Cynthia A. Stuenkel

Estrogen and progestogen use in postmenopausal women: July 2008 position statement of The North American Menopause Society

Objective:To update for both clinicians and the lay public the evidence-based position statement published by The North American Menopause Society (NAMS) in March 2007 regarding its recommendations for menopausal hormone therapy (HT) for postmenopausal women, with consideration for the therapeutic benefit-risk ratio at various times through menopause and beyond. Design:An Advisory Panel of clinicians and researchers expert in the field of womens health was enlisted to review the March 2007 NAMS position statement, evaluate new evidence through an evidence-based analysis, and reach consensus on recommendations. The Panels recommendations were reviewed and approved by the NAMS Board of Trustees as an official NAMS position statement. The document was provided to other interested organizations to seek their endorsement. Results:Current evidence supports a consensus regarding the role of HT in postmenopausal women, when potential therapeutic benefits and risks around the time of menopause are considered. This paper lists all these areas along with explanatory comments. Conclusions that vary from the 2007 position statement are highlighted. Addenda include a discussion of risk concepts, a new component not included in the 2007 paper, and a recommended list of areas for future HT research. A suggested reading list of key references is also provided. Conclusions:Recent data support the initiation of HT around the time of menopause to treat menopause-related symptoms; to treat or reduce the risk of certain disorders, such as osteoporosis or fractures in select postmenopausal women; or both. The benefit-risk ratio for menopausal HT is favorable close to menopause but decreases with aging and with time since menopause in previously untreated women.

Menopausal symptoms in older women and the effects of treatment with hormone therapy.

OBJECTIVE In some women, hot flashes and other symptoms attributed to menopause persist for many years after the cessation of menses. The frequency and severity of such symptoms and response to hormone therapy in older women have not been well documented. METHODS We used data from the Heart and Estrogen/Progestin Replacement Study, a blinded, clinical trial among 2763 women with documented coronary disease and a uterus who were randomized to receive either conjugated estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg in one tablet or placebo. Participants were queried at baseline and annually regarding menopausal symptoms. Breast symptoms were self‐reported, and uterine bleeding was recorded on a daily diary. RESULTS Symptoms associated with menopause were relatively common among Heart and Estrogen/Progestin Replacement Study participants, whose average age was 67 years and who averaged 18 years since menopause. At baseline, 16% of women reported frequent hot flashes, 26% vaginal dryness, 10% genital irritation, 55% trouble sleeping, and 53% early awakening. Women assigned to hormone therapy reported less frequent hot flashes, vaginal dryness, and trouble sleeping compared with women assigned to placebo, but more frequent vaginal discharge, genital irritation, uterine bleeding, and breast symptoms. The reporting of breast symptoms among women in the hormone group decreased from 40% at 1 year to 13% by the 4th year. Uterine bleeding was reported by 31% and spotting by an additional 33% of women in the hormone group during the 1st year of treatment; by the 4th year, these proportions had fallen to 11% and 20%, respectively. CONCLUSION Symptoms typically attributed to menopause are common in elderly women. Postmenopausal hormone therapy reduces hot flashes, trouble sleeping, and vaginal dryness, but at standard doses in elderly women is associated with vaginal discharge, genital irritation, uterine bleeding, and breast symptoms.

Treatment of Symptoms of the Menopause: An Endocrine Society Clinical Practice Guideline

OBJECTIVE The objective of this document is to generate a practice guideline for the management and treatment of symptoms of the menopause. PARTICIPANTS The Treatment of Symptoms of the Menopause Task Force included six experts, a methodologist, and a medical writer, all appointed by The Endocrine Society. EVIDENCE The Task Force developed this evidenced-based guideline using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and the quality of evidence. The Task Force commissioned three systematic reviews of published data and considered several other existing meta-analyses and trials. CONSENSUS PROCESS Multiple e-mail communications, conference calls, and one face-to-face meeting determined consensus. Committees of The Endocrine Society, representatives from endorsing societies, and members of The Endocrine Society reviewed and commented on the drafts of the guidelines. The Australasian Menopause Society, the British Menopause Society, European Menopause and Andropause Society, the European Society of Endocrinology, and the International Menopause Society (co-sponsors of the guideline) reviewed and commented on the draft. CONCLUSIONS Menopausal hormone therapy (MHT) is the most effective treatment for vasomotor symptoms and other symptoms of the climacteric. Benefits may exceed risks for the majority of symptomatic postmenopausal women who are under age 60 or under 10 years since the onset of menopause. Health care professionals should individualize therapy based on clinical factors and patient preference. They should screen women before initiating MHT for cardiovascular and breast cancer risk and recommend the most appropriate therapy depending on risk/benefit considerations. Current evidence does not justify the use of MHT to prevent coronary heart disease, breast cancer, or dementia. Other options are available for those with vasomotor symptoms who prefer not to use MHT or who have contraindications because these patients should not use MHT. Low-dose vaginal estrogen and ospemifene provide effective therapy for the genitourinary syndrome of menopause, and vaginal moisturizers and lubricants are available for those not choosing hormonal therapy. All postmenopausal women should embrace appropriate lifestyle measures.

