Associations of reproductive and breastfeeding history with anti-Müllerian hormone concentration among African-American women of reproductive age.

RESEARCH QUESTION: Are gravidity, parity and breastfeeding history associated with anti-Müllerian hormone concentration among African-American women of reproductive age? DESIGN: This study included baseline data from the Study of the Environment, Lifestyle and Fibroids, a 5-year longitudinal study of African-American women. Within this community cohort, data from 1392 women aged 25-35 years were analysed. The primary outcome was serum anti-Müllerian hormone concentration measured using the Ansh Labs picoAMH assay, an enzyme-linked immunosorbent assay. Multivariable linear regression models were used to estimate mean differences in anti-Müllerian hormone concentration (ß) and 95% CI by self-reported gravidity, parity and breastfeeding history, with adjustment for potential confounders. RESULTS: Of the 1392 participants, 1063 had a history of gravidity (76.4%). Of these, 891 (83.8%) were parous and 564 had breastfed. Multivariable-adjusted regression analyses found no appreciable difference in anti-Müllerian hormone concentration between nulligravid participants and those with a history of gravidity (ß = -0.025, 95% CI -0.145 to 0.094). Among participants with a history of gravidity, there was little difference in anti-Müllerian hormone concentration between parous and nulliparous participants (ß = 0.085, 95% CI -0.062 to 0.232). There was also little association between anti-Müllerian hormone concentration and breastfeeding history (ever versus never: ß = 0.009, 95% CI -0.093 to 0.111) or duration of breastfeeding (per 1-month increase: ß = -0.002, 95% CI -0.010 to 0.006). CONCLUSIONS: Gravidity, parity and breastfeeding history were not meaningfully associated with anti-Müllerian hormone concentration in this large sample of the Study of the Environment, Lifestyle and Fibroids cohort.

Glycemic and metabolic sub-classification of prediabetes and risk factors for cardiovascular disease in the D2d cohort.

Objectives: Prediabetes represents a spectrum of metabolic abnormalities, including insulin resistance and secretory impairment, that carries increased cardiovascular disease (CVD) risk. It is unclear whether specific glycemic and metabolic sub-classifications are associated with CVD risk. This cross-sectional analysis of 3946 participants from the Vitamin D and Type 2 Diabetes (D2d) study cohort aimed to determine the associations between various baseline CVD risk factors, glycemic sub-classifications of prediabetes (FPG, 2hPG, and HbA1c), and measures of insulin sensitivity and secretion from an OGTT. Methods: The metabolic syndrome and atherosclerotic cardiovascular disease (ASCVD) risk scores were determined for tertiles of insulin sensitivity (HOMA2S) and insulinogenic index (IGI). Unadjusted analyses showed elevated CVD risk factors in the lowest tertile for both IGI and HOMA2S. Results: After adjustment for age, gender, race, obesity, and smoking status, the association remained between HOMA2S and ASCVD score (r = -0.11, p< 0.001) but not for IGI. Those who met at least 2 diagnosic criteria for prediabetes had the largest proportion (> 40%) of participants with high ASCVD risk score >20. A higher percentage of individuals that met all 3 criteria for prediabetes had metabolic syndrome and ASCVD risk score >20 (87.2% and 15.3%, respectively) than those who only met 1 prediabetes criterion (51.6% and 7.1%, respectively). Conclusions: In conclusion, multiple metabolic (HOMA2S, IGI) and glycemic criteria of prediabetes (FPG, 2hPG, & HbA1c) are needed to fully recognize the elevated CVD risk profile that can manifest in prediabetes.

Obesity-related alterations in protein expression in human follicular fluid from women undergoing in vitro fertilization.

OBJECTIVE: To compare the proteomic composition of follicular fluid from women with normal weight vs. women with obesity but without a history of polycystic ovary syndrome or known ovarian dysfunction undergoing in vitro fertilization. DESIGN: Cross-sectional. SETTING: Academic medical center. PATIENT(S): Eight women with normal weight and 8 women with obesity undergoing in vitro fertilization and without a history of polycystic ovary syndrome, ovulatory dysfunction, diminished ovarian reserve, or known endometriosis were included in the analysis. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Proteomic assessment using liquid chromatography-mass spectrometry analysis. RESULT(S): The mean age of women with normal weight was similar to that of women with obesity (32.9 vs. 32.6 years, not significant). The mean body mass index of women with normal weight was 21.2 kg/m2 compared with a body mass index of 37.1 kg/m2 in women with obesity. A total of 1,174 proteins were identified with ≥2 peptides present. Twenty-five proteins were found to be significantly altered in the follicular fluid from women with obesity. Of these 25 proteins, 19 were up-regulated and 6 were down-regulated. Notably, C-reactive protein was 11-fold higher in the follicular fluid from women with obesity than in the follicular fluid from women with normal weight. CONCLUSION(S): Obesity is associated with dysregulation at the level of the follicle, including alterations in proteins related to inflammation and metabolism. These include proteins with emerging roles in energy homeostasis and follicular regulation.

