a promo&#231;&#227;o da colabora&#231;&#227;o multidisciplinar s&#227;o essenciais para melhorar os desfechos em sa&#250;de de mulheres na meia-idade.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave:</title>
        <kwd>Menopausa</kwd>
        <kwd>Sa&#250;de Bucal</kwd>
        <kwd>Saliva</kwd>
        <kwd>Gl&#226;ndulas Salivares</kwd>
        <kwd>Sa&#250;de Vascular</kwd>
      </kwd-group>
      <funding-group>
        <award-group>
          <funding-source>FAPESP</funding-source>
          <award-id>2022/12807-5</award-id>
          <award-id>2025/03765-5</award-id>
          <award-id>2025/03920-0</award-id>
        </award-group>
        <funding-statement><bold>Fontes de Financiamento</bold>: O presente estudo foi financiado pela FAPESP 2022/12807-5, 2025/03765-5, 2025/03920-0.</funding-statement>
      </funding-group>
      <counts>
        <fig-count count="2"/>
        <table-count count="2"/>
        <equation-count count="0"/>
        <ref-count count="47"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introdu&#231;&#227;o</title>
      <p>A menopausa representa um importante marco biol&#243;gico na vida da mulher. &#201; caracterizada por um decl&#237;nio progressivo dos n&#237;veis circulantes de estrog&#234;nio e progesterona, culminando na cessa&#231;&#227;o permanente da menstrua&#231;&#227;o por pelo menos 12 meses consecutivos. Esse processo resulta da interrup&#231;&#227;o da fun&#231;&#227;o folicular ovariana.<sup><xref ref-type="bibr" rid="B1">1</xref>-<xref ref-type="bibr" rid="B3">3</xref></sup> A transi&#231;&#227;o geralmente ocorre entre 45 e 55 anos de idade e &#233; acompanhada por uma s&#233;rie de altera&#231;&#245;es sist&#234;micas impulsionadas por mudan&#231;as nos n&#237;veis dos horm&#244;nios sexuais femininos. De acordo com o <italic>Red Latinoamericana de Investigaci&#243;n en Climaterio</italic>, a idade m&#233;dia da menopausa na regi&#227;o &#233; de 48,6 anos.<sup><xref ref-type="bibr" rid="B4">4</xref></sup></p>
      <p>A transi&#231;&#227;o para a menopausa, conhecida como per&#237;odo climat&#233;rico, compreende tr&#234;s fases principais. A perimenopausa refere-se aos anos que antecedem a menopausa, durante os quais come&#231;am as irregularidades menstruais e frequentemente surgem sintomas vasomotores, como fogachos e sudorese noturna. A menopausa &#233; definida retrospectivamente ap&#243;s 12 meses consecutivos sem menstrua&#231;&#227;o. A p&#243;s-menopausa abrange os anos subsequentes &#224; menopausa, per&#237;odo em que os n&#237;veis de estrog&#234;nio permanecem persistentemente baixos. Apesar desses marcos cl&#237;nicos, as fases iniciais ou prematuras do climat&#233;rio ainda n&#227;o est&#227;o completamente definidas.<sup><xref ref-type="bibr" rid="B3">3</xref>-<xref ref-type="bibr" rid="B6">6</xref></sup></p>
      <p>A menopausa afeta significativamente a qualidade de vida e est&#225; associada &#224; altera&#231;&#227;o da homeostase sist&#234;mica, dist&#250;rbios do sono, disfun&#231;&#227;o sexual, ansiedade, depress&#227;o, dor musculoesquel&#233;tica, redu&#231;&#227;o da massa muscular e leve decl&#237;nio cognitivo.<sup><xref ref-type="bibr" rid="B6">6</xref>,<xref ref-type="bibr" rid="B7">7</xref></sup> Embora as manifesta&#231;&#245;es som&#225;ticas e psicol&#243;gicas da menopausa, como sintomas vasomotores, dist&#250;rbios do sono e altera&#231;&#245;es de humor, estejam bem documentadas, seu impacto na sa&#250;de oral permanece sub-reconhecido tanto na pr&#225;tica cl&#237;nica quanto nas pol&#237;ticas de sa&#250;de p&#250;blica.</p>
      <p>O estrog&#234;nio desempenha papel central na manuten&#231;&#227;o da integridade estrutural e funcional de m&#250;ltiplos sistemas, incluindo os sistemas cardiovascular, esquel&#233;tico, tegumentar e os tecidos orais. O estrog&#234;nio plasm&#225;tico circulante existe em tr&#234;s formas principais: 17&#946;-estradiol (E2), estrona e estriol. O E2 &#233; a forma mais potente e biologicamente ativa, sendo predominantemente produzido pelos ov&#225;rios em mulheres na pr&#233;-menopausa. Em mulheres na p&#243;s-menopausa, a estrona, forma menos potente, torna-se o principal estrog&#234;nio circulante. Os n&#237;veis de ambos os horm&#244;nios diminuem aproximadamente dez vezes ap&#243;s a menopausa. Durante esse per&#237;odo, a aromatase expressa no tecido adiposo, na pele, no c&#233;rebro e no osso torna-se a principal fonte de E2 e estrona circulantes.<sup><xref ref-type="bibr" rid="B8">8</xref></sup></p>
      <p>A defici&#234;ncia de estrog&#234;nio contribui para um estado de inflama&#231;&#227;o sist&#234;mica cr&#244;nica de baixo grau e est&#225; associada a condi&#231;&#245;es como doen&#231;a cardiovascular, osteoporose e atrofia urogenital. Tamb&#233;m compromete a homeostase oral.<sup><xref ref-type="bibr" rid="B9">9</xref></sup> Nas &#250;ltimas d&#233;cadas, o interesse cient&#237;fico pelas consequ&#234;ncias orais da menopausa tem crescido, especialmente no contexto do envelhecimento populacional global. A menopausa pode desencadear ou agravar diversas condi&#231;&#245;es orais, incluindo xerostomia, s&#237;ndrome da ard&#234;ncia bucal (SAB), periodontite, atrofia da mucosa e perda &#243;ssea alveolar. Essas altera&#231;&#245;es podem prejudicar fun&#231;&#245;es orais essenciais, como alimenta&#231;&#227;o, fala e degluti&#231;&#227;o, al&#233;m de influenciar a sa&#250;de sist&#234;mica.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B10">10</xref>-<xref ref-type="bibr" rid="B12">12</xref></sup></p>
      <p>A rela&#231;&#227;o entre menopausa e sa&#250;de oral vai al&#233;m de manifesta&#231;&#245;es localizadas. Evid&#234;ncias emergentes destacam uma associa&#231;&#227;o bidirecional entre sa&#250;de oral e sa&#250;de sist&#234;mica, particularmente com condi&#231;&#245;es cardiovasculares, que s&#227;o mais prevalentes em mulheres na p&#243;s-menopausa.<sup><xref ref-type="bibr" rid="B13">13</xref>-<xref ref-type="bibr" rid="B16">16</xref></sup> Assim, ampliar o conhecimento sobre as manifesta&#231;&#245;es orais da menopausa e integrar o cuidado odontol&#243;gico &#224;s estrat&#233;gias abrangentes de sa&#250;de da mulher constituem prioridades importantes.</p>
      <p>Esta revis&#227;o narrativa, baseada em artigos recuperados do PubMed publicados entre 2000 e 2025, utilizando os descritores "menopause", "oral health", "hormonal changes", "cardiovascular disease", "xerostomia", "salivary glands", "periodontitis" e "postmenopausal women", tem como objetivo sintetizar as evid&#234;ncias atuais sobre os mecanismos biol&#243;gicos, as manifesta&#231;&#245;es cl&#237;nicas e as perspectivas ampliadas da sa&#250;de oral em mulheres na menopausa. Tamb&#233;m enfatiza a necessidade de cuidado interdisciplinar e de dire&#231;&#245;es futuras de pesquisa para aprimorar a preven&#231;&#227;o, o diagn&#243;stico e o manejo (<xref ref-type="fig" rid="f1">Figura Central</xref>).</p>
      <fig id="f1">
        <graphic xlink:href="1678-4170-abc-123-05-e20250737-50737-gf01.tif"/></fig>
      <sec>
        <title>Menopausa, saliva e gl&#226;ndulas salivares: associa&#231;&#245;es com altera&#231;&#245;es orais comuns</title>
        <p>A cavidade oral n&#227;o &#233; tradicionalmente considerada um alvo prim&#225;rio dos horm&#244;nios sexuais; no entanto, &#233; altamente sens&#237;vel &#224;s flutua&#231;&#245;es hormonais.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B9">9</xref>,<xref ref-type="bibr" rid="B12">12</xref>,<xref ref-type="bibr" rid="B14">14</xref>,<xref ref-type="bibr" rid="B17">17</xref></sup> Os estrog&#234;nios desempenham papel fundamental na manuten&#231;&#227;o de sua integridade estrutural e funcional. Em condi&#231;&#245;es fisiol&#243;gicas, tecidos moles, osso alveolar, vasculatura, gl&#226;ndulas salivares e microbioma oral interagem dinamicamente para preservar a homeostase. Durante a menopausa, o decl&#237;nio progressivo do estrog&#234;nio e da progesterona circulantes desencadeia uma cascata de altera&#231;&#245;es nos tecidos orais, nas gl&#226;ndulas salivares e na regula&#231;&#227;o imunol&#243;gica, aumentando coletivamente a suscetibilidade a doen&#231;as orais.<sup><xref ref-type="bibr" rid="B10">10</xref>,<xref ref-type="bibr" rid="B11">11</xref>,<xref ref-type="bibr" rid="B13">13</xref>,<xref ref-type="bibr" rid="B14">14</xref></sup></p>
        <p>Receptores de estrog&#234;nio (ER&#945; e ER&#946;) foram identificados na mucosa oral, nas gl&#226;ndulas salivares e nos tecidos periodontais.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B12">12</xref></sup> Esses receptores mediam a modula&#231;&#227;o hormonal da prolifera&#231;&#227;o celular, da diferencia&#231;&#227;o e das respostas inflamat&#243;rias. O estrog&#234;nio tamb&#233;m regula a permeabilidade vascular e o metabolismo do col&#225;geno, processos essenciais para manter a resili&#234;ncia dos tecidos moles e a integridade do tecido conjuntivo gengival.<sup><xref ref-type="bibr" rid="B18">18</xref></sup></p>
        <p>Os estrog&#234;nios influenciam a fun&#231;&#227;o das gl&#226;ndulas salivares ao promover a atividade das c&#233;lulas acinares e vasculariza&#231;&#227;o. As gl&#226;ndulas par&#243;tidas e submandibulares, em particular, parecem responder &#224; modula&#231;&#227;o hormonal.<sup><xref ref-type="bibr" rid="B19">19</xref></sup> Em mulheres na menopausa, n&#237;veis reduzidos de estrog&#234;nio t&#234;m sido associados a altera&#231;&#245;es relatadas na fun&#231;&#227;o das gl&#226;ndulas salivares e na quantidade e qualidade da saliva, embora os achados ainda sejam inconsistentes.<sup><xref ref-type="bibr" rid="B20">20</xref></sup></p>
        <p>A saliva &#233; um ultrafiltrado plasm&#225;tico processado pelas gl&#226;ndulas salivares e &#233; essencial para a manuten&#231;&#227;o e prote&#231;&#227;o das estruturas orais. Desempenha papel central na homeostase oral. A saliva humana cont&#233;m numerosos componentes conhecidos e ainda n&#227;o identificados que contribuem para a capacidade tamp&#227;o, lubrifica&#231;&#227;o, defesa antimicrobiana e prote&#231;&#227;o tecidual. Entre eles est&#227;o mieloperoxidase, &#243;xido n&#237;trico (NO), imunoglobulina A (IgA), enzimas e eletr&#243;litos.<sup><xref ref-type="bibr" rid="B21">21</xref>,<xref ref-type="bibr" rid="B22">22</xref></sup></p>
        <p>O NO &#233; um potente vasodilatador e desempenha papel na regula&#231;&#227;o da fun&#231;&#227;o dos cardiomi&#243;citos, entre outros efeitos sist&#234;micos. Sua concentra&#231;&#227;o na saliva excede a encontrada no plasma. O NO tamb&#233;m atua como mol&#233;cula sinalizadora, neurotransmissor e mediador na defesa imune e nos processos inflamat&#243;rios.<sup><xref ref-type="bibr" rid="B23">23</xref></sup> Contribui para a secre&#231;&#227;o salivar e &#233; considerado mol&#233;cula-chave na manuten&#231;&#227;o da homeostase. O nitrato da dieta (ex&#243;geno) e o nitrato derivado da oxida&#231;&#227;o end&#243;gena do NO s&#227;o absorvidos pelo trato gastrointestinal para a corrente sangu&#237;nea. Aproximadamente 25% do nitrato circulante &#233; captado ativamente pelas gl&#226;ndulas salivares, especialmente pela gl&#226;ndula par&#243;tida, e secretado na saliva. Desse total, cerca de 20% &#233; reduzido a nitrito por bact&#233;rias orais. O nitrato e o nitrito restantes s&#227;o deglutidos e retornam &#224; circula&#231;&#227;o sist&#234;mica, compondo o ciclo enterossalivar nitrato-nitrito-NO. Notavelmente, aproximadamente 80% do nitrito circulante &#233; gerado por essa via.<sup><xref ref-type="bibr" rid="B23">23</xref></sup> As concentra&#231;&#245;es salivares de nitrato s&#227;o cerca de dez vezes superiores &#224;s plasm&#225;ticas.<sup><xref ref-type="bibr" rid="B24">24</xref></sup></p>
