Karen E. Elkind-Hirsch

Women pre- or post-menopause and living with obesity are at an increased risk of obesity-related complications such as polycystic ovary syndrome, infertility, cardiovascular disease, and breast and uterine cancers. Previously, it has been demonstrated that a clinically meaningful weight loss of ≥5% of total body weight can have benefits for women living with gynecological conditions related to obesity and can improve the symptoms of polycystic ovary syndrome, improve fertility, and reduce the risk of gynecological and breast cancers. In this review article, we provide an overview of the impact of obesity on women’s health and evaluate the current pharmacological treatment landscape for weight management, with particular emphasis on incretin-based therapies, as relevant treatment options for obstetrician-gynecologists and gynecologists treating women at an increased risk of obesity-related complications. Literature searches were conducted using PubMed to identify articles published between 2015 and 2026, with the search date range subsequently expanded to articles published within the last 30 years. English language and adult only were specified in the filters for the search criteria, as was publication type (narrative reviews, systematic reviews, and randomized controlled trials were included). Searches were also conducted without any filters. With glucagon-like peptide-1 receptor agonists established as effective weight-management tools, obstetrician-gynecologists and gynecologists can offer evidence-based treatment options to women with obesity-related complications as an addition to lifestyle interventions (such as a reduced-calorie diet and increased physical activity) to aid weight loss. Obstetrician-gynecologists and gynecologists are ideally placed to diagnose and treat obesity in women who present with obesity-related gynecological complications. We hope that the clinical data presented, and the practical tips shared in this review, encourage obstetrician-gynecologists and gynecologists to initiate weight-loss conversations in everyday clinical practice to support women in achieving clinically meaningful weight loss and improve outcomes in women with obesity-related complications.

Introduction: This analysis investigated whether use of real-time continuous glucose monitoring (CGM) compared with blood glucose monitoring (BGM) results in rapidly improved glycemic management in adults with type 2 diabetes (T2D) treated with basal insulin. Research design and methods: Using data from the MOBILE study where adults (n=175) with T2D treated with basal insulin without prandial insulin were randomized (2:1) to either CGM (n=116) or BGM (n=59), the treatment effect on glycemic management was determined over 3 months. The main outcome was a between-group difference in hemoglobin A _1c (HbA _1c ) at 3 months adjusted for baseline value. Other outcomes included changes in CGM-derived glucose metrics and hypoglycemic events. Results: After 3 months, there was a greater reduction from baseline in mean HbA _1c in the CGM group compared with the BGM group, from 9.1±1.0% (76±11 mmol/mol) to 8.0±1.2% (64±13 mmol/mol) in the CGM group and from 9.0±0.9% (75±10 mmol/mol) to 8.5±1.5% (69±16 mmol/mol) in the BGM group (adjusted difference, −0.6% (95% CI –0.9% to −0.3%); −6.6 mmol/mol (95% CI –10.2 to –2.9), p13.9 mmol/L) with CGM (adjusted difference, −5.8% (95% CI −10.4% to −1.2%), p1c over 3 months. Trial registration number: NCT03566693 .

Understanding the risk factors for breakthrough coronavirus disease 2019 (COVID-19) (BC19) is critical to inform policy. Herein, we assessed Delta (Lineage B.1.617.2) variant-specific effectiveness of the BNT162b2 (Pfizer) vaccine and characterized Delta-driven BC19 cases (fully vaccinated individuals who get infected) with known-time-since-vaccination. In this longitudinal prospective study (January 21–October 30, 2021), 90 naïve and 15 convalescent individuals were enrolled at the initiation of vaccination. Samples from 27 unvaccinated individuals with previous laboratory-confirmed COVID-19 diagnosis were collected at a single time point. Longitudinal serology profile (antibodies against severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] S and N proteins) and live-virus-based neutralization capacities were assessed while controlling for age. Sex, age, history of reactions to the COVID-19 vaccine, and viral neutralization capacities were identified as significant risk factors for breakthrough COVID-19. At 8 months postvaccination, male sex, individuals ⩾65 years of age, and individuals who experienced noticeable side effects with the COVID-19 vaccine were at 5.47 ( p-value = 0.0102), 4.33 ( p-value = 0.0236), and 4.95 ( p-value = 0.0159) fold greater risk of BC19 as compared to their peers, respectively. Importantly, every five-fold increase in viral neutralization capacities (by live-virus-based assays) was significantly associated with ~4-fold reduction in the risk occurrence of breakthrough COVID-19 ( p-value = 0.045). Vaccine boosting remarkably increased these viral neutralization capacities by 16.22-fold ( p- value = 0.0005), supporting the importance of the BNT162b2 booster in efforts to control the incursion of future variants into the population at large. Strikingly, BC19 cases exhibited a delayed/absent antibody response to the N protein, suggesting limited exposure to the virus. Since antibodies against N protein are widely used to evaluate the extent of virus spread in communities, our finding has important implications on the utility of existing serological diagnostic and surveillance for COVID-19.

