Estrogen,inflammation, and platelet phenotype

Background: Although exogenous estrogenic therapies increase the risk of thrombosis, the effects of estrogen on formed elements of blood are uncertain.Objective: This article examines the genomic and nongenomic actions of estrogen on platelet phenotype that may contribute to increased thrombotic risk.Methods: To determine aggregation, secretion, protein expression, and thrombin generation, platelets were collected from experimental animals of varying hormonal status and from women enrolled in the Kronos Early Estrogen Prevention Study.Results: Estrogen receptor β predominates in circulating platelets. Estrogenic treatment in ovariectomized animals decreased platelet aggregation and adenosine triphosphate (ATP) secretion. However, acute exposure to 17β-estradiol did not reverse decreases in platelet ATP secretion invoked by lipopolysaccharide. Thrombin generation was positively correlated to the number of circulating microvesicles expressing phosphatidylserine.Conclusion: Assessing the effect of estrogen treatments on blood platelets may lead to new ways of identifying women at risk for adverse thrombotic events with such therapies.     

A Review of Breast Development in Cisgender Women and Implications for Transgender Women

Objective: The objective of this article is to describe the hormonal pathways required for breast development in cisgender women and to review the current available literature describing breast growth and breast cancer risk in transgender women.Methods: Literature review and discussion.Results: Early mammary tissue development occurs prenatally. This process is hormone-independent and occurs similarly in males and females. Breast tissue is quiescent until puberty, at which time surging estrogen levels in cisgender girls mediate breast development and growth. Adult breast tissue composition further evolves in cisgender women during pregnancy, lactation, and menopause, revealing the ever-changing interplay between breast structure and hormonal environment.Conclusion: Breast growth is a significant physical endpoint in the hormonal treatment of transgender women. Transgender hormone regimens, which typically pair an estrogen with an anti-androgen, can help achieve this goal.     

Identification of 10-dehydrooxyglycyuralin E as a selective human estrogen receptor alpha partial agonist

Selective estrogen receptor modulators (SERMs) act as either agonist or antagonist of estrogen receptor (ER) in a tissue selective manner and have been used in several diseases such as breast cancer, postmenopausal syndrome, osteoporosis, and cardiovascular diseases. However, current SERMs may also increase the risk of serious side effects and trigger drug resistance. Herein, a screening program, that was designed to search for novel SERMs, resulted in the identification of a series of 2-arylbenzofuran-containing compounds that are ligands for ERα, when applying the Gaussia-luciferase reporter assay. One of these compounds, 10-dehydrooxyglycyuralin E (T9) was chemically synthesized. T9 showed anti-estrogenic/proliferative activity in ERα-positive breast cancer cells. Pretreatment of T9 prevented the mRNA expression of GREB1, which is an estrogen response gene. Furthermore, by an in silico docking simulation study we demonstrated that T9 showed interactions directly to ERα. Taken together, these results demonstrated that T9 is a candidate of SERMs and a useful seed compound for the foundation of the selective activity of SERMs.     

Tissue selectivity of ospemifene: Pharmacologic profile and clinical implications

The multifactorial consequences of menopausal estrogen deficiency affect numerous tissues throughout the body. Supplemental hormonal therapies carry the burden of a risk/benefit ratio that must be highly individualized. Selective estrogen receptor modulators (SERMs) are estrogen receptor (ER) agonist/antagonists designed to induce benefits comparable with estrogen while minimizing adverse effects. Here, we review the estrogen agonist/antagonist profile of ospemifene, a novel triphenylethylene derivative recently approved to treat dyspareunia, a symptom of vulvar and vaginal atrophy (VVA) due to menopause, both preclinically and clinically. Ospemifene binds ERα and ERβ with approximately equal affinities. In preclinical models, ospemifene increased vaginal and uterine epithelial thickness and mucification to the same extent as estrogen. Ospemifene did not induce endometrial hyperplasia in animal models; there also was no stimulatory effect on endometrial cells. In rat and human mammary cells in vitro, ospemifene evokes a dose-dependent inhibition on estrogen-induced cell responses and cell proliferation, supporting an antiestrogenic effect in breast. In contrast, ospemifene has an estrogenic effect on bone, as seen by improved bone mineral density, strength, mass, and histomorphometry in preclinical models, consistent with improvements in markers of bone resorption and formation in postmenopausal women. Based on the preclinical evidence, ospemifene has beneficial estrogen-like effects on the vaginal epithelium, preliminary evidence to support a neutral endometrial profile, antiproliferative effects in breast, and estrogenic effects in bone. Taken together, especially regarding estrogen-like effects on the vaginal epithelium, ospemifene presents a profile of tissue-specific effects that appear novel among available SERMs and well-suited for the treatment of VVA.     