        <p>Abadi et al. demonstraram que os n&#237;veis salivares de NO s&#227;o significativamente menores em pacientes diab&#233;ticos com xerostomia em compara&#231;&#227;o com aqueles sem xerostomia, sugerindo que o NO pode contribuir para a manuten&#231;&#227;o da sa&#250;de oral.<sup><xref ref-type="bibr" rid="B25">25</xref></sup> No entanto, a rela&#231;&#227;o entre o metabolismo do NO, as altera&#231;&#245;es das gl&#226;ndulas salivares durante a menopausa e a fun&#231;&#227;o cardiovascular permanece insuficientemente explorada.</p>
        <p>Apesar de a xerostomia ser uma das queixas mais frequentemente relatadas por mulheres na menopausa, os estudos que avaliam a taxa de fluxo salivar e a resposta das gl&#226;ndulas salivares nesse per&#237;odo ainda s&#227;o limitados.<sup><xref ref-type="bibr" rid="B26">26</xref></sup> Xerostomia &#233; definida como a sensa&#231;&#227;o subjetiva de boca seca e n&#227;o necessariamente se correlaciona com redu&#231;&#245;es mensur&#225;veis do fluxo salivar. Embora multifatorial, acredita-se que o hipoestrogenismo prejudique a fun&#231;&#227;o das gl&#226;ndulas salivares, potencialmente reduzindo tanto o fluxo salivar n&#227;o estimulado quanto o estimulado.</p>
        <p>Em um estudo post mortem, Moraes et al. observaram altera&#231;&#245;es vasculares nas gl&#226;ndulas salivares de mulheres de meia-idade e idosas, incluindo trombose com comprometimento acentuado da perfus&#227;o.<sup><xref ref-type="bibr" rid="B27">27</xref></sup> Essas altera&#231;&#245;es vasculares podem prejudicar a nutri&#231;&#227;o do par&#234;nquima, levando &#224; atrofia glandular e &#224; substitui&#231;&#227;o por tecido adiposo. Kawamoto et al. corroboraram esses achados, relatando altera&#231;&#245;es na composi&#231;&#227;o do par&#234;nquima salivar e substitui&#231;&#227;o adiposa associadas &#224; hipertens&#227;o, uma comorbidade comum em mulheres na menopausa.<sup><xref ref-type="bibr" rid="B16">16</xref>,<xref ref-type="bibr" rid="B27">27</xref></sup></p>
        <p>Clinicamente, a xerostomia em mulheres na menopausa est&#225; associada a preju&#237;zo da fala, mastiga&#231;&#227;o e degluti&#231;&#227;o. A redu&#231;&#227;o do fluxo salivar e altera&#231;&#245;es na composi&#231;&#227;o podem resultar em pH salivar mais baixo, menor capacidade tamp&#227;o e atividade antimicrobiana diminu&#237;da.<sup><xref ref-type="bibr" rid="B20">20</xref></sup> Em conjunto, essas altera&#231;&#245;es criam um ambiente mais suscet&#237;vel &#224; c&#225;rie dent&#225;ria, infec&#231;&#245;es orais e halitose.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B28">28</xref>,<xref ref-type="bibr" rid="B29">29</xref></sup> A xerostomia tamb&#233;m pode afetar negativamente as intera&#231;&#245;es sociais, e sua gravidade parece correlacionar-se com a dura&#231;&#227;o da menopausa.<sup><xref ref-type="bibr" rid="B10">10</xref></sup></p>
        <p>As pesquisas permanecem inconsistentes. Alguns autores relatam redu&#231;&#227;o do fluxo salivar ap&#243;s a menopausa, enquanto outros descrevem altera&#231;&#245;es na composi&#231;&#227;o salivar sem redu&#231;&#227;o mensur&#225;vel do fluxo.<sup><xref ref-type="bibr" rid="B20">20</xref>,<xref ref-type="bibr" rid="B22">22</xref>,<xref ref-type="bibr" rid="B30">30</xref></sup> Quando presente, a redu&#231;&#227;o do fluxo salivar n&#227;o estimulado e estimulado contribui para xerostomia e aumenta o risco de c&#225;rie dent&#225;ria, candidose e desconforto mucoso.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Al&#233;m disso, redu&#231;&#245;es na capacidade tamp&#227;o e em componentes antimicrobianos, como lisozima, lactoferrina e IgA, podem comprometer ainda mais os mecanismos de defesa oral.<sup><xref ref-type="bibr" rid="B20">20</xref></sup></p>
        <p>Salvolini et al. n&#227;o observaram diferen&#231;as significativas na produ&#231;&#227;o salivar em pacientes idosas, mas relataram n&#237;veis aumentados de per&#243;xidos lip&#237;dicos, sugerindo maior estresse oxidativo e poss&#237;vel dano tecidual.<sup><xref ref-type="bibr" rid="B22">22</xref></sup> Al&#233;m disso, a saliva de mulheres na p&#243;s-menopausa tem sido associada a valores de pH mais baixos correlacionados com n&#237;veis plasm&#225;ticos de adiponectina, marcador ligado ao risco cardiometab&#243;lico pr&#243;-inflamat&#243;rio e a dist&#250;rbios metab&#243;licos como diabetes tipo 2 e obesidade.<sup><xref ref-type="bibr" rid="B21">21</xref>,<xref ref-type="bibr" rid="B31">31</xref></sup></p>
        <p>A xerostomia predisp&#245;e a altera&#231;&#245;es mucosas. A combina&#231;&#227;o de redu&#231;&#227;o do fluxo salivar, atrofia da mucosa e altera&#231;&#245;es das respostas imunes favorece infec&#231;&#245;es oportunistas, particularmente candidose oral.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Embora geralmente manej&#225;vel, a candidose recorrente pode servir como indicador cl&#237;nico de xerostomia subjacente ou desequil&#237;brio sist&#234;mico em mulheres na menopausa.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B8">8</xref>,<xref ref-type="bibr" rid="B27">27</xref>,<xref ref-type="bibr" rid="B28">28</xref></sup></p>
        <p>Semelhante &#224; mucosa genital, a mucosa oral pode tornar-se mais fina, menos el&#225;stica e mais suscet&#237;vel a traumas ap&#243;s o decl&#237;nio do estrog&#234;nio. As pacientes podem relatar sensa&#231;&#227;o de repuxamento, desconforto ao consumir alimentos &#225;cidos ou condimentados, ou maior sensibilidade a varia&#231;&#245;es de temperatura. Achados cl&#237;nicos podem incluir glossite atr&#243;fica (l&#237;ngua lisa e despapilada), queilite angular e palidez da mucosa. Essas altera&#231;&#245;es podem ser exacerbadas pela redu&#231;&#227;o da lubrifica&#231;&#227;o salivar.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B2">2</xref></sup></p>
        <p>A menopausa tamb&#233;m pode estar associada a dist&#250;rbios sensoriais, incluindo SAB e disgeusia. A altera&#231;&#227;o da percep&#231;&#227;o do paladar pode estar relacionada a mudan&#231;as na taxa de fluxo salivar e no processamento central dos est&#237;mulos gustativos. As altera&#231;&#245;es do paladar s&#227;o frequentemente subnotificadas; algumas mulheres descrevem sensa&#231;&#245;es met&#225;licas ou amargas persistentes, enquanto outras relatam redu&#231;&#227;o da sensibilidade aos sabores doce ou salgado. Os mecanismos propostos incluem altera&#231;&#245;es na composi&#231;&#227;o da saliva, mudan&#231;as na densidade dos receptores gustativos e efeitos hormonais sobre as vias gustativas centrais.<sup><xref ref-type="bibr" rid="B2">2</xref></sup></p>
        <p>A SAB &#233; definida como uma condi&#231;&#227;o de dor neurop&#225;tica cr&#244;nica caracterizada por sensa&#231;&#227;o de queima&#231;&#227;o na aus&#234;ncia de les&#245;es mucosas vis&#237;veis ou altera&#231;&#245;es laboratoriais. Foi relatada em at&#233; 18% das mulheres na p&#243;s-menopausa e comumente afeta l&#237;ngua, l&#225;bios e palato duro. A etiologia permanece incompletamente compreendida, mas acredita-se envolver disfun&#231;&#227;o neurop&#225;tica perif&#233;rica ou central modulada por fatores hormonais, psicol&#243;gicos e sist&#234;micos.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Condi&#231;&#245;es psiqui&#225;tricas e polimorfismos gen&#233;ticos podem contribuir. Fatores sist&#234;micos associados &#224; SAB incluem diabetes mellitus, defici&#234;ncias de vitaminas do complexo B (B1, B2, B6 e B12), folato e ferro, dist&#250;rbios gastrointestinais, desequil&#237;brios hormonais e efeitos relacionados a medicamentos. A maior preval&#234;ncia de SAB em mulheres na menopausa levou &#224; hip&#243;tese de que estrog&#234;nio e progesterona possam exercer efeitos neuroprotetores ou moduladores neurossensoriais que diminuem ap&#243;s a menopausa. Os sintomas geralmente surgem entre 3 e 12 anos ap&#243;s o in&#237;cio da menopausa.<sup><xref ref-type="bibr" rid="B17">17</xref></sup></p>
        <p>Os estudos existentes s&#227;o limitados por tamanhos amostrais reduzidos e heterogeneidade metodol&#243;gica. S&#227;o necess&#225;rias pesquisas adicionais para elucidar os mecanismos subjacentes &#224; senesc&#234;ncia das gl&#226;ndulas salivares e &#224;s altera&#231;&#245;es funcionais durante a menopausa. Al&#233;m disso, comorbidades relacionadas &#224; idade e medicamentos, como anti-hipertensivos, antidepressivos e anticolin&#233;rgicos, podem influenciar adicionalmente o fluxo salivar nessa popula&#231;&#227;o.</p>
        <p>Um resumo integrado dos achados salivares e periodontais ao longo dos est&#225;gios da menopausa &#233; apresentado na <xref ref-type="table" rid="t1">Tabela 1</xref>.</p>
        <table-wrap id="t1">
          <label>Tabela 1</label>
          <caption>
            <title>Panorama de estudos cl&#237;nicos e experimentais sobre altera&#231;&#245;es relacionadas &#224; menopausa na fun&#231;&#227;o das gl&#226;ndulas salivares, homeostase oral e sa&#250;de periodontal</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup width="20%">
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
            </colgroup>
            <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
              <tr style="background-color:#76B4CF">
                <th align="left" valign="middle">ID do estudo</th>
                <th align="center" valign="middle">Popula&#231;&#227;o (n, status)</th>
                <th align="center" valign="middle">Metodologia</th>
                <th align="center" valign="middle">Principais achados</th>
                <th align="center" valign="middle">Relev&#226;ncia translacional</th>
              </tr>
            </thead>
            <tbody style="border-bottom: thin solid; border-color: #000000">
              <tr>
                <td align="left" valign="middle">Tremblay et al., 2012<sup><xref ref-type="bibr" rid="B31">31</xref></sup></td>
                <td align="center" valign="middle">151 mulheres (53 pr&#233;-menopausa; 98 p&#243;s-menopausa)</td>
                <td align="center" valign="middle">pH da STNE; adiponectina plasm&#225;tica (ELISA); medidas antropom&#233;tricas</td>
                <td align="center" valign="middle">pH salivar correlacionou-se positivamente com adiponectina plasm&#225;tica em mulheres na menopausa</td>
                <td align="center" valign="middle">N&#237;veis mais baixos de adiponectina e pH salivar reduzido foram observados em mulheres na menopausa, sugerindo associa&#231;&#227;o com perfil cardiometab&#243;lico pr&#243;-inflamat&#243;rio; requer valida&#231;&#227;o longitudinal</td>
              </tr>
              <tr style="background-color:#C7DFEC;">
                <td align="left" valign="middle">Salvolini et al., 2000<sup><xref ref-type="bibr" rid="B22">22</xref></sup></td>
                <td align="center" valign="middle">169 indiv&#237;duos saud&#225;veis de ambos os sexos divididos em cinco faixas et&#225;rias (10-24 anos, n = 38; 25-39 anos, n = 52; 40-54 anos, n = 40; 55-69 anos, n = 27; &#8805; 70 anos, n = 12)</td>
                <td align="center" valign="middle">Avalia&#231;&#227;o de prote&#237;na total, atividade da peroxidase, malondialde&#237;do e n&#237;veis de NO na STNE</td>
                <td align="center" valign="middle">Sem diferen&#231;as no volume salivar; redu&#231;&#227;o da atividade da peroxidase e aumento dos n&#237;veis de NO com o envelhecimento</td>
                <td align="center" valign="middle">Sugere estresse oxidativo relacionado &#224; idade na saliva independentemente do volume salivar; aus&#234;ncia de perfil hormonal direto</td>
