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IMS Menopause Live

Commentaries from the IMS on recently published scientific papers that may be of interest. The latest articles from September 2018 onward are available to Members only when logged in. Selected articles are open to public.

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Smell identification, cognition and hormone therapy

14 November, 2016

Failure to identify odors may be an early sign of cognitive impairment. A recent study included persons aged 65 years or older without dementia (males and females, n = 1037) [1]. They were asked to identify 40 different odors, and their success rate was scored. Also, a brain MRI and a battery of cognitive tests were performed. Follow-up at 2 and 4 years in 757 participants showed that low baseline scores correlated with cognitive decline and the appearance of Alzheimer's disease. MRI hippocampal volume did not show predictive utility in this cohort. The investigators suggested that the inexpensive smell test could be useful as a predictor of future cognitive impairment.


The above study by Devanand and colleagues is one of several similar ones showing that low performance in smell testing correlated with a higher risk of cognitive impairment [1]. In a recent study among 1430 cognitively normal participants (mean age 79.5 ± 5.3 years, 49.4% men, mean 3.5 years of follow-up), there were 250 incident cases of minimal cognitive impairment (MCI). An association between decreasing olfactory identification, as measured by a decrease in the number of correct responses in Brief Smell Identification Test score, and an increased risk of MCI was established [2]. The same was demonstrated in patients with Parkinson's disease: worse baseline olfaction was associated with long-term cognitive decline [3]. Interestingly, even a simple test, using a container of 14 g of peanut butter, which was opened and moved up 1 cm at a time during the participant's exhale-until-odor detection, while measuring the distance between the subject's nostril and container, appeared to be a sensitive and specific test for probable Alzheimer's disease [4]. A nice overview on the influence of age on the olfactory system and pathways mentioned that the magnitude of olfactory deficits, which occur in neurodegenerative and neurodevelopmental diseases, appears to be associated with the relative damage to the basal cholinergic system [5]. Perhaps the link between cognition and olfactory function involves the apolipoprotein E É›4 allele (ApoE) that has been associated with increased cognitive and olfactory deficits [6].

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Fish and omega-3: no cardiovascular benefit?

24 October, 2016

The benefits of the Mediterranean diet in regard to cardiovascular health and metabolic risk factors in postmenopausal women are well recognized [1, 2]. Seafood is considered as one of the major components of the Mediterranean diet. So could one make a clear link between a regular consumption of fish and cardiovascular benefits? Most of us would say 'yes, certainly', but a recent publication challenges this common perception. The newest data come from a prospective cohort study of US women participating in the Women's Health Initiative from 1993 to 2014 [3]. A total of 39,876 women who were aged ≥ 45 years and free of cardiovascular disease at baseline provided dietary data on food frequency questionnaires. Analyses used Cox proportional hazards models to evaluate the association between fish and energy-adjusted omega-3 polyunsaturated fatty acid intake and the risk of major cardiovascular disease, defined as a composite outcome of myocardial infarction, stroke, and cardiovascular death. The final analytic sample included 38,392 women (mean age 55 years). During 713,559 person-years of follow-up, 1941 cases of incident major cardiovascular disease were confirmed. Tuna and dark fish (mackerel, salmon, sardines, bluefish, and swordfish) intake was not associated with the risk of incident major cardiovascular disease (p-trend > 0.05). Neither α-linolenic acid nor marine omega-3 fatty acid intake was associated with major cardiovascular disease or with individual cardiovascular outcomes (all p-trend > 0.05). There was no effect modification by age, body mass index, or baseline history of hypertension.

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New guidelines for risk assessment, diagnosis and treatment of postmenopausal osteoporosis

17 October, 2016

The American Association of Clinical Endocrinologists and the American College of Endocrinology recently updated their guidelines for the diagnosis and treatment of postmenopausal osteoporosis [1]. These guidelines are presented in a very methodological way, with answers to common core questions. While the full text can be seen in the link below, I decided to pick only the recommendations which seem the most important or bring some new insights. Each statement is graded (in brackets). The article includes a clear and simple treatment algorithm as well.

