Review of the International Position Paper on Women’s Health and Menopause
2003; Lippincott Williams & Wilkins; Volume: 107; Issue: 9 Linguagem: Inglês
10.1161/01.cir.0000054674.89019.1a
ISSN1524-4539
AutoresRodolfo Paoletti, Nanette K. Wenger,
Tópico(s)Menopause: Health Impacts and Treatments
ResumoHomeCirculationVol. 107, No. 9Review of the International Position Paper on Women's Health and Menopause Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessReview ArticlePDF/EPUBReview of the International Position Paper on Women's Health and MenopauseA Comprehensive Approach Rodolfo Paoletti and Nanette K. Wenger Rodolfo PaolettiRodolfo Paoletti From the Department of Pharmacological Sciences, University of Milan, Milan, Italy (R.P.); and Division of Cardiology, Emory University School of Medicine, Atlanta, Ga (N.K.W.). and Nanette K. WengerNanette K. Wenger From the Department of Pharmacological Sciences, University of Milan, Milan, Italy (R.P.); and Division of Cardiology, Emory University School of Medicine, Atlanta, Ga (N.K.W.). Originally published11 Mar 2003https://doi.org/10.1161/01.CIR.0000054674.89019.1ACirculation. 2003;107:1336–1339On July 31, 2002, the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) published the International Position Paper on Women's Health and Menopause: A Comprehensive Approach.1 This landmark report was developed over a period of 4 years by an international, interdisciplinary team of experts in collaboration with the NHLBI, the Giovanni Lorenzini Medical Science Foundation, and the NIH Office of Research on Women's Health (ORWH).The Need for a New, Comprehensive, Integrated ApproachThere is need for a new, comprehensive approach to women's health and menopause. Scientific evidence worldwide supports this redirection in the management of women's health during and after the menopause transition. This perspective highlights some of the findings and conclusions in the executive summary. Comment is added regarding pivotal studies published subsequent to the completion of the International Position Paper.Expanding Field of Women's Health and Menopause, Nationally and GloballyWomen's health and menopause is a rapidly expanding field of medical practice and scientific investigation. It has great social importance and economic impact nationally and globally, in both developed and developing countries. The International Position Paper is a joint effort to begin to address these challenges at the global level.Purpose and Goal of the International Position PaperThis multidisciplinary monograph is designed to enhance the composite health of menopausal women on a global basis, with consideration of sociocultural concerns and economic issues. Importantly, a goal of this monograph is that the materials be reproduced and translated in individual countries for optimal global dissemination, which will be furthered by presentations at topic-related scientific meetings.Development of the International Position PaperThis monograph represents the culmination of 7 years of cooperation between the NHLBI and the Giovanni Lorenzini Medical Science Foundation in a public/private partnership in the development and cosponsorship of 4 international conferences on Women's Health and Menopause since the mid-1990s. These conferences have addressed not only cardiovascular disease, but other health issues such as cancer, osteoporosis, mental health, Alzheimer's disease, aging, neurological aspects, sexuality, and the use and impact of hormone replacement therapy (HRT) worldwide.Twenty-eight authors and 46 reviewers from 14 countries contributed to this critical review and rating of the scientific evidence, which was coordinated by the NHLBI through a series of meetings on the NIH campus as well as electronic exchanges of information and data. The interdisciplinary team included experts from Australia, Belgium, Chile, Denmark, Finland, France, Italy, Korea, Japan, Netherlands, Sweden, Switzerland, the United Kingdom, and the United States.Scope of the International Position PaperThe authors have developed a valuable resource for use by policy makers, physicians, and scientists in making informed decisions regarding prevention and control strategies at national and community levels, as well as for individual women seeking advice about treatment options and information regarding the risks and benefits of different strategies for menopausal health. Individual chapters, as well as the document as a whole, were reviewed by internationally acknowledged leaders in their fields.The chapters address the definition of menopause, as well as the benefits and risks of HRT and related therapies to control menopausal symptoms. Other topics include sociocultural issues, cardiovascular and pulmonary disease and their relation to menopause and its treatments, and the relationship of menopause and aging. Osteoporosis, menopausal therapies and cancer, mental health, Alzheimer's disease and other neurological disorders, sexuality, and gynecological and urinary aspects are also discussed. The document presents new information on estrogen receptors and the pharmacological modulation of estrogen receptor activity. The final chapter on "Best Clinical Practices: