<?xml version="1.0" encoding="ISO-8859-1"?><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
<front>
<journal-meta>
<journal-id>0871-3413</journal-id>
<journal-title><![CDATA[Arquivos de Medicina]]></journal-title>
<abbrev-journal-title><![CDATA[Arq Med]]></abbrev-journal-title>
<issn>0871-3413</issn>
<publisher>
<publisher-name><![CDATA[ArquiMed - Edições Científicas AEFMUP ]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S0871-34132006000400005</article-id>
<title-group>
<article-title xml:lang="en"><![CDATA[Safety of hormone replacement therapy: a review]]></article-title>
<article-title xml:lang="pt"><![CDATA[Segurança da Terapêutica Hormonal de Substituição]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Lucas]]></surname>
<given-names><![CDATA[Raquel]]></given-names>
</name>
</contrib>
</contrib-group>
<aff id="A01">
<institution><![CDATA[,Universidade do Porto Faculdade de Medicina Serviço de Higiene e Epidemiologia]]></institution>
<addr-line><![CDATA[ ]]></addr-line>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>09</month>
<year>2006</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>09</month>
<year>2006</year>
</pub-date>
<volume>20</volume>
<numero>5-6</numero>
<fpage>179</fpage>
<lpage>182</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://scielo.pt/scielo.php?script=sci_arttext&amp;pid=S0871-34132006000400005&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://scielo.pt/scielo.php?script=sci_abstract&amp;pid=S0871-34132006000400005&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://scielo.pt/scielo.php?script=sci_pdf&amp;pid=S0871-34132006000400005&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="en"><p><![CDATA[The recent publication of a number of large observational and experimental studies that assessed the safety of hormone replacement therapy (HRT) raised a generalised debate. These studies were conducted during a period of clear and rapid expansion of HRT in almost every country, and provided alarming associations between this therapy and several frequent chronic diseases. Subsequently to these findings, a substantial drop in the volume of prescriptions was observed internationally. However, many of the findings of these studies had already been suggested previously. Moreover, a number of methodological issues concerning the recent studies was raised and the validity of their associations questioned. The current absence of clear-cut guidelines on the use of HRT is probably a consequence of the conflicting evidence. In the Portuguese population this may partially account for the notorious lack of association between this therapy and hysterectomy or oophorectomy. Additionally, although sales data seemed to indicate an increasing trend in the prevalence of HRT up to 2002, the uptake of HRT was then a privilege of women in higher socioeconomic strata. Presently, the contribution of long-term hormone replacement therapy to women’s health remains unclear and this subject increasingly demands a multidisciplinary approach.]]></p></abstract>
<abstract abstract-type="short" xml:lang="pt"><p><![CDATA[Nos últimos anos, a publicação dos resultados de estudos observacionais e experimentais que avaliaram a segurança da terapêutica hormonal de substituição (THS) ocasionou um debate generalizado. Estes estudos indicaram associações alarmantes entre esta terapêutica e algumas doenças de elevada frequência e foram realizados durante um período de grande expansão da THS na maioria dos países. Como consequência, observou-se uma descida pronunciada no volume de prescições de THS a nível internacional. No entanto, uma grande parte dos resultados destes estudos tinha já sido sugerida anteriormente. Adicionalmente, alguns dos seus aspectos metodológicos foram criticados, com as consequentes dúvidas respeitantes