BackgroundThe efficacy of lifestyle modifications for established obesity is limited in women with polycystic ovary syndrome (PCOS) and more aggressive interventions are needed. We assessed the efficacy and safety of the GLP-1 analogue liraglutide 3mg (LIRA 3mg) versus placebo (PL) for reduction of body weight and hyperandrogenism in women with obesity and PCOSMethodsThis randomized, double-blind, placebo-controlled study enrolled women from a single-outpatient center diagnosed with PCOS (NIH criteria) with a body-mass index of at least 30 kg/m.² Participants were randomly allocated (2:1) to treatment with a subcutaneous injection LIRA 3mg or visually matching placebo, once daily for 32 weeks, plus lifestyle intervention. Study visits at baseline, and 32 weeks included weight, blood pressure (BP), waist (WC) measures and body composition evaluated by dual-energy X-ray absorptiometry (DXA). Oral glucose tolerance tests (OGTT) were done to assess glycemia, mean blood glucose (MBG), and compute insulin sensitivity (SI) and secretion (IS) measures. Sex steroids, free androgen index (FAI), complete metabolic profile and lipid profiles were measured in the fasting sample. Co-primary endpoints were change in body weight (BW) and FAI. Safety was assessed in all patients who received at least one dose of study drug. This study was registered with ClinicalTrials.gov NCT03480022FindingsFrom October 2018 to June 2020, 88 patients were screened, of whom 82 were randomly assigned to LIRA 3mg (n = 55) or PL (n = 27). Change in mean BW from baseline to week 32 was − 5.7% (SE 0·.75) with LIRA 3mg vs. -1.4% (1.09) with PL (P < 0.002). At week 32, more patients on LIRA 3 mg than on placebo achieved weight reductions of at least 5% (25[57%] of 44 vs. 5 [22%] of 23; (p < 0·007). LIRA 3mg resulted in significant reduction of FAI, improvements in SI and IS as well as OGTT MBG, and improved body fat by DXA. Gastrointestinal adverse events, which were mostly mild to moderate, were reported in 32 (58.2%) of 55 patients with LIRA 3mg, and 5 (18.5%) of 27 with PL.InterpretationIn obese women with PCOS, LIRA 3mg once daily achieved a superior and clinically meaningful decrease in BW and androgenicity and improved cardiometabolic parameters compared with placebo.

Context: Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors reduce weight and improve insulin sensitivity via different mechanisms. Objective: The efficacy of once-weekly exenatide (EQW) and dapagliflozin (DAPA) alone and coadministered (EQW/DAPA), DAPA/extended-release (ER) metformin (DAPA/MET), and phentermine topiramate extended release (PHEN/TPM) on metabolic parameters, body composition, and sex hormones were examined in obese women with PCOS. Methods: Nondiabetic women (n = 119; aged 18-45 years) with a body mass index (BMI) greater than 30 and less than 45 and polycystic ovary syndrome (National Institutes of Health criteria) were randomly assigned in a single-blinded fashion to EQW (2 mg weekly); DAPA (10 mg daily), EQW/DAPA (2 mg weekly/10 mg daily), DAPA (10 mg)/MET (2000 mg XR daily), or PHEN (7.5 mg)/TPM (46 mg ER daily) treatment for 24 weeks. Study visits at baseline and 24 weeks included weight, blood pressure (BP), waist (WC) measures, and body composition evaluated by dual-energy x-ray absorptiometry (DXA). Oral glucose tolerance tests were conducted to assess glycemia and mean blood glucose (MBG), and compute insulin sensitivity (SI) and secretion (IS) measures. Sex steroids, free androgen index (FAI), and lipid profiles were measured in the fasting sample. Results: EQW/DAPA and PHEN/TPM resulted in the most loss of weight and total body fat by DXA, and WC. Despite equivalent reductions in BMI and WC with PHEN/TPM, only EQW/DAPA and EQW resulted in significant improvements in MBG, SI, and IS. Reductions in fasting glucose, testosterone, FAI, and BP were seen with all drugs. Conclusion: Dual therapy with EQW/DAPA was superior to either alone, DAPA/MET and PHEN/TPM in terms of clinical and metabolic benefits in this patient population.

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