Disease In Postmenopausal Women Research Articles

Evaluation of the Relationship Between Hot Flashes and Night Sweats and Severity of Coronary Artery Disease in Postmenopausal Women

Introduction: Hot flashes (HF) and night sweats (NS) are due to vasomotor instability and could be recognized as cardiovascular risk markers. Therefore, this study aimed to evaluate the relationship between vasomotor instability and severity of coronary artery disease (CAD) in postmenopausal women. Materials and Methods: This observational cross sectional study, was performed in Chamran Hospital, Isfahan University of medical sciences, Isfahan, Iran from 2011-2012. In this study, womenwithin the age range of 45-60 years with angiography documented CAD were enrolled. Participants included 25 women with hot flashes, night sweats, or both and 17 women without these symptoms, respectively. In all participants, levels of follicular stimulating hormone/luteinizinghormone (FSH/LH) were measured. The severity of CAD was calculated using Gensini score. In order to evaluate the relationship between severity of CAD and other variables, Gensini scores lower than 50 and ≥50 were considered as low and high Gensini scores, respectively. Moreover, data analysis was performed using SPSS version 15.0.Results: Our findings demonstrated that NS and HF were not associated with severity of CAD, determined by Gensini scores (P-values>0.05). However, a significant positive relationship was observed between FSH levels and severity of CAD in all participants (P=0.048). In cases in low Gensini score group, the relationship between LH and Gensini score was negative and non-significant, while Gensini score showed a positive and non-significant relationship (P-value> 0.05).Conclusions: No significant association was observed between vasomotor symptoms of menopause and the severity of CAD. In addition, elevated FSH levels could be considered as a marker of severity of CAD.

Lipid Changes Around the Final Menstrual Period Predict Carotid Subclinical Disease in Postmenopausal Women.

Atherogenic changes in lipids occur among women around the time of the natural menopause, that is, within 1 year of the final menstrual period (FMP). We investigated whether lipid changes around the FMP are related to carotid intima-media thickness, interadventitial diameter, and plaque in postmenopausal women. A total of 863 natural postmenopausal women with no history of heart attack or stroke underwent carotid ultrasound scans at follow-up year 12 or 13 of the Study of Women's Health Across the Nation. Estimates of their annual change in lipids were segmented into the year before and after the FMP, before the year before FMP, and 1 year after FMP. Multivariate analyses were adjusted for sociodemographic characteristics, time from FMP to scan, baseline body mass index and systolic blood pressure, and use of medications for hypertension and diabetes mellitus at the scan. Smaller increases in high-density lipoprotein cholesterol and apolipoprotein A1 within 1 year of the FMP were related to greater interadventitial diameter, β (SE)=-0.036 (0.015), P=0.02, and β (SE)=-0.035 (0.013), P=0.006, respectively. Greater increases in low-density lipoprotein cholesterol within 1 year of FMP were related to greater likelihood of plaque scores ≥2, odds ratio, 1.071; 95% confidence interval, 1.018-1.127; P=0.009. Magnitude of associations was reduced but remained significant with further adjustment for premenopausal lipid levels. The difference in probability of elevated plaque scores was 50% between those in the highest and lowest low-density lipoprotein cholesterol change tertiles. Changes in lipids as women approach the FMP provide useful clinical information for understanding postmenopausal carotid indices.

Progress with palbociclib in breast cancer: latest evidence and clinical considerations.

