Cardiovascular Risk Factors and Subclinical Atherosclerosis in Middle Aged Women With a History of Polycystic Ovary Syndrome

The final menstrual period defines menopause and signifies depletion of ovarian follicular reserve and endogenous estradiol. Diminished estradiol underscores postmenopausal increases in chronic health conditions of non-reproductive tissues namely the vascular, skeletal, and central nervous systems. Polycystic ovary syndrome (PCOS) is a prevalent disorder associated with an increased risk for type 2 diabetes and an adverse cardiovascular disease (CVD) risk profile evident at younger ages. It is well established that the risk of CVD increases among women following menopause. However, no definitive studies exist demonstrating increased cardiovascular morbidity or mortality among older women with a history of PCOS. Further, the association between menopause and CVD risk factors has not been fully explored in women with a history of PCOS. Women with PCOS report less menstrual cycle irregularity across time that may reflect varying degrees of ovarian function that in turn may augment CVD risk factors. We evaluated the hypotheses that menopause and lifetime menstrual cycle irregularity would have a modifying effect on CVD risk factors and markers of subclinical atherosclerosis in 152 women with PCOS and 169 normal reproductive controls ages 35 to 67 years. We found that the typical reproductive presentation and the adverse lipid profile observed in younger PCOS women was not as apparent in older PCOS cases compared to controls. Twenty-five percent of menopausal cases, however had type 2 diabetes. Coronary artery calcification (CAC) was greater in cases compared to controls and increased with age. PCOS cases reporting the greatest menstrual irregularity across time had higher total and free testosterone levels and greater CAC compared to cases with more frequent cycles. Our studies support the importance of diabetes prevention in aging women with a history of PCOS to reduce risk for early cardiovascular disease. Further, women with PCOS who present with the greater cycle irregularity may be more likely to have cardiovascular consequences. Relevance to Public Health: Because preventing PCOS is unlikely, interventions focused on promoting healthy aging among women with a history of the condition represents an important undertaking that will temper long-term health burden and improve quality of life

Preparing clinicians to be site investigators in multicenter clinical trials: A training program at an academic medical center

Clinical trials are essential in the translation of biomedical discoveries to new clinical interventions and therapeutics. Successful multisite clinical trials require qualified site investigators with an understanding of the full spectrum of processes and requirements from trial identification through closeout. New site investigators may be deterred by competing demands on their time, the complexity of administrative and regulatory processes for trial initiation and conduct, and limited access to experienced mentor networks. We established a Clinical Trialist Training Program (CTTP) and complimentary Clinical Trials Bootcamp at our institution to address these barriers and increase the number of local site investigators enabled to lead successful clinical trials. An initial cohort of four CTTP scholars received salary support with protected time, didactic training, assistance with study identification and start-up navigation, and quarterly progress meetings. By the end of the 12-month program, this initial cohort identified 33 new trials, utilized feasibility assessments, and reported being on target to sustain their protected time from new clinical trials. Bootcamp attendees demonstrated increased knowledge of resources, offices, and processes associated with clinical trial conduct. Our results support providing compensated protected time, training, and access to experienced clinical research professionals to enable clinicians to become successful site investigators

Perinatal Outcomes in HIV Positive Pregnant Women with Concomitant Sexually Transmitted Infections

Objective. To evaluate whether HIV infected pregnant women with concomitant sexually transmitted infection (STIs) are at increased risk of adverse perinatal and neonatal outcomes. Methods. We conducted a cohort study of HIV positive women who delivered at an inner-city hospital in Atlanta, Georgia, from 2003 to 2013. Demographics, presence of concomitant STIs, prenatal care information, and maternal and neonatal outcomes were collected. The outcomes examined were the association of the presence of concomitant STIs on the risk of preterm birth (PTB), postpartum hemorrhage, chorioamnionitis, preeclampsia, intrauterine growth restriction, small for gestational age, low Apgar scores, and neonatal intensive care admission. Multiple logistic regression was performed to adjust for potential confounders. Results. HIV positive pregnant women with concomitant STIs had an increased risk of spontaneous PTB (odds ratio (OR) 2.11, 95% confidence interval [CI] 1.12–3.97). After adjusting for a history of preterm birth, maternal age, and low CD4+ count at prenatal care entry the association between concomitant STIs and spontaneous PTB persisted (adjusted OR 1.96, 95% CI 1.01–3.78). Conclusions. HIV infected pregnant women with concomitant STIs relative to HIV positive pregnant women without a concomitant STI are at increased risk of spontaneous PTB

Perinatal Outcomes in HIV Positive Pregnant Women with Concomitant Sexually Transmitted Infections