Influence of menopause on diabetes and diabetes risk

Many postmenopausal women live with diabetes mellitus; however, little information is available about how the changes that occur around the time of menopause might uniquely affect management of diabetes mellitus in this population. Although the weight gain that commonly occurs during the menopausal transition is largely attributable to aging rather than the transition itself, changes in body composition have been independently associated with menopausal status. These changes in body composition have, in turn, been associated with alterations in insulin sensitivity and glucose metabolism in postmenopausal women. Hormone therapy seems to have neutral or beneficial effects on the adverse changes in body composition associated with menopause. Whether menopausal status independently influences diabetes risk remains controversial. Nevertheless, consistent findings from large clinical trials suggest that postmenopausal hormone therapy decreases the risk of developing diabetes mellitus. Similarly, many studies suggest that postmenopausal hormone therapy has neutral or beneficial effects on glycemic control among women already diagnosed as having diabetes mellitus. Future studies are needed to elucidate the mechanisms that underlie these relationships and to determine how these observations should influence recommendations for the care of postmenopausal women with diabetes mellitus.

The North American Menopause Society recommendations for clinical care of midlife women

In celebration of the 25th anniversary of The North American Menopause Society (NAMS), the Society has compiled a set of key points and clinical recommendations for the care of midlife women. NAMS has always been a premier source of information about menopause for both healthcare providers and midli

Sexual activity and function in postmenopausal women with heart disease.

Objective: To examine the prevalence and correlates of sexual activity and function in postmenopausal women with heart disease. Methods: We included baseline self-reported measures of sexual activity and the sexual problem scale from the Medical Outcomes Study in the Heart and Estrogen/Progestin Replacement Study (HERS), a study of 2,763 postmenopausal women, average age 67 years, with coronary disease and intact uteri. We used multivariable linear and logistic regression to identify independent correlates of sexual activity and dysfunction. Results: Approximately 39% of the women in HERS were sexually active, and 65% of these reported at least 1 of 5 sexual problems (lack of interest, inability to relax, difficulty in arousal or in orgasm, and discomfort with sex). In multivariable analysis, factors independently associated with being sexually active included younger age, fewer years since menopause, being married, better self-reported health, higher parity, moderate alcohol use, not smoking, lack of chest discomfort, and not being depressed. Among the 1,091 women who were sexually active, lower sexual problem scores were associated with being unmarried, being better educated, having better self-reported health, and having higher body mass index. Conclusion: Many women with heart disease continue to engage in sexual activity into their 70s, and two thirds of these report discomfort and other sexual function problems. Physicians should be aware that postmenopausal patients are sexually active and address the problems these women experience. Level of Evidence: II-2

Why the product labeling for low-dose vaginal estrogen should be changed

This commentary summarizes the activities of several clinicians and researchers to encourage modifications to the labeling of low-dose vaginal estrogen. Motivated by concerns of practicing clinicians that the boxed warning on the labels and package inserts for these products overstate potential risk

Algorithm and mobile app for menopausal symptom management and hormonal/non-hormonal therapy decision making: a clinical decision-support tool from The North American Menopause Society.