Deregulation of the cell cycle is a hallmark of cancer, and research on cell cycle control has allowed identification of potential targets for anticancer treatment. Palbociclib is a selective inhibitor of the cyclin-dependent kinases 4 and 6 (CDK4/6), which are involved, with their coregulatory partners cyclin D, in the G1-S transition. Inhibition of this step halts cell cycle progression in cells in which the involved pathway, including the retinoblastoma protein (Rb) and the E2F family of transcription factors, is functioning, although having been deregulated. Among breast cancers, those with functioning cyclin D-CDK4/6-Rb-E2F are mainly hormone-receptor (HR) positive, with some HER2-positive and rare triple-negative cases. Deregulation results from genetic or otherwise occurring hyperactivation of molecules subtending cell cycle progression, or inactivation of cell cycle inhibitors. Based on results of randomized clinical trials, palbociclib was granted accelerated approval by the US Food and Drug Administration (FDA) for use in combination with letrozole as initial endocrine-based therapy for metastatic disease in postmenopausal women with HR-positive, HER2-negative breast cancer, and was approved for use in combination with fulvestrant in women with HR-positive, HER2-negative advanced breast cancer with disease progression following endocrine therapy. This review provides an update of the available knowledge on the cell cycle and its regulation, on the alterations in cyclin D-CDK4/6-Rb-E2F axis in breast cancer and their roles in endocrine resistance, on the preclinical activity of CDK4/6 inhibitors in breast cancer, both as monotherapy and as partners of combinatorial synergic treatments, and on the clinical development of palbociclib in breast cancer.

Ovariectomy-Induced Mitochondrial Oxidative Stress, Apoptosis, and Calcium Ion Influx Through TRPA1, TRPM2, and TRPV1 Are Prevented by 17β-Estradiol, Tamoxifen, and Raloxifene in the Hippocampus and Dorsal Root Ganglion of Rats.

Relative 17β-estradiol (E2) deprivation and excessive production of mitochondrial oxygen free radicals (OFRs) with a high amount of Ca2+ influx TRPA1, TRPM2, and TRPV1 activity is one of the main causes of neurodegenerative disease in postmenopausal women. In addition to the roles of tamoxifen (TMX) and raloxifene (RLX) in cancer and bone loss treatments, regulator roles in Ca2+ influx and mitochondrial oxidative stress in neurons have not been reported. The aim of this study was to evaluate whether TMX and RLX interactions with TRPA1, TRPM2, and TRPV1 in primary hippocampal (HPC) and dorsal root ganglion (DRG) neuron cultures of ovariectomized (OVX) rats. Forty female rats were divided into five groups: a control group, an OVX group, an OVX+E2 group, an OVX+TMX group, and an OVX+RLX group. The OVX+E2, OVX+TMX, and OVX+RLX groups received E2, TMX, and RLX, respectively, for 14days after the ovariectomy. E2, ovariectomy-induced TRPA1, TRPM2, and TRPV1 current densities, as well as accumulation of cytosolic free Ca2+ in the neurons, were returned to the control levels by E2, TMX, and RLX treatments. In addition, E2, TMX, and RLX via modulation of TRPM2 and TRPV1 activity reduced ovariectomy-induced mitochondrial membrane depolarization, apoptosis, and cytosolic OFR production. TRPM2, TRPV1, PARP, and caspase-3 and caspase-9 expressions were also decreased in the neurons by the E2, TMX, and RLX treatments. In conclusion, we first reported the molecular effects of E2, TMX, and RLX on TRPA1, TRPM2, and TRPV1 channel activation in the OVX rats. In addition, we observed neuroprotective effects of E2, RLX, and TMX on oxidative and apoptotic injuries of the hippocampus and peripheral pain sensory neurons (DRGs) in the OVX rats. Graphical Abstract Possible molecular pathways of involvement of DEX in cerebral ischemia-induced apoptosis, oxidative stress, and calcium accumulation through TRPA1,TRPM2 and TRPV1 in the hippocampus and DRG neurons of rats. The N domain of the TRPM2 contains ADP-ribose (ADPR) pyrophosphate enzyme, which is separately activated by ADPR and oxidative stress, although the channel is reversibly inhibited by N-(p-amylcinnamoyl) anthranilic acid (ACA). The TRPV1 is also activated by mitochondrial oxidative stress and capsaicin, and it is blocked by capsazepine (CPZ). TRPA1 is also activated by oxidative stress it is inhibited by AP18. Increased cytosolic Ca2+ concentration through TRPA1,TRPM2 and TRPV1 in ovariectomized (OVX) rats may lead to neuronal toxicity, reactive oxygen species (ROS) processes, and eventual cell death. 17β-Estradiol (E2), tamoxifen (TMX), and raloxifene (RLX) reduced oxidative stress, apoptosis (including caspase-3 and caspase-9), mitochondrial membrane depolarization, and Ca2+ influx through the inhibition of TRPA1,TRPM2 and TRPV1 activation.