How is fracture risk assessed and osteoporosis diagnosed?

Evaluate all postmenopausal women aged ≥ 50 years for osteoporosis risk (Grade B; downgraded due to gaps in evidence).

Osteoporosis should be diagnosed based on the presence of fragility fractures in the absence of other metabolic bone disorders (Grade B) or a T-score of −2.5 or lower in the lumbar spine, femoral neck, total hip, and/or one-third radius even in the absence of a prevalent fracture (Grade B).

Osteoporosis may also be diagnosed in patients with osteopenia and increased fracture risk using FRAX® country-specific thresholds (Grade B).

What are the fundamental measures for bone health?

Maintain serum 25-hydroxyvitamin D (25(OH)D) ≥ 30 ng/ml in patients with osteoporosis (preferable range, 30–50 ng/ml) (Grade B, upgraded based on expert consensus).

Supplement with vitamin D3 if needed; 1000–2000 IU of daily maintenance therapy is typically needed to maintain an optimal serum 25(OH)D level (Grade C, upgraded based on expert consensus).

Counsel patients to maintain adequate dietary intake of calcium, to a total intake (including diet plus supplement, if needed) of 1200 mg/day for women ≥ 50 years (Grade B).

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When and how to propose chemical prevention to women at risk for breast cancer?

26 September, 2016

The management of women at high risk for breast cancer has evolved during the past years. This management includes the identification of these women and potentially offers them a preventive strategy. Chemical prevention by selective estrogen receptors modulators (SERMs) and aromatase inhibitors (AI) has been shown to decrease the risk of primary breast cancer, precancerous lesions, bilateral breast cancer and recurrence. Despite recommendations to use these treatments for prevention in some countries, a very low number of women use them. The main reason is fear of side-effects. The only alternative so far is surgical mastectomy.

A debate was organized at the Beth Israel Deaconess Medical Center to discuss the administration of these preventive medications and how to overcome women’s resistances [1]. A clinical case of Mrs Z, a premenopausal 51-year-old woman with a strong family history of breast cancer (mother at the age of 57, a sister at the age of 40, a maternal aunt at the age of 47 and a maternal grandmother who died of an unknown cancer at the age of 37) and no BRCA1/2 mutation, was the basis for the discussion. Three questions were addressed to two experts, Dr N. M. Tung (Associate Professor, Medicine, Harvard Medical School Director, Cancer Risk and Prevention Program) and Dr M. A. Schonberg (Assistant Professor, Medicine, Harvard Medical School, Instructor in Medicine, General Medicine and Primary Care). They recall that, 'In the US, 15% of women aged 35–76 years have more than a 1.7% chance of developing breast cancer in the 5 years and only 0.03% of these women report using tamoxifen and 0.21% of 50–79-year-olds report using raloxifene.'

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Migraine and cardiovascular risk in the menopause

8 August, 2016

Long ago it was perceived that migraineurs have a higher risk for ischemic stroke, mainly because of short-term pro-thrombotic alterations during attacks [1, 2]. Migraine with aura confers a lifelong 2–2.5-fold elevated risk of stroke. Frequency of migraine directly correlates with higher stroke risk, but only minimal evidence supports reducing migraine frequency with medications to reduce stroke risk. Women suffering from migraine with aura who smoke have a 9-fold increased risk of stroke. There are several potential mechanisms for the increased risk of ischemic stroke in migraineurs. Migraine may increase ischemic stroke risk via vasospasm-induced cerebrovascular hypoperfusion, platelet activation, increased platelet aggregation, and increased concentrations and activity of various vascular pro-coagulant factors. Still, the absolute risk of migraine-associated stroke in women is relatively low.