à validade das associações encontradas. A actual inexistência de orientações técnicas sobre o uso de THS é provavelmente uma consequência da evidência contraditória. Daí poderá também resultar a ausência de associação encontrada na população portuguesa entre esta terapêutica e a histerectomia ou a ooforectomia. Antes, a THS, cujo volume de vendas vinha aumentando até 2002, era um privilégio das mulheres de estratos socio-económicos elevados. Presentemente, o papel da terapêutica hormonal de substituição a longo prazo na saúde da mulher permanece incerto, constituindo um tema que cada vez mais exige uma abordagem multidisciplinar.]]></p></abstract>
<kwd-group>
<kwd lng="en"><![CDATA[hormone replacement therapy]]></kwd>
<kwd lng="en"><![CDATA[medicine safety]]></kwd>
<kwd lng="en"><![CDATA[research design]]></kwd>
<kwd lng="en"><![CDATA[review]]></kwd>
<kwd lng="pt"><![CDATA[terapêutica hormonal de substituição]]></kwd>
<kwd lng="pt"><![CDATA[segurança de medicamentos]]></kwd>
<kwd lng="pt"><![CDATA[desenho de estudo]]></kwd>
<kwd lng="pt"><![CDATA[revisão]]></kwd>
</kwd-group>
</article-meta>
</front><body><![CDATA[ <P><B>Safety of Hormone Replacement Therapy </b> </P>     <p>A Review </p >     <p>&nbsp;</p >     <p>Raquel Lucas </p >         <P   ><I>Servi&ccedil;o de Higiene e Epidemiologia, Faculdade de Medicina da Universidade    do Porto </I></P >     <P   >&nbsp;</P >     <P   ><b>Abstract</b></P >         <P   >The recent publication of a number of large observational and experimental studies        that assessed the safety of hormone replacement therapy (HRT) raised a generalised        debate. These studies were conducted during a period of clear and rapid        expansion of HRT in almost every country, and provided alarming associations        between this therapy and several frequent chronic diseases. Subsequently        to these findings, a substantial drop in the volume of prescriptions was        observed internationally. However, many of the findings of these studies        had already been suggested previously. Moreover, a number of methodological        issues concerning the recent studies was raised and the validity of their        associations questioned. The current absence of clear-cut guidelines on        the use of HRT is probably a consequence of the conflicting evidence. In        the Portuguese population this may partially account for the notorious lack        of association between this therapy and hysterectomy or oophorectomy. Additionally,        although sales data seemed to indicate an increasing trend in the prevalence        of HRT up to 2002, the uptake of HRT was then a privilege of women in higher        socioeconomic strata. Presently, the contribution of long-term hormone replacement        therapy to women&rsquo;s health remains unclear and this subject increasingly        demands a multidisciplinary approach. </P >          <P   ><B>Key-words</B>: hormone replacement therapy; medicine safety; research design;    review. </P>     <P   >&nbsp;</P>     ]]></body>
<body><![CDATA[<P   ><b>Seguran&ccedil;a da Terap&ecirc;utica Hormonal de Substitui&ccedil;&atilde;o</b></P>     <P   ><b>Resumo</b></P>     <P   >Nos &uacute;ltimos anos, a publica&ccedil;&atilde;o dos resultados de estudos    observacionais e experimentais que avaliaram a seguran&ccedil;a da terap&ecirc;utica    hormonal de substitui&ccedil;&atilde;o (THS) ocasionou um debate generalizado.    Estes estudos indicaram associa&ccedil;&otilde;es alarmantes entre esta terap&ecirc;utica    e algumas doen&ccedil;as de elevada frequ&ecirc;ncia e foram realizados durante    um per&iacute;odo de grande expans&atilde;o da THS na maioria dos pa&iacute;ses.    