What Is Breast in the Bone?

The normal developmental program that prolactin generates in the mammary gland is usurped in the cancerous process and can be used out of its normal cellular context at a site of secondary metastasis. Prolactin is a pleiotropic peptide hormone and cytokine that is secreted from the pituitary gland, as well as from normal and cancerous breast cells. Experimental and epidemiologic data suggest that prolactin is associated with mammary gland development, and also the increased risk of breast tumors and metastatic disease in postmenopausal women. Breast cancer spreads to the bone in approximately 70% of cases with advanced breast cancer. Despite treatment, new bone metastases will still occur in 30%–50% of patients. Only 20% of patients with bone metastases survive five years after the diagnosis of bone metastasis. The breast cancer cells in the bone microenvironment release soluble factors that engage osteoclasts and/or osteoblasts and result in bone breakdown. The breakdown of the bone matrix, in turn, enhances the proliferation of the cancer cells, creating a vicious cycle. Recently, it was shown that prolactin accelerated the breast cancer cell-mediated osteoclast differentiation and bone breakdown by the regulation of breast cancer-secreted proteins. Interestingly, prolactin has the potential to affect multiple proteins that are involved in both breast development and likely bone metastasis, as well. Prolactin has normal bone homeostatic roles and, combined with the natural “recycling” of proteins in different tissues that can be used for breast development and function, or in bone function, increases the impact of prolactin signaling in breast cancer bone metastases. Thus, this review will focus on the role of prolactin in breast development, bone homeostasis and in breast cancer to bone metastases, covering the molecular aspects of the vicious cycle.

The association between vitamin D receptor gene polymorphisms (<em>TaqI</em> and <em>FokI</em>), Type 2 diabetes, and micro-/macrovascular complications in postmenopausal women

IntroductionSince there is evidence of the action of vitamin D as a modulator of insulin release and atherosclerosis, it may well be that the vitamin D receptor polymorphisms are associated with diabetes and its chronic complications.AimsTo examine the associations between vitamin D receptor polymorphisms (FokI and TaqI) and Type 2 diabetes (T2DM) and its associated chronic complications in postmenopausal women.MethodsThis cross-sectional study analyzed 100 postmenopausal women with T2DM (mean age 65.7±7.18 years) and 100 postmenopausal women without diabetes in the control group (mean age 65.1±9.18 years; P=0.1608). We evaluated clinical and metabolic parameters and analyzed TaqI and FokI polymorphisms.ResultsThere were no significant differences in genotype and allele frequencies between patients and controls in either of the polymorphisms studied. In the group of patients with diabetes, there were no significant differences in either polymorphism in relation to stroke, retinopathy, nephropathy, or neuropathy. However, in patients with T2DM and coronary artery disease, f genotype (P=0.0361) and the combination of Ff + ff genotypes were observed less frequently (P=0.0462).ConclusionThis study suggests the potential protective factor of FokI polymorphism for coronary artery disease in postmenopausal women with T2DM in the recessive model.

