Carolyn Alexander

Use of metformin in polycystic ovary syndrome.

Women with polycystic ovary syndrome (PCOS) have a myriad of phenotypic and clinical features that may guide therapeutic options for metabolic protection and ovulation induction. The use of metformin may prove beneficial in a subset of the population of women with PCOS. Hyperinsulinemia, as demonstrated by elevated insulin levels on a 2-hour 75-g load glucose tolerance test, is an important parameter in deciding whether or not to initiate metformin therapy to women with PCOS with the hope of preventing or delaying the onset of type 2 diabetes mellitus (DM). Cardiovascular risk factors including markers of subclinical inflammation, and dyslipidemia may also be improved by metformin therapy. For ovulation induction, metformin is not as effective as clomiphene citrate as first-line therapy for women with PCOS. There are no clear data to suggest that metformin reduces pregnancy loss or improves pregnancy outcome in PCOS, and it is currently recommended that metformin be discontinued with the first positive pregnancy test result, unless there are other medical indications (eg, type 2 DM). This review addresses practical management guidelines for the uses of metformin in women with PCOS.

BRCA1 germline mutations may be associated with reduced ovarian reserve

OBJECTIVE To determine whether BRCA carriers have a decreased ovarian reserve compared with women without BRCA mutations, because BRCA mutations may lead to accelerated oocyte apoptosis due to accumulation of damaged DNA. DESIGN Cross-sectional study. SETTING Academic tertiary care center. PATIENT(S) A total of 143 women, aged 18-45 years, who underwent clinical genetic testing for BRCA deleterious mutations because of a family history of cancer, were included. The cohort was classified into three groups: BRCA1 carriers, BRCA2 carriers, and women without BRCA mutations (controls). None had a personal history of breast or ovarian cancer. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) The main outcome was serum antimüllerian hormone (AMH) level. Linear and logistic regression models adjusting for age and body mass index (BMI) were performed to determine the association between BRCA mutations and AMH. RESULT(S) BRCA1 mutation carriers had a significant decrease in AMH levels compared with controls after adjusting for age and BMI (0.53 ng/mL [95% confidence interval (CI) 0.33-0.77 ng/mL] vs. 1.05 ng/mL [95% CI 0.76-1.40 ng/mL]). Logistic regression confirmed that BRCA1 carriers had a fourfold greater odds of having AMH <1 ng/mL compared with controls (odds ratio 4.22, 95% CI 1.48-12.0). There was no difference in AMH levels between BRCA2 carriers and controls. CONCLUSION(S) BRCA1 carriers have lower age- and BMI-adjusted serum AMH levels compared with women without BRCA mutations. Our results contribute to the current body of literature regarding BRCA carriers and their reproductive outcomes. Larger prospective studies with clinical outcomes such as infertility and age at menopause in this population are needed to further substantiate our findings.

Oral contraceptive pill use and abnormal menstrual cycles in women with severe condylar resorption: A case for low serum 17β-estradiol as a major factor in progressive condylar resorption

INTRODUCTION Progressive condylar resorption has been described for many years. Because condylar resorption favors women over men, many have thought that a prominent systemic factor for the pathogenesis of this disease might be related to sex hormones. METHODS Over a 3-year period, 27 women without autoimmune disease came to our office for orthognathic surgical correction of their skeletal deformity secondary to severe condylar resorption. They all showed radiographic evidence of severe condylar resorption. Sex hormone dysfunction was evaluated, and midcycle serum levels of 17beta-estradiol were measured. Use of exogenous hormones was also documented. RESULTS Twenty-six of the 27 women with severe condylar resorption had either laboratory findings of low 17beta-estradiol or a history of extremely irregular menstrual cycles. Of the 27 women, 25 showed abnormally low levels of serum 17beta-estradiol at midcycle. Two subsets were identified in the group with low 17beta-estradiol. The first did not produce estrogen naturally (8 of 27), and the second had low 17beta-estradiol levels secondary to oral contraceptive pill (OCP) use (19 of 27). Of the 19 OCP users, all 19 reported that chin regression and open bite changes occurred after starting OCP use. Nine of the 19 reported these condylar resorption symptoms within the first 6 months of starting the OCP. CONCLUSIONS Whether induced by ethinyl estradiol birth control or by premature ovarian failure, low circulating 17beta-estradiol makes it impossible for the natural reparative capacity of the condyle to take place in the face of local inflammatory factors. This leads to cortical and medullary condylar lysis.