A Comprehensive Approach" addresses the menopause transition, fractures, cardiovascular disease, cancers (breast, cervix, colorectal, endometrial, ovary, and lung), dementia, and mental health.Rating of the Scientific Evidence for Benefits and Risks of Various TherapiesThe International Position Paper provides a benchmark of current clinical practice. It emphasizes a comprehensive approach to women's health that is based on critical evaluation and rating of the current scientific evidence for these practices. The international experts rated the scientific evidence according to 4 evidence categories: (1) randomized, controlled trials (rich body of data); (2) randomized controlled trials (limited body of data); (3) nonrandomized trials and/or observational studies; and (4) expert judgment based on the authors' synthesis of evidence from research described in the literature that does not meet the above-listed criteria.New Advances in Basic ResearchNatural estrogens modulate cell activities by bindings to 2 known estrogen receptors (ER): ERα3 and ERβ.4 The International Position Paper reviews recent findings in estrogen receptor physiological roles, obtained through use of knock-out animal models, ERKO, βERKO, and DERKO mice, in which the expression of ERα, ERβ, or both has been abolished, respectively.5Observation of differential actions of estrogens, as dependent on target cell types, has led to the search for new compounds, selective for both estrogen receptor subtype and target organs, the latter being the so-called SERMs (selective estrogen receptor modulators).6 Ideal SERMs act as estrogen agonists in target tissues such as bone and liver, whereas they behave as antagonists in reproductive organs. The volume illustrates the pharmacological profiles of well-known molecules, such as tamoxifen and raloxifene, and of novel SERMs (eg, toremifene, idoxifene, droloxifene) under preclinical or clinical investigation.7Global Scope of Cardiovascular DiseaseCardiovascular disease (CVD) is the major cause of death and disability for women in most of the world. Improved quality of health for women is a global concern. It is projected that worldwide there will be about 2 billion (1970 million) people >65 years of age in 2050, compared with 580 million in 1980, and the majority of these will be women. As a result, there is a growing need to address the health issues for these 1 billion women. The quality of life of such women will to a large extent depend on the ability of societies to address the medical, social, and economic challenges of the menopausal years.Definition of MenopauseMenopause is defined as the permanent cessation of menstruation resulting from the loss of ovarian follicular activity. In discussing the issues and health problems associated with the menopause transition, the international experts emphasize that menopause is a normal event in a woman's life, not a disease. Some women view it as a positive and liberating experience. Others think of it as a negative event. Menopause offers the primary care health provider an opportunity to assess a woman's health, her concerns, and her needs for health promotion and disease prevention measures.Challenges of Menopausal and Postmenopausal YearsIn the developed world, the percentage of women over 50 years of age has tripled in the last 100 years. During this period, the mean life expectancy of women in the United States has increased from 50 to 81.7 years, indicating that menopause will occur at a time when women have yet to experience more than one-third of their total life span. An estimated 40 million US women will experience menopause during the next 20 years.Hormone Replacement TherapyDifferent forms and regimens of HRT have been in use in the United States since the 1940s. Currently, from 20% to 45% of US women between the ages of 50 and 75 take some form of HRT. According to pharmaceutical industry estimates, about 8 million US women use estrogen alone and about 6 million US women use estrogen-progestin therapy. Approximately 20% of women who use HRT do so for more than 5 years.Past predominantly observational studies reviewed in the International Position Paper suggested that postmenopausal HRT might prevent or reduce certain long-term effects of aging, heart disease, and osteoporosis, in addition to alleviating symptoms of menopause. Because menopause and current treatment options affect so many medical conditions such as CVD, osteoporosis, breast cancer, uterine cancer, colorectal cancer, and blood clots, the international expert panel advised a comprehensive approach to the patient's individual clinical and risk factor profile and advocated against basing therapeutic approaches on the potential risk of 1 condition, such as osteoporosis, CVD, or cancer.Cardiovascular Disease in WomenThe International Position Paper highlights the major problem of CVD in women, identifies the importance of lifestyle changes, and recommends a comprehensive and integrated approach to health promotion and disease prevention. CVD afflicts more women than any other disease, and there is a steep increase in the incidence of CVD with age. CVD is a more common cause of death and disability for women in