Association of obesity with serum estrogen level in postmenopausal women

Incidence of obesity among postmenopausal women is increasing throughout the world, leading to life threatening medical problem like cardiovascular diseases, type 2 diabetes mellitus. Estrogen deficiency that develops during menopause is likely the etiological factors for development of abdominal obesity. Increased incidence of cardiovascular diseases in postmenopausal women may be due to abdominal obesity caused by lower level of estrogen hormone. The study was carried out to observe the association of obesity with serum estrogen level in postmenopausal women. This cross sectional study was conducted in the Department of Physiology, Dhaka Medical College, Dhaka, during the period of January 2011 to December 2011. A total number of 90 female subjects were selected from different areas of Dhaka city. Among them, 60 postmenopausal women with age ranging from 50 to 60 years were taken as study group and 30 apparently healthy premenopausal women with age ranging from 20 to 30 years were included as control group for comparison. Waist circumference was measured and body mass index (BMI) was calculated in both groups. Serum estrogen level was estimated in order to assess the hormonal level of postmenopausal women. The value of waist circumference was higher in postmenopausal women than those of premenopausal women and result was statistically non significant. Body mass index value was significantly (p<0.001) higher in postmenopausal women in comparison to those of premenopausal women. In postmenopausal women serum estrogen level was lower than premenopausal women and serum estrogen level showed negative correlation with waist circumference and body mass index values. All these correlations were statistically non significant. Present study revealed that there is association of obesity with serum estrogen level in postmenopausal women.Bangladesh Med J. 2016 May; 45 (2): 79-84

Associations between osteoporosis and coronary artery disease in postmenopausal women

Objective: Coronary artery disease (CAD) and osteoporosis are major causes of mortality and morbidity in postmenopausal women. We aimed to investigate the association between osteoporosis and CAD in asymptomatic postmenopausal women at a single center.Methods: This study included 863 postmenopausal women without histories of cardiovascular diseases who visited the Health Promotion Center from June 1, 2004 to May 31, 2015. All subjects were screened for bone mineral density (BMD) by dual-energy X-ray absorptiometry and for the degree of CAD by multidetector computed tomography.Results: Low BMD including osteopenia and osteoporosis was found to be significantly associated with old age, low body mass index, and a higher prevalence of diabetes mellitus. The incidences of CAD including a high coronary artery calcium score (≥100), obstructive coronary artery disease, and multivessel disease were significantly higher in subjects with low BMD. After adjusting for age and cardiovascular risk factors, osteoporosis was associated with a high coronary artery calcium score (p = 0.015) and with obstructive coronary artery disease (p = 0.002). There was a trend toward significance with multivessel disease (p = 0.052).Conclusions: High coronary artery calcium score and obstructive coronary artery disease, as revealed by multidetector computed tomography, were associated with osteoporosis in asymptomatic postmenopausal women, independent of cardiovascular risk factors and age.

Omentin-1 and Nonfatal Ischemic Heart Disease in Postmenopausal Women: A Population-Based Study

There is growing evidence that supports the existence of a link between lower levels of circulating omentin-1 and the pathogenesis of coronary atherosclerosis. However, no population-based study has been performed to elucidate the cardioprotective role of this beneficial adipocytokine. A total of 378 healthy, postmenopausal women were randomly selected from 13 clusters in the port city of Bushehr, Iran. The prevalence of nonfatal ischemic heart disease (IHD) was assessed using the Minnesota code with a 12-lead resting electrocardiogram (EKG). EKG with evidence of IHD (IHD-EKG) was defined as myocardial infarction (codes 1.1 and 1.2) and ischemia (codes 1.3, 4.1 to 4.4, 5.1 to 5.3, and 7.1) occurring together. Serum omentin-1 and adiponectin levels were measured using enzyme-linked immunosorbent assay methods. The prevalence of IHD-EKG among the studied population was 41.8% (159 women). Serum levels of omentin-1 were significantly lower in women with ischemic EKG than in normal subjects (geometric mean ×/multiplicative standard deviation, 10.31 ×/2.35 ng/mL versus 12.44 ×/2.12 ng/mL, respectively; P = .038). Multiple logistic regression analysis indicated that higher serum levels of omentin-1 were significantly associated with a lower prevalence of ischemic EKG after adjusting for potential confounders, including classical cardiovascular risk factors and circulating adiponectin levels (odds ratio, 0.48; confidence interval, 0.24 to 0.95; P = .038). A higher level of circulating omentin-1 is independently associated with a lower prevalence of nonfatal IHD in postmenopausal women. The cardioprotective role of this novel adipocytokine needs to be further elucidated in large-scale longitudinal studies. BMI = body mass index EKG = electrocardiogram ELISA = enzyme-linked immunosorbent assay HDL = high-density lipoprotein IHD = ischemic heart disease LDL = low-density lipoprotein.