Obesity-induced follicular phase endometrial proteome dysregulation in a well-phenotyped population.

OBJECTIVE: Despite obesity's significant impact on reproduction, its influence on the physiology of the human endometrium is largely understudied. We hypothesized that endometrial proteomic differences exist between obese (OW; body mass index [BMI] ≥30 kg/m2) and normal-weight women (NWW; BMI, 18.5-24.9 kg/m2). DESIGN: Clinical cross-sectional study. SETTING: Academic Medical Center. PATIENT(S): Healthy, normally-cycling, 18 to 40-year-old women (n = 6 OW and n = 6 NWW). MAIN OUTCOME MEASURE(S): Participants underwent screening and midfollicular phase visits. Demographic and anthropometric characteristics, blood samples, ultrasounds, and follicular phase endometrial biopsies were collected. Proteomic analyses of endometrial samples (liquid chromatography-mass spectrometry) were performed. Proteins with ≥2-fold difference and a false discovery rate of <0.1 were considered statistically significant (Benjamini-Hochberg adjustment). RESULT(S): Reproductive hormone levels did not differ between the two groups. Mean BMI, serum leptin concentration, and bioelectrical impedance analysis indices of adiposity were higher in OW than in NWW. Histological examination of the endometrial samples confirmed normal-appearing endometrium in both OW and NWW. A total of 2,930 proteins were detected across all samples, with an average number of proteins per sample of 2,059 ± 482 in NWW and 2,437 ± 187 in OW. A total of 17 proteins were differentially expressed in OW vs. NWW; 2 were more abundant, whereas 15 were underexpressed in OW, including the progesterone receptor. CONCLUSION(S): In this well-phenotyped population of healthy women, obesity was associated with significant endometrial proliferative phase proteomic differences affecting the hormonal and immunologic pathways. These could contribute to an increased risk of menstrual bleeding abnormalities and create an altered environment for future luteinization.

The Environment, Leiomyomas, Latinas, and Adiposity Study: rationale and design.

BACKGROUND: Uterine leiomyomas, commonly known as fibroids, are benign tumors in postmenarchal females. By the age of 35 years, approximately 30% of females will have fibroids, and by the age of 50 years, the prevalence approaches 70% with some studies reporting >85% prevalence in African American females. Previous studies evaluating the prevalence of fibroids have largely relied on self-reported fibroid diagnoses, which could have falsely underestimated prevalence because many females with fibroids are asymptomatic. Despite known differences in fibroid prevalence by race, there are very limited data on fibroid prevalence by ethnicity. The Latino population is the largest ethnic minority in the United States, yet there is no large study that utilizes ultrasound to confirm the presence of fibroids in Latina/Latinx females. In addition, fibroids have been associated with obesity and with diabetes mellitus, but the data have been inconsistent and at times conflicting. OBJECTIVE: The Environment, Leiomyomas, Latinas, and Adiposity Study was designed to quantify the prevalence of uterine fibroids among Latina/Latinx females and understand the relationships between obesity, glucose dysregulation, and fibroid prevalence and growth. This article presents the study's design and reports early enrollment data. STUDY DESIGN: The Environment, Leiomyomas, Latinas, and Adiposity Study is a 5-year longitudinal cohort study based in Southeast Michigan with the goal of recruiting 600 Latina/Latinx females between the ages of 21 and 50 years. Given the recruitment goals, developing a respectful, transparent, and trusting relationship between the study investigators and the community was a major priority. Thus, a community-engaged research approach was utilized in the design of the Environment, Leiomyomas, Latinas, and Adiposity Study. A community advisory board containing community leaders, largely from the Latinx community, provided input and direction during the entirety of the Environment, Leiomyomas, Latinas, and Adiposity Study design and rollout process. A minimum of 3 visits (orientation and consent, baseline, follow-up) will be conducted for each participant, with baseline and follow-up visits approximately 18 to 30 months apart. At each visit, interviewer and self-administered surveys will assess sociodemographic factors, health behaviors, health history, and social determinants of health. In addition, participants undergo a pelvic ultrasound examination and biologic samples are collected. RESULTS: Using community-engaged approaches, we have successfully enrolled 633 Latina/Latinx females. The mean participant age is 37.5±7.04 years. The mean body mass index is 30.0±6.54 kg/m2. First study visits have been initiated. CONCLUSION: The objective of the Environment, Leiomyomas, Latinas, and Adiposity Study is to address the knowledge gap regarding uterine fibroids in the Latina/Latinx population. The Environment, Leiomyomas, Latinas, and Adiposity Study will generate ultrasound-confirmed evidence of the prevalence and growth patterns of uterine fibroids in this specific population while also examining the associations between obesity and laboratory-confirmed glucose dysregulation with uterine fibroid prevalence and growth patterns.