OVERVIEW The Menopause Decision-Support Algorithm (Fig. 1) and companion MenoPro iPhone/iPad app, developed in collaboration with The North American Menopause Society (NAMS), are designed to help clinicians decide which patients are candidates for pharmacologic treatment of menopausal symptoms, understand what the treatment options are, and gain experience deciding among the options. Menopausal symptoms vary dramatically among women. Some women are good candidates for hormonal treatments and others, due to their personal preferences or risk factor profiles, are not appropriate candidates and should consider non-hormonal options. One of the most complex health care decisions facing women in mid-life is whether to use prescription medications for menopausal symptom management, and the array of pharmacologic options has expanded markedly in recent years. The new MenoPro app, which can be downloaded free of charge on a mobile phone or tablet device, helps clinicians and patients work together to Bpersonalize[ treatment decisions, based on risk stratification and the patient_s personal preferences. The mobile app has two modes, one for clinicians and a companion mode for patients, to facilitate shared decision making and patient-centered care. The algorithm and MenoPro mobile app address options for Bmoderate to severe[ hot flashes and/or night sweats (defined as bothersome enough to interfere with daily activities, impair quality of life, and/or interrupt sleep), as well as genitourinary symptoms (including vaginal dryness or pain with intercourse or other sexual activities). Convenient links provide information about treatment options, formulations and doses, and contraindications to therapy. The app calculates an atherosclerotic cardiovascular disease (CVD) risk score for each patient, which is relevant to the decision regarding initiation of systemic menopausal hormone therapy (HT). Women at high risk of, or with significant concern about, breast cancer should be informed about availability of non hormonal therapies. Once the clinician becomes familiar with the algorithm, personalized decision-making for most patients will require only 2-3 minutes, and the app provides a summary at the end that can be printed out or directly emailed to the patient. The tool can be used for women with menopausal symptoms who are ages Q45 years old. The algorithm can also be used for women who have had removal of both ovaries, regardless of age. Women below age 45 or those who are not clearly menopausal, as well as women who have had endometrial ablation, progestinreleasing intrauterine device/system, or hysterectomy without removal of ovaries, may need additional clinical evaluation before applying this algorithm (evaluation may include hCG, FSH, TSH, prolactin, and other tests). The algorithm encourages all patients to try lifestyle modifications for at least 3 months before beginning HT or other pharmacologic therapies. For information on lifestyle modifications, cognitive behavioral therapy, and/or alternative remedies, clinicians may want to print out the materials for the patient at the below link (or send the link by email via the app): http://www.menopause.org/docs/for-women/ mnflashes.pdf. Women at high risk of osteoporotic fracture and unable to tolerate standard preventive medications may also be candidates for HT (NAMS Hormone Therapy Position Statement: http://www.menopause.org/docs/default-document-library/ psht12.pdf ?sfvrsn=2). The algorithm also addresses considerations relevant to decisions about duration of treatment, including balancing risks of breast cancer, cardiovascular disease, and osteoporosis. Each step of the algorithm should be reassessed at least once every 12 months or if health status changes.

A decade after the Women's Health Initiative—the experts do agree

Cynthia A. Stuenkel, M.D., N.C.M.P., Margery L. S. Gass, M.D., N.C.M.P., JoAnn E. Manson, M.D., Dr.PH., N.C.M.P., Rogerio A. Lobo, M.D., Lubna Pal, M.B.B.S., M.R.C.O.G., M.Sc., N.C.M.P., Robert W. Rebar, M.D., and Janet E. Hall, M.D. a Clinical Professor of Medicine, Endocrinology and Metabolism, University of California, San Diego, California; b Executive Director, The North American Menopause Society, Consultant, Cleveland Clinic Center for Specialized Womens Health, Clinical Professor, Department of Reproductive Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio; c Professor of Medicine and the Michael and Lee Bell Professor of Womens Health, Harvard Medical School, Chief of Preventive Medicine, Co-Director, Connors Center for Womens Health and Gender Biology, Brigham and Womens Hospital, Boston, Massachusetts; d Professor, Department of Obstetrics and Gynecology, Columbia University, New York, New York; e Associate Professor, Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, Director, Program for Polycystic Ovarian Syndrome, Director, Program for Reproductive Aging and Bone Health, New Haven, Connecticut; f Executive Director, American Society for Reproductive Medicine, Birmingham, Alabama; and g Professor, Department of Medicine, Harvard Medical School, Boston, Massachusetts

Raloxifene use in clinical practice: efficacy and safety.

Objective and Methods: In this article, we provide an interdisciplinary concise review of the effects of raloxifene on breast, bone, and reproductive organs, as well as the adverse events that may be associated with its use. Results: Raloxifene has been shown to prevent osteoporosis in postmenopausal women (PMW) with low bone mass and prevent vertebral fractures in those with osteoporosis/low bone mass; it has not been shown to reduce the risk of nonvertebral fractures. Raloxifene reduces the risk of invasive breast cancer in PMW with osteoporosis or at high risk of breast cancer. The risk of venous thromboembolism has been consistently shown to be increased with raloxifene, so it should not be used in women at high risk of venous thromboembolism. Although raloxifene does not increase, nor decrease, the risk of coronary or stroke events overall, in the raloxifene trial of PMW at increased risk of coronary events, the incidence of fatal stroke was higher in women assigned raloxifene versus placebo. Conclusions: Based on its approved indications, it is appropriate to prescribe raloxifene to prevent or treat osteoporosis, as well as to reduce the risk of invasive breast cancer in PMW with osteoporosis or at high risk of breast cancer. Women at increased risk of both fracture and invasive breast cancer are those most likely to receive a dual benefit with raloxifene. Decision making must involve the incorporation of the womans personal feelings about the risks and benefits of raloxifene therapy, balanced with her interest in reducing risk of fractures and breast cancer through pharmacological intervention.