IMS Menopause Live

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).

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.'

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.

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.

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.

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.

22 February, 2016: 

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.

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).

18 January, 2016: 

To determine whether there is a risk of cardiovascular death upon withdrawal of hormone therapy (HT), Mikkola and colleagues used the Finnish National Death Registry (including 30% autopsy data) to conduct a nation-wide population study of 332,202 women who discontinued menopausal HT analyzed over 15 years with 2 million years of follow-up [1]. From 1994 to 2009, there were 3177 cardiac deaths and 1952 stroke deaths; mean HT exposure was 6.2 ± 6.0 years and mean follow-up after HT withdrawal was 5.5 ± 3.8 years. Comparing the actual death rates in the background population, the standardized mortality ratio (SMR) within the first year of HT withdrawal was elevated for cardiac and stroke death; SMR = 1.27 (95% CI 1.17–1.37) and SMR = 1.63 (95% CI 1.47–1.79), respectively. When compared to women who continued to use HT, the risk of discontinuing HT was even greater and elevated in women within as well as beyond the first year of withdrawal for both cardiac and stroke death; SMR = 2.30 (95% CI 2.12–2.50) and SMR = 2.52 (95% CI 2.28–2.77), respectively within the first year of HT withdrawal, and SMR = 1.26 (95% CI 1.21–.31) and SMR = 1.25 (95% CI 1.19–1.31), respectively beyond the first year of HT withdrawal. A similar risk pattern was shown when women were stratified by age at HT initiation or discontinuation. In women who discontinued HT at < 60 years, but not in women aged ≥ 60 years, cardiac mortality risk was elevated, SMR = 1.94 (95% CI 1.51–2.48) as was risk of stroke death, SMR = 2.87 (95% CI 2.29–3.55).

Comment

These newest findings by Mikkola and colleagues are the largest and most robust data to date confirming that both cardiac and stroke mortality are potentially increased after discontinuing HT [1]. Although these data were derived from an observational study, rates of fatal cardiac and stroke events were unlikely influenced by biases. The data from Mikkola and colleagues are consistent with studies showing increased health hazards after stopping HT that have substantial mortality such as hip fractures [2].

 desirable levels of vitamin D and supplementation

21 December, 2015: 

In a recent article in JAMA, Hansen and colleagues presented a randomized clinical trial of treatment of vitamin D insufficiency in postmenopausal women [1]. The trial compared the effects of placebo, low-dose cholecalciferol, and high-dose cholecalciferol on 1-year changes in total fractional calcium absorption, bone mineral density (BMD), timed-up-and-go and five sit-to-stand tests, and muscle mass in postmenopausal women with vitamin D insufficiency. This randomized, double-blind, placebo-controlled trial studied a total of 230 postmenopausal women 75 years or younger with baseline levels of 25-hydroxyvitamin D or 25(OH)D of 14–27 ng/ml and no osteoporosis. Outcome measures were 1-year change in total fractional calcium absorption using two stable isotopes, BMD and muscle mass, using dual-energy X-ray absorptiometry. After baseline absorption was controlled for, calcium absorption increased by 1% (10 mg/day) in the high-dose arm but decreased by 2% in the low-dose arm (p = 0.005 vs. high-dose arm) and 1.3% in the placebo arm (p = 0.03 vs. high-dose arm). We found no between-arm changes in spine, mean total hip, mean femoral neck, or total body BMD, trabecular bone score, muscle mass, and timed-up-and-go or five sit-to-stand test scores. Likewise, we found no between-arm differences for number of falls, number of fallers, physical activity, or functional status.

High-dose cholecalciferol therapy increased calcium absorption, but the effect was small and did not translate into beneficial effects on BMD, muscle function, muscle mass, or falls. We found no data to support experts’ recommendations to maintain serum 25(OH)D levels of 30 ng/ml or higher in postmenopausal women. Instead, we found that low- and high-dose cholecalciferol were equivalent to placebo in their effects on bone and muscle outcomes in this cohort of postmenopausal women with 25(OH)D levels less than 30 ng/ml.

Comment

In the US National Library of Medicine [2], we can read that vitamin D includes both cholecalciferol and ergocalciferol. Vitamin D is a hormone since it is formed in the skin by action of ultraviolet rays upon the precursors, 7-dehydrocholesterol and ergosterol, and acts on vitamin D receptors to regulate calcium in opposition to parathyroid hormone (PTH). But, because in our times, exposure to sunlight is so difficult, vitamin D is really a vitamin, as we need take vitamin D with meals; however, we have another problem: a diet does not usually contain a sufficient amount of vitamin D, as it is present in very few foods.