Pregnancy outcomes in very advanced maternal age pregnancies: the impact of assisted reproductive technology

OBJECTIVE To determine whether there are differences in adverse pregnancy outcomes in very advanced maternal age (vAMA) women who conceived with assisted reproductive technologies (ART) compared with spontaneous conceptions. DESIGN Retrospective cohort study. SETTING Academic tertiary care medical center. PATIENT(S) A total of 472 women aged ≥45 years who delivered at one institution. INTERVENTION(S) Mode of conception. MAIN OUTCOME MEASURE(S) Maternal and neonatal outcomes. RESULT(S) For singleton pregnancies, vAMA women who conceived with ART were significantly older (47.0 ± 2.3 vs. 45.6 ± 0.1 years), more likely to be white (88.1% vs. 75.6%), and less parous (0.4 ± 0.9 vs. 1.2 ± 1.8) than vAMA women who conceived spontaneously. They were at significantly increased risk for cesarean delivery (CD) (75.1% vs. 49.7%) and were more likely to undergo elective primary CD without labor (25.4% vs. 9.4%). Risk of retained placenta was also significantly higher (2.7% vs. 0%). Rates of other maternal complications and neonatal outcomes were similar. Subgroup analysis of ART singleton pregnancies did not demonstrate differences in women using autologous oocytes versus donor oocytes. CONCLUSION(S) Very advanced maternal age women who conceive after ART are more likely to be white, older, primiparous, and are more likely to proceed with an elective CD compared with vAMA women who conceive spontaneously. The increased risk of retained placenta in women who conceive with ART may indicate an underlying risk for placentation defects.

Differentially expressed genes in adipocytokine signaling pathway of adipose tissue in pregnancy

Objective To profile the differential gene expression of the KEGG Adipocytokine Signaling pathway in omental compared to subcutaneous tissue in normal pregnancy. Study Design Subjects included 14 nonobese, normal glucose tolerant, healthy pregnant women. Matched omental and subcutaneous tissue were obtained at elective cesarean delivery. Gene expression was evaluated using microarray and validated by RT-PCR. Differential gene expression was defined as ≥1.5 fold increase at p < 0.05. Results Six genes were significantly downregulated with two upregulated genes in omental tissue. Downregulation of Adiponectin and Insulin Receptor substrate, key genes mediating insulin sensitivity, were observed with borderline upregulation of GLUT-1. There were downregulations of CD36 and acyl-CoA Synthetase Long-chain Family Member 1which are genes involved in fatty acid uptake and activation. There was a novel expression of Carnitine palmitoyltransferase 1C. Conclusion Differential gene expression of Adipocytokine Signaling Pathway in omental relative to subcutaneous adipose tissue in normal pregnancy suggests a pattern of insulin resistance, hyperlipidemia, and inflammation.

Basal metabolic rate in women with PCOS compared to eumenorrheic controls.

PCOS is associated with obesity and insulin resistance. Efforts have focused on whether an abnormal energy homeostasis contributes to the development of obesity in these patients. There are conflicting results in the literature regarding whether women with PCOS have an altered basal metabolic rate (BMR), thereby leading to difficulties in weight loss. The objective of this study is to compare basal metabolic rate (BMR) in women with PCOS and controls.

Conflict Styles in a Cohort of Graduate Medical Education Administrators, Residents, and Board-Certified Physicians

OBJECTIVE To assess conflict styles and construct validity of the Thomas-Kilmann Mode of Conflict Instrument (TKI) among medical education personnel. METHODS From 2006 to 2009, 23 board-certified physicians (faculty), 46 residents, and 31 graduate medical education (GME) administrators participated in 3 behavior surveys. We used self-reported data (as completed by participants on the questionnaire). The TKI defines 5 conflict styles: competing, collaborating, compromising, accommodating, and avoiding. The My Best Communication Style Survey assesses 4 styles of communication: bold, expressive, sympathetic, and technical. The Interpersonal Influence Inventory categorizes 4 behavior styles: openly aggressive, assertive, concealed aggressive, and passive behaviors. A P value of < .05 was significant. RESULTS Avoiding was the conflict style most chosen, closely followed by compromising and accommodating, whereas collaborating was the least likely to be selected. Collaborating percentiles were highest in GME administrators and lowest in faculty. Competing percentiles decreased from faculty to GME administrators (r  =  -0.237, P  =  .017). Openly aggressive scores were highest in faculty and lowest in GME administrators (P  =  .028). Technical communication scores were highest in residents and lowest in GME administrators (P  =  .008). Technical communication scores were highest in African Americans (P  =  .000). Asian Americans were more likely to be high in accommodating style (P  =  .019). Midwest respondents selected the collaborating style more than others did (41.3% versus 25%) (P  =  .009). Competing conflict style correlated positively with openly aggressive behavior and bold communication but negatively with expressive and sympathetic communications. CONCLUSION There are differences in behavior patterns among faculty, residents, and GME administrators with suggestions of ethnic and geographic influences. Correlation among instruments supported theoretical relationships of construct validity.