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1.
Osteoporosis in Premenopausal Women: A Clinical Narrative Review by the ECTS and the IOF.
Pepe, J, Body, JJ, Hadji, P, McCloskey, E, Meier, C, Obermayer-Pietsch, B, Palermo, A, Tsourdi, E, Zillikens, MC, Langdahl, B, et al
The Journal of clinical endocrinology and metabolism. 2020;(8)
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Abstract
CONTEXT Consensus regarding diagnosis and management of osteoporosis in premenopausal women (PW) is still lacking due to few studies carried out in this population. DESIGN The European Calcified Tissue Society and the International Osteoporosis Foundation convened a working group to produce an updated review of literature published after 2017 on this topic. RESULTS Fragility fractures in PW are rare and mostly due to secondary osteoporosis (ie, in presence of an underlying disease such as hormonal, inflammatory, or digestive disorders). In absence of another disorder, low bone mineral density (BMD) together with fragility fractures qualifies as idiopathic osteoporosis. In contrast, low BMD alone does not necessarily represent osteoporosis in absence of bone microarchitectural abnormalities. BMD increases in PW with osteoporosis when the underlying disease is treated. For example, in celiac disease, an increase of 9% in radius trabecular volumetric density was achieved after 1 year of gluten-free diet, while anti-tumor necrosis factor alpha improved BMD in PW with inflammatory bowel diseases. In amenorrhea, including anorexia nervosa, appropriately delivered estrogen replacement therapy can also improve BMD. Alternatively, antiresorptive or anabolic therapy has been shown to improve BMD in a variety of conditions, the range of improvement (3%-16%) depending on skeletal site and the nature of the secondary cause. No studies were powered to demonstrate fracture reduction. The effects of bisphosphonates in childbearing women have been scantly studied and caution is needed. CONCLUSION The majority of PW with osteoporosis have an underlying disease. Specific therapy of these diseases, as well as antiresorptive and anabolic drugs, improve BMD, but without evidence of fracture reduction.
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Lipid profile differences during menopause: a review with meta-analysis.
Ambikairajah, A, Walsh, E, Cherbuin, N
Menopause (New York, N.Y.). 2019;(11):1327-1333
Abstract
OBJECTIVES The aim of the study was to determine lipid profile differences between premenopausal and postmenopausal women. METHODS The present review used a meta-analytic approach. Sixty-six studies were included, which provided a total sample of 114,655 women consisting of 68,394 that were premenopausal and 46,261 that were postmenopausal. RESULTS The main findings were that (1) lipoproteins were significantly higher in postmenopausal women compared to premenopausal women including triglycerides (0.27 mmol/L, 95% confidence interval, 0.22-0.31), total cholesterol (0.58, 0.50-0.65), low-density lipoprotein (0.45, 0.38-0.53), and total cholesterol to high-density lipoprotein levels (0.39, 0.16-0.62); (2) there was no difference in high-density lipoprotein levels between premenopausal and postmenopausal women (0.02, -0.00-0.04); and (3) the differences in lipid levels was partly attributable to the mean age difference between premenopausal and postmenopausal women. CONCLUSIONS These findings are important as they provide precise estimates of lipid differences in women around menopause. Furthermore the results suggest that the unfavorable lipid profile that develops in postmenopausal women puts them at higher risk of cardiovascular disease such as heart disease and stroke if appropriate lifestyle/pharmacological interventions are not implemented.
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Effects of low-fat diet on serum lipids in premenopausal and postmenopausal women: a meta-analysis of randomized controlled trials.
Wu, L, Ma, D, Walton-Moss, B, He, Z
Menopause (New York, N.Y.). 2014;(1):89-99
Abstract
OBJECTIVE This study aims to conduct a meta-analysis to evaluate the effects of a low-fat diet, in comparison with participants' usual diet, on serum lipids in premenopausal and postmenopausal women. METHODS Ten electronic databases were searched for relevant articles reporting randomized controlled trials through August 31, 2012, including PubMed/Medline, EMBASE, Cochrane Library, CINAHL, Web of Science, SCOPUS, ProQuest Dissertations and Theses, SinoMed, CNKI (Chinese database), and WanFang (Chinese database). This systematic review and meta-analysis, which evaluated the effects of a low-fat diet, in comparison with the participants' usual diet, was conducted according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. All analyses were performed using RevMan version 5 (Cochrane Collaboration). RESULTS From 512 potentially relevant publication citations reviewed, 8 randomized clinical trials were included in the meta-analysis, representing 22 groups (11 intervention groups and 11 control groups). A total of 1,536 women (900 in the intervention group and 636 in the control group) met the inclusion criteria. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) values changed more favorably in participants randomized to low-fat diets than in participants randomized to their usual diets. Low-fat diet was found to induce significant reductions in TC (random-effects model: mean difference [MD], -0.49 mmol/L; 95% CI, -0.69 to -0.29; I = 42%; Peffect < 0.00001), HDL-C (MD, -0.12 mmol/L; 95% CI, -0.20 to -0.05; I = 49%; Peffect = 0.00006), and LDL-C (MD, -0.24 mmol/L; 95% CI, -0.38 to -0.09; I = 42%; Peffect = 0.001) for two groups. For subgroup analysis, low-fat diet was efficacious in reducing TC, HDL-C, and LDL-C in premenopausal women but did not significantly reduce the same outcomes in postmenopausal women. However, there were also no statistically significant differences in triglycerides (TG) and TC-to-HDL-C ratio between a low-fat diet and the participants' usual diet (TG: MD, 0.04 mmol/L; 95% CI, -0.02 to 0.11; I = 0%; Peffect = 0.16; TC-to-HDL-C ratio: MD, 0.08 mmol/L; 95%, CI -0.21 to 0.36; I = 0%; Peffect = 0.59) in two groups. CONCLUSIONS Overall results suggest that a low-fat diet is efficacious in reducing the concentrations of TC, HDL-C, and LDL-C but not in reducing TG and TC-to-HDL-C ratio in women. A low-fat diet is efficacious in reducing TC, HDL-C, and LDL-C in premenopausal women. Additional studies are needed to further address its effects on postmenopausal women.
