Management of postmenopausal women: Collège National des Gynécologues et Obstétriciens Français (CNGOF) and Groupe d'Etude sur la Ménopause et le Vieillissement (GEMVi) Clinical Practice Guidelines.

AIM: The aim of these recommendations is to set forth an individualized approach to the management of early postmenopausal women (i.e., within the first 10 years after natural menopause) covering all aspects of lifestyle and therapeutic management, with or without menopause hormone therapy (MHT). MATERIALS AND METHODS: Literature review and consensus of French expert opinion. Recommendations were graded according to the HAS methodology and levels of evidence derived from the international literature, except when there was no good-quality evidence. SUMMARY RECOMMENDATIONS: The beginning of menopause is an ideal time for each woman to evaluate her health status by assessing her bone, cardiovascular, and cancer-related risk factors that may be amplified by postmenopausal estrogen deficiency and by reviewing her lifestyle habits. Improving lifestyle, including nutrition and physical activity, and avoiding risk factors (notably smoking), should be recommended to all women. MHT remains the most effective treatment for vasomotor symptoms but it could be also recommended as first-line treatment for the prevention of osteoporosis in early postmenopausal women at low to moderate risk for fracture. The risks of MHT differ depending on its type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used. There is reasonable evidence that using transdermal estradiol in association with micronized progesterone or dydrogesterone may limit both the venous thromboembolic risk associated with oral estrogens and the risk of breast cancer associated with synthetic progestins. Treatment should be individualized to each woman, by using the best available evidence to maximize benefits and minimize risks, with periodic reevaluation of its benefit-risk balance. For bothersome genitourinary syndrome of menopause (GSM) symptoms, vaginal treatment with lubricants and moisturizers is recommended as first-line treatment together with low-dose vaginal estrogen therapy, depending on the clinical course. No recommendation of an optimal duration of MHT can be made, but it must take into consideration the initial indication for MHT as well as each woman's benefit-risk balance. Management of gynecological side-effects of MHT is also examined. These recommendations are endorsed by the Groupe d'Etude sur la Ménopause et le Vieillissement hormonal (GEMVI) and the Collège National des Gynécologues-Obstétriciens Français (CNGOF).

[Nutritional advices for postmenopausal woman. Postmenopausal women management: CNGOF and GEMVi clinical practice guidelines]. / Conseils nutritionnels pour la femme ménopausée. RPC Les femmes ménopausées du CNGOF et du GEMVi.

Menopause is a key period for health due to physiological changes, particularly of body composition (with decrease of lean mass and increase of fat mass) and of body fat distribution, leading to a higher risk for bone and muscular health and cardiometabolic health. Nutritional advices, associated to physical activity advices, may partially prevent these effects. The energy balance will be moderately negative if there is a weight gain, while the protein intake will be preserved and a regular physical activity will be increased. A Mediterranean style diet will be beneficial on cardiovascular health. Dairy products will be preserved, but restrictive and dietary exclusion will be avoided.

Correction to: Impact of whole dairy matrix on musculoskeletal health and aging-current knowledge and research gaps.

The article Impact of whole dairy matrix on musculoskeletal health and aging-current knowledge and research gaps written by N.R.W. Geiker, C. Mølgaard, S. Iuliano, R. Rizzoli,Y. Manios, L.J.C. van Loon, J.-M. Lecerf, G. Moschonis, J.-Y. Reginster, I. Givens, A. Astrup.

Impact of whole dairy matrix on musculoskeletal health and aging-current knowledge and research gaps.