Age at Menopause and Extent of Coronary Artery Disease Among Postmenopausal Women with Acute Coronary Syndromes

BackgroundEpidemiological studies have shown a higher risk of cardiovascular mortality associated with early menopause, but the relation between menopausal age and extent of coronary artery disease after menopause is unknown. We assessed the relation between menopausal age and extent of coronary disease in postmenopausal women with an acute coronary syndrome. MethodsA prospective study was conducted in patients ≥55 years old undergoing coronary angiography for an acute coronary syndrome. Enrollment was stratified by sex (women/men ratio 2:1) and age (55-64, 65-74, 75-85, and >85 years). Women were administered menopause questionnaires during admission. An independent core lab quantified coronary artery disease extent using the Gensini Score, which classifies both significant (>50%) and nonsignificant lesions. Linear correlation was used to appraise the association between the Gensini score and menopausal age. ResultsWe enrolled 675 patients, 249 men and 426 women (mean age 74 years). The mean Gensini score was 60 ± 36 in men vs 50 ± 32 in women (P <.001), being higher among men at any age. The median menopausal age of women was 50 years. Risk factors and age at first acute coronary syndrome were identical among women below and above the median menopausal age. The Gensini score in women showed a weak association with age (R = 0.127; P = .0129), but not with menopausal age (R = 0.063; P = .228). At multivariable analysis, ejection fraction, female sex, and ST elevation myocardial infarction were independent predictors of the Gensini score in the overall population. ConclusionsMenopausal age was not associated with the extent of coronary artery disease. Age at first acute coronary syndrome presentation, risk factors, and prior cardiovascular events were not affected by menopausal age. (The LADIES ACS study: NCT01997307).

Inhaled medication usage in post-menopausal women and lifetime tobacco smoke exposure: The Women’s Health Initiative Observational Study

ObjectiveWhile active smoking is a causal agent in respiratory disease, the independent role of secondhand smoke (SHS) merits further investigation. We investigated associations between lifetime active smoking and exposure to secondhand smoke – studied independently – and current use of 1 or more inhaled medications as a surrogate for prevalent pulmonary disease in post-menopausal women. Study designInformation on lifetime active and passive tobacco exposure and inhaled pulmonary medication usage at enrollment was collected from 88,185 postmenopausal women aged 50–79 enrolled in the Women’s Health Initiative Observational Study from 1993 to 1998 at 40 centers in the United States. Participants were recruited from localities surrounding the study centers using a variety of methods, including informational mailings and mass media campaigns. Main outcome measuresMultivariate adjusted regression models were used to estimate odds ratios and 95% CI according to levels of active smoking and SHS exposure, and trends were tested across categories. ResultsEver active smokers had an overall OR of 1.97 (95% CI 1.58–2.45) for having one or more prescribed inhaled medication compared with never-smoking women not exposed to active or passive smoke. The overall OR for using inhalers for never-smoking women exposed to any SHS compared with the same reference group was 1.33 (95% CI 1.07–1.65). In a quantified analysis of SHS, never-smoking women with the highest levels of lifetime SHS exposure had an estimated risk of inhaled medication usage of 1.74 (95% CI 1.32–2.30). ConclusionsThe risk of requiring one or more prescribed inhaled medications for pulmonary disease was significantly higher in post-menopausal women who ever smoked or who had lifetime exposure to SHS.

Polycystic ovary syndrome phenotype does not increase prevalence of coronary artery disease in postmenopausal women

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Treatment with estrogen protects against ovariectomy-induced hepatic steatosis by increasing AQP7 expression.