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Failure to consider the menstrual cycle phase may cause misinterpretation of clinical and research findings of cardiometabolic biomarkers in premenopausal women.
Schisterman, EF, Mumford, SL, Sjaarda, LA
Epidemiologic reviews. 2014;(1):71-82
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Abstract
Biomarker assessment plays a critical role in the study and prevention of disease. However, variation in biomarkers attributable to the menstrual cycle in premenopausal women may impair understanding the role of certain biomarkers in disease development and progression. Thus, in light of the recently increasing evidence of menstrual cycle variability in multiple cardiometabolic biomarkers, a reexamination of approaches for appropriately studying and diagnosing cardiovascular disease in premenopausal women is warranted. We reviewed studies (from 1934 through 2012) evaluating changes in cardiometabolic biomarkers across phases of the menstrual cycle, including markers of oxidative stress, lipids, insulin sensitivity, and systemic inflammation. Each was observed to vary significantly during the menstrual cycle. For example, nearly twice as many women had elevated cholesterol levels warranting therapy (≥200 mg/dL) during the follicular phase compared with the luteal phase (14.3% vs. 7.9%), with only 3% having consistently high levels during all phases of the cycle. Similarly, nearly twice as many women were classified as being at an elevated risk of cardiovascular disease (high sensitivity C-reactive protein >3 mg/L) during menses compared with other phases (12.3% vs. 7.4%). Menstrual cycle-associated variability in cardiometabolic biomarkers is an important source of variability that should be accounted for in both research and clinical settings.
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Plasma vitamin D levels, menopause, and risk of breast cancer: dose-response meta-analysis of prospective studies.
Bauer, SR, Hankinson, SE, Bertone-Johnson, ER, Ding, EL
Medicine. 2013;(3):123-131
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Abstract
Previous evidence suggests that higher circulating 25-hydroxyvitamin D (25[OH]D) levels are variably associated with lower breast cancer risk; however, prospective studies and clinical trials have been inconsistent, particularly between older and younger women of differing menopausal status. We conducted a quantitative nonlinear dose-response meta-analysis of prospective studies evaluating the association between circulating 25(OH)D and breast cancer risk, stratified by menopause. A systematic search of MEDLINE and EMBASE included studies published through May 2011. We reviewed references from retrieved articles and contacted relevant investigators for additional data from prospective studies on circulating 25(OH)D levels and incident breast cancers. Prospective studies of circulating vitamin D and breast cancer risk were reviewed, and no language restrictions were imposed. Information on study population, menopausal status, 25(OH)D levels, and relative risk (RR) estimates were extracted using a standardized protocol.A total of 9 prospective studies were included, comprising 5206 cases and 6450 controls. Data were pooled using dose-response random-effects meta-regression models. Identifying nonlinear effects, spline models were optimized for thresholds. The relationship between circulating 25(OH)D and breast cancer risk differed by menopausal status (p = 0.05 for effect modification). While no association was found in premenopausal women, dose-response modeling revealed a nonlinear inverse association among postmenopausal women. Notably, a flat association was observed in the lowest range of 25(OH)D levels <27 ng/mL (RR = 1.01 per 5 ng/mL; 95% confidence interval [CI], 0.98-1.04). In contrast, postmenopausal breast cancer risk decreased with 25(OH)D levels 27-<35 ng/mL (p = 0.02 for nonlinear risk change), where a 5 ng/mL increase in 25(OH)D was associated with a 12% lower risk of breast cancer (RR = 0.88 per 5 ng/mL; 95% CI, 0.79-0.97), with suggestive flattening at higher doses >35 ng/mL. The significant inverse association did not appear to vary across strata of invasive/in-situ cases, body mass index adjustment, region, postmenopausal hormone use, or assay method.In summary, this dose-response meta-analysis of prospective studies of plasma 25(OH)D suggested a breast cancer risk differential by menopause, whereby a step-wise inverse association was observed beyond a threshold of 27 ng/mL, but with flattening of effects above 35 ng/mL, in postmenopausal women. These findings help resolve prior inconsistent findings and may carry important clinical and public health implications.