Dairy products are included in dietary guidelines worldwide, as milk, yoghurt, and cheese are good sources of calcium and protein, vital nutrients for bones and muscle mass maintenance. Bone growth and mineralization occur during infancy and childhood, peak bone mass being attained after early adulthood. A low peak bone mass has consequences later in life, including increased risk of osteoporosis and fractures. Currently, more than 200 million people worldwide suffer from osteoporosis, with approximately 9 million fractures yearly. This poses a tremendous economic burden on health care. Between 5% and 10% of the elderly suffer from sarcopenia, the loss of muscle mass and strength, further increasing the risk of fractures due to falls. Evidence from interventional and observational studies support that fermented dairy products in particular exert beneficial effects on bone growth and mineralization, attenuation of bone loss, and reduce fracture risk. The effect cannot be explained by single nutrients in dairy, which suggests that a combined or matrix effect may be responsible similar to the matrix effects of foods on cardiometabolic health. Recently, several plant-based beverages and products have become available and marketed as substitutes for dairy products, even though their nutrient content differs substantially from dairy. Some of these products have been fortified, in efforts to mimic the nutritional profile of milk, but it is unknown whether the additives have the same bioavailability and beneficial effect as dairy. We conclude that the dairy matrix exerts an effect on bone and muscle health that is more than the sum of its nutrients, and we suggest that whole foods, not only single nutrients, need to be assessed in future observational and intervention studies of health outcomes. Furthermore, the importance of the matrix effect on health outcomes argues in favor of making future dietary guidelines food based.

[The behavioral goals of the coronary patient: No longer smoke, eat better, move more and better]. / Les objectifs comportementaux du patient coronarien : ne plus fumer, manger mieux, bouger plus et mieux.

The behavioral goals of the coronary patient require active management by the cardiologist. Every smoker must be clearly informed about the cardiovascular consequences of smoking and the major benefits of smoking cessation. The only advice to "quit smoking" is not enough. Validated "treatments" (cognitive-behavioral therapy, nicotine replacement therapy, varenicline, bupropion) must be used, with a precise strategy and prolonged follow-up. All drugs assistance can be prescribed in coronary patients and nicotine replacement therapy can even be used just after a myocardial infarction. Nutrition plays a significant role in cardiovascular prevention. Counseling today is based on solid evidence, although evidence is harder to obtain than with drugs. It should no longer be advisable only to "suppress cooked fats and starches" because these recommendations are unclear and/or false. Today we need positive food-based benchmarks and complex dietary patterns in which fruits and vegetables, fish, whole grains, pulses, nuts, olive oil and a diet closed to the Mediterranean diet. Dairy products have their place. Sugary foods should be limited especially in case of overweight and metabolic syndrome. Physical activity is part of good nutrition. Indeed, the fight against a very sedentary lifestyle and physical inactivity in coronary and heart failure patients is part of the lifelong treatment of these patients. The cardiologist and the general practitioner must be much more involved in their prescription and education to hope for good compliance.

How French subjects describe well-being from food and eating habits? Development, item reduction and scoring definition of the Well-Being related to Food Questionnaire (Well-BFQ©).

Providing well-being and maintaining good health are main objectives subjects seek from diet. This manuscript describes the development and preliminary validation of an instrument assessing well-being associated with food and eating habits in a general healthy population. Qualitative data from 12 groups of discussion (102 subjects) conducted with healthy subjects were used to develop the core of the Well-being related to Food Questionnaire (Well-BFQ). Twelve other groups of discussion with subjects with joint (n = 34), digestive (n = 32) or repetitive infection complaints (n = 30) were performed to develop items specific to these complaints. Five main themes emerged from the discussions and formed the modular backbone of the questionnaire: "Grocery shopping", "Cooking", "Dining places", "Commensality", "Eating and drinking". Each module has a common structure: items about subject's food behavior and items about immediate and short-term benefits. An additional theme - "Eating habits and health" - assesses subjects' beliefs about expected benefits of food and eating habits on health, disease prevention and protection, and quality of ageing. A preliminary validation was conducted with 444 subjects with balanced diet; non-balanced diet; and standard diet. The structure of the questionnaire was further determined using principal component analyses exploratory factor analyses, with confirmation of the sub-sections food behaviors, immediate benefits (pleasure, security, relaxation), direct short-term benefits (digestion and satiety, energy and psychology), and deferred long-term benefits (eating habits and health). Thirty-three subscales and 14 single items were further defined. Confirmatory analyses confirmed the structure, with overall moderate to excellent convergent and divergent validity and internal consistency reliability. The Well-BFQ is a unique, modular tool that comprehensively assesses the full picture of well-being related to food and eating habits in the general population.

