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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 February 2017 onward are available to Members only when logged in. Selected articles are open to public.

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Role of breastfeeding in postmenopausal osteoporosis

09 January, 2017

Osteoporosis is a huge public health problem for menopausal women all over the world, both in developing and in developed countries. Roughly one in three menopausal women suffers from osteoporosis and one in two from osteopenia. Prevention is the main stay for osteoporosis. It is very important to study all aspects of a woman’s life that can lead to later development of postmenopausal osteoporosis.

Osteoporosis has been studied extensively in relationship to ethnicity, geographical variations and estrogen depletion in menopause. However, the negative relationship of lactation duration and effect of pregnancies with postmenopausal osteoporosis is still inconclusive. The definite role of hormone replacement therapy in the prevention of osteoporosis is now a resolved issue. In a study by Hwang and colleagues [1], a cross-sectional survey based on the Korea National Health and Nutrition Examination Survey (KNHANES) 2010 and 2011 data (n = 1222 postmenopausal women), showed that a duration of breastfeeding longer than 37 months was associated with higher prevalence of osteoporosis in postmenopause and more fractures of the lumbar spine. A duration of lactation longer than 37 months was associated with low bone mineral density (BMD) in the lumbar spine and hip; the number of spinal fractures was increased (37 or more months, odds ratio (OR) 3.292; 95% confidence interval (CI) 1.485–7.23). But, interestingly, the number of deliveries had no relationship with postmenopausal BMD. 

Comment

A woman’s life is a continuous cycle and various landmark changes have an effect on later development of postmenopausal problems; osteoporosis is one of these debilitating diseases, leading to poor quality of life and mortality.

Except for the above study by Huang [1], additional studies have looked into the role of lactation in women and later development of osteoporosis. Grimes and Wimalawansa believe that not only duration and frequency of lactation and return of normal menses, but also pre-pregnancy weight are related with postmenopausal osteoporosis [2]. The conclusion of the authors was that the importance of lactation and its effect on postmenopausal osteoporosis are very aptly considered as a public health problem needing new policy decisions, and so more work is required in this area.

Another interesting study was conducted in Jordan [3]. Multiple regression analysis at different bone sites revealed that there was a negative effect associated with the number of children (live births) and frequency of lactation but it was only evident at the femoral neck. In the final multivariable logistic regression model of variables that rendered significantly independent risk factors after adjustment for age and body mass index, it was found that ever-lactation, frequent lactation for four or more times, a lactation interval of 1–6 months, and clinical hyperthyroidism were significant protective factors. The authors concluded that, although osteoporosis is a large public health problem, in this study the number of pregnancies in their multiparous female population showed a negative impact on femoral neck BMD; no evidence of increased risk of osteoporosis among ever-pregnant women was noted.

Another analysis of data from the Korean KNHANES study [4] has reported that a significant increase (two- to three-fold) in the risk of osteoporosis is apparent in postmenopausal women with prolonged breast-feeding histories (24 or more months), particularly in those with inadequate serum vitamin D levels and calcium intake (>800 mg/day).

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Endocrine-disrupting chemicals – are they of concern and can we really reduce our exposure

15 December, 2016

There is increasing interest in chemicals called 'endocrine-disrupting chemicals'. These are chemicals, which may be natural or synthetic, that through exposure interfere with an organism's normal hormone balance. The actions of these chemicals are complex. Some have weak endocrine-like actions and others interfere with the pathways through which our hormones normally work, hence the term 'disrupters'. Endocrine disrupter chemicals include chemicals such as DDT and other pesticides, and plasticizers, such as bisphenol A (BPA) as well as phthalates and parabens.

The Endocrine Society guideline on this issue in 2009 [1] stated that 'The evidence for adverse reproductive outcomes (infertility, cancers, malformations) from exposure to endocrine-disrupting chemicals is strong, and there is mounting evidence for effects on other endocrine systems, including thyroid, neuroendocrine, obesity and metabolism, and insulin and glucose homeostasis.' The Endocrine Society's Second Scientific Statement on Endocrine-Disrupting Chemicals, 2015 [2] recognizes this to be an international problem and that more public awareness as to how to minimize personal exposure, plus more research in this area, is needed. Of considerable concern is that endocrine disrupters can cause epigenetic changes, such as DNA methylation which can be transmitted to offspring [2].

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HRT, dry eyes and other ocular manifestations

28 November, 2016

From time to time, we have to remind ourselves and the health-care providers that estrogen and the other sex steroids are actually involved in all the body organs, and that their physiological effects are not limited to fertility, treatment of menopausal symptoms, or cardiovascular and bone protection. Menopause Live has addressed in the past the effects of estrogen on other tissues and bodily functions, such as the skin, the voice or hearing. This time, I put the eye and sight into this context. A small, but double-blind, placebo-controlled study (n = 40, age 63.9 ± 5.1 years, 13.2 ± 6.3 years postmenopause) investigated the outcomes of estrogen, testosterone or their combination in hysterectomized women with dry eyes [1]. The results demonstrated estrogen-related worsening in dryness intensity after 8 weeks of estradiol gel 1 mg/g as compared to placebo; 1% testosterone cream showed a neutral effect, but a combination of the two hormones led to a significant increase in tear secretion.

Comment

Dry eye syndrome, also known as keratoconjunctivitis sicca, is a common condition which is the result of low production of tears or too quick evaporation. Symptoms include irritation, redness, discharge, easily fatigued eyes and blurred vision. This can result from meibomian gland dysfunction, allergies, autoimmune disorders, pregnancy, local surgery, smoking, conjunctival infections and other etiologies. Among relevant medications that may cause dry eyes are anti-depressants, which are frequently prescribed in midlife and beyond. Postmenopausal hormone replacement (HRT) has been mentioned in this framework as well. However, there seems to be some controversy in regard to the impact of HRT on dry eyes.

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Recent studies on natural alternatives to hormone therapy

21 November, 2016

Have you noticed the increased number of publications on natural remedies for menopause symptoms in good-quality journals? The reason for these studies, in my view, is not only the alleged problematic benefit–risk balance of hormone therapy (HT) or other approved medications, but the higher awareness of women to achieve better quality of life during midlife and beyond. This may be more prominent in developing countries where traditional medicine is popular, but is certainly valid in the Western world too. The willingness of Editors of journals with a medium to high impact factor to accept such papers, provided that these meet the quality standards of the aforementioned journals, gives a tail wind to this trend. Here are a few such examples.

A randomized controlled trial (RCT) in 82 postmenopausal women compared Pueraria mirifica gel to a conjugated estrogen cream [1]. Pueraria mirifica is a widely used, herbal female hormone supplement derived from a plant found in the wild in certain regions in Thailand. Use for 12 weeks showed that Pueraria mirifica was efficacious and safe for the treatment of vulvovaginal atrophy. Yet, conjugated estrogen cream was found to be more beneficial in improving signs of vaginal atrophy and restoring vaginal epithelium at 6 and 12 weeks.

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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.

Comment

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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