              </tr>
              <tr>
                <td align="left" valign="middle">Foglio-Bonda et al., 2019<sup><xref ref-type="bibr" rid="B37">37</xref></sup></td>
                <td align="center" valign="middle">120 mulheres (60 p&#243;s-menopausa; 60 f&#233;rteis)</td>
                <td align="center" valign="middle">pH e taxa de fluxo da STNE; CPOD</td>
                <td align="center" valign="middle">pH salivar mais baixo e fluxo reduzido no grupo menopausa; &#237;ndice CPOD semelhante</td>
                <td align="center" valign="middle">Coleta padronizada de STNE demonstra hipofun&#231;&#227;o salivar modesta, por&#233;m significativa</td>
              </tr>
              <tr style="background-color:#C7DFEC;">
                <td align="left" valign="middle">Bosman et al., 2022<sup><xref ref-type="bibr" rid="B43">43</xref></sup></td>
                <td align="center" valign="middle">50 mulheres saud&#225;veis (24 com 22-45 anos; 26 com 55-92 anos)</td>
                <td align="center" valign="middle">STNE; metabol&#244;mica n&#227;o direcionada via CL-EM</td>
                <td align="center" valign="middle">Altera&#231;&#245;es no perfil metabol&#244;mico salivar associadas &#224; idade</td>
                <td align="center" valign="middle">Metab&#243;litos diferencialmente expressos em mulheres mais velhas relacionados ao metabolismo de amino&#225;cidos, ciclo de Krebs, metabolismo de &#225;cidos graxos e s&#237;ntese de &#225;cidos nucleicos</td>
              </tr>
              <tr>
                <td align="left" valign="middle">Soundarya et al., 2022<sup><xref ref-type="bibr" rid="B36">36</xref></sup></td>
                <td align="center" valign="middle">60 mulheres (20 menstruadas, 20 pr&#233;-menopausa, 20 p&#243;s-menopausa)</td>
                <td align="center" valign="middle">STNE; estradiol salivar (ELISA); c&#225;lcio salivar; &#237;ndices de xerostomia e periodontais</td>
                <td align="center" valign="middle">Menores n&#237;veis de estradiol salivar e maiores n&#237;veis de c&#225;lcio no grupo p&#243;s-menopausa; estradiol reduzido associado a maiores escores de xerostomia e doen&#231;a periodontal</td>
                <td align="center" valign="middle">Potenciais marcadores de triagem; requer padroniza&#231;&#227;o</td>
              </tr>
              <tr style="background-color:#C7DFEC;">
                <td align="left" valign="middle">Harika et al., 2024<sup><xref ref-type="bibr" rid="B26">26</xref></sup></td>
                <td align="center" valign="middle">60 mulheres (30 pr&#233;-menopausa; 30 p&#243;s-menopausa)</td>
                <td align="center" valign="middle">STNE; limiares gustativos; n&#237;veis s&#233;ricos de zinco</td>
                <td align="center" valign="middle">Mulheres p&#243;s-menopausa apresentaram redu&#231;&#227;o na percep&#231;&#227;o dos sabores doce e amargo; sem diferen&#231;as no fluxo salivar ou n&#237;veis de zinco</td>
                <td align="center" valign="middle">Altera&#231;&#245;es do paladar podem ser multifatoriais, al&#233;m da defici&#234;ncia de zinco ou redu&#231;&#227;o do fluxo; considerar fatores neurossensoriais</td>
              </tr>
              <tr>
                <td align="left" valign="middle">Moraes et al., 2024<sup><xref ref-type="bibr" rid="B27">27</xref></sup></td>
                <td align="center" valign="middle">85 mulheres submetidas &#224; aut&#243;psia (fase reprodutiva &#8804; 44 anos, n = 18; climat&#233;rio 45-55 anos, n = 21; p&#243;s-menopausa &#8805; 56 anos, n = 46)</td>
                <td align="center" valign="middle">An&#225;lise morfol&#243;gica de gl&#226;ndulas salivares menores labiais</td>
                <td align="center" valign="middle">Envelhecimento associado a fibrose e atrofia acinar, metaplasia serosa, substitui&#231;&#227;o adiposa e microtrombose</td>
                <td align="center" valign="middle">Fornece base anat&#244;mica para hipofun&#231;&#227;o salivar; sem correla&#231;&#227;o com sintomas cl&#237;nicos</td>
              </tr>
              <tr style="background-color:#C7DFEC;">
                <td align="left" valign="middle">Garc&#237;a-Alfaro et al., 2025<sup><xref ref-type="bibr" rid="B42">42</xref></sup></td>
                <td align="center" valign="middle">3.211 mulheres peri- (n = 1.170) e p&#243;s-menopausa (n = 2.041), 40-90 anos</td>
                <td align="center" valign="middle">IX; qualidade de vida relacionada &#224; sa&#250;de oral (OHIP-14)</td>
                <td align="center" valign="middle">Maior preval&#234;ncia de xerostomia em mulheres peri- e p&#243;s-menopausa; associada a pior qualidade de vida</td>
                <td align="center" valign="middle">Apoia triagem rotineira de xerostomia em servi&#231;os focados na menopausa</td>
              </tr>
              <tr>
                <td align="left" valign="middle">Scardina &amp; Messina, 2012<sup><xref ref-type="bibr" rid="B44">44</xref></sup></td>
                <td align="center" valign="middle">27 mulheres pr&#233;-menopausa e 27 p&#243;s-menopausa</td>
                <td align="center" valign="middle">Avalia&#231;&#227;o da microcircula&#231;&#227;o oral (videocapilaroscopia); &#237;ndices periodontais</td>
                <td align="center" valign="middle">Redu&#231;&#227;o da densidade capilar periodontal, aumento da tortuosidade vascular e diminui&#231;&#227;o do di&#226;metro das al&#231;as em mulheres p&#243;s-menopausa</td>
                <td align="center" valign="middle">Sugere contribui&#231;&#227;o vascular para maior vulnerabilidade periodontal</td>
              </tr>
              <tr style="background-color:#C7DFEC;">
                <td align="left" valign="middle">LaMonte et al., 2013<sup><xref ref-type="bibr" rid="B45">45</xref></sup></td>
                <td align="center" valign="middle">1.025 mulheres p&#243;s-menopausa (acompanhamento de 5 anos)</td>
                <td align="center" valign="middle">Avalia&#231;&#227;o longitudinal da progress&#227;o da doen&#231;a periodontal</td>
                <td align="center" valign="middle">Progress&#227;o associada a fatores sist&#234;micos; aus&#234;ncia de progress&#227;o generalizada; mulheres com periodontite grave pr&#233;via apresentaram perda &#243;ssea acelerada</td>
                <td align="center" valign="middle">Estudo de coorte robusto; indica necessidade de estratifica&#231;&#227;o de risco</td>
              </tr>
              <tr>
                <td align="left" valign="middle">Wactawski-Wende et al., 2020<sup><xref ref-type="bibr" rid="B14">14</xref></sup></td>
                <td align="center" valign="middle">1.342 mulheres p&#243;s-menopausa na linha de base; 1.026 (acompanhamento de 5 anos); 518 (acompanhamento de 5 anos)</td>
                <td align="center" valign="middle">Exames orais abrangentes; densidade &#243;ssea e composi&#231;&#227;o corporal; microbioma subgengival (sequenciamento 16S)</td>
                <td align="center" valign="middle">Achados integrados orais e sist&#234;micos em mulheres envelhecendo</td>
                <td align="center" valign="middle">Base de dados de refer&#234;ncia para modelos de risco oral-sist&#234;mico</td>
              </tr>
              <tr style="background-color:#C7DFEC;">
                <td align="left" valign="middle">Ahmad et al., 2024<sup><xref ref-type="bibr" rid="B39">39</xref></sup></td>
                <td align="center" valign="middle">100 mulheres p&#243;s-menopausa</td>
                <td align="center" valign="middle">Exame periodontal completo; densitometria &#243;ssea</td>
                <td align="center" valign="middle">Idade identificada como fator de risco significativo para perda &#243;ssea em mulheres p&#243;s-menopausa</td>
                <td align="center" valign="middle">Apoia triagem periodontal baseada em risco; desenho observacional limita infer&#234;ncia causal</td>
              </tr>
              <tr>
                <td align="left" valign="middle">Yakar et al., 2024<sup><xref ref-type="bibr" rid="B46">46</xref></sup></td>
                <td align="center" valign="middle">75 p&#243;s-menopausa (38-65 anos); 71 pr&#233;-menopausa (33-52 anos)</td>
                <td align="center" valign="middle">Citocinas no soro e saliva (TNF-&#945;, IL-6, IL-10, IL-7); IMC; <italic>Women's Health Questionnaire</italic>; avalia&#231;&#227;o periodontal</td>
                <td align="center" valign="middle">Sem diferen&#231;as significativas nas citocinas ap&#243;s ajuste por idade; menos dentes no grupo p&#243;s-menopausa; sem diferen&#231;as nos par&#226;metros periodontais</td>
                <td align="center" valign="middle">Idade como importante fator de confus&#227;o; citocinas salivares isoladamente podem n&#227;o diferenciar <italic>status</italic> menopausal; refor&#231;a etiologia multifatorial</td>
              </tr>
              <tr style="background-color:#C7DFEC;">
                <td align="left" valign="middle">Yakar et al., 2025<sup><xref ref-type="bibr" rid="B47">47</xref></sup></td>
                <td align="center" valign="middle">77 pr&#233;-menopausa; 81 p&#243;s-menopausa</td>
                <td align="center" valign="middle">Hibridiza&#231;&#227;o DNA-DNA em painel (40 esp&#233;cies) e sequenciamento 16S; estradiol s&#233;rico (ELISA); SMDI modificado</td>
                <td align="center" valign="middle">Apesar de periodontite mais grave, n&#227;o foi observada disbiose microbiana relacionada &#224; menopausa; duas esp&#233;cies correlacionaram-se com estradiol na pr&#233;-menopausa</td>
                <td align="center" valign="middle">Varia&#231;&#227;o microbiana parece associada &#224; gravidade da doen&#231;a e n&#227;o ao status hormonal; destaca regula&#231;&#227;o sist&#234;mica da ecologia oral</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN1">
              <p>16S: sequenciamento do gene do RNA riboss&#244;mico 16S; CL-EM: cromatografia l&#237;quida acoplada &#224; espectrometria de massas; CPOD: &#237;ndice de Dentes Cariados, Perdidos e Obturados; ELISA: ensaio imunoenzim&#225;tico; IL-6: interleucina 6; IL-7: interleucina 7; IL-10: interleucina 10; IMC: &#237;ndice de massa corporal; IX: Invent&#225;rio de Xerostomia; NO: &#243;xido n&#237;trico; OHIP-14: Oral Health Impact Profile, vers&#227;o de 14 itens; SMDI: Subgingival Microbial Dysbiosis Index; STNE: saliva total n&#227;o estimulada; TNF-&#945;: fator de necrose tumoral alfa.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec>
        <title>Sa&#250;de oral, menopausa e doen&#231;a cardiovascular</title>
        <p>O decl&#237;nio do estrog&#234;nio durante a menopausa afeta n&#227;o apenas a cavidade oral, mas tamb&#233;m acelera o risco cardiovascular, que permanece como a principal causa de morte em mulheres. Mulheres em idade reprodutiva apresentam menor incid&#234;ncia de doen&#231;a cardiovascular em compara&#231;&#227;o aos homens; no entanto, essa diferen&#231;a diminui ap&#243;s a menopausa, quando o risco cardiovascular aumenta substancialmente.<sup><xref ref-type="bibr" rid="B8">8</xref>,<xref ref-type="bibr" rid="B32">32</xref></sup> A transi&#231;&#227;o menopausal representa, portanto, uma etapa crucial na sa&#250;de cardiometab&#243;lica feminina.</p>