Como consequ&ecirc;ncia, observou-se uma descida pronunciada no volume de presci&ccedil;&otilde;es    de THS a n&iacute;vel internacional. No entanto, uma grande parte dos resultados    destes estudos tinha j&aacute; sido sugerida anteriormente. Adicionalmente,    alguns dos seus aspectos metodol&oacute;gicos foram criticados, com as consequentes    d&uacute;vidas respeitantes &agrave; validade das associa&ccedil;&otilde;es    encontradas. A actual inexist&ecirc;ncia de orienta&ccedil;&otilde;es t&eacute;cnicas    sobre o uso de THS &eacute; provavelmente uma consequ&ecirc;ncia da evid&ecirc;ncia    contradit&oacute;ria. Da&iacute; poder&aacute; tamb&eacute;m resultar a aus&ecirc;ncia    de associa&ccedil;&atilde;o encontrada na popula&ccedil;&atilde;o portuguesa    entre esta terap&ecirc;utica e a histerectomia ou a ooforectomia. Antes, a THS,    cujo volume de vendas vinha aumentando at&eacute; 2002, era um privil&eacute;gio    das mulheres de estratos socio-econ&oacute;micos elevados. Presentemente, o    papel da terap&ecirc;utica hormonal de substitui&ccedil;&atilde;o a longo prazo    na sa&uacute;de da mulher permanece incerto, constituindo um tema que cada vez    mais exige uma abordagem multidisciplinar.</P>     <P   > <B>Palavras-chave</B>: terap&ecirc;utica hormonal de substitui&ccedil;&atilde;o;    seguran&ccedil;a de medicamentos; desenho de estudo; revis&atilde;o. </font></P>     <P   >&nbsp;</P>     <P   >&nbsp;</P>     <P   >Texto completo dispon&iacute;vel apenas em PDF.</P>     <p>Full text only available in PDF format.</p>     <P   >&nbsp;</P>     <P   >&nbsp;</P>     ]]></body>
<body><![CDATA[<P   ><B>REFERENCES </B></P>     <P   align="justify" >1 -Auchincloss C, Haagensen DC. Cancer of the breast possibly          induced by estrogenic substances. JAMA 1940;114:1517-23. Cited in: Krieger          N, Lowy I, Aronowitz R, Bigby J, Dickersin K, Garner E, et al. Hormone          replacement therapy, cancer, controversies, and women&rsquo;s          health: historical, epidemiological, biological, clinical, and advocacy          perspectives. J Epidemiol Community Health 2005;59:740-8. </P >           <!-- ref --><P   align="justify" >2 -Wilson RA. Feminine forever. New York: Evans; 1966. </P >    &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;[&#160;<a href="javascript:void(0);" onclick="javascript: window.open('/scielo.php?script=sci_nlinks&ref=000025&pid=S0871-3413200600040000500001&lng=','','width=640,height=500,resizable=yes,scrollbars=1,menubar=yes,');">Links</a>&#160;]<!-- end-ref --><P   align="justify" >3 -Oram D, Chakravarti S, Studd J. Letter: Hormone replacement therapy. Lancet 1975;2:131. </P >    <P   align="justify" >4 -Maddison J. Hormone replacement therapy for menopausal symptoms. Lancet 1973;1:1507. </P >    <P   align="justify" >5 -Utian WH. Hormone replacement therapy for menopausal symptoms. Lancet 1973;2:733. </P >    <P   align="justify" >6 -Schleyer-Saunders E. Hormone replacement therapy for menopausal symptoms. Lancet 1973;2:389. </P >    <P   align="justify" >7 -Hemminki E, Kennedy DL, Baum C, McKinlay SM. Prescribing of noncontraceptive estrogens and progestins in the United States, 1974-86. Am J Public Health 1988;78: 1479-81. </P >    <P   align="justify" >8 -Wysowski DK, Golden L, Burke L. Use of menopausal estro-gens and medroxyprogesterone in the United States, 1982-1992. Obstet Gynecol 1995;85:6-10. </P >    <P   align="justify" >9 -Grodstein F, Manson JE, Colditz GA, Willett WC, Speizer FE, Stampfer MJ. A prospective, observational study of postmenopausal hormone therapy and primary prevention of cardiovascular disease. Ann Intern Med 2000;133: 933--41. </P >    ]]></body>