Effects of botanical dietary supplements on cardiovascular,cognitive, and metabolic function in males and females

Background: The onset of menopause marks a pivotal time in which the incidence of hypertension and of cardiovascular disease (CVD) begins to increase dramatically in women. Before menopause, the incidences of these diseases are significantly lower in women than in age-matched men. After menopause, the rates of these diseases in women eventually approximate those in men. The loss of endogenous estrogen at menopause has been traditionally believed to be the primary factor involved in these changes.Objective: This review summarizes recent findings regarding the effectiveness of botanicals in the treatment of some menopausal symptoms and other symptoms of aging (eg, rise in arterial pressure, cognitive decline, insulin resistance, and hyperlipidemia).Methods: Articles were selected for inclusion in this review based on the significance of the research and contribution to the current understanding of how each botanical elicits cardioprotective effects. To this end, PubMed and MEDLINE databases were searched, using terms that included the name of the specific botanical along with the relevant aspects of its action(s), such as blood pressure, glycemic control, and lipids. Most of the articles used were published within the past 5 years, although some older articles that were seminal in advancing the current understanding of botanicals were also included.Results: Soy has been found to lower plasma lipid concentrations and arterial pressure in postmenopausal women and age-matched men, and to have protective effects in heart disease and atherosclerosis of the carotid and coronary circulation. Soy was also found to lower fasting insulin concentrations and glycosylated hemoglobin concentrations. Grape seed extract, another frequently used botanical, contains polyphenols that have been found to reduce arterial pressure and salt-sensitive hypertension in estrogendepleted animal models.Conclusion: Several botanical compounds have been found to have beneficial effects in the treatment of the symptoms of menopause and other symptoms of aging, including CVD, cognitive decline, and metabolic diseases.     

Inhibition of neutral lipid synthesis by avarols from a marine sponge

The effects of 14 sesquiterpene hydroquinones, including 8 marine sponge-derived avarols (1–8) and 6 semisynthetic derivatives (9–14), on lipid droplet accumulation and neutral lipid synthesis in Chinese hamster ovary (CHO) K1 cells were investigated. In intact CHO-K1 cell assays, avarol (1) markedly decreased the number and size of lipid droplets in CHO-K1 cells and exhibited the most potent inhibitory activity on the synthesis of cholesteryl ester (CE) and triglyceride (TG) with IC₅₀ values of 5.74 and 6.80 µM, respectively. In enzyme assays, sterol O-acyltransferase (SOAT), the final enzyme involved in CE biosynthesis, and diacylglycerol acyltransferase (DGAT), the final enzyme involved in TG biosynthesis, were inhibited by 1 with IC₅₀ values of 7.31 and 20.0 µM, respectively, which correlated well with those obtained in the intact cell assay. These results strongly suggest that 1 inhibited SOAT and DGAT activities in CHO-K1 cells, leading to a reduction in the accumulation of CE and TG in lipid droplets.     

Gender differences in insulin resistance,body composition,and energy balance

Background: Men and women differ substantially in regard to degrees of insulin resistance, body composition, and energy balance. Adipose tissue distribution, in particular the presence of elevated visceral and hepatic adiposity, plays a central role in the development of insulin resistance and obesity-related complications.Objective: This review summarizes published data on gender differences in insulin resistance, body composition, and energy balance, to provide insight into novel gender-specific avenues of research as well as gender-tailored treatments of insulin resistance, visceral adiposity, and obesity.Methods: English-language articles were identified from searches of the PubMed database through November 2008, and by reviewing the references cited in these reports. Searches included combinations of the following terms: gender, sex, insulin resistance, body composition, energy balance, and hepatic adipose tissue.Results: For a given body mass index, men were reported to have more lean mass, women to have higher adiposity. Men were also found to have more visceral and hepatic adipose tissue, whereas women had more peripheral or subcutaneous adipose tissue. These differences, as well as differences in sex hormones and adipokines, may contribute to a more insulin-sensitive environment in women than in men. When normalized to kilograms of lean body mass, men and women had similar resting energy expenditure, but physical energy expenditure was more closely related to percent body fat in men than in women.Conclusion: Greater amounts of visceral and hepatic adipose tissue, in conjunction with the lack of a possible protective effect of estrogen, may be related to higher insulin resistance in men compared with women.     