Objective. To evaluate whether HIV infected pregnant women with concomitant sexually transmitted infection (STIs) are at increased risk of adverse perinatal and neonatal outcomes. Methods. We conducted a cohort study of HIV positive women who delivered at an inner-city hospital in Atlanta, Georgia, from 2003 to 2013. Demographics, presence of concomitant STIs, prenatal care information, and maternal and neonatal outcomes were collected. The outcomes examined were the association of the presence of concomitant STIs on the risk of preterm birth (PTB), postpartum hemorrhage, chorioamnionitis, preeclampsia, intrauterine growth restriction, small for gestational age, low Apgar scores, and neonatal intensive care admission. Multiple logistic regression was performed to adjust for potential confounders. Results. HIV positive pregnant women with concomitant STIs had an increased risk of spontaneous PTB (odds ratio (OR) 2.11, 95% confidence interval [CI] 1.12-3.97). After adjusting for a history of preterm birth, maternal age, and low CD4+ count at prenatal care entry the association between concomitant STIs and spontaneous PTB persisted (adjusted OR 1.96, 95% CI 1.01-3.78). Conclusions. HIV infected pregnant women with concomitant STIs relative to HIV positive pregnant women without a concomitant STI are at increased risk of spontaneous PTB

An algorithm for treatment of infertile women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a common condition with both a reproductive and metabolic phenotype. Women with PCOS often seek care because of infertility or menstrual cycle irregularities that result from chronic anovulation interspersed with occasional ovulatory cycles. Initially, it is important to delineate a differential diagnosis for oligo- or amenorrhea and to evaluate for disorders that may “masquerade” as PCOS. If fertility is a desired goal, then it is critical to optimize health conditions that impact fertility and gestation. Lifestyle modifications, including nutritional counseling and weight loss, should be a part of all treatment plans. Even minimal (5%) weight loss in obese women with PCOS improves both ovulation and pregnancy rates. The first line of treatment for ovulation induction remains the selective estrogen receptor modulator (SERM) clomiphene citrate. The role of insulin sensitizers, particularly metformin, remains unclear. A recent consensus panel recommended against its routine use in the absence of an elevated glucose or hemoglobin A1c. If a woman fails to achieve pregnancy after a trial of weight loss and six ovulatory cycles induced by clomiphene citrate, then ovulation induction with exogenous gonadotropin, with or without timed intrauterine insemination, or in vitro fertilitization, is a reasonable next step. Women with PCOS are particularly prone to excessive follicle development and are at increased risk for ovarian hyperstimulation syndrome (OHSS). Although limited data exist comparing approaches to ovulation induction or controlled ovarian stimulation in women with PCOS, the American Society for Reproductive Medicine recommends the use of “step-up” or “step-down” protocols in which a low dose of exogenous FSH or combined gonadotropins are employed in an attempt to constrain ovarian responsiveness. In vitro fertilization allows for the transfer of only one embryo or for cryopreservation of all embryos with subsequent transfer of a single embryo in a subsequent cycle without ovarian stimulation. Countless questions regarding pathogenesis and treatment of PCOS create opportunity for basic and clinical research and for refinement of existing therapeutic approaches

DataSheet1_Supporting clinical research professionals through educational innovations.PDF

Clinical Research Professionals (CRPs) are essential members of the Clinical and Translational Research Workforce. Many academic medical institutions struggle to recruit and retain these vital team members. One strategy to increase job satisfaction and promote the retention of CRPs is through educational initiatives that provide training and professional development. The South Carolina Clinical and Translational Research (SCTR) Institute Workforce Development (WD) team at the Medical University of South Carolina (MUSC) developed several trainings as part of our larger educational portfolio for CRPs. In 2022 WD implemented a digital badge micro-credential for SCTR’s Core Clinical Research Training (CCRT) course in collaboration with institution-wide education and technology offices. Beginning in January 2023, individuals were able to earn the CCRT Certified Digital Badge upon successful completion of the CCRT course.</p

Acute Serum Hormone Levels: Characterization and Prognosis after Severe Traumatic Brain Injury

Experimental traumatic brain injury (TBI) studies report the neuroprotective effects of female sex steroids on multiple mechanisms of injury, with the clinical assumption that women have hormonally mediated neuroprotection because of the endogenous presence of these hormones. Other literature indicates that testosterone may exacerbate injury. Further, stress hormone abnormalities that accompany critical illness may both amplify or blunt sex steroid levels. To better understand the role of sex steroid exposure in mediating TBI, we 1) characterized temporal profiles of serum gonadal and stress hormones in a population with severe TBI during the acute phases of their injury; and 2) used a biological systems approach to evaluate these hormones as biomarkers predicting global outcome. The study population was 117 adults (28 women; 89 men) with severe TBI. Serum samples (n=536) were collected for 7 days post-TBI for cortisol, progesterone, testosterone, estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Hormone data were linked with clinical data, including acute care mortality and Glasgow Outcome Scale (GOS) scores at 6 months. Hormone levels after TBI were compared to those in healthy controls (n=14). Group based trajectory analysis (TRAJ) was used to develop temporal hormone profiles that delineate distinct subpopulations in the cohort. Structural equations models were used to determine inter-relationships between hormones and outcomes within a multivariate model. Compared to controls, acute serum hormone levels were significantly altered after severe TBI. Changes in the post-TBI adrenal response and peripheral aromatization influenced hormone TRAJ profiles and contributed to the abnormalities, including increased estradiol in men and increased testosterone in women. In addition to older age and greater injury severity, increased estradiol and testosterone levels over time were associated with increased mortality and worse global outcome for both men and women. These findings represent a paradigm shift when thinking about the role of sex steroids in neuroprotection clinically after TBI