most of the world than osteoporosis and cancer combined.Cardiovascular disease risks and prevention and treatment strategies are discussed in chapters 1, 8, and 13 of the International Position Paper, providing in-depth evaluation and discussion of coronary heart disease (CHD), stroke, peripheral vascular disease, and the role of HRT in venous thromboembolism. The scientists conclude that major modifiable risk factors for CHD are similar in women and men and include dyslipidemia, hypertension, diabetes mellitus, cigarette smoking, lack of physical activity, and obesity. There is no definitive evidence-based rationale to recommend HRT for the prevention of CHD. Also, there are insufficient data to make recommendations regarding the use of soy phytoestrogens or SERMs for the prevention of CHD. Women are more likely than men to die of stroke, although both sexes have similar stroke rates.Future DirectionsOptimal medical management for menopausal women in accordance with scientific evidence is likely to undergo major changes and continuing revisions as policy makers, health professionals, and women themselves continue to assess and critically review new research findings on the benefits and risks of current and emerging therapies. Results from 2 major NIH studies, released in July, 2002, as the International Position Paper went to press, as well as results of a secondary prevention trial, are relevant in this regard, as is a reanalysis of cardiovascular observational data. Whereas prior observational studies of menopausal hormone therapy and meta-analyses of these studies suggested a 35% to 50% reduction in coronary events, particularly among current hormone users, a recent meta-analysis of these observational studies that adjusted for socioeconomic status, education, and major coronary risk factors failed to demonstrate cardiac protection and to support hormone use for the primary prevention of coronary and cardiovascular disease.8The 1998 report of the Heart and Estrogen/progestin Replacement Study (HERS) found no significant difference between the hormone and placebo groups in nonfatal myocardial infarction plus coronary death in women with documented CHD randomized to conjugated equine estrogen plus medroxyprogesterone acetate compared with placebo. Within the null outcome, there was a significant time trend with an excess of coronary events in the hormone group during the first year of treatment and fewer events in years 3 to 5. To ascertain whether this trend would persist with additional follow-up and result in an overall decrease in the risk of coronary events, 93% of the surviving HERS participants were followed for an additional 2.7 years in an observational study (HERS II) and encouraged to remain on their original drug assignment. HERS II results9 identified that this hormone therapy did not reduce the risk of coronary events, even after adjustment for potential confounders; nor were results altered with analysis of women adherent to randomized treatment assignment. In association with the lack of cardiovascular benefit, potential harm included a 2-fold increased risk of venous thromboembolism, predominantly in the initial years, and a nearly 50% increased rate of gallbladder disease that required surgery. Therefore, in older women with established CHD, this estrogen/progestin regimen did not provide cardiovascular benefit and caused significant harm; it should not be used to decrease the risk of cardiovascular events.The Women's Health Initiative (WHI), which enrolled predominantly healthy menopausal women 50 to 79 years of age, randomized approximately 27 000 women in a placebo-controlled hormone trial. They were assigned to conjugated equine estrogen plus medroxyprogesterone acetate versus placebo if they had an intact uterus, or conjugated equine estrogen versus placebo if they had had hysterectomy. In July, 2002, the estrogen/progestin therapy arm of the WHI hormone trial was discontinued prematurely after an average follow-up of 5.2 years because of an increased risk of invasive breast cancer combined with a lack of global risk benefit.10 The parallel estrogen-only arm versus placebo is continuing. In addition to the increased risk for invasive breast cancer with estrogen/progestin therapy, risks included an increased likelihood of coronary events, stroke, and venous thromboembolism, in contrast to decreased risk for colorectal cancer, hip fracture, and total fracture. Although the majority of WHI women had no adverse events, the population risk is substantial, such that the global risk:benefit profile does not warrant recommendation of this therapy as a widespread preventive intervention.The recently completed National Cancer Institute cohort study, the Breast Cancer Detection Demonstration Project (BCDDP), identified 329 cases of ovarian cancer.11 The relative risk for estrogen-only users was 1.6 and increased to 1.8 for 10 to 19 years of use and to 3.2 for >20 years of use. Data were inadequate to evaluate estrogen/progestin therapy. Many questions remain to be clarified, such as the duration versus dose of estrogen therapy, the duration of estrogen/progestin therapy, the impact of switching from one therapy to another, the