Lower postprandial oxidative stress in women compared with men

Background: Previous studies indicate that oxidative stress is increased following intake of a high-fat meal, mediated in large part by the triglyceride (TG) response to feeding as well as fasting oxidative stress values. It has been suggested that women may process TG more efficiently after high-fat meals, based on the antilipidemic properties of estrogen. It has also been reported that women present with lower fasting oxidative stress values than do men. It is possible that women experience attenuated postprandial oxidative stress compared with men.Objective: The purpose of this study was to compare the postprandial TG and oxidative stress response after a lipid meal in healthy men and women.Methods: This study was conducted at The University of Memphis in Memphis, Tennessee, from October to December 2008. Blood samples were collected before (in a 10-hour fasted state), and at 1, 2, 4, and 6 hours after ingestion of a lipid load (heavy whipping cream at 1 g · kg^?1). Blood samples were analyzed for TG, malondialdehyde (MDA), hydrogen peroxide (H₂O₂), and nitrate/nitrite (NOx). The AUC was calculated for each variable and results were compared using a t test. Effect-size calculations were performed using Cohen's d.Results: Samples from 10 men and 10 women, aged 18 to 47 years (17 subjects aged <37 years), were compared. AUC data were not significantly different for TG (mean [SEM] 330 [48] vs 354 [34] mg · dL^?1 · 6h^?1 for men and women, respectively; effect size = 0.09) or NOx (165 [25] vs 152 [17] μmol · L^?1 · 6h^?1 for men and women; effect size = 0.09). However, significant differences were noted for MDA (10.7 [1.3] vs 6.1 [0.5] μmol · L^?1 · 6h^?1 for men and women, respectively; P = 0.002; effect size = 0.61) and H₂O₂ (154 [23] vs 86 [8] μmol · L^?1 · 6h^?1 for men and women; P = 0.013; effect size = 0.53).Conclusions: These data indicate that women experience lower oxidative stress than do men, with regard to MDA and H₂O₂, after ingestion of a lipid load in the form of heavy whipping cream. Considering the strong association between oxidative stress and cardiovascular disease, lower postprandial oxidative stress may be one mechanism associated with decreased risk of cardiovascular disease in women compared with men. Further research is needed to confirm this hypothesis.     

Unexpected equivalent potency of a constrained chromene enantiomeric pair rationalized by co-crystal structures in complex with estrogen receptor alpha

Despite tremendous progress made in the understanding of the ERα signaling pathway and the approval of many therapeutic agents, ER+?breast cancer continues to be a leading cause of cancer death in women. We set out to discover compounds with a dual mechanism of action in which they not only compete with estradiol for binding with ERα, but also can induce the degradation of the ERα protein itself. We were attracted to the constrained chromenes containing a tetracyclic benzopyranobenzoxepine scaffold, which were reported as potent selective estrogen receptor modulators (SERMs). Incorporation of a fluoromethyl azetidine side chain yielded highly potent and efficacious selective estrogen receptor degraders (SERDs), such as 16aa and surprisingly, also its enantiomeric pair 16ab. Co-crystal structures of the enantiomeric pair 16aa and 16ab in complex with ERα revealed default (mimics the A-D rings of endogenous ligand estradiol) and core-flipped binding modes, rationalizing the equivalent potency observed for these enantiomers in the ERα degradation and MCF-7 anti-proliferation assays.     

Substrate channeling in the glycerol-3-phosphate pathway regulates the synthesis,storage and secretion of glycerolipids

The successive acylation of glycerol-3-phosphate (G3P) by glycerol-3-phosphate acyltransferases and acylglycerol-3-phosphate acyltransferases produces phosphatidic acid (PA), a precursor for CDP-diacylglycerol-dependent phospholipid synthesis. PA is further dephosphorylated by LIPINs to produce diacylglycerol (DG), a substrate for the synthesis of triglyceride (TG) by DG acyltransferases and a precursor for phospholipid synthesis via the CDP-choline and CDP–ethanolamine (Kennedy) pathways. The channeling of fatty acids into TG for storage in lipid droplets and secretion in lipoproteins or phospholipids for membrane biogenesis is dependent on isoform expression, activity and localization of G3P pathway enzymes, as well as dietary and hormonal and tissue-specific factors. Here, we review the mechanisms that control partitioning of substrates into lipid products of the G3P pathway.     