Postprandial glycaemic and insulinaemic responses in adults after consumption of dairy desserts and pound cakes containing short-chain fructo-oligosaccharides used to replace sugars.

The present studies aimed to evaluate the glycaemic and insulinaemic responses, in healthy adults, to short-chain fructo-oligosaccharides (scFOS) from sucrose used to replace sugars in foods. Two study populations aged 18-50 years were recruited and they consumed dairy desserts or pound cakes containing either standard sugar content or scFOS to replace 30 % of the sugar content. For each study, the two products were tested once under a double-blind and cross-over design with at least 7 d between the two tests. Glucose and insulin were measured using standard methods in blood samples collected with a venous catheter for 120 min during a kinetic test. For the dairy desserts, replacing 30 % of the sugars with scFOS significantly reduced postprandial glycaemic (AUC0-120 min; P = 0·020) and insulinaemic (AUC0-120 min; P = 0·003) responses. For the pound cakes, the glycaemic response was not altered (AUC0-120 min; P =  0·322) while the insulinaemic response tended to be lower (AUC0-120 min; P = 0·067). This study showed that scFOS can be used to replace sugars with the benefit of lowering the postprandial glycaemic response without increasing the insulinaemic response. The effect might be modulated by other parameters (e.g. fat content) of the food matrices.

Effect of phytosterols/stanols on LDL concentration and other surrogate markers of cardiovascular risk.

Plant sterols and stanols are well-known to reduce LDL-cholesterol (LDL-C) concentrations. It is generally accepted that supplementation with 2g/day of sterols/stanols leads to a 10% reduction in LDL. However, most of the clinical trials supporting this conclusion were of short-term duration, and the results of longer interventions are scanty. In four studies, interventions lasting>6 months were carried out and the LDL-C-lowering effects were maintained over this longer duration, although some results suggest that a reduced effect may be observed with sterols, while stanols maintain their effect. In any case, the data are too limited to be definitive. In a free-living population as well as in multiparametric interventional studies, however, the LDL-C-lowering effect has been confirmed, although to a lesser extent than in clinical studies. In the absence of data on cardiovascular morbidity and mortality, data for surrogate markers of cardiovascular risk could be considered adequate alternatives. Several studies have been conducted on this basis, but their results failed to demonstrate any favourable effects. The present report summarizes the different results obtained in long-term studies, and in those comparing the effects of sterols and stanols on lipids and other surrogate markers of cardiovascular risk.

[Nutrition and age-related macular degeneration]. / Nutrition et dégénérescence maculaire liée à l'âge.

Age-related macular degeneration is a growing burden disease with a high prevalence in elderly: it is the first cause of blindness in developped countries. It is a multifactorial disease with genetic factors and nutritional factors. Carotenoids, lutein and zeaxanthin are components of macular pigment and they have a filter role for blue light and an antioxidant role. Other nutritional factors might play a role as antioxidants: zinc, selenium, vitamin E, vitamin C… which lead to the ARED Study. It is the only one study with proven positive effects on the disease progression (stages 3 and 4). A high glycemic index increases oxidative stress. Long chain omega-3 polyunsaturated fatty acids have a protective effect. Available data are presented and discussed. These are new preventive issues.

Effects of two marine dietary supplements with high calcium content on calcium metabolism and biochemical marker of bone resorption.