Recent evidence has suggested that the marked decrease in ovarian secretion of estrogens in postmenopausal women may be associated with the development of non-alcoholic fatty liver disease. The present study aimed to elucidate the mechanisms by which low levels of estrogen induce fatty liver disease using an ovariectomized (OVX) mouse model and an invitro cell model. A total of 24female C57/BL6 mice were divided into four groups: Sham operation, sham operation plus subcutaneous implantation of tamoxifen (TAM), bilateral OVX, and OVX plus subcutaneous implantation of 17β-estradiol (E2). Marked hepatic steatosis and increased expression of lipogenic genes (acetyl‑CoA carboxylase, fatty acid synthase and glycerol-3-phosphate acyltransferase) was observed in the estrogen‑depleted mice (TAM and OVX groups), as compared with in the sham operation group. Treatment with E2 significantly improved hepatic steatosis by decreasing the expression of the aforementioned lipogenic genes. Furthermore, hepatic aquaporin7 (AQP7) expression was decreased in the estrogen‑depleted mice, but was increased in the OVX+E2 treatment group, as compared with in the sham operation group. These results suggested an association between AQP7 and low estrogen‑induced hepatic steatosis. Subsequently, the functions of AQP7 in hepatic steatosis were investigated using an oleic acid‑induced HepG2 cell model of steatosis. Treatment with E2 alleviated lipid accumulation and decreased the expression of lipogenic genes invitro; however, such effects were attenuated following transfection with AQP7 small interferingRNA. The present study suggested a mechanism by which low levels of estrogen induce fatty liver disease, and may provide useful information regarding the prevention and treatment of fatty liver disease in postmenopausal women.

The association between MDA-oxidised LDL, antibodies against oxidised LDL and ischemic heart disease in postmenopausal women: a population-based study

The association between MDA-oxidised LDL, antibodies against oxidised LDL and ischemic heart disease in postmenopausal women: a population-based study

Menopausal hormone therapy – a course on individuality

Actuality of menopausal hormone therapy is due to demographic realities and expectations, the changing social role of women. According to WHO projections, by 2050 the number of elderly people in developed countries will be twice as much as the children; most of the world’s population will be women over the age of 45 years. The growing social role of women and the pursuit of active longevity put before medicine two important tasks: relief of menopause symptoms and the prevention of related conditions, that threaten the lives or severely reducing its quality.Menopausal hormone therapy is now recognized as the most effective treatment for vasomotor and urogenital atrophy syndromes, effective prevention of osteoporosis, cardiovascular diseases in postmenopausal women. Timely and individualized approach is the main condition for its effectiveness and safety.The article suggests various options for medical support for premenopausal women, depending on the hormonal changes. Emphasis is placed on cyclic estrogen-progestin therapy.Contrary to the traditional passion for “natural” progestins, the authors have shown the benefits of “synthetic” hormones in combination: estradiol valerate and levonorgestrel (hormonal contraceptive klimonorm).Residual androgenic activity of levonorgestrel turns into advantage if the clinical picture is dominated by fatigue, asthenia, decreased libido, pain in bones and joints, osteoporosis.As a 19-norsteroid it provides protection from endometrial proliferative processes, which makes it possible for safe use of menopausal hormone therapy in women with hyperplasia and endometrial polyps in the history. The seven-day break in the cyclic intake provides a reliable control of the menstrual cycle, which improves adherence to treatment. Klimonorm may also be recommended to women with ovarian failure syndrome undergoing surgery ovariectomy.Thus, rejection of the templates in menopausal hormone therapy, an individualized approach may maximize the therapeutic and prophylactic preparations effects, reduce the number of adverse reactions and complications, and increase the number of its supporters among doctors and patients.

11,12-Epoxyecosatrienoic acids mitigate endothelial dysfunction associated with estrogen loss and aging: Role of membrane depolarization