        <p>O hipoestrogenismo na menopausa est&#225; associado &#224; redu&#231;&#227;o da biodisponibilidade de NO, mol&#233;cula com propriedades anti-inflamat&#243;rias, antioxidantes e antiaterog&#234;nicas.<sup><xref ref-type="bibr" rid="B18">18</xref></sup> Ao mesmo tempo, a menopausa &#233; caracterizada por aumento na produ&#231;&#227;o de mediadores pr&#243;-inflamat&#243;rios, incluindo fator de necrose tumoral-&#945;, interleucina-6 e prote&#237;na C reativa. Essas citocinas, inclusive aquelas originadas de tecidos periodontais inflamados, podem alcan&#231;ar a circula&#231;&#227;o sist&#234;mica e contribuir para disfun&#231;&#227;o endotelial, aterog&#234;nese e instabilidade de placas, mecanismos centrais na patologia cardiovascular.</p>
        <p>No sistema cardiovascular, a menopausa est&#225; associada &#224; disfun&#231;&#227;o endotelial e da musculatura lisa vascular, al&#233;m de aterosclerose microvascular. Essas altera&#231;&#245;es podem levar &#224; doen&#231;a arterial coronariana n&#227;o obstrutiva mediada por disfun&#231;&#227;o microvascular coronariana.<sup><xref ref-type="bibr" rid="B17">17</xref></sup> Nos Estados Unidos, mulheres na p&#243;s-menopausa com defici&#234;ncia de estrog&#234;nio representam parcela substancial dos pacientes diagnosticados com doen&#231;a arterial coronariana n&#227;o obstrutiva.<sup><xref ref-type="bibr" rid="B33">33</xref></sup></p>
        <p>Em paralelo &#224;s evid&#234;ncias de disfun&#231;&#227;o microvascular no sistema cardiovascular, Uhl et al. relataram que diversas condi&#231;&#245;es patol&#243;gicas das gl&#226;ndulas salivares est&#227;o associadas &#224; doen&#231;a microvascular relacionada &#224; inflama&#231;&#227;o.<sup><xref ref-type="bibr" rid="B34">34</xref></sup> No entanto, o impacto inflamat&#243;rio da menopausa sobre a microvasculatura das gl&#226;ndulas salivares e suas consequ&#234;ncias para a composi&#231;&#227;o e o fluxo salivar permanecem insuficientemente investigados. Alguns estudos sugerem que altera&#231;&#245;es tromb&#243;ticas microvasculares nas gl&#226;ndulas salivares, combinadas aos efeitos sist&#234;micos do hipoestrogenismo, como hipertens&#227;o, podem comprometer o par&#234;nquima glandular. Esse processo pode levar &#224; atrofia glandular e &#224; manifesta&#231;&#227;o cl&#237;nica de xerostomia.<sup><xref ref-type="bibr" rid="B16">16</xref>,<xref ref-type="bibr" rid="B27">27</xref></sup></p>
        <p>Um corpo crescente de evid&#234;ncias sustenta uma rela&#231;&#227;o interdependente entre menopausa, doen&#231;a periodontal e risco cardiovascular. O estrog&#234;nio exerce efeitos vasodilatadores, anti-inflamat&#243;rios e antioxidantes sobre o endot&#233;lio vascular, em parte por meio da manuten&#231;&#227;o dos n&#237;veis de NO.<sup><xref ref-type="bibr" rid="B8">8</xref></sup> Sua redu&#231;&#227;o durante a menopausa tem sido associada ao aumento da rigidez arterial, altera&#231;&#245;es adversas no perfil lip&#237;dico e mudan&#231;as nos padr&#245;es de coagula&#231;&#227;o, fatores que contribuem para maior risco cardiovascular.<sup><xref ref-type="bibr" rid="B35">35</xref></sup></p>
        <p>Simultaneamente, o hipoestrogenismo promove atrofia da mucosa oral, disfun&#231;&#227;o salivar e reabsor&#231;&#227;o &#243;ssea alveolar, criando condi&#231;&#245;es favor&#225;veis ao desenvolvimento de doen&#231;a periodontal.<sup><xref ref-type="bibr" rid="B7">7</xref>,<xref ref-type="bibr" rid="B14">14</xref>,<xref ref-type="bibr" rid="B36">36</xref></sup> Esses mecanismos paralelos sugerem que o estrog&#234;nio exerce papel regulador central tanto na sa&#250;de oral quanto na sa&#250;de cardiovascular. Al&#233;m disso, altera&#231;&#245;es no pH salivar t&#234;m sido associadas ao estado inflamat&#243;rio, ao estresse oxidativo e ao metabolismo do NO, com poss&#237;veis implica&#231;&#245;es cardiovasculares sist&#234;micas.<sup><xref ref-type="bibr" rid="B22">22</xref>,<xref ref-type="bibr" rid="B37">37</xref></sup></p>
        <p>Mulheres na menopausa apresentam maior preval&#234;ncia e gravidade de gengivite e periodontite. Essas altera&#231;&#245;es podem resultar de efeitos hormonais diretos, bem como de modifica&#231;&#245;es sist&#234;micas, incluindo redu&#231;&#227;o da densidade mineral &#243;ssea e desregula&#231;&#227;o da resposta imune.<sup><xref ref-type="bibr" rid="B14">14</xref>,<xref ref-type="bibr" rid="B38">38</xref></sup> A defici&#234;ncia de estrog&#234;nio parece amplificar a resposta inflamat&#243;ria aos pat&#243;genos periodontais, aumentar a degrada&#231;&#227;o do tecido conjuntivo e comprometer a remodela&#231;&#227;o do osso alveolar. Esses processos aceleram a perda de inser&#231;&#227;o periodontal e podem, em &#250;ltima inst&#226;ncia, levar &#224; mobilidade e perda dent&#225;ria quando n&#227;o tratados.<sup><xref ref-type="bibr" rid="B14">14</xref>,<xref ref-type="bibr" rid="B39">39</xref></sup></p>
        <p>A osteoporose p&#243;s-menopausa pode agravar ainda mais a perda &#243;ssea alveolar, refor&#231;ando um poss&#237;vel elo entre sa&#250;de esquel&#233;tica, inflama&#231;&#227;o cr&#244;nica e doen&#231;a cardiovascular.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B39">39</xref>,<xref ref-type="bibr" rid="B40">40</xref></sup> A inflama&#231;&#227;o cr&#244;nica de baixo grau associada &#224; periodontite tem sido implicada no desenvolvimento e na progress&#227;o da doen&#231;a arterial coronariana, do acidente vascular cerebral e da doen&#231;a arterial perif&#233;rica. Esse processo &#233; iniciado pela disbiose microbiana oral e perpetuado pela resposta imune do hospedeiro.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B39">39</xref>,<xref ref-type="bibr" rid="B41">41</xref></sup></p>
        <p>Para os cl&#237;nicos, o reconhecimento dessa tr&#237;ade, menopausa, doen&#231;a oral e risco cardiovascular, deve orientar a anamnese e a estratifica&#231;&#227;o de risco de forma abrangente. O estado periodontal pode atuar como marcador de inflama&#231;&#227;o sist&#234;mica e vulnerabilidade cardiovascular. Por outro lado, sintomas orais inexplicados em mulheres na p&#243;s-menopausa podem justificar avalia&#231;&#227;o metab&#243;lica e vascular mais ampla.<sup><xref ref-type="bibr" rid="B40">40</xref></sup> Estrat&#233;gias de sa&#250;de p&#250;blica direcionadas a mulheres de meia-idade devem integrar a promo&#231;&#227;o da sa&#250;de oral aos programas de preven&#231;&#227;o cardiovascular, especialmente em popula&#231;&#245;es envelhecidas e socialmente vulner&#225;veis.</p>
        <p>Al&#233;m dos mecanismos inflamat&#243;rios, as condi&#231;&#245;es orais e cardiovasculares relacionadas &#224; menopausa compartilham diversos fatores de risco modific&#225;veis, incluindo tabagismo, diabetes mellitus, obesidade, sedentarismo e padr&#245;es alimentares n&#227;o saud&#225;veis. Estresse psicossocial e dist&#250;rbios do sono, ambos comuns durante a menopausa, podem intensificar a inflama&#231;&#227;o sist&#234;mica e reduzir a busca por cuidados em sa&#250;de, ampliando o risco tanto de doen&#231;a periodontal quanto de doen&#231;a cardiovascular.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B14">14</xref>,<xref ref-type="bibr" rid="B42">42</xref></sup></p>
      </sec>
      <sec>
        <title>Lacunas de conhecimento e perspectivas futuras</title>
        <p>Apesar do reconhecimento crescente da rela&#231;&#227;o entre menopausa e sa&#250;de oral, persistem lacunas substanciais tanto na evid&#234;ncia cient&#237;fica quanto na implementa&#231;&#227;o cl&#237;nica. Essas limita&#231;&#245;es dificultam o desenvolvimento de fluxos assistenciais padronizados e de interven&#231;&#245;es baseadas em evid&#234;ncias direcionadas &#224;s mulheres na menopausa.</p>
        <p>A menopausa &#233; uma transi&#231;&#227;o biopsicossocial que vai al&#233;m das altera&#231;&#245;es fisiol&#243;gicas, frequentemente afetando o humor, a cogni&#231;&#227;o e a resili&#234;ncia emocional. As manifesta&#231;&#245;es orais nesse per&#237;odo podem influenciar significativamente a autoimagem, a participa&#231;&#227;o social e a qualidade de vida. Tamb&#233;m podem contribuir para estresse psicol&#243;gico, ansiedade e sintomas depressivos. Apesar de seu impacto, essas queixas orais s&#227;o frequentemente subnotificadas pelas pacientes e sub-reconhecidas tanto na pr&#225;tica m&#233;dica quanto odontol&#243;gica.</p>
        <p>A integridade oral &#233; essencial para mastiga&#231;&#227;o, degluti&#231;&#227;o, fona&#231;&#227;o e comunica&#231;&#227;o n&#227;o verbal. Sintomas orais da menopausa, especialmente aqueles relacionados &#224; atrofia mucosa, comprometimento dent&#225;rio ou hipofun&#231;&#227;o salivar, podem prejudicar essas fun&#231;&#245;es fundamentais. Dificuldades para comer e falar em contextos sociais podem levar ao constrangimento e ao isolamento social. A insatisfa&#231;&#227;o com a est&#233;tica oral, incluindo escurecimento dent&#225;rio, perda dent&#225;ria e altera&#231;&#245;es da mucosa, pode afetar negativamente a autoestima e a imagem corporal, que j&#225; podem estar fragilizadas nessa fase da vida.</p>
        <p>O enfrentamento dessas lacunas exige uma agenda de pesquisa multidisciplinar coordenada, pol&#237;ticas p&#250;blicas de apoio e a transi&#231;&#227;o para modelos assistenciais centrados na paciente e baseados no curso de vida. A separa&#231;&#227;o hist&#243;rica entre odontologia e medicina permanece como importante barreira para o manejo integral. Embora sintomas orais sejam comuns na menopausa, poucas mulheres recebem avalia&#231;&#227;o odontol&#243;gica estruturada como parte do acompanhamento ginecol&#243;gico, cardiol&#243;gico ou da aten&#231;&#227;o prim&#225;ria. Da mesma forma, profissionais da odontologia podem n&#227;o dispor de protocolos padronizados para rastrear condi&#231;&#245;es sist&#234;micas, como osteoporose, doen&#231;a cardiovascular ou s&#237;ndrome metab&#243;lica, que influenciam a sa&#250;de oral.</p>
        <p>Tecnologias emergentes, incluindo diagn&#243;sticos salivares, sequenciamento do microbioma e avalia&#231;&#227;o periodontal digital, oferecem ferramentas promissoras para identifica&#231;&#227;o mais precoce e precisa das condi&#231;&#245;es orais relacionadas &#224; menopausa. S&#227;o necess&#225;rias pesquisas adicionais para validar essas abordagens em popula&#231;&#245;es menop&#225;usicas diversas e para avaliar sua aplicabilidade cl&#237;nica na pr&#225;tica rotineira.</p>
        <p>Uma melhor compreens&#227;o da rela&#231;&#227;o entre dist&#250;rbios orais e sintomas cardiovasculares, como angina ou altera&#231;&#245;es isqu&#234;micas card&#237;acas, tamb&#233;m pode contribuir para uma estratifica&#231;&#227;o mais abrangente do risco cardiovascular em mulheres na menopausa.</p>
      </sec>
    </sec>
  </body>
  <back>
    <fn-group>
      <fn fn-type="financial-disclosure" id="fn1">
        <label>Fontes de Financiamento</label>
        <p>O presente estudo foi financiado pela FAPESP 2022/12807-5, 2025/03765-5, 2025/03920-0.</p>
      </fn>
      <fn fn-type="other" id="fn2">
        <label>Vincula&#231;&#227;o Acad&#234;mica</label>
        <p>N&#227;o h&#225; vincula&#231;&#227;o deste estudo a programas de p&#243;s-gradua&#231;&#227;o.</p>
      </fn>
      <fn fn-type="other" id="fn3">
        <label>Aprova&#231;&#227;o &#201;tica e Consentimento Informado</label>
        <p>Este artigo n&#227;o cont&#233;m estudos com humanos ou animais realizados por nenhum dos autores.</p>
      </fn>
      <fn fn-type="other" id="fn4">
        <label>Uso de Intelig&#234;ncia Artificial</label>
        <p>Os autores n&#227;o utilizaram ferramentas de intelig&#234;ncia artificial no desenvolvimento deste trabalho.</p>
      </fn>
    </fn-group>
    <sec sec-type="data-availability" specific-use="data-in-article">
      <title>Disponibilidade de Dados</title>
      <p>Os conte&#250;dos subjacentes ao texto da pesquisa est&#227;o contidos no manuscrito.</p>