BACKGROUND/OBJECTIVE: Calcium is essential for the bone metabolism but daily calcium requirements are not met in a significant proportion of the population. Fortunately, oral calcium supplementation can help to meet these needs; however, the calcium bioavailability depends on the calcium sources. The calcium absorption and bioavailability of dietary supplements from marine sources are not known. The objectives of this study were to evaluate the effects of two marine dietary supplements with a high calcium content: a fishbone powder (Phoscalim) and a ray cartilage hydrolysate (Glycollagene), in comparison with milk, and a placebo (maltodextrin), on calcium metabolism and a biochemical marker of bone resorption, using the oral calcium tolerance test. SUBJECTS: Twenty male volunteers were randomized to eat 836 mg of calcium from different sources compared to maltodextrin during a Latin square study. Serum calcium concentrations and other parameters of the calcium metabolism, such as serum intact parathyroid hormone (iPTH) and serum C telopeptides (s-CTX), were measured after an acute oral calcium load based on the Pak protocol. RESULTS: An increase in serum-corrected calcium areas under the curve (AUC) occurred with Phoscalim and Glycollagene when compared to milk. Significantly lower iPTH concentrations were observed with Glycollagene than with milk at T0+1 h, T0+3 h, T0+6 h and with Phoscalim than with milk at T0+6 h. A significantly lower s-CTX concentration was observed with Glycollagene than with milk and Phoscalim at T0+6 h. Furthermore, the urinary calcium/creatinine ratio increased significantly more with Glycollagen than with milk in T0 h+3 h and T3 h+6 h. CONCLUSION: These two dietary supplements from marine sources constitute oral calcium sources when compared to milk on calcium absorption and bone resorption markers on short time.

[Some notions about possible harmlessness and/or toxicity of the antioxidant micronutriments]. / Quelques notions sur l'innocuité et la toxicité éventuelles des supplémentations en micronutriments antioxydants.

Report # 8 of the Age Related Eye Disease Study (AREDS) showed the interest of a cocktail of antioxidant micronutrients for the uni- or bilateral intermediate forms and the unilateral evolved forms of Age related Macular Degeneration. This use of supranutritional amounts aiming at obtaining a therapeutic effect corresponds to the concept of "neutraceuticals" which can be opposed to the concept of nutritional amounts. Although the AREDS was carried out under strict conditions, the evolution of knowledge in micronutrition since its design has led to some criticism of both the amounts of the micronutrients and the composition of the formulation. For example several authors pointed out that beta-carotene used at 3 fold the daily recommendations could have harmful effects, especially among smokers or former smokers. Other authors pointed out that vitamin E, at amounts corresponding to 40 to 60 fold the amounts recommended could be correlated with a lethal risk. We develop here some notions about safety and/or harmlessness of the antioxidant micronutrients.

Nutritional intervention study with argan oil in man: effects on lipids and apolipoproteins.

AIM: To evaluate whether the consumption of virgin argan oil (VAO) is associated with a change in serum lipids and reduces the risk of cardiovascular disease in healthy Moroccans. METHODS: Sixty volunteers consumed butter (25 g/day) during 2 weeks (stabilization period) and were randomly divided into two groups: the treatment group received 25 g/day of VAO during 3 weeks (intervention period), and the control group received 25 g/day of extra virgin olive oil (EVO). Throughout the study, weight, blood pressure, and daily food intake were measured. Serum total cholesterol and low- and high-density lipoprotein cholesterol, triglycerides, and apolipoproteins A-I and B were measured at the end of each diet period. RESULTS: Analysis of food intake showed that the daily diet is isocaloric for the butter regimen (2,537 +/- 244 kcal/day) as well as for the VAO and EVO regimens (2,561+/- 246 and 2,560 +/- 253 kcal/day, respectively). Analysis of the lipid intake showed a reduction in saturated fatty acids with VAO and EVO regimens (27 +/- 1.4 and 26.4 +/- 3.4%, respectively) as compared with the stabilization period (41.6 +/- 2.4%). The analysis of serum lipids showed a significant increase in high-density lipoprotein cholesterol and apolipoprotein A-I in both VAO group (8.4%, p = 0.012, and 5.2%, p = 0.027, respectively) and EVO group (17.3%, p = 0.001, and 5.9%, p = 0.036, respectively). However, low-density lipoprotein cholesterol and apolipoprotein B (13.8%, p = 0.037, and 7.8%, p = 0.039, respectively) decreased significantly only in EVO group as compared with the stabilization period, while triglycerides decreased significantly by 17.5% (p = 0.039) only in VAO group. CONCLUSION: These results confirm the cholesterol-lowering effect of EVO and show for the first time the triglyceride-lowering effect of VAO in men.

[Nutrition and age-related macular degeneration]. / Nutrition et dégénérescence maculaire liée à l'âge.