<body><![CDATA[<P   align="justify" >10 -Falkeborn M, Persson I, Terent A, Adami HO, Lithell H, Bergstrom R. Hormone replacement therapy and the risk of stroke. Follow-up of a population-based cohort in Sweden. Arch Intern Med 1993;153:1201-9. </P >    <P   align="justify" >11 -Prince RL, Smith M, Dick IM, et al. Prevention of postmenopausal osteoporosis. A comparative study of exercise, calcium supplementation, and hormone-replacement therapy. N Engl J Med,1991; 325:1189-95. </P >    <P   align="justify" >12 -Binder EF, Williams DB, Schechtman KB, Jeffe DB, Kohrt WM. Effects of hormone replacement therapy on serum lipids in elderly women. a randomized, placebo-controlled trial. Ann Intern Med 2001;134:754-60. </P >    <P   align="justify" >13 -Writing Group for the PEPI Trial. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estro-gen/Progestin Interventions (PEPI) Trial. The Writing Group for the PEPI Trial. JAMA 1995;273:199-208. </P >    <P   align="justify" >14 -Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA 1998; 280:605-13. </P >     <P   align="justify" >15 -Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen    plus progestin in healthy postmenopausal women: principal results From the Women&rsquo;s    Health Initiative randomized controlled trial. JAMA 2002;288:321-33. </P >     <P   align="justify" >16 -Beral V, Bull D, Reeves G. Endometrial cancer and hor-mone-replacement therapy    in the Million Women Study. Lancet 2005;365:1543-51. </P >     <P   align="justify" >17 -Beral V. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet 2003;362:419-27. </P >    <P   align="justify" >18 -Krieger N, Lowy I, Aronowitz R, et al. Hormone replacement therapy, cancer, controversies, and women&rsquo;s health: historical, epidemiological, biological, clinical, and advocacy perspectives. J Epidemiol Community Health 2005;59:740--8. </P >    <P   align="justify" >19 -Barlow DH. Menopause and HRT&mdash;the state of the art in Europe. Maturitas 2005;51:40-7. </P >    ]]></body>
<body><![CDATA[<P   align="justify" >20 -Armitage M, Nooney J, Evans S. Recent concerns surrounding HRT. Clin Endocrinol (Oxf) 2003;59:145-55. </P >     <P   align="justify" >21 -EMEA Public Statement on recent publications regarding hormone replacement    therapy. The European Agency for the Evaluation of Medicinal Products; 2003.    EMEA. URL: <a href="http://www.emea.europa.eu/pdfs/human/press/pus/%203306503en.pdf" target="_blank">www.emea.europa.eu/pdfs/human/press/pus/    3306503en.pdf</a>. </P >     <P   align="justify" >22 -Skouby SO, Al-Azzawi F, Barlow D, Calaf-Alsina Erdogan Ertungealp J, Gompel A, Graziottin A, et al. Climacteric medicine: European Menopause and Andropause Society (EMAS) 2004/2005 position statements on peri- and postmenopausal hormone replacement therapy. Maturitas 2005;51:8-14. </P >     <P   align="justify" >23 -Instituto Nacional da Farm&aacute;cia e do Medicamento (INFARMED). Terap&ecirc;utica    Hormonal de Substitui&ccedil;&atilde;o (THS) -Women&rsquo;s Health Initiative    (WHI). INFARMED 2002.URL:<a href="http://www.infarmed.pt/portal/page/portal/INFARMED/MAIS_ALERTAS/DETALHE_ALERTA?itemid=44768" target="_blank">http://www.infarmed.pt/portal/page/portal/INFARMED/MAIS_ALERTAS/ALERTAS_DE_SE-GURANCA/Terap%EAutica%20Hormonal%20de%20-Substitui%E7%E3o%20(THS)%20-%20Women%-92s%20Health</a>.  </P >     <P   align="justify" >24 -Instituto Nacional da Farm&aacute;cia e do Medicamento (INFARMED). Informa&ccedil;&atilde;o    de seguran&ccedil;a adicional sobre terap&ecirc;utica hormonal de substitui&ccedil;&atilde;o    (THS) - THS deixa de ser recomendada como tratamento de primeira escolha na    Preven&ccedil;&atilde;o de Osteoporose. INFARMED 2003 URL: <a href="http://www.infarmed.pt/portal/page/portal/INFARMED/MAIS_NOVIDADES/MAIS_NOVIDADES/2003/nt_03_12_2003.doc" target="_blank">http:/    /www.infarmed.pt/portal/page/portal/INFARMED/MAIS_NOVIDADES/ANOS_ANTERIORES/NOVIDADES_2003/nt_03_12_2003.doc</a>.  </P >     <P   align="justify" >25 -Instituto Nacional da Farm&aacute;cia e do Medicamento (INFARMED). Uso da    Terap&ecirc;utica Hormonal de Substitui&ccedil;&atilde;o (THS) para Preven&ccedil;&atilde;o    de Osteoporose: Informa&ccedil;&atilde;o Importante para Mulheres Utilizadoras    da THS. INFARMED 2003. URL: <a href="http://www.infarmed.pt/portal/page/portal/INFARMED/MAIS_ALERTAS/DETALHE_ALERTA?itemid=44832" target="_blank">http://www.infarmed.pt/portal/page/portal/INFARMED/MAIS_ALERTAS/    ALERTAS_DE_SEGU-RANCA/0D7A159A49BB9057E04010AC31204B86</a>. </P >     <P   >26 -Instituto Nacional da Farm&aacute;cia e do Medicamento (INFARMED). Terap&ecirc;utica    Hormonal de Substitui&ccedil;&atilde;o (THS) e cancro da mama. INFARMED 2003.    URL: <a href="http://www.infarmed.pt/portal/page/portal/INFARMED/MAIS_ALERTAS/DETALHE_ALERTA?itemid=44778" target="_blank">http://www.infarmed.pt/portal/page/portal/INFARMED/MAIS_ALERTAS/ALERTAS_DE_SEGURANCA/    Terap%EAutica%20Hormonal%20de%20Substitui% E7% E3o%20(THS) %20e%20cancro %20da%20mama.</a>\  </P >     <P   >27 -Instituto Nacional da Farm&aacute;cia e do Medicamento (INFARMED). Recomenda&ccedil;&otilde;es    relativas &agrave; seguran&ccedil;a da Terap&ecirc;utica Hormonal de Substitui&ccedil;&atilde;o    (THS). INFARMED 2003. URL: <a href="http://www.infarmed.pt/portal/pls/portal/docs/1/21455.PDF" target="_blank">http://www.infarmed.pt/portal/pls/portal/docs/1/21455.PDF</a>.  </P >     <P   >28 -Instituto Nacional da Farm&aacute;cia e do Medicamento (INFARMED). Actualiza&ccedil;&atilde;o    da informa&ccedil;&atilde;o relativa &agrave; Terap&ecirc;utica Hormonal de    Substitui&ccedil;&atilde;o, resultantes do estudo Million Women. INFARMED 2003.    URL: <a href="http://www.infarmed.pt/portal/pls/portal/docs/1/21373.PDF" target="_blank">http://www.infarmed.pt/portal/pls/portal/docs/1/21373.PDF</a>.  </P >     <P   >29 -Rocha O, Lunet N, Costa L, Barros H. Osteoporosis treatment in Portugal: trends and geographical variation. Acta Med Port in press. </P >    ]]></body>
<body><![CDATA[<P   >30 -Lucas R, Barros H. Life prevalence and determinants of hormone replacement therapy in women living in Porto, Portugal. Maturitas in press. </P >    <P   >31 -Mohammed-Cherif S, Briancon S, Potier de Courcy G, et al. Factors determining the use of hormone replacement therapy in recent naturally postmenopausal women participating in the French SU.VI.MAX cohort. Eur J Epidemiol 2000;16:477-82. </P >    <P   >32 -Manzoli L, Di Giovanni P, Del Duca L, et al. Use of hormone replacement therapy in Italian women aged 50-70 years. Maturitas 2004;49:241-51. </P >    <P   >33 -Cornuz J, Krieg MA, Sandini L, et al. Factors associated with the use of hormone replacement therapy among older women. Age Ageing 2003;32:675-8. Wright J. Hormone replacement therapy: an example of </P >     <P   >34 -McKinlay&rsquo;s theory on the seven stages of medical innovation. J Clin    Nurs 2005;14:1090-7. </P >     <P   >&nbsp;</P >     <P   ><B>Correspond&ecirc;ncia: </B></P >     <P   >Dr.&ordf; Raquel Lucas </P >     <P   >Servi&ccedil;o de Higiene e Epidemiologia</P >     <P   > Faculdade de Medicina da Universidade do Porto </P >     ]]></body>
<body><![CDATA[<P   >Alameda Prof. Hern&acirc;ni Monteiro</P >     <P   > 4200-319 Porto </P >     <P   >e-mail: <a href="mailto:rlucas@med.up.pt">rlucas@med.up.pt</a> </P > </DIV ></DIV ></DIV >     ]]></body><back>
<ref-list>
<ref id="B1">
<nlm-citation citation-type="book">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Wilson]]></surname>
<given-names><![CDATA[RA]]></given-names>
</name>
</person-group>
<source><![CDATA[Feminine forever]]></source>
<year>1966</year>
<publisher-loc><![CDATA[New York ]]></publisher-loc>
<publisher-name><![CDATA[Evans]]></publisher-name>
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</ref>
</ref-list>
</back>
</article>