    </sec>
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  <sub-article article-type="translation" id="S1" xml:lang="en">
    <front-stub>
      <article-id pub-id-type="doi">10.36660/abc.20250737i</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Review Article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>The Silent Shift of Menopause: The Intersection between Salivary Glands, Oral Cavity Status, and Cardiovascular Health</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Louren&#231;o</surname>
            <given-names>Silvia Vanessa</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff5">
            <sup>2</sup>
          </xref>
          <role>Conception and design of the research</role>
          <role>Acquisition of data and Analysis and interpretation of the data</role>
          <role>Obtaining financing</role>
          <role>Writing of the manuscript and Critical revision of the manuscript for intellectual content</role>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-5328-0937</contrib-id>
          <name>
            <surname>Florezi</surname>
            <given-names>Giovanna Piacenza</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff5">
            <sup>2</sup>
          </xref>
          <xref ref-type="corresp" rid="c2"/>
          <role>Acquisition of data and Analysis and interpretation of the data</role>
          <role>Writing of the manuscript and Critical revision of the manuscript for intellectual content</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Pelissari</surname>
            <given-names>Cibele</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff5">
            <sup>2</sup>
          </xref>
          <role>Writing of the manuscript and Critical revision of the manuscript for intellectual content</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Hojaij</surname>
            <given-names>Flavio Carneiro</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">
            <sup>1</sup>
          </xref>
          <role>Writing of the manuscript and Critical revision of the manuscript for intellectual content</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Otoch</surname>
            <given-names>Jos&#233; Pinhata</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">
            <sup>1</sup>
          </xref>
          <role>Obtaining financing</role>
          <role>Writing of the manuscript and Critical revision of the manuscript for intellectual content</role>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ramires</surname>
            <given-names>Jos&#233; Antonio Franchini</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">
            <sup>3</sup>
          </xref>
          <role>Conception and design of the research</role>
          <role>Acquisition of data and Analysis and interpretation of the data</role>
          <role>Obtaining financing</role>
          <role>Writing of the manuscript and Critical revision of the manuscript for intellectual content</role>
        </contrib>
        <aff id="aff4">
          <label>1</label>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Departamento de Cirurgia, Faculdade de Medicina, Universidade de S&#227;o Paulo, S&#227;o Paulo, SP &#8211; Brazil</institution>
        </aff>
        <aff id="aff5">
          <label>2</label>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Instituto de Medicina Tropical, Universidade de S&#227;o Paulo, S&#227;o Paulo, SP &#8211; Brazil</institution>
        </aff>
        <aff id="aff6">
          <label>3</label>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Departamento Cardiopulmonar, Instituto do Cora&#231;&#227;o do Hospital das Cl&#237;nicas da Faculdade de Medicina da Universidade de S&#227;o Paulo, S&#227;o Paulo, SP &#8211; Brazil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c2"><label>Mailing Address:</label><bold>Giovanna P. Florezi</bold> &#8226; Faculdade de Medicina da Universidade de S&#227;o Paulo - Av. Dr. Arnaldo, 455. Postal Code <postal-code>01246-903</postal-code>, S&#227;o Paulo, SP - Brazil Email: <email>giovanna.florezi@usp.br</email> </corresp>
        <fn fn-type="coi-statement">
          <label>Potential Conflict of Interest</label>
          <p>No potential conflict of interest relevant to this article was reported.</p>
        </fn>
        <fn fn-type="edited-by">
          <label>Editor responsible for the review:</label>
          <p>Gl&#225;ucia Maria Moraes de Oliveira</p>
        </fn>
      </author-notes>
      <abstract>
        <title>Abstract</title>
        <sec>
          <title>Background:</title>
          <p>Menopause represents a major biological transition in a woman's life, defined by the cessation of ovarian function and a marked decline in estrogen levels. Although its systemic consequences, including osteoporosis and increased cardiovascular risk, are well established, its impact on oral health remains insufficiently recognized by both medical and dental professionals.</p>
        </sec>
        <sec>
          <title>Objective:</title>
          <p>To examine the influence of menopause on women's oral health, emphasizing key pathophysiological mechanisms, clinical manifestations, and interdisciplinary strategies for prevention and management.</p>
        </sec>
        <sec>
          <title>Methods:</title>
          <p>A narrative review was conducted using articles retrieved from the PubMed database published between 2000 and 2025. The following keywords were used: "menopause," "oral health," "hormonal changes," "cardiovascular disease," "xerostomia," "salivary glands," "periodontitis," and "postmenopausal women."</p>
        </sec>
        <sec>
          <title>Results:</title>
          <p>Hormonal changes during menopause are associated with a range of oral manifestations, including xerostomia, burning mouth syndrome, periodontal disease, and taste alterations. Estrogen deficiency appears to contribute to reduced salivary flow, mucosal atrophy, and an increased inflammatory response in periodontal tissues. Emerging evidence also suggests an association between oral health during menopause and cardiovascular disease, among other systemic conditions. However, important knowledge gaps persist regarding clinical management and interdisciplinary care for menopausal women.</p>
        </sec>
        <sec>
          <title>Conclusion:</title>
          <p>Oral health during menopause reflects a complex interplay of hormonal, systemic, and behavioral factors. Because of increasing life expectancy worldwide, oral health education and research programs should prioritize this topic. Strengthening awareness and fostering multidisciplinary collaboration are essential to improving health outcomes in midlife women.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <title>Keywords:</title>
        <kwd>Menopause</kwd>
        <kwd>Oral Health</kwd>
        <kwd>Saliva</kwd>
        <kwd>Salivary Glands</kwd>
        <kwd>Vascular Health</kwd>
      </kwd-group>
      <funding-group>
        <award-group>
          <funding-source>This study was funded by FAPESP</funding-source>
          <award-id>2022/12807-5</award-id>
          <award-id>2025/03765-5</award-id>
          <award-id>2025/03920-0</award-id>
        </award-group>
        <funding-statement><bold>Sources of Funding</bold> This study was funded by FAPESP 2022/12807-5, 2025/03765-5, 2025/03920-0.</funding-statement>
      </funding-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introduction</title>
        <p>Menopause represents a major biological milestone in a woman's life. It is characterized by a progressive decline in circulating estrogen and progesterone levels, culminating in the permanent cessation of menstruation for at least 12 consecutive months. This process results from the cessation of ovarian follicular function.<sup><xref ref-type="bibr" rid="B1">1</xref>-<xref ref-type="bibr" rid="B3">3</xref></sup> The transition typically occurs between 45 and 55 years of age and is accompanied by a range of systemic changes driven by alterations in female sex hormone levels. According to the Collaborative Group for Research of the Climacteric in Latin America, the average age of menopause in the region is 48.6 years.<sup><xref ref-type="bibr" rid="B4">4</xref></sup></p>
        <p>The transition into menopause, known as the climacteric period, comprises three principal phases. Perimenopause refers to the years preceding menopause, during which menstrual irregularities begin and are often accompanied by vasomotor symptoms such as hot flashes and night sweats. Menopause is defined retrospectively after 12 consecutive months without menstruation. Postmenopause encompasses the years following menopause, during which estrogen levels remain persistently low. Despite these clinical landmarks, the early or premature phases of the climacteric period remain incompletely defined.<sup><xref ref-type="bibr" rid="B3">3</xref>-<xref ref-type="bibr" rid="B6">6</xref></sup></p>
        <p>Menopause significantly affects quality of life and is associated with altered systemic homeostasis, sleep disturbances, sexual dysfunction, anxiety, depression, musculoskeletal pain, reduced muscle mass, and mild cognitive decline.<sup><xref ref-type="bibr" rid="B6">6</xref>,<xref ref-type="bibr" rid="B7">7</xref></sup> Although the somatic and psychological manifestations of menopause, such as vasomotor symptoms, sleep disturbances, and mood changes, are well documented, its impact on oral health remains underrecognized in both clinical practice and public health settings.</p>
        <p>Estrogen plays a central role in maintaining the structural and functional integrity of multiple systems, including the cardiovascular, skeletal, integumentary, and oral tissues. Circulating plasma estrogen exists in three main forms: 17&#946;-estradiol (E2), estrone, and estriol. E2 is the most potent and biologically active form and is predominantly produced by the ovaries in premenopausal women. In postmenopausal women, estrone, a less potent form, becomes the predominant circulating estrogen. The levels of both hormones decrease approximately tenfold after menopause. During this period, aromatase expressed in adipose tissue, skin, brain, and bone becomes the primary source of circulating E2 and estrone.<sup><xref ref-type="bibr" rid="B8">8</xref></sup></p>
        <p>Estrogen deficiency contributes to a state of low-grade chronic systemic inflammation and is associated with conditions such as cardiovascular disease, osteoporosis, and urogenital atrophy. It also disrupts oral homeostasis.<sup><xref ref-type="bibr" rid="B9">9</xref></sup> In recent decades, growing scientific interest has focused on the oral consequences of menopause, particularly in the context of global population aging. Menopause may precipitate or exacerbate several oral conditions, including xerostomia, burning mouth syndrome (BMS), periodontitis, mucosal atrophy, and loss of alveolar bone. These alterations may impair essential oral functions such as eating, speaking, and swallowing and may also influence systemic health.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B10">10</xref>-<xref ref-type="bibr" rid="B12">12</xref></sup></p>
        <p>The relationship between menopause and oral health extends beyond localized manifestations. Emerging evidence highlights a bidirectional association between oral and systemic health, particularly with cardiovascular conditions, which are more prevalent in postmenopausal women.<sup><xref ref-type="bibr" rid="B13">13</xref>-<xref ref-type="bibr" rid="B16">16</xref></sup> Thus, improving knowledge of the oral manifestations of menopause and integrating oral care into comprehensive women's health strategies represent important priorities.</p>