The nutritional factors involved in the pathogenesis of age-related macular degeneration (AMD) include antioxidants or antioxidant cofactors: vitamins A, C, etc.; zinc, etc.; anti-free-radicals such as beta-carotene and carotenoids, including lutein and zeaxanthin; micronutrients protecting from blue light such as lutein and zeaxanthin; and finally components of the membranes of the photoreceptors docosahexaenoic acid (DHA). These nutritional factors are closely related to environmental risk factors such as smoking and chronic blue light exposure. Although the experimental and epidemiological data are concordant and coherent, the protective role of these micronutrients is not clearly established, mainly because there are very few clinical studies. However, a first observation study showed positive effects at stages 3 and 4 of AMD. Report #8 of the Age-Related Eye Disease Study (AREDS) provides important results for preventing complications of AMD (secondary prevention), and the cocktail of micronutrients proposed even encourages complementary studies on, for example, lutein and zeaxanthin instead of beta-carotene. The outcome of observation studies including a supplementation of long-chain polyunsaturated fatty acids (PUFA) of the omega-3 family (DHA) is also important, as it addresses primary prevention of the disease. A supplementation of omega-3 PUFAs could be proposed to certain subjects at risk for AMD for primary prevention and a supplementation with an antioxidant cocktail of micronutrients could be proposed to patients presenting AMD at stages 3 or 4 or to subjects with a nutritional imbalance. These conceivable supplementations are compatible with simple dietary advice. The supplements currently proposed could be optimized to increase their advantages. New research and new clinical studies are necessary to definitively validate these formulations in order to grant them an authentic drug status.

[Evaluation of discomfort and complications in a population of 18,102 patients overweight or obese patients]. / Evaluation de la gêne et des complications chez 18,102 patients en surpoids ou obèses.

AIMS: The burden of disorders associated with overweight and obesity is a major public health problem. It is therefore important to better identify these concomitant disorders and how their frequencies vary with sex and age. METHODS: A survey was carried out during a 5 month-period from September 2001 to January 2002) among 4 727 general practitioners distributed throughout France in 18 102 patients with a body mass index (BMI)>25 kg/m2. The practitioners evaluated the presence of concomitant disorders using a closed questionnaire. The patients assessed global discomfort linked to overweight using an analog visual scale. Univariate and multivariate analyses of the concomitant disorders and self-reported discomfort depending on age, gender and BMI were performed. RESULTS: The survey population comprised 66.8% of women (W) and 33.2% of men (M). Mean age was 48.0 +/- 13.2 years and mean BMI was 34.6 +/- 6.1, with no differences between the two sexes. The most frequent concomitant disorders were back pain (44.6%), hypertension (44.2%), dyslipidemia (39.9%), knee osteoarthritis (30.8%), lower limb edema (24.3%), hypersudation (23.8%), skin fold mycosis (22.8%) and type 2 diabetes (21.6%). In multivariate analyses, the distribution of these disorders varied with sex: hypertension, type 2 diabetes, dyslipidemia, and hypersudation were more frequent in men, whereas knee osteoarthritis, back pain, and skin fold mycosis were more frequent in women. The prevalence (odd ratio, OR) of back pain and dyslipidemia did not increase with higher BMI and the prevalence of back pain did not increase with age. Overall discomfort related to overweight was rated as 61.3 +/- 19.9 mm on a 0 to 100-mm scale. Discomfort was less marked in men, decreased with age and increased with BMI (and with the consultations in the Paris area). CONCLUSIONS: This study shows the complexity of relationships between concomitant diseases, overall discomfort, BMI, age and sex (in the population of overweight and obese patients) and should improve the management of such patients and their complications.

Human single-chain Fv intrabodies counteract in situ huntingtin aggregation in cellular models of Huntington's disease.