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Sorry folks, we were wrong at the time

18 April 2016

Despite the availability of effective hormonal and non-hormonal treatments for menopausal symptoms, few women with these symptoms are evaluated or treated  

Whoever can download from The New England Journal of Medicine and read the paper by Manson and Kunitz entitled 'Menopause management: getting clinical care back on track', or from the relevant commentary in Medscape must do so at their earliest convenience [1,2]. As a reminder, the authors were among the WHI study investigators, and Manson was also a Steering Committee member. Needless to detail again the consequences of the misinterpretation of the initial WHI study results, which reduced the use of postmenopausal hormone therapy (HT) by 80% or even more, just because of misunderstanding of its safety profile in recently menopausal women. Many later studies discussed the adverse outcomes of banning HT, mainly related to quality of life issues and bone health. The best would be just to bring some quotes from the article (in italics).

Despite the availability of effective hormonal and non-hormonal treatments for menopausal symptoms, few women with these symptoms are evaluated or treated. Leading medical societies devoted to the care of menopausal women agree that systemic hormone therapy is the most effective treatment currently available for these symptoms and should be recommended for women with moderate-to-severe vasomotor symptoms, in the absence of contraindications. Such criteria apply to approximately 20% of women in early menopause, most of whom remain untreated despite having symptoms that adversely affect their daily activities, sleep, and quality of life. Women's decisions regarding such therapy are now surrounded by anxiety and confusion. The WHI trial was designed to address the risks and benefits of long-term use of hormone therapy for the prevention of chronic disease in postmenopausal women who were on average 63 years of age at initiation of therapy. But the results are now being used inappropriately in making decisions about treatment for women in their 40s and 50s who have distressing vasomotor symptoms. The new generation of medical graduates and primary-care providers often lacks training and core competencies in management of menopausal symptoms and prescribing of hormonal treatments. Most primary-care residency programs in the United States don't provide adequate education in women's health in general or in menopause management in particular. Reluctance to treat menopausal symptoms has derailed and fragmented the clinical care of midlife women, creating a large and unnecessary burden of suffering.

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Does menopause start earlier in smokers?

21 March, 2016: 

Paula and colleagues in 2013 conducted a cross-sectional study to investigate the association between smoking and early onset of menopause [1]. The study included 1222 female employees on the campuses of Rio de Janeiro university. All participants were aged over 35 years. Smoking status was determined by questioning whether the participant had smoked at least 100 cigarettes during her lifetime, and whether she currently smoked. Women were classified as current smokers, former smokers or women who had never smoked. The researchers used a Cox proportional hazards model to investigate the data and the correlations between smoking status and age at the onset of menopause.

Among current smokers, there was an increase of 56% (hazard ratio 1.56; 95% confidence interval 1.06-2.31) in the risk of menopause, when compared with those who had never smoked (p = 0.02), while former smoking was not associated with the outcome. The results obtained from the study revealed that women who smoke are 1.8 years younger at the onset of menopause when compared to non-smoking women. There was no significant difference between the survival curves for former smokers and women who had never smoked, adding a very interesting conclusion: once a woman gives up smoking, her age at onset of menopause may be roughly equivalent to that of women who have never smoked. The results obtained from the study emphasize the importance of efforts to control cigarette smoking.

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Does quitting smoking decrease the risk of midlife hot flushes?

14 March, 2016: 

The effect of quitting smoking on hot flushes in women aged 45–54 years of age at baseline followed for 1–7 years was examined by Smith and his colleagues [1] in a longitudinal analysis published recently. A cohort study of hot flushes among women 45–54 years of age was conducted starting in 2006 among residents of Baltimore and its surrounding counties. Menopausal status was defined as follows: premenopausal women were those who experienced their last menstrual period within the past 3 months and reported 11 or more periods within the past year; perimenopausal women were those who experienced (1) their last menstrual period within the past year, but not within the past 3 months, or (2) their last menstrual period within the past 3 months and experienced 10 or fewer periods within the past year; postmenopausal women were those women who had not experienced a menstrual period within the past year. Participants were asked to complete a brief questionnaire during a clinic visit 3 weeks after the baseline visit, then annually after that. This questionnaire repeated all previous questions about hot flushes and smoking. Interestingly, they concluded that women who quit smoking were less likely to suffer from hot flushes, less likely to have severe hot flushes, and less likely to have frequent hot flushes than women who continued to smoke, but were more likely to suffer from any hot flushes, more severe hot flushes, and more frequent hot flushes than women who never smoked.