        <p>This narrative review, based on articles retrieved from PubMed published between 2000 and 2025 using the keywords "menopause," "oral health," "hormonal changes," "cardiovascular disease," "xerostomia," "salivary glands," "periodontitis," and "postmenopausal women," aims to synthesize current evidence on the biological mechanisms, clinical manifestations, and broader perspectives of oral health in menopausal women. It also emphasizes the need for interdisciplinary care and future research directions to improve prevention, diagnosis, and management (<xref ref-type="fig" rid="f2">Central Illustration</xref>).</p>
        <fig id="f2">
          <graphic xlink:href="1678-4170-abc-123-05-e20250737-50737-gf01-en.tif"/></fig>
        <sec>
          <title>Menopause, saliva, and salivary glands: associations with common oral changes</title>
          <p>The oral cavity is not traditionally considered a primary target of sex hormones; however, it is highly sensitive to hormonal fluctuations.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B9">9</xref>,<xref ref-type="bibr" rid="B12">12</xref>,<xref ref-type="bibr" rid="B14">14</xref>,<xref ref-type="bibr" rid="B17">17</xref></sup> Estrogens play a fundamental role in maintaining its structural and functional integrity. Under physiological conditions, soft tissues, alveolar bone, vasculature, salivary glands, and the oral microbiome interact dynamically to preserve homeostasis. During menopause, the progressive decline in circulating estrogen and progesterone triggers a cascade of changes in oral tissues, salivary glands, and immune regulation, collectively increasing susceptibility to oral diseases.<sup><xref ref-type="bibr" rid="B10">10</xref>,<xref ref-type="bibr" rid="B11">11</xref>,<xref ref-type="bibr" rid="B13">13</xref>,<xref ref-type="bibr" rid="B14">14</xref></sup></p>
          <p>Estrogen receptors (ER&#945; and ER&#946;) have been identified in the oral mucosa, salivary glands, and periodontal tissues.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B12">12</xref></sup> These receptors mediate hormonal modulation of cellular proliferation, differentiation, and inflammatory responses. Estrogen also regulates vascular permeability and collagen metabolism, processes that are essential for maintaining soft tissue resilience and gingival connective tissue integrity.<sup><xref ref-type="bibr" rid="B18">18</xref></sup></p>
          <p>Estrogens influence salivary gland function by promoting acinar cell activity and vascularization. The parotid and submandibular glands, in particular, appear responsive to hormonal modulation.<sup><xref ref-type="bibr" rid="B19">19</xref></sup> In menopausal women, reduced estrogen levels have been associated with reported alterations in salivary gland function and in both the quantity and quality of saliva, although findings remain inconsistent.<sup><xref ref-type="bibr" rid="B20">20</xref></sup></p>
          <p>Saliva is a plasma ultrafiltrate processed by the salivary glands and is essential for maintaining and protecting oral structures. It plays a central role in oral homeostasis. Human saliva contains numerous known and yet-to-be-identified components that contribute to buffering capacity, lubrication, antimicrobial defense, and tissue protection. These include myeloperoxidase, nitric oxide (NO), immunoglobulin A (IgA), enzymes, and electrolytes.<sup><xref ref-type="bibr" rid="B21">21</xref>,<xref ref-type="bibr" rid="B22">22</xref></sup></p>
          <p>NO is a potent vasodilator and plays a role in regulating cardiomyocyte function, among other systemic effects. Its concentration in saliva exceeds that found in plasma. NO also functions as a signaling molecule, neurotransmitter, and mediator in immune defense and inflammatory processes.<sup><xref ref-type="bibr" rid="B23">23</xref></sup> It contributes to salivary secretion and is considered a key molecule in maintaining homeostasis. Dietary nitrate (exogenous) and nitrate derived from endogenous NO oxidation are absorbed through the gastrointestinal tract into the bloodstream. Approximately 25% of circulating nitrate is actively taken up by the salivary glands, particularly the parotid gland, and secreted into saliva. Of this amount, about 20% is reduced to nitrite by oral bacteria. The remaining nitrate and nitrite are swallowed and re-enter systemic circulation, forming part of the enterosalivary nitrate-nitrite-NO cycle. Notably, approximately 80% of circulating nitrite is generated through this pathway.<sup><xref ref-type="bibr" rid="B23">23</xref></sup> Salivary nitrate concentrations are approximately 10-fold higher than plasma levels.<sup><xref ref-type="bibr" rid="B24">24</xref></sup></p>
          <p>Abadi et al. demonstrated that salivary NO levels are significantly lower in diabetic patients with xerostomia compared with those without xerostomia, suggesting that NO may contribute to oral health maintenance.<sup><xref ref-type="bibr" rid="B25">25</xref></sup> However, the relationship between NO metabolism, salivary gland alterations during menopause, and cardiovascular function remains insufficiently explored.</p>
          <p>Despite xerostomia being one of the most frequently reported complaints among menopausal women, studies evaluating salivary flow rate and salivary gland response during menopause remain limited.<sup><xref ref-type="bibr" rid="B26">26</xref></sup> Xerostomia is defined as the subjective sensation of oral dryness and is not necessarily correlated with measurable reductions in salivary flow. Although multifactorial, hypoestrogenism is thought to impair salivary gland function, potentially reducing both unstimulated and stimulated salivary flow.</p>
          <p>In a postmortem study, de Moraes et al. observed vascular alterations in the salivary glands of midlife and older women, including thrombosis with marked perfusion compromise.<sup><xref ref-type="bibr" rid="B27">27</xref></sup> These vascular changes may impair parenchymal nutrition, leading to glandular atrophy and replacement by adipose tissue. Kawamoto et al. corroborated these findings, reporting alterations in salivary parenchymal composition and adipose replacement associated with hypertension, a common comorbidity in menopausal women.<sup><xref ref-type="bibr" rid="B16">16</xref>,<xref ref-type="bibr" rid="B27">27</xref></sup></p>
          <p>Clinically, xerostomia in menopausal women is associated with impairment of speech, mastication, and swallowing. Reduced salivary output and compositional changes may result in lower salivary pH, decreased buffering capacity, and diminished antimicrobial activity.<sup><xref ref-type="bibr" rid="B20">20</xref></sup> Together, these alterations create an environment more susceptible to dental caries, oral infections, and halitosis.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B28">28</xref>,<xref ref-type="bibr" rid="B29">29</xref></sup> Xerostomia may also negatively affect social interactions, and its severity appears to correlate with menopause duration.<sup><xref ref-type="bibr" rid="B10">10</xref></sup></p>
          <p>Research remains inconsistent. Some authors report reduced salivary flow after menopause, whereas others describe changes in salivary composition without measurable flow reduction.<sup><xref ref-type="bibr" rid="B20">20</xref>,<xref ref-type="bibr" rid="B22">22</xref>,<xref ref-type="bibr" rid="B30">30</xref></sup> When present, reduced unstimulated and stimulated salivary flow contributes to xerostomia and increases the risk of dental caries, candidosis, and mucosal discomfort.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Additionally, reductions in buffering capacity and antimicrobial components, such as lysozyme, lactoferrin, and IgA, may further compromise oral defense mechanisms.<sup><xref ref-type="bibr" rid="B20">20</xref></sup></p>
          <p>Salvolini et al. did not observe significant differences in salivary output in older patients but reported increased lipid peroxide levels, suggesting enhanced oxidative stress and potential tissue damage.<sup><xref ref-type="bibr" rid="B22">22</xref></sup> Moreover, postmenopausal saliva has been associated with lower pH values correlated with plasma adiponectin levels, a marker linked to pro-inflammatory cardiometabolic risk and metabolic disorders such as type 2 diabetes and obesity.<sup><xref ref-type="bibr" rid="B21">21</xref>,<xref ref-type="bibr" rid="B31">31</xref></sup></p>
          <p>Xerostomia predisposes to mucosal alterations. The combination of reduced salivary flow, mucosal atrophy, and altered immune responses favors opportunistic infections, particularly oral candidosis.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Although typically manageable, recurrent candidosis may serve as a clinical indicator of underlying xerostomia or systemic imbalance in menopausal women.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B8">8</xref>,<xref ref-type="bibr" rid="B27">27</xref>,<xref ref-type="bibr" rid="B28">28</xref></sup></p>
          <p>Similar to the genital mucosa, the oral mucosa may become thinner, less elastic, and more susceptible to trauma following estrogen decline. Patients may report tightness, discomfort when consuming acidic or spicy foods, or increased sensitivity to temperature changes. Clinical findings may include atrophic glossitis (smooth, depapillated tongue), angular cheilitis, and mucosal pallor. These alterations may be exacerbated by reduced salivary lubrication.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B2">2</xref></sup></p>
          <p>Menopause may also be associated with sensory disturbances, including BMS and dysgeusia. Altered taste perception may be related to changes in salivary flow rate and central processing of gustatory stimuli. Taste disturbances are often underreported; some women describe persistent metallic or bitter sensations, whereas others experience reduced sensitivity to sweet or salty tastes. Proposed mechanisms include changes in salivary composition, alterations in taste receptor density, and hormonal effects on central gustatory pathways.<sup><xref ref-type="bibr" rid="B2">2</xref></sup></p>
          <p>BMS is defined as a chronic neuropathic pain condition characterized by burning sensations in the absence of visible mucosal lesions or laboratory abnormalities. It has been reported in up to 18% of postmenopausal women and commonly affects the tongue, lips, and anterior palate. The etiology remains incompletely understood but is thought to involve peripheral or central neuropathic dysfunction modulated by hormonal, psychological, and systemic factors.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Psychiatric conditions and genetic polymorphisms may contribute. Systemic factors associated with BMS include diabetes mellitus, deficiencies of B vitamins (B1, B2, B6, and B12), folate, and iron, gastrointestinal disorders, hormonal imbalances, and medication-related effects. The higher prevalence of BMS in menopausal women has led to the hypothesis that estrogen and progesterone may exert neuroprotective or neurosensory modulatory effects that diminish after menopause. Symptoms typically emerge 3 to 12 years after menopause onset.<sup><xref ref-type="bibr" rid="B17">17</xref></sup></p>