Reduced estrogen in menopause may predispose women to takotsubo cardiomyopathy

Background: Takotsubo cardiomyopathy (apical ballooning syndrome) has been reported with increased frequency, most commonly in postmenopausal women. Despite the gender disparity, no clear link between estrogen and its possible cardioprotective effects has been shown.Objectives: We present a case series of takotsubo cardiomyopathy in women and examine the prevalence of estrogen replacement therapy (ERT), in addition to conducting a systematic literature review on this topic.Methods: Consecutive cases of takotsubo cardiomyopathy were identified at our institution, Cleveland Clinic Florida, from January 2006 to December 2008, and patient-level data were extracted for analysis. For the literature review, we searched the MEDLINE database from January 1990 to March 2008 for English-language publications, using the terms apical ballooning syndrome, takotsubo, and stress cardiomyopathy, and identified case reports and series of takotsubo cardiomyopathy. Articles describing female patients and their medication use at time of presentation were included in the study.Results: Eighteen cases of takotsubo cardiomyopathy were identified at our institution, all in postmenopausal women except for 2 who were still menstruating. Of the 16 postmenopausal cases, none were taking ERT at time of presentation. From the literature review, >400 publications were queried, of which 296 were recognized as case reports or series, with 7 articles meeting all of our inclusion criteria. From these reports, 13 women were identified, none of whom were taking ERT at time of presentation.Conclusions: Lack of estrogen replacement in the postmenopausal state may predispose women to takotsubo cardiomyopathy. Further studies are needed to establish the link more firmly.     

Impact of serum estradiol on postprandial lipemia,oxidative stress,and inflammation across a single menstrual cycle

Background: An abrupt rise in circulating lipids, oxidative stress, and inflammatory biomarkers is a common finding after ingestion of a high-fat meal. Estradiol, typically provided via hormone replacement therapy to postmenopausal women, has been reported to possess lipidemic, antioxidant, and antiinflammatory properties, all of which may minimize postprandial oxidative stress.Objective: The purpose of this study was to compare the postprandial triglyceride (TG), oxidative stress, and inflammatory responses after a lipid meal in menstruating women during the early follicular (days 1–3) and preovulatory (day 14) phases of the menstrual cycle.Methods: Healthy normolipidemic women (fasting blood TG, <200 mg/dL) with regular menstrual cycles reported to the Cardiorespiratory/Metabolic Laboratory at the University of Memphis, Memphis, Tennessee (October-December 2008) and consumed an identical lipid meal (heavy whipping cream and water) on 2 separate days during the menstrual cycle. Blood samples were collected premeal and 1, 2, 4, and 6 hours postmeal, then assayed for TG, malondialdehyde (MDA), hydrogen peroxide, Trolox equivalent antioxidant capacity (TEAL), nitrate/nitrite, and C-reactive protein (CRP). The AUC was calculated for each variable, and a 2 (menstrual cycle phase) × 5 (time) ANOVA with Tukey post hoc testing was also conducted. Estradiol concentration was measured in premeal samples for verification of cycle phase.Results: Ten women (mean [SD] age, 29 [11] years; 8 white, 2 black; body mass index, 22 [3] kg/m²) participated in the study. Despite a higher serum estradiol concentration on day 14 (113 [56] pg/mL) compared with the early follicular phase (61 [34] pg/mL), the TG, oxidative stress, and inflammatory AUC responses to feeding were not significantly different. TG (P = 0.03), MDA (P = 0.02), and hydrogen peroxide (P < 0.001) were significantly increased in response to feeding (time effect), whereas nitrate/nitrite was decreased (P = 0.01). TEAC and CRP were not significantly affected.Conclusions: These data indicate that estradiol, at the concentrations noted in the present study, had no significant effect on postprandial TG or biomarkers of oxidative stress or inflammation in a sample of young, healthy women. It is possible that a greater divergence in circulating estradiol may be needed for significant differences to be detected, as may be the case with chronic hormone replacement therapy in postmenopausal women.     