ObjectiveEndothelial dysfunction, including upregulation of inflammatory adhesion molecules and impaired vasodilatation, is a key element in cardiovascular disease. Aging and estrogen withdrawal in women are associated with endothelial inflammation, vascular stiffness and increased cardiovascular disease. Epoxyecosatrienoic acids (EETs), the products of arachidonic acid metabolism mediated by cytochrome P450 (CYP) 2J, 2C and other isoforms, are regulated by soluble epoxide hydrolase (sEH)-catalyzed conversion into less active diols. We hypothesized that 11,12-EETs would reduce the endothelial dysfunction associated with aging and estrogen loss. Approach/resultsWhen stabilized by an sEH inhibitor (seHi), 11,12-EET at a physiologically low dose (0.1nM) reduced cytokine-stimulated upregulation of adhesion molecules on human aorta endothelial cells (HAEC) and monocyte adhesion under shear flow through marked depolarization of the HAEC when combined with TNFα. Mechanistically, neither 11,12-EETs nor 17β-estradiol (E2) at physiologic concentrations prevented activation of NFκB by TNFα. E2 at physiological concentrations reduced sEH expression in HAEC, but did not alter CYP expression, and when combined with TNFα depolarized the cell. We also examined vascular dysfunction in adult and aged ovariectomized Norway brown rats (with and without E2 replacement) using an ex-vivo model to analyze endothelial function in an intact segment of artery. sEHi and 11,12-EET with or without E2 attenuated phenylephrine induced constriction and increased endothelial-dependent dilation of aortic rings from ovariectomized rats. ConclusionsIncreasing 11,12-EETs through sEH inhibition effectively attenuates inflammation and may provide an effective strategy to preserve endothelial function and prevent atherosclerotic heart disease in postmenopausal women.

Advanced Endometrial Carcinoma with Polycystic Ovarian Syndrome

Introduction Endometrial cancer is the most common cancer in Europe and North America and the second most common gynecological malignancy world wide according to WHO. It is a disease of postmenopausal women. The disease is rare in young women. However, patients with anovulatory polycystic ovarian syndrome are at risk of developing endometrial carcinoma. The disease may be advanced when diagnosed, thereby depriving the woman of the option for fertility-sparing conservative approach.

Abstract MP38: Plasma Lipophilic Index and Risk of Coronary Heart Disease in Postmenopausal Women

Introduction: Fatty acids (FAs) are essential components of cell membranes and play an integral role in membrane fluidity. The lipophilic index (LI, defined as the sum of the products between FA percentage and melting points (°C) of each FA, divided by the total percentage of FAs) is a novel index that captures the overall FA profile and reflects lipoprotein fluidity. Limited studies have evaluated the relationship between plasma LI and CHD risk, and none has assessed this association among postmenopausal women. Hypothesis: Higher plasma LI is associated with increased CHD risk among postmenopausal women. Methods: In a nested case-control study in Women’s Health Initiative Observational Study, we measured levels of plasma phospholipid FAs, expressed as molar percentage (mol%), in 1214 matched CHD cases (including myocardial infarction and coronary death) and controls. Multivariate conditional logistic regression was used to calculate ORs for CHD risk between each quartiles (based on controls) of LI after adjusting for confounders. Results: The mean age of the women was 67.8±6.8 years, average BMI was 27.6±6.0, 89.5% were White, 6.6% were current smokers, 41.2% were hypertensive, and 15.2% had dyslipidemia. The median plasma LI among cases and controls were 22.5 and 22.1, respectively. Palmitic acid (16:0) and stearic acid (18:0), oleic acid (18:1), linoleic acid (18:2), and docosahexaenoic acid (22:6) were the most common saturated, monounsaturated, n-6 and n-3 polyunsaturated FAs, respectively. The association between quartiles of LI and CHD risk are shown in Table below. After multivariate adjustment in the parsimonious model, plasma LI was significantly associated with an increased risk of CHD: OR=1.61 (95% CI 1.25-2.07, P for trend&lt;0.01) comparing extreme quartiles. This association was attenuated to 1.57 (1.22 - 2.03, P for trend&lt;0.01) in the fully adjusted model. Conclusion: Our study indicated that higher plasma LI, which represents lower FA fluidity, was associated with higher risk of CHD among postmenopausal women.