          <p>Existing studies are limited by small sample sizes and methodological heterogeneity. Further research is needed to elucidate the mechanisms underlying salivary gland senescence and functional alterations during menopause. In addition, age-related comorbidities and medications, such as antihypertensives, antidepressants, and anticholinergics, may further influence salivary flow in this population.</p>
          <p>An integrated summary of salivary and periodontal findings across menopausal stages is presented in <xref ref-type="table" rid="t2">Table 1</xref>.</p>
          <table-wrap id="t2">
            <label>Table 1</label>
            <caption>
              <title>Overview of clinical and experimental studies on menopause-related changes in salivary gland function, oral homeostasis, and periodontal health</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup width="20%">
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead style="border-top: thin solid; border-bottom: thin solid; border-color: #000000">
                <tr style="background-color:#76B4CF">
                  <th align="left" valign="middle">Study ID</th>
                  <th align="center" valign="middle">Population (n, status)</th>
                  <th align="center" valign="middle">Methodology</th>
                  <th align="center" valign="middle">Key findings</th>
                  <th align="center" valign="middle">Translational relevance</th>
                </tr>
              </thead>
              <tbody style="border-bottom: thin solid; border-color: #000000">
                <tr>
                  <td align="left" valign="middle">Tremblay et al., 2012<sup><xref ref-type="bibr" rid="B31">31</xref></sup></td>
                  <td align="center" valign="top">151 women (53 premenopausal; 98 postmenopausal)</td>
                  <td align="center" valign="top">UWS pH; plasma adiponectin (ELISA); anthropometric measurements</td>
                  <td align="center" valign="top">Salivary pH positively correlated with plasma adiponectin in menopausal women</td>
                  <td align="center" valign="top">Lower adiponectin levels and reduced salivary pH were observed in menopausal women, suggesting an association with a proinflammatory cardiometabolic risk profile; requires longitudinal validation</td>
                </tr>
                <tr style="background-color:#C7DFEC;">
                  <td align="left" valign="middle">Salvolini et al., 2000<sup><xref ref-type="bibr" rid="B22">22</xref></sup></td>
                  <td align="center" valign="top">169 healthy subjects of both sexes divided into five age groups (10-24 years, n = 38; 25-39 years, n = 52; 40-54 years, n = 40; 55-69 years, n = 27; &#8805; 70 years, n = 12)</td>
                  <td align="center" valign="top">Assessment of total protein content, peroxidase activity, malondialdehyde, and NO levels in UWS</td>
                  <td align="center" valign="top">No differences in salivary volume; decreased peroxidase activity and increased NO levels with aging</td>
                  <td align="center" valign="top">Suggests age-related oxidative stress in saliva independent of salivary volume; lacked direct hormonal profiling</td>
                </tr>
                <tr>
                  <td align="left" valign="middle">Foglio-Bonda et al., 2019<sup><xref ref-type="bibr" rid="B37">37</xref></sup></td>
                  <td align="center" valign="top">120 women (60 postmenopausal; 60 fertile)</td>
                  <td align="center" valign="top">UWS pH and flow rate; DMFT index</td>
                  <td align="center" valign="top">Lower salivary pH and reduced flow rate in menopausal group; similar DMFT index</td>
                  <td align="center" valign="top">Standardized UWS collection demonstrates modest but significant salivary hypofunction</td>
                </tr>
                <tr style="background-color:#C7DFEC;">
                  <td align="left" valign="middle">Bosman et al., 2022<sup><xref ref-type="bibr" rid="B43">43</xref></sup></td>
                  <td align="center" valign="top">50 healthy women (24 aged 22-45 years; 26 aged 55-92 years)</td>
                  <td align="center" valign="top">UWS; untargeted metabolomics via LC-MS</td>
                  <td align="center" valign="top">Age-associated shifts in salivary metabolomic profile</td>
                  <td align="center" valign="top">Most differentially expressed metabolites in older women were related to amino acid metabolism, the Krebs cycle, fatty acid metabolism, and nucleic acid synthesis</td>
                </tr>
                <tr>
                  <td align="left" valign="middle">Soundarya et al., 2022<sup><xref ref-type="bibr" rid="B36">36</xref></sup></td>
                  <td align="center" valign="top">60 women (20 menstruating, 20 premenopausal, 20 postmenopausal)</td>
                  <td align="center" valign="top">UWS; salivary estradiol (ELISA); salivary calcium; xerostomia and periodontal indices</td>
                  <td align="center" valign="top">Lower salivary estradiol and higher calcium levels in postmenopausal group; decreased estradiol associated with higher xerostomia and periodontal scores</td>
                  <td align="center" valign="top">Potential screening markers; standardization required</td>
                </tr>
                <tr style="background-color:#C7DFEC;">
                  <td align="left" valign="middle">Divya Harika et al., 2024<sup><xref ref-type="bibr" rid="B26">26</xref></sup></td>
                  <td align="center" valign="top">60 women (30 premenopausal; 30 postmenopausal)</td>
                  <td align="center" valign="top">UWS; taste thresholds; serum zinc levels</td>
                  <td align="center" valign="top">Postmenopausal women exhibited reduced sweet and bitter taste perception; no differences in salivary flow or zinc levels</td>
                  <td align="center" valign="top">Taste alterations may be multifactorial beyond zinc deficiency or flow reduction; neurosensory factors should be considered</td>
                </tr>
                <tr>
                  <td align="left" valign="middle">de Moraes et al., 2024<sup><xref ref-type="bibr" rid="B27">27</xref></sup></td>
                  <td align="center" valign="top">85 autopsied women (reproductive phase &#8804; 44 years, n = 18; climacteric phase 45-55 years, n = 21; postmenopause &#8805; 56 years, n = 46)</td>
                  <td align="center" valign="top">Morphological analysis of labial minor salivary glands</td>
                  <td align="center" valign="top">Aging associated with acinar fibrosis and atrophy, serous metaplasia, adipose replacement, and microthrombosis</td>
                  <td align="center" valign="top">Provides anatomical basis for salivary hypofunction; lacks correlation with clinical symptoms</td>
                </tr>
                <tr style="background-color:#C7DFEC;">
                  <td align="left" valign="middle">Garc&#237;a-Alfaro et al., 2025<sup><xref ref-type="bibr" rid="B42">42</xref></sup></td>
                  <td align="center" valign="top">3,211 peri- (n = 1,170) and postmenopausal (n = 2,041) women aged 40-90 years</td>
                  <td align="center" valign="top">XI; oral health-related quality of life (OHIP-14)</td>
                  <td align="center" valign="top">Higher prevalence of xerostomia in peri- and postmenopausal women; associated with poorer quality of life</td>
                  <td align="center" valign="top">Supports routine xerostomia screening in menopause-focused care settings</td>
                </tr>
                <tr>
                  <td align="left" valign="middle">Scardina &amp; Messina, 2012<sup><xref ref-type="bibr" rid="B44">44</xref></sup></td>
                  <td align="center" valign="top">27 premenopausal and 27 postmenopausal women</td>
                  <td align="center" valign="top">Oral microcirculation assessment (videocapillaroscopy); periodontal indices</td>
                  <td align="center" valign="top">Reduced periodontal capillary density, increased vascular tortuosity, and decreased loop diameter in postmenopausal women</td>
                  <td align="center" valign="top">Suggests vascular contribution to increased periodontal vulnerability</td>
                </tr>
                <tr style="background-color:#C7DFEC;">
                  <td align="left" valign="middle">LaMonte et al., 2013<sup><xref ref-type="bibr" rid="B45">45</xref></sup></td>
                  <td align="center" valign="top">1,025 postmenopausal women (5-year follow-up)</td>
                  <td align="center" valign="top">Longitudinal assessment of periodontal disease progression</td>
                  <td align="center" valign="top">Disease progression linked to systemic factors; overall no generalized progression observed; women with prior severe periodontitis experienced accelerated bone loss</td>
                  <td align="center" valign="top">High-quality cohort study; indicates risk stratification is necessary</td>
                </tr>
                <tr>
                  <td align="left" valign="middle">Wactawski-Wende et al., 2020<sup><xref ref-type="bibr" rid="B14">14</xref></sup></td>
                  <td align="center" valign="top">1,342 postmenopausal women at baseline; 1,026 (5-year follow-up); 518 (17-year follow-up)</td>
                  <td align="center" valign="top">Comprehensive oral examinations; bone density and body composition assessment; subgingival microbiome (16S sequencing)</td>
                  <td align="center" valign="top">Integrated oral and systemic findings in aging women</td>
                  <td align="center" valign="top">Landmark dataset informing oral-systemic risk models</td>
                </tr>
                <tr style="background-color:#C7DFEC;">
                  <td align="left" valign="middle">Ahmad et al., 2024<sup><xref ref-type="bibr" rid="B39">39</xref></sup></td>
                  <td align="center" valign="top">100 postmenopausal women</td>
                  <td align="center" valign="top">Full periodontal examination; bone densitometry</td>
                  <td align="center" valign="top">Age identified as a significant risk factor for bone loss in postmenopausal women</td>
                  <td align="center" valign="top">Supports risk-based periodontal screening; observational design limits causal inference</td>
                </tr>
                <tr>
                  <td align="left" valign="middle">Yakar et al., 2024<sup><xref ref-type="bibr" rid="B46">46</xref></sup></td>
                  <td align="center" valign="top">75 postmenopausal (38-65 years); 71 premenopausal (33-52 years)</td>
                  <td align="center" valign="top">Cytokine levels in serum and saliva (TNF-&#945;, IL-6, IL-10, IL-7); BMI; Women's Health Questionnaire; periodontal assessment</td>
                  <td align="center" valign="top">No significant cytokine differences after age adjustment; fewer teeth in postmenopausal group; no differences in periodontal parameters</td>
                  <td align="center" valign="top">Age is a major confounder; salivary cytokines alone may not differentiate menopausal status; supports multifactorial etiology</td>
                </tr>
                <tr style="background-color:#C7DFEC;">
                  <td align="left" valign="middle">Yakar et al., 2025<sup><xref ref-type="bibr" rid="B47">47</xref></sup></td>
                  <td align="center" valign="top">77 premenopausal; 81 postmenopausal women</td>
                  <td align="center" valign="top">Checkerboard DNA-DNA hybridization (40 species) and 16S sequencing; serum estradiol (ELISA); modified SMDI</td>