Activated brown adipose tissue and its relationship to adiposity and metabolic markers: an exploratory study.

Objective: To explore relationships between PET/CT characteristics of cold-activated brown adipose tissue (BAT), measures of adiposity and metabolic markers.Methods: We conducted a post-hoc analysis of a study which utilized PET/CT to characterize BAT. 25 men ages 18-24 (BMI 19.4 to 35.9 kg/m2) were studied. Fasting blood samples were collected. Body composition was measured using DXA. An individualized cooling protocol was utilized to activate BAT prior to imaging with PET/CT.Results: There was an inverse relationship between fasting serum glucose and BAT volume (r = -0.40, p = 0.048). A marginally significant inverse relationship was also noted between fasting glucose and total BAT activity (r = -0.40, p = 0.05). In addition, a positive correlation was observed between serum FGF21 and SUVmax (r = 0.51, p = 0.01). No significant correlations were noted for measures of BAT activity or volume and other indicators of adiposity or glucose metabolism.Conclusions: The presence of active BAT may be associated with lower fasting glucose in young men. BAT activity may also be correlated with levels of FGF21, suggesting that BAT may lower glucose levels via an FGF21 dependent pathway. Further studies are needed to clarify mechanisms by which BAT may impact glucose metabolism.

Knowledge of obesity and its impact on reproductive health outcomes among urban women.

This prospective survey study assessed the knowledge of reproductive outcomes that are affected by obesity among women in an urban community. A total of 207 women attending a community fair on the south side of Chicago participated in the study. A survey assessing knowledge of BMI and of the effects of obesity on general, cardiometabolic and reproductive health outcomes was administered. Subjects ranged in age from 18 to 70 years (mean ± SD, 48.6 ± 12.9 years) and ranged in BMI from 17.3 to 52.1 kg/m(2) (mean ± SD, 31.2 ± 6.7 kg/m(2)). The following percentages of women were aware that obesity increases the risk of miscarriage (37.5 %), irregular periods (35.8 %), infertility (33.9 %), cesarean section (30.8 %), breast cancer (28.0 %), birth defects (23.7 %), stillbirth (14.1 %), and endometrial cancer (18.1 %). This study found that while women in an urban community are aware of the cardiometabolic risks associated with obesity, they demonstrate limited knowledge of the effects of obesity on reproductive outcomes. Public education is needed to increase knowledge and awareness of the reproductive consequences of obesity. Women of reproductive age may be uniquely responsive to obesity education and weight loss intervention.

Infertility patients' knowledge of the effects of obesity on reproductive health outcomes.

OBJECTIVE: The objective of the study was to assess the infertility patient knowledge of reproductive outcomes affected by obesity. STUDY DESIGN: This was a prospective survey study of 150 female infertility patients in an academic medical center. Subjects were administered the Rapid Estimate of Adult Literacy in Medicine-Short Form and a questionnaire on the health risks of obesity, and investigators obtained height and weight measurements. RESULTS: Subjects' age ranged from 21 to 45 years (mean 34.8 ± 4.94 SD) and body mass index ranged from 17.9 to 62.9 kg/m(2) (mean 26.5 ± 7.54 SD). The following percentages of women were aware that obesity increases the risk of infertility (82.7%), irregular periods (70.0%), miscarriage (60.7%), cesarean section (48.7%), breast cancer (38.7%), birth defects (29.3%), stillbirth (22.7%), and endometrial cancer (20.7%). CONCLUSION: Among women with infertility, there is limited knowledge of reproductive outcomes affected by obesity. Public education is needed to increase awareness. Women undergoing fertility treatment are motivated for reproductive success and may be uniquely receptive to obesity education and weight loss intervention.