Need for research on estrogen receptor function: Importance for postmenopausal hormone therapy and atherosclerosis

Background: Cardiovascular disease is the leading cause of morbidity and mortality in men and women worldwide. Although rare in premenopausal women, its incidence rises sharply after menopause, indicating atheroprotective effects of endogenous estrogens.Objective: This review discusses the differential effects of estrogen receptor function on atherosclerosis progression in pre- and postmenopausal women, including aspects of gender differences in vascular physiology of estrogens and androgens.Methods: Recent advances in the understanding of the pathogenesis of atherosclerosis, estrogen receptor function, and hormone therapy are reviewed, with particular emphasis on clinical and molecular issues.Results: Whether hormone therapy can improve cardiovascular health in postmenopausal women remains controversial. Current evidence suggests that the vascular effects of estrogen are affected by the stage of reproductive life, the time since menopause, and the extent of subclinical atherosclerosis. The mechanisms of vascular responsiveness to sex steroids during different stages of atherosclerosis development remain poorly understood in women and men.Conclusion: In view of the expected increase in the prevalence of atherosclerotic vascular disease worldwide due to population aging, research is needed to determine the vascular mechanism of endogenous and exogenous sex steroids in patients with atherosclerosis. Such research may help to define new strategies to improve cardiovascular health in women and possibly also in men.     

Insulin-Like Growth Factors,Insulin, and Growth Hormone Signaling in Breast Cancer: Implications for Targeted Therapy

ObjectiveIn recent decades, multiple therapeutics targeting the estrogen and human epidermal growth factor-2 (HER2) receptors have been approved for the treatment of breast cancer.MethodsThis review discusses a number of growth factor pathways that have been implicated in resistance to both anti-estrogen and HER2-targeted therapies. The association between growth factors and breast cancer is well established. Over decades, numerous laboratories have studied the link between insulin-like growth factor (IGF), insulin, and growth hormone (GH) to the development and progression of breast cancer.ResultsAlthough preclinical data demonstrates that blockade of these receptors inhibits breast cancer growth, progression, and drug resistance, therapies targeting the IGF, insulin, and GH receptors (GHRs) have not been successful in producing significant increases in progression- free, disease-free, or overall survival for patients with breast cancer. The failure to demonstrate a benefit of growth factor blockade in clinical trials can be attributed to redundancy in IGF, insulin, and GHR signaling pathways. All 3 receptors are able to activate oncogenic phosphoinositide- 3 kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways.ConclusionConsequently, multitargeted blockade of growth factor receptors and their common downstream kinases will be necessary for the successful treatment of breast cancer. (Endocr Pract. 2014;20:1214-1221)     

Role of Androgen in Liver Fat Content in Women: Metabolically Advantageous or Disadvantageous?

Objective: Androgens have a controversial effect on liver fat content (LFC) in androgen-excess females and androgen-deficient males. Polycystic ovarian syndrome (PCOS) is often associated with hyperandrogenism and nonalcoholic fatty liver disease. The aim of this study was to explore the association between hyperandrogenemia and increased liver fat content in women with PCOS, independent of other metabolic parameters.Methods: This case series study included 501 women with PCOS and 112 aged-matched controls in the outpatient department of a tertiary hospital. Anthropometric measurements, hepatic and renal function, glucose and lipid metabolism parameters, and sex hormones were examined in these women. LFC was measured by quantitative ultrasonography.Results: Women with hyperandrogenism (P<.001), an oligomenorrhoea/anovulation phenotype (P = .0064), and a diagnosis of PCOS (P<.001) had higher LFC. Androgen level is an important factor among the 9 independent risk factors of LFC (P = .0239) and may have a dimorphic impact on LFC. In all women, when the free androgen index (FAI) was less than 41.94, LFC increased with the elevated FAI; when the FAI was greater than 41.94, LFC decreased with the elevated FAI (P<.001). In women with PCOS, receiver operating characteristic curve analysis demonstrated that LFC could at least partially predict impaired glucose regulation, impaired lipid metabolism, and insulin resistance (P<.0001 for all).Conclusion: Androgen level is associated with LFC in dimorphic directions. LFC may be a predictive factor of insulin resistance, impaired glucose regulation, and impaired lipid metabolism in women with PCOS.     