kinds of estrogen/progestin regimens used, and the method of administration.A scientific review conducted for the US Preventive Services Task Force12 evaluated hormone risks and benefits and found an increased risk of coronary events, stroke, and venous thromboembolism, with the thromboembolic risk highest in the first year; an increased risk of breast cancer that increased with duration of use; an increased risk of endometrial cancer and cholecystitis; protection against osteoporotic fracture; a decreased risk for colon cancer; cognition improvement only in women with menopausal symptoms; and no definitive information from dementia studies. Menopausal hormone therapy was not advised for the prevention of chronic conditions.In summary, the recently published data emphasize the complexity of weighing the risks and benefits of different kinds of HRT and other treatment options. They advise women to consult with their healthcare providers on an individual basis regarding their specific clinical and risk/benefit profiles and to discuss whether to use HRT or other therapies.The International Position Paper on Women's Health and Menopause should serve as a resource to enhance and strengthen interest in further research on women's health and lead to the adoption of integrated and improved strategies for health promotion and disease prevention for women nationally and internationally.The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.The development and publication of the International Position Paper on Women's Health and Menopause: A Comprehensive Approach were supported by the National Heart, Lung, and Blood Institute, the National Institutes of Health, and the Giovanni Lorenzini Medical Science Foundation in Milan, Italy, and Houston, Texas.FootnotesCorrespondence to Rodolfo Paoletti, MD, President, Giovanni Lorenzini Foundation, Via Appiani 7, 20121 Milan, Italy. E-mail [email protected] or [email protected] References 1 National Heart, Lung, and Blood Institute, NIH Office of Research on Women's Health, and Giovanni Lorenzini Medical Science Foundation. International Position Paper on Women's Health and Menopause: A Comprehensive Approach. Bethesda, Md: National Heart, Lung, and Blood Institute; 2002. NIH Publication No. 02–3284. Available at: http://www.nhlbi.nih.gov/health/prof/heart/other/wm_menop.htm. Accessed January 23, 2003.Google Scholar2 Deleted in proof.Google Scholar3 Greene GL, Gilna P, Waterfield M, et al. Sequence and expression of human estrogen receptor complementary DNA. Science. 1986; 231: 1150–1154.CrossrefMedlineGoogle Scholar4 Kuiper GG, Enmark E, Pelto-Huikko M, et al. Cloning of a novel estrogen receptor expressed in rat prostate and ovary. Proc Natl Acad Sci U S A. 1996; 93: 5925–5930.CrossrefMedlineGoogle Scholar5 Couse JF, Korach KS. Estrogen receptor null mice: what have we learned and where will they lead us? Endocr Rev. 1999; 20: 358–417.CrossrefMedlineGoogle Scholar6 Dhingra K. Antiestrogens: tamoxifen, SERMs, and beyond. Invest New Drugs. 1999; 17: 285–311.CrossrefMedlineGoogle Scholar7 Howell A. Future use of selective estrogen receptor modulators and aromatase inhibitors. Clin Cancer Res. 2001; 7: 4402s–4410s.MedlineGoogle Scholar8 Humphrey LL, Chan BK, Sox HC. Postmenopausal hormone replacement therapy and the primary prevention of cardiovascular disease. Ann Intern Med. 2002; 137: 273–284.CrossrefMedlineGoogle Scholar9 Grady D, Herrington D, Bittner V, et al. Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA. 2002; 288: 49–57.CrossrefMedlineGoogle Scholar10 Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women. JAMA. 2002; 288: 321–333.CrossrefMedlineGoogle Scholar11 Lacey JW Jr, Mink PJ, Lubin JH, et al. Menopausal hormone replacement therapy and risk of ovarian cancer. JAMA. 2002; 288: 334–341.CrossrefMedlineGoogle Scholar12 Nelson HD, Humphrey LL, Nygren P, et al. Postmenopausal hormone replacement therapy: scientific review. JAMA. 2002; 288: 872–881.CrossrefMedlineGoogle Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetailsCited By Aldana Calva E and Cervantes Álvarez G (2021) Disfunciones y trastornos sexuales en mujeres en climaterio: pacientes del Instituto Nacional de Perinatología, Revista Colombiana de Ciencias Sociales, 10.21501/22161201.3534, 12:2, (563) Jelveh Moghaddam H, Avazeh A, Saifi S, Khoshfetrat M, Sedaghat A, Shahrami R, Hatamian S, Amirsavadkouhi A, Ghahremani M, Mohammadmasoud Moosavinasab S, Khabirikhatiri M, Forooghirad H, Baghernezhad F, Safaeepoor L and Rahimibashar F (2015) An Epidemiological Study of Cardiovascular Risk Factors in Patients with Myocardial Infarction: A Prospective Study, Archives of Critical Care Medicine, 10.17795/accm-8538, 1:4 Cortés-Bonilla M, Bernardo-Escudero R, Alonso-Campero R, Francisco-Doce M, Hernández-Valencia M, Celis-González C, Márquez-Oñate R, Chedraui P and Uribe J (2015) Treatment of menopausal symptoms with three low-dose continuous sequential 17 β -estradiol/progesterone parenteral monthly formulations using novel non-polymeric microsphere technology , Gynecological Endocrinology, 10.3109/09513590.2015.1019853, 31:7, (552-559), Online publication date: 3-Jul-2015. 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