This investigation was pursued to test the use of intracellular antibodies (intrabodies) as a means of blocking the pathogenesis of Huntington's disease (HD). HD is characterized by abnormally elongated polyglutamine near the N terminus of the huntingtin protein, which induces pathological protein-protein interactions and aggregate formation by huntingtin or its exon 1-containing fragments. Selection from a large human phage display library yielded a single-chain Fv (sFv) antibody specific for the 17 N-terminal residues of huntingtin, adjacent to the polyglutamine in HD exon 1. This anti-huntingtin sFv intrabody was tested in a cellular model of the disease in which huntingtin exon 1 had been fused to green fluorescent protein (GFP). Expression of expanded repeat HD-polyQ-GFP in transfected cells shows perinuclear aggregation similar to human HD pathology, which worsens with increasing polyglutamine length; the number of aggregates in these transfected cells provided a quantifiable model of HD for this study. Coexpression of anti-huntingtin sFv intrabodies with the abnormal huntingtin-GFP fusion protein dramatically reduced the number of aggregates, compared with controls lacking the intrabody. Anti-huntingtin sFv fused with a nuclear localization signal retargeted huntingtin analogues to cell nuclei, providing further evidence of the anti-huntingtin sFv specificity and of its capacity to redirect the subcellular localization of exon 1. This study suggests that intrabody-mediated modulation of abnormal neuronal proteins may contribute to the treatment of neurodegenerative diseases such as HD, Alzheimer's, Parkinson's, prion disease, and the spinocerebellar ataxias.

Measurement of apolipoprotein B concentration in plasma lipoproteins by combining selective precipitation and mass spectrometry.

The measurement of apolipoprotein B (apoB) in purified lipoproteins by immunological assays is subject to criticism because of denatured epitopes or immunoreactivity differences between purified lipoproteins and standard. Chemical methods have therefore been developed, such as the selective precipitation of apoB followed by quantification of the precipitate. In this study, we present the measurement of apoB concentration in lipoproteins purified by ultracentrifugation by combining isopropanol precipitation and gas chromatography/mass spectrometry. Very low density lipoprotein (VLDL; d < 1.006 g/mL); VLDL plus intermediate density lipoprotein (VLDL + IDL; d < 1.019 g/mL); and VLDL, IDL, and low density lipoprotein (VLDL + IDL + LDL; d < 1.063 g/mL) were purified by ultracentrifugation. Apolipoprotein B-100 was selectively precipitated by isopropanol. The leucine content of the pellet was then determined by gas chromatography/mass spectrometry, using norleucine as internal standard. Knowledge of the number of leucine molecules in one apoB-100 molecule makes it possible to calculate the plasma concentration of apoB in the various lipoprotein fractions. ApoB in IDL (d 1.006-1.019 g/mL) and LDL (d 1.019-1.063 g/mL) were then determined by subtracting VLDL-apoB from apoB in lipoproteins d < 1.019 and apoB in lipoproteins d < 1.019 g/mL from apoB in lipoproteins d < 1.063 g/mL, respectively. The isopropanol precipitate was verified as pure apoB (>97%) in lipoprotein fractions isolated from normo- and hyperlipidemic plasma and the method appeared reproducible. The combination of isopropanol precipitation and the GC/MS method appears therefore to be a precise and reliable method for kinetic and epidemiological studies.

Monocyte tissue factor response is decreased in patients with hyperlipidemia.

Monocytes are potent regulators of blood coagulation through the expression of tissue factor (TF) on stimulation and of tissue factor pathway inhibitor (TFPI), a selective inhibitor of TF pathway. As hyperlipidemia can modify some monocyte functions, we compared the TF and TFPI expression by circulating monocytes and the plasma TFPI levels between 65 healthy normolipemic controls and 38 nontreated hyperlipemic patients. TF and TFPI relationships with plasma lipoproteins are also examined. TF and TFPI expression were evaluated in peripheral mononuclear cells after isolation from blood by density gradient centrifugation and after short culture with or without lipopolysaccharide (LPS). TF and TFPI activity and antigen were measured in mononuclear cell lysates using amidolytic assay and enzyme-linked immunosorbent assay, respectively. TFPI activity and antigen were measured in plasma using the same methods. Plasma factor VII (FVII) activity and antigen were also determined. LPS-stimulated monocyte TF activity and antigen were lower in hyperlipidemic patients than in controls (0.0001