Anabolic Therapy and Optimal Treatment Sequences for Patients With Osteoporosis at High Risk for Fracture

Objective: Provide an update regarding anabolic medications for osteoporosis, which are often considered to be the last resort for patients with osteoporosis, after multiple fractures have already occurred and other medications have already been administered.Methods: Literature review and discussion.Results: Recent pivotal trial data for anabolic agents and randomized trials comparing anabolic and antiresorptive medications suggest that three anabolic agents (teriparatide, abaloparatide, and romosozumab) reduce nonvertebral and vertebral fractures faster and to a greater extent than potent antiresorptive treatments. Furthermore, bone density accrual is maximized when patients are given anabolic agents first, followed by potent antiresorptive therapy. Since total hip bone density during or after osteoporosis treatment has emerged as an excellent surrogate for future fracture risk, attaining a greater hip bone mineral density is a treatment goal for high-risk osteoporosis patients.Conclusion: This review defines the highest-risk patients and summarizes the rationale for the evolving role of anabolic therapy in the management of postmenopausal women at high risk for fracture.Abbreviations: ACTIVE = Abaloparatide Comparator Trial in Vertebral Endpoints; ARCH = Active Controlled Fracture Study in Postmenopausal Women with Osteoporosis at High Risk; BMD = bone mineral density; FRAME = Fracture Study in Postmenopausal Women with Osteoporosis; FRAX = Fracture Risk Assessment Tool; PTH = parathyroid hormone; TBS = trabecular bone score     

饮食疗法对妊娠期糖尿病孕妇血脂代谢动态变化的研究

目的:探讨脂代谢紊乱在妊娠期糖尿病(GDM)中的作用,为妊娠期糖尿病的预防及指导临床干预提供理论依据。方法:观察妊娠期糖尿病患者和糖耐量正常孕妇血脂水平及胰岛素抵抗程度差异,分析妊娠期糖尿病患者饮食治疗前后的血脂及炎症标志物的动态变化,于孕12W、24W及36W分别抽取两组孕妇空腹静脉血,测定糖、脂代谢指标及炎症标志物水平,计算血浆致动脉粥样硬化指数(atherogenic index of the plasma,AIP);应用稳态模型胰岛素抵抗指数(HOMA-IR)及胰岛分泌功能指数(HBCI),评价胰岛素抵抗指数(IR)程度及胰岛功能。结果:(1)GDM组的C肽、FINS、HOMA-IR明显高于糖耐量正常组(normal glucose tolerance,NGT)组(p0.05),GDM组HBCI指数低于NGT组(p0.05)。(2)干预组与对照组比较,12W时,TC、TG、HDL、LDL差异均无统计学意义(p0.05);24W及32W差异均有统计学意义(p0.05),均较对照组高。(3)对GDM组中TC、TG、HDL、LDL、AIP、hs-CRP、N及WBC值进行分析,TG、TC、LDL、AIP、hs-CRP、N及WBC值24W较36W及12W高(p0.05);HDL水平24W较36W及12W低(p0.05)。(4)NGT组中TG、TC、LDL、AIP、hs-CRP、N及WBC值36W较24W及12W高(p0.05);HDL水平36W较24W及12W高(p0.05)。结论:GDM孕妇存在着明显的胰岛素抵抗和胰岛β细胞分泌功能受损。GDM孕妇合并较正常妊娠更为严重的炎症反应,血脂水平明显升高,饮食治疗后对改善IR有益,提示在妊娠期糖尿病患者中,通过适当的饮食治疗进而对血糖及血脂的调整可以显著减少母儿并发症。     

A Simple Intervention Raised Resident-Physician Willingness to Assist Transgender Patients Seeking Hormone Therapy