Diet-induced weight loss reduces colorectal inflammation: implications for colorectal carcinogenesis.

BACKGROUND: Epidemiologic data have shown that obesity independently increases colorectal cancer (CRC) risk, but the mechanisms are poorly understood. Obesity is an inflammatory state, and chronic colonic inflammation induces CRC. OBJECTIVE: We conducted this proof-of-principle study to seek evidence of obesity-associated colorectal inflammation and to evaluate effects of diet-induced weight loss. DESIGN: We measured inflammatory cytokines, gene arrays, and macrophage infiltration in rectosigmoid mucosal biopsies of 10 obese premenopausal women [mean ± SD body mass index (in kg/m(2)): 35 ± 3.5] before and after weight loss induced by a very-low-calorie diet. RESULTS: Subjects lost a mean (±SD) of 10.1 ± 1% of their initial weight. Weight loss significantly reduced fasting blood glucose, total cholesterol, triglycerides, LDL, tumor necrosis factor-α (TNF-α), and interleukin (IL)-8 concentrations (P < 0.05). After weight loss, rectosigmoid biopsies showed a 25-57% reduction in TNF-α, IL-1ß, IL-8, and monocyte chemotactic protein 1 concentrations (P < 0.05). T cell and macrophage counts decreased by 28% and 42%, respectively (P < 0.05). Gene arrays showed dramatic down-regulation of proinflammatory cytokine and chemokine pathways, prostaglandin metabolism, and the transcription factors STAT3 (signal transducer and activator of transcription 3) and nuclear transcription factor κB. Weight loss reduced expression of FOS and JUN genes and down-regulated oxidative stress pathways and the transcription factors ATF (activating transcription factor) and CREB (cyclic AMP response element-binding). CONCLUSIONS: Our data show that diet-induced weight loss in obese individuals reduces colorectal inflammation and greatly modulates inflammatory and cancer-related gene pathways. These data imply that obesity is accompanied by inflammation in the colorectal mucosa and that diet-induced weight loss reduces this inflammatory state and may thereby lower CRC risk.

Temozolomide in the treatment of an invasive prolactinoma resistant to dopamine agonists.

Prolactinomas are common tumors of the anterior pituitary gland. While conventional therapies, including dopamine agonists, transsphenoidal surgery and radiotherapy, are usually effective in controlling tumor growth, some patients develop treatment-resistant tumors. In this report, we describe a patient with an invasive prolactinoma resistant to conventional therapy that responded to the administration of the alkylating agent, temozolomide.

Pharmacotherapy for obesity.

Obesity is a chronic metabolic disorder that affects one third of American adults. Modest weight losses of just 5% to 10% of body weight, which are achievable with lifestyle modification and pharmacotherapy, can lead to remarkable improvements in many obesity-associated co-morbidities, including dyslipidemia, hypertension, and type 2 diabetes. In this review, the indications for pharmacotherapy and the goals of treatment are discussed, and current and future pharmacologic approaches to the treatment of obesity are examined. Current pharmacologic therapies for obesity are limited, but recent advances in our understanding of the complex and overlapping endocrine pathways that regulate body weight have led to new opportunities for antiobesity drug development. Important drug targets that are highlighted in this review include adipocyte-derived hormones, hypothalamic neuropeptides, and gastrointestinal hormones.

Current directions in hemochromatosis research: towards an understanding of the role of iron overload and the HFE gene mutations in the development of clinical disease.

Since the discovery of a candidate gene (HFE) thought to be involved in the development of hereditary hemochromatosis, there has been much interest in the potential use of genetic testing as a screening tool for the disease in the general population. However, a recent study suggests that less than 1% of subjects who are homozygous for the gene mutations will go on to develop the full-blown disease of hereditary hemochromatosis, historically termed "bronzed diabetes." The study also suggests that homozygotes have no higher risk of mortality or of any clinically significant morbidity than normal control subjects. This conclusion contradicts earlier findings that linked iron overload and HFE mutations to a number of devastating diseases, including cardiovascular disease, diabetes, and cancer.