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Dietary guidelines for Americans 2015–2020

22 February, 2016

USA dietary guidelines

The new dietary guidelines for Americans were recently published by the US Department of Agriculture and the Department of Health and Human Services. These guidelines are updated once in 5 years, and thus the current version is for 2015–2020. The basic rationale and general principles are phrased as follows: healthy eating patterns support a healthy body weight and can help prevent and reduce the risk of chronic disease throughout periods of growth, development, and aging as well as during pregnancy. All foods consumed as part of a healthy eating pattern fit together like a puzzle to meet nutritional needs without exceeding limits, such as those for saturated fats, added sugars, sodium, and total calories. All forms of foods, including fresh, canned, dried, and frozen, can be included in healthy eating patterns. Individuals should aim to meet their nutrient needs through healthy eating patterns that include nutrient-dense foods. Foods in nutrient-dense forms contain essential vitamins and minerals and also dietary fiber and other naturally occurring substances that may have positive health effects. In some cases, fortified foods and dietary supplements may be useful in providing one or more nutrients that otherwise may be consumed in less than recommended amounts.

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The benefits and harms of alcohol consumption in women: cardiovascular aspects

8 February, 2016

Alcohol consumption has been associated with both benefits and harms, but most studies investigated men rather than women, or analyzed data from mixed cohorts composed of males and females, with necessary adjustments for age and sex. Also, most studies focused on one alcohol-related outcome or on a single group of related diseases rather than seeing the entire spectrum of human health. Despite a wealth of information on the outcomes of drinking alcohol, there is still inconsistency on some bottom-line guiding messages related to consumption patterns (quantity, frequency, and stratified combinations), and types of alcohol consumed. Ethnicity, socio-economical features, age and gender may be factors that influence disease protection or risk.

A recent study addressed the outcomes of drinking alcohol in a large cohort which included people from 12 countries in five continents with different socio-economical characteristics [1]. The PURE study included 114,970 adults, of whom 12,904 (11%) were from high-income countries, 24,408 (21%) were from upper-middle-income countries, 48,845 (43%) were from lower-middle-income countries, and 28,813 (25%) were from low-income countries. Mean age was 50 (41–58) years; median follow-up was 4.3 years (IQR 3.0–6.0). In the high- and upper-middle income countries, around 50% of the cohorts were women, but there were only 4% of women in the low-income countries. Overall, 74,685 (65%) participants were never drinkers, 4255 (4%) were former drinkers, and 36,030 (31%) were current drinkers. Of current drinkers, 26,025 (72%) had low intake, 6114 (17%) had moderate intake, and 2931 (8%) had high intake. Associations with mortality (n = 2723), cardiovascular disease (n = 2742), myocardial infarction (n = 979), stroke (n = 817), alcohol-related cancer (n = 764), injury (n = 824), admission to hospital (n = 8786), and for a composite of these outcomes (n = 11 963) were calculated. Data was adjusted for age and sex. Current drinking was associated with reduced myocardial infarction risk (HR 0.76; 95% CI 0.63–0.93), but with increased alcohol-related cancers (HR 1.51; 95% CI 1.22–1.89) and injury (HR 1.29; 95% CI 1.04–1.61). High intake was associated with increased mortality (HR 1.31; 95% CI 1.04–1.66). Compared with never drinkers, significantly reduced hazards for the composite outcome for current drinkers in high-income countries and upper-middle-income countries (HR 0.84; 95% CI 0.77–0.92), but not in lower-middle-income countries and low-income countries, for which there were no reductions in this outcome (HR 1.07; 95% CI 0.95–1.2).

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