Dry eye in postmenopausal women

This review examines the etiology and pathophysiology of dry eye disease in postmenopausal women, and describes the steroid reproductive hormone influences that may contribute to its development. We have reviewed the relevant studies on dry eye disease related to hormonal status and hormone therapy (HT) in both animal models and humans. Although both low and high estrogen levels have been associated with symptoms of dry eye disease, low androgen levels are a more consistent factor in its etiology. Postmenopausal HT with estrogen or estrogen plus progestogen has shown a limited benefit for dry eye symptoms and may even result in progression of meibomian gland dysfunction, decreased tear film break up time, and tear flow reduction. However, systemic or local androgen treatment has shown promising results in improving dry eye symptoms. Because of the high incidence of dry eye among postmenopausal women that may be related to the hormonal treatment, we propose that a multidisciplinary approach should be considered between gynecologists and ophthalmologists in management of this disorder.

Abstract P1-01-10: Pleomorphic lobular carcinoma in situ (PLCIS)-presentation, associated lesions and outcome

Abstract Pleomorphic lobular carcinoma in situ (PLCIS) is an uncommon lesion characterised by dyscohesive lobular cells showing high grade nuclei. It is commonly associated with comedo necrosis and luminal calcifications and hence diagnosed on mammographic screening. Data on the presentation, focality, associated lesions, optimal treatment and outcome of PLCIS is patchy. Methods Cases diagnosed as PLCIS between 2005 and 2015 were identified from the imaging and pathology databases of two UK large breast screening units. Cases diagnosed on diagnostic core biopsy/VAB or surgical excisions were included. Comprehensive data was collected on age, mode of presentation (screening vs symptomatic), imaging (mammography, ultrasound and MRI), surgical management, histological features on core biopsy and excision including type, grade and immunohistochemical profile of associated ductal carcinoma in situ (DCIS) and invasive carcinoma. Results 86 cases with the diagnosis of PLCIS (confirmed by review and e-cadherin negativity) were identified. The mean patient age at diagnosis was 61.04 years, range: 39-84 years. 32 cases were treated with wide local excision with/without axillary procedure. A total of 38 patients were screen detected &amp; 36 cases were diagnosed in the symptomatic setting. Others presented as incidental calcifications on family history screening, incidental histological findings in breast reductions and risk reducing mastectomy. On mammography, 6 patients presented with an asymmetrical density, with or without calcifications, 25 with calcifications, 44 as a mass and 2 as stromal deformity. No mammographic abnormality was found in 9 cases. PLCIS was multifocal in 19.7% of cases, diffuse in 9.9%, focal in 69% and multi-centric in 1.4% on imaging. Histologically, PLCIS was the most advanced lesion on core biopsy without associated DCIS or invasive disease (pure PLCIS) in 23 patients. Of these, surgical excision revealed an invasive carcinoma in 7 cases (upgrade rate =30.4%). Six more patients presented as DCIS and PLCIS on core biopsy; three of whom (50%) had invasive disease on excision. Classical LCIS was associated with PLCIS in 27/86 cases (31.3%). The most common type of associated invasive carcinoma on surgical excision was invasive classical lobular carcinoma (ILC, 40 cases), followed by invasive pleomorphic lobular carcinoma (IPLC, 27 cases). Ductal no special type carcinoma, solid papillary and tubulo-lobular carcinoma were also identified. The size of PLCIS on excision ranged from 1-80mm. DCIS was associated in 26.7% of cases. The majority of invasive cancers were of grade 2 (53.5%) and 3 (19%). The tumors were ER positive (53 cases), PR positive (43 cases) and HER2 negative (52 cases). Conclusion PLCIS is an uncommon in situ carcinoma presenting via mammographic and also in the symptomatic setting. Unlike classical LCIS, PLCIS is a disease of postmenopausal women. It is multifocal in approximately one fifth of the cases. PLCIS is commonly associated with classical LCIS and both ILC and IPLC. When identified in core biopsy, the upgrade rate in this series was 30.4% which increased to 50% if the lesion co-existed with DCIS. The associated cancers are often ER positive, HER2 negative. These findings support managing those lesions surgically as per DCIS. Citation Format: Shaaban AM, Smith S, Bradley S, McMahon M, Sharma N. Pleomorphic lobular carcinoma in situ (PLCIS)-presentation, associated lesions and outcome. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-01-10.