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Premenopausal osteoporosis, an overlooked consequence of anorexia nervosa.
Teng, K
Cleveland Clinic journal of medicine. 2011;(1):50-8
Abstract
Many young women with anorexia nervosa develop premenopausal osteoporosis. In particular, female athletes have a much higher incidence of disordered eating than their peers and therefore are at a much higher risk of stress fractures and other traumatic bone pathology. This review summarizes factors affecting the development of premenopausal osteoporosis in these patients and identifies potential targets for intervention.
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Effect on bone health of estrogen preparations in premenopausal women with anorexia nervosa: a systematic review and meta-analyses.
Sim, LA, McGovern, L, Elamin, MB, Swiglo, BA, Erwin, PJ, Montori, VM
The International journal of eating disorders. 2010;(3):218-25
Abstract
OBJECTIVE Because estrogen therapies are widely prescribed for amenorrhea associated with anorexia nervosa (AN), we conducted a systematic review and meta-analyses to estimate the influence of estrogen preparations (EP) on bone mineral density in women with AN. METHOD Prospective cohort studies and randomized clinical trials (RCTs) comparing the effect of EP use to no treatment or placebo on bone mineral density and bone fractures were included. Independent reviewers selected studies for inclusion and extracted study characteristics, markers of methodologic quality, and outcomes for the intention-to-treat population. RESULTS Using random-effects meta-analyses and inconsistency across trials using the I(2) statistic, data were combined across two eligible prospective cohort studies and four RCTs; none reported effects on bone fractures. Compared with placebo or no treatment, low quality evidence found EPs have a moderate effect on bone mineral density in the lumbar spine [ES (effect size) 0.33, 95% CI (confidence interval) 0.09, 0.56; I(2) = 0%)], but no significant effect on the femoral neck (ES 0.13, 95% CI -0.16, 0.43; I(2) = 0%). There were no significant treatment-subgroup interactions. DISCUSSION In general, EPs have uncertain benefit and should be avoided by women with AN in whom the success of weight and nutritional rehabilitation is judged by menses resumption.
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Cardiovascular risk and events in polycystic ovary syndrome.
Carmina, E
Climacteric : the journal of the International Menopause Society. 2009;:22-5
Abstract
Young women with polycystic ovary syndrome (PCOS) present a high risk for cardiovascular disease because of the presence of abdominal obesity, insulin resistance and androgen excess. In addition, they present with endothelial dysfunction and early signs of atherosclerosis (increased carotid intima-media thickness and increased coronary calcium). However, the evidence of increased cardiovascular events during the postmenopausal age is relatively small, although some recent studies have indicated a slight increase in the severity of cardiovascular disease in women who had PCOS during their fertile age. The discrepancy between cardiovascular risk in young age and postmenopausal cardiovascular events may depend on changes in the risk that happen during the late fertile age or on overestimation of early atherosclerotic signs.
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Low bone mineral density in premenopausal women.
Lewiecki, EM
Southern medical journal. 2004;(6):544-50
Abstract
With the proliferation of bone densitometers, an increasing number of premenopausal women are having their bone density tested. Approximately 15% of premenopausal women have bone mineral density that is more than 1 standard deviation less than the young-adult mean, and approximately 0.6% are more than 2.5 standard deviation below young-adult mean bone density. Most premenopausal women with low bone density have low peak bone mass, stable bone density, and low short-term absolute risk of fracture. The management of these patients involves nonpharmacologic lifestyle measures and reassurances that fracture risk is low. A minority of premenopausal women with low bone density have increased short-term absolute fracture risk with contributing diseases, conditions, or medications that should be identified and treated. Premenopausal women with fractures are at increased risk for fractures later in life. Methods for evaluating these patients and selecting those who require additional care are reviewed.
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[The perimenopause. Problems and therapeutic changes].
Tinelli, A, Torresin, L, Menis, T
Minerva ginecologica. 2002;(4):339-48
Abstract
The female life period in which hormonal share begins to drop and the first menopausal clinical symptoms occur, is called perimenopausal period. During this female life phase, frequently, time of regular function and time of ovarian dysfunctions occur, with a limited luteal phase and an estrogen production fall. So, perimenopausal clinical symptoms begin: hot flushes, tiredness and libido decrease; to these problems, others can be connected to inadequate luteal phase, as breast pain, nervousness and body increase. Therefore, it's possible to affirm that the perimenopause is a particularly delicate period, either because it represents a transient moment to climateric phase, or because it's possible to detect a great hormonal instability, fundamental step for clinical problems. In our investigation we discuss this problem, explain the causes and the possible remedies to delay the onset of symptoms or to treat hormonal perimenopausal modifications.