Objective: Lack of physician knowledge about transgender medicine is a barrier to care. An intervention with medical students changed attitudes about providing transgender medical care, but it is unknown whether at the level of postgraduate education an intervention could have a similar effect. We conducted such an intervention with resident-physicians.Methods: An intervention on transgender medicine covering the durability of gender identity and hormonal treatment regimens was added to the curriculum for residents. An anonymous survey assessed the residents' knowledge and willingness to assist with hormonal therapy before and after the lecture.Results: The percent of residents who agreed that they felt sufficiently knowledgeable to assist with hormonal therapy for a female-to-male patient increased significantly, from 5% before to 76% following the lecture (χ², 24.7; degrees of freedom, 1; P<.001). The percent of residents who reported that they felt sufficiently knowledgeable to assist with hormonal therapy for a male-to-female patient increased significantly, from 5% before to 71% following the lecture (χ², 24.0; degrees of freedom, 1; P<.001). The intervention increased resident knowledge about hormonal therapy for hypogonadal men (χ², 11.4; degrees of freedom, 1; P<.001) and women (χ², 9.4; degrees of freedom, 1; P = .002). The intervention made more residents agree that gender identity has a biologic basis that remains constant (P<.001) and that hormonal and surgical therapies should be offered (P = .047).Conclusion: The lecture significantly increased residents' knowledge and willingness to assist with hormonal therapy for transgender patients.Abbreviation: PGY = postgraduate year     

Temporal Occurrences and Recurrence Patterns of Hypoglycemia During Hospitalization

Objective: To describe the temporal distribution of hypoglycemia and its rate of recurrence during hospitalization to aid in the development of strategies to prevent hypoglycemia in hospitalized patients.Methods: Retrospective review of hypoglycemia (blood glucose <50 mg/dL) audit data in adult hospitalized patients at 2 academic hospitals. Demographics, timing, and blood glucose values were recorded. Antihyperglycemic medications, number of recurrent events, and change in basal insulin dose following the hypoglycemic event were also extracted.Results: A total of 274 index occurrences of hypoglycemia were analyzed. The mean age of the patients was 53.8 years, with roughly equal gender distributions. Twenty-eight percent of the events occurred in the absence of antihyperglycemic therapy. The incidence of hypoglycemia peaked between midnight and 6 AM. There were 36 instances of recurrent hypoglycemia associated with antihyperglycemic therapy, with 78% (n = 28) cases involving basal insulin. Patients on basal insulin who developed hypoglycemia did not have their dose changed prior to the time of the next administration in 75% of the cases.Conclusion: Hypoglycemia in hospitalized patients may occur with greater frequency overnight. Although cumbersome, routine nocturnal glycemic testing should be considered. Education regarding insulin management in the hospital and improved communication between night and day staff may aid in decreasing subsequent hypoglycemic events.Abbreviations: BG = blood glucose EHR = electronic health record ICU = intensive care unit IV = intravenous     

Familial Chylomicronemia Syndrome: A Clinical Guide for Endocrinologists

Objective: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder caused by mutations in lipoprotein lipase, resulting in accumulation of chylomicrons in plasma and hypertriglyceridemia. Elevated triglycerides cause several complications in patients, the most serious being episodes of acute pancreatitis. This review focuses on expert guidance and opinion from an experienced lipidologist and endocrinologist as well as a current review of the literature, as there are no specific guidelines on FCS.Methods: Discussion of expert guidance and opinion review of current literature.Results: To date, there is no pharmacologic treatment for affected patients, and management options primarily include adoption of an extremely restricted, very-low-fat diet, along with avoidance of certain medications and alcohol. Endocrinologists often diagnose and manage patients with metabolic disorders, including patients with high triglyceride levels, but rare diseases like FCS can be missed or poorly evaluated due to knowledge gaps about disease state. Given endocrinologists' role in the treatment of lipid disorders, it is important that they understand the clinical signs and symptoms of FCS to correctly diagnose patients. Patients with FCS can be identified based on a defined clinical criteria and a thorough review of medical history, after excluding differential diagnoses and secondary factors. Typical manifestations include hypertriglyceridemia characterized by lipemic serum, history of abdominal pain, and acute/recurrent pancreatitis. Secondary factors to be excluded are pregnancy, alcohol abuse, uncontrolled diabetes, and use of certain medications.Conclusion: FCS is a rare, inherited lipid disorder disease that often goes underdiagnosed and unmanaged. This review provides a summary of clinical characteristics of FCS that can be potentially used to screen patients in an endocrinologist's office and direct them to the appropriate standard of care.Abbreviations: apoB = apolipoprotein B; apoC-III = apolipoprotein CIII; ASO = antisense oligonucleotide; FCS = familial chylomicronemia syndrome; HTG = hypertriglyceridemia; LPL = lipoprotein lipase; LPLD = lipoprotein lipase deficiency