                  <td align="center" valign="top">Despite more severe periodontitis, no menopause-related microbial dysbiosis observed; two species correlated with estradiol in premenopause</td>
                  <td align="center" valign="top">Microbial variation appears associated with disease severity rather than hormonal status; highlights systemic regulation of oral ecology</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN2">
                <p>16S: 16S ribosomal RNA gene sequencing; BMI: body mass index; DMFT: Decayed, Missing, and Filled Teeth; ELISA: enzyme-linked immunosorbent assay; IL-6: interleukin 6; IL-7: interleukin 7; IL-10: interleukin 10; LC-MS: liquid chromatography-mass spectrometry; NO: nitric oxide; OHIP-14: Oral Health Impact Profile, 14-item version; SMDI: Subgingival Microbial Dysbiosis Index; TNF-&#945;: tumor necrosis factor alpha; UWS: unstimulated whole saliva; XI: Xerostomia Inventory.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </sec>
        <sec>
          <title>Oral health, menopause, and cardiovascular disease</title>
          <p>The decline in estrogen during menopause affects not only the oral cavity but also accelerates cardiovascular risk, which remains the leading cause of death in women. Women of reproductive age exhibit a lower incidence of cardiovascular disease compared with men; however, this difference diminishes after menopause, when cardiovascular risk increases substantially.<sup><xref ref-type="bibr" rid="B8">8</xref>,<xref ref-type="bibr" rid="B32">32</xref></sup> The menopausal transition therefore represents a pivotal stage in women's cardiometabolic health.</p>
          <p>Hypoestrogenism during menopause is associated with reduced NO bioavailability, a molecule with anti-inflammatory, antioxidant, and anti-atherogenic properties.<sup><xref ref-type="bibr" rid="B18">18</xref></sup> At the same time, menopause is characterized by increased production of pro-inflammatory mediators, including tumor necrosis factor-&#945;, interleukin-6, and C-reactive protein. These cytokines, including those originating from inflamed periodontal tissues, may enter systemic circulation and contribute to endothelial dysfunction, atherogenesis, and plaque instability, which are central mechanisms in cardiovascular pathology.</p>
          <p>Within the cardiovascular system, menopause is associated with endothelial and vascular smooth muscle dysfunction as well as microvascular atherosclerosis. These alterations may lead to nonobstructive coronary artery disease driven by coronary microvascular dysfunction.<sup><xref ref-type="bibr" rid="B17">17</xref></sup> In the United States, postmenopausal women with estrogen deficiency represent a substantial proportion of patients diagnosed with non-obstructive coronary artery disease.<sup><xref ref-type="bibr" rid="B33">33</xref></sup></p>
          <p>Paralleling the evidence of microvascular dysfunction in the cardiovascular system, Uhl et al. reported that several pathological conditions of the salivary glands are associated with inflammation-related microvascular disease.<sup><xref ref-type="bibr" rid="B34">34</xref></sup> However, the inflammatory impact of menopause on salivary gland microvasculature and its consequences for salivary composition and flow remain insufficiently investigated. Some studies have suggested that microvascular thrombotic changes in salivary glands, combined with systemic effects of hypoestrogenism such as hypertension, may impair glandular parenchyma. This process may lead to glandular atrophy and the clinical manifestation of xerostomia.<sup><xref ref-type="bibr" rid="B16">16</xref>,<xref ref-type="bibr" rid="B27">27</xref></sup></p>
          <p>A growing body of evidence supports an interdependent relationship between menopause, periodontal disease, and cardiovascular risk. Estrogen exerts vasodilatory, anti-inflammatory, and antioxidant effects on the vascular endothelium, partly through maintenance of NO levels.<sup><xref ref-type="bibr" rid="B8">8</xref></sup> Its decline during menopause has been associated with increased arterial stiffness, adverse lipid profile changes, and altered coagulation patterns, all of which contribute to increased cardiovascular risk.<sup><xref ref-type="bibr" rid="B35">35</xref></sup></p>
          <p>Simultaneously, hypoestrogenism promotes oral mucosal atrophy, salivary dysfunction, and alveolar bone resorption, creating conditions conducive to periodontal disease.<sup><xref ref-type="bibr" rid="B7">7</xref>,<xref ref-type="bibr" rid="B14">14</xref>,<xref ref-type="bibr" rid="B37">37</xref></sup> These parallel mechanisms suggest that estrogen serves a central regulatory role in both oral and cardiovascular health. Additionally, changes in salivary pH have been associated with inflammatory status, oxidative stress, and NO metabolism, which may have systemic cardiovascular implications.<sup><xref ref-type="bibr" rid="B22">22</xref>,<xref ref-type="bibr" rid="B37">37</xref></sup></p>
          <p>Menopausal women demonstrate increased prevalence and severity of gingivitis and periodontitis. These changes may result from direct hormonal effects as well as systemic alterations, including reduced bone mineral density and dysregulated immune responses.<sup><xref ref-type="bibr" rid="B14">14</xref>,<xref ref-type="bibr" rid="B38">38</xref></sup> Estrogen deficiency appears to amplify inflammatory responses to periodontal pathogens, increase connective tissue breakdown, and impair alveolar bone remodeling. These processes accelerate loss of periodontal attachment and may ultimately lead to tooth mobility and tooth loss if untreated.<sup><xref ref-type="bibr" rid="B14">14</xref>,<xref ref-type="bibr" rid="B39">39</xref></sup></p>
          <p>Postmenopausal osteoporosis may further exacerbate loss of alveolar bone, reinforcing a potential link between skeletal health, chronic inflammation, and cardiovascular disease.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B39">39</xref>,<xref ref-type="bibr" rid="B40">40</xref></sup> Chronic low-grade inflammation associated with periodontitis has been implicated in the development and progression of coronary artery disease, stroke, and peripheral arterial disease. This process is initiated by oral microbial dysbiosis and perpetuated by host immune responses.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B39">39</xref>,<xref ref-type="bibr" rid="B41">41</xref></sup></p>
          <p>For clinicians, recognition of this triad, menopause, oral disease, and cardiovascular risk, should inform comprehensive history-taking and risk assessment. Periodontal status may serve as a marker of systemic inflammation and cardiovascular vulnerability. Conversely, unexplained oral symptoms in postmenopausal women may justify broader metabolic and vascular evaluation.<sup><xref ref-type="bibr" rid="B40">40</xref></sup> Public health strategies targeting midlife women should integrate oral health promotion into cardiovascular prevention programs, particularly in aging and underserved populations.</p>
          <p>Beyond inflammatory mechanisms, menopause-related oral and cardiovascular conditions share several modifiable risk factors, including smoking, diabetes mellitus, obesity, physical inactivity, and unhealthy dietary patterns. Psychosocial stress and sleep disturbances, both common during menopause, may further exacerbate systemic inflammation and reduce health-seeking behaviors, compounding the risk of both periodontal and cardiovascular disease.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B14">14</xref>,<xref ref-type="bibr" rid="B42">42</xref></sup></p>
        </sec>
        <sec>
          <title>Knowledge gaps and future directions</title>
          <p>Despite increasing recognition of the relationship between menopause and oral health, substantial gaps remain in both scientific evidence and clinical implementation. These limitations hinder the development of standardized care pathways and evidence-based interventions tailored to menopausal women.</p>
          <p>Menopause is a biopsychosocial transition that extends beyond physiological changes, often affecting mood, cognition, and emotional resilience. Oral manifestations occurring during this period may significantly influence self-perception, social participation, and overall quality of life. They may also contribute to psychological stress, anxiety, and depressive symptoms. Despite their impact, these oral complaints are frequently underreported by patients and underrecognized in both medical and dental practice.</p>
          <p>Oral integrity is essential for mastication, swallowing, phonation, and nonverbal communication. Menopausal oral symptoms, particularly those related to mucosal atrophy, compromised dentition, or salivary hypofunction, may impair these fundamental functions. Eating and speaking difficulties in social contexts may lead to embarrassment and social withdrawal. Dissatisfaction with oral aesthetics, including tooth discoloration, tooth loss, and mucosal changes, may further negatively affect self-esteem and body image, which may already be vulnerable during this life stage.</p>
          <p>Addressing these knowledge gaps requires a coordinated multidisciplinary research agenda, supportive health policies, and a transition toward patient-centered, life-course-based care models. The longstanding separation between dental and medical care remains a major barrier to comprehensive management. Although oral symptoms are common during menopause, few women receive structured dental evaluation as part of routine gynecologic, cardiologic, or primary care visits. Conversely, dental professionals may lack standardized protocols to screen for systemic conditions such as osteoporosis, cardiovascular disease, or metabolic syndrome that influence oral health.</p>
          <p>Emerging technologies, including salivary diagnostics, microbiome sequencing, and digital periodontal assessment, offer promising tools for earlier and more precise identification of menopause-related oral conditions. Further research is required to validate these approaches in diverse menopausal populations and to evaluate their clinical applicability in routine practice.</p>
          <p>Improved understanding of the relationship between oral disturbances and cardiovascular symptoms, such as angina or ischemic heart changes, may also contribute to more comprehensive cardiovascular risk stratification in menopausal women.</p>
        </sec>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="financial-disclosure" id="fn5">
          <label>Sources of Funding</label>
          <p>This study was funded by FAPESP 2022/12807-5, 2025/03765-5, 2025/03920-0.</p>
        </fn>
        <fn fn-type="other" id="fn6">
          <label>Study Association</label>
          <p>This study is not associated with any thesis or dissertation work.</p>
        </fn>
        <fn fn-type="other" id="fn7">
          <label>Ethics Approval and Consent to Participate</label>
          <p>This article does not contain any studies with human participants or animals performed by any of the authors.</p>
        </fn>
        <fn fn-type="other" id="fn8">
          <label>Use of Artificial Intelligence</label>
          <p>The authors did not use any artificial intelligence tools in the development of this work.</p>
        </fn>
      </fn-group>
      <sec sec-type="data-availability" specific-use="data-in-article">
        <title>Availability of Research Data</title>
        <p>The underlying content of the research text is contained within the manuscript.</p>
      </sec>
    </back>
  </sub-article>
</article>
