A randomized trial of standard vs restricted opioid prescribing following midurethral sling.

BACKGROUND: Postoperative opioid prescribing has historically lacked information crucial to balancing the pain control needs of the individual patient with our professional responsibility to judiciously prescribe these high-risk medications. OBJECTIVE: This study aimed to evaluate pain control, satisfaction with pain control, and opioid use among patients undergoing isolated midurethral sling randomized to 1 of 2 different opioid-prescribing regimens. STUDY DESIGN: Patients who underwent isolated midurethral sling placement from June 1, 2020, to November 22, 2021, were offered enrollment into this prospective, randomized, open-label, noninferiority clinical trial. Participants were randomized to receive either a standard prescription of ten 5-mg oxycodone tablets provided preoperatively (standard) or an opioid prescription provided only during patient request postoperatively (restricted). Preoperatively, all participants completed baseline demographic and pain surveys, including the 9-Question Central Sensitization Index, Pain Catastrophizing Scale, and Likert pain score (scale 0-10). The participants completed daily surveys for 1 week after surgery to determine the average daily pain score, number of opioids used, other forms of pain management, satisfaction with pain control, perception of the number of opioids prescribed, and need to return to care for pain management. The online Prescription Drug Monitoring Program was used to determine opioid filling in the postoperative period. The primary outcome was average postoperative day 1 pain score, and an a priori determined margin of noninferiority was set at 2 points. RESULTS: Overall, 82 patients underwent isolated midurethral sling placement and met the inclusion criteria: 40 were randomized to the standard arm, and 42 were randomized to the restricted group. Concerning the primary outcome of average postoperative day 1 pain score, the restricted arm (mean pain score, 3.9±2.4) was noninferior to the standard arm (mean pain score, 3.7±2.7; difference in means, 0.23; 95% confidence interval, -∞ to 1.34). Of note, 23 participants (57.5%) in the standard arm vs 8 participants (19.0%) in the restricted arm filled an opioid prescription (P<.001). Moreover, 18 of 82 participants (22.0%) used opioids during the 7-day postoperative period, with 10 (25.0%) in the standard arm and 8 (19.0%) in the restricted arm using opioids (P=.52). Of participants using opioids, the average number of tablets used was 3.4±2.3, and only 3 participants used ≥5 tablets. On a scale of 1="prescribed far more opioids than needed" to 5="prescribed far less opioids than needed," the means were 1.9±1.0 in the standard arm and 2.7±1.0 in the restricted arm (P<.001). CONCLUSION: Restricted opioid prescription was noninferior to standard opioid prescription in the setting of pain control and satisfaction with pain control after isolated midurethral placement. Participants in the restricted arm filled fewer opioid prescriptions than participants in the standard arm. On average, only 3.4 tablets were used by those that filled prescriptions in both groups. Restrictive opioid-prescribing practices may reduce unused opioids in the community while achieving similar pain control.

Impact of hormonal contraception and weight loss on high-density lipoprotein cholesterol efflux and lipoprotein particles in women with polycystic ovary syndrome.

OBJECTIVE: To study the effects of oral contraceptive pills (OCP), the first-line treatment for PCOS, on high-density lipoprotein cholesterol (HDL-C) function (reverse cholesterol efflux capacity) and lipoprotein particles measured using nuclear magnetic resonance spectroscopy in obese women. DESIGN: Secondary analysis of a randomized controlled trial (OWL-PCOS) of OCP or Lifestyle (intensive Lifestyle modification) or Combined (OCP + Lifestyle) treatment groups for 16 weeks. PATIENTS: Eighty-seven overweight/obese women with PCOS at two academic centres. MEASUREMENTS: Change in HDL-C efflux capacity and lipoprotein particles. RESULTS: High-density lipoprotein cholesterol efflux capacity increased significantly at 16 weeks in the OCP group [0·11; 95% confidence interval (CI) 0·03, 0·18, P = 0·008] but not in the Lifestyle (P = 0·39) or Combined group (P = 0·18). After adjusting for HDL-C and TG levels, there was significant mean change in efflux in the Combined group (0·09; 95% CI 0·01, 0·15; P = 0·01). Change in HDL-C efflux correlated inversely with change in serum testosterone (rs = -0·21; P = 0·05). In contrast, OCP use induced an atherogenic low-density lipoprotein cholesterol (LDL-C) profile with increase in small (P = 0·006) and large LDL-particles (P = 0·002). Change in small LDL-particles correlated with change in serum testosterone (rs = -0·31, P = 0·009) and insulin sensitivity index (ISI; rs = -0·31, P = 0·02). Both Lifestyle and Combined groups did not show significant changes in the atherogenic LDL particles. CONCLUSIONS: Oral contraceptive pills use is associated with improved HDL-C function and a concomitant atherogenic LDL-C profile. Combination of a Lifestyle program with OCP use improved HDL-C function and mitigated adverse effects of OCP on lipoproteins. Our study provides evidence for use of OCP in overweight/obese women with PCOS when combined with Lifestyle changes.

Management of gestational hypertension - the impact of HYPITATa.

AIMS: The objective of this study was to examine the impact of one trial (the HYPITAT trial) on management of gestational hypertension. STUDY DESIGN: This is a retrospective cohort study of 5077 patients delivered at our institution from 7/1/2008 to 6/15/2011. "Pre-HYPITAT" was defined as 7/1/2008-9/30/2009 and "Post-HYPITAT" as 10/1/2009-6/15/2011. The primary outcome is the rate of delivery intervention for gestational hypertension. Secondary maternal and neonatal outcomes were analyzed in patients with gestational hypertension only. Statistical analyses included the χ2-test, Fisher's exact test, and the two-sample t-test. RESULTS: The rate of delivery intervention Pre-HYPITAT was 1.9%, compared to 4% Post-HYPITAT (P<0.001). There was no significant change in secondary outcomes. CONCLUSION: There was a statistically significant increase in delivery intervention for gestational hypertension at our institution after the publication of the HYPITAT trial. There was no significant change in immediate maternal or neonatal outcomes for patients with gestational hypertension.

Effect of adolescent pregnancy on final adult height in non-Hispanic white women.

PURPOSE: The objective of this study is to examine the effect of pregnancy on final adult height in women whose first live birth occurred in adolescence (

Liberal vs. restricted opioid prescribing following midurethral sling dataset.

Postoperative opioid prescribing has historically lacked information critical to balancing the pain control needs of the individual patient with our professional responsibility to judiciously prescribe these high-risk medications. This data evaluates pain control, satisfaction with pain control, and opioid utilization among patients undergoing isolated mid-urethral sling (MUS) randomized to one of two different opioid prescribing regimens. This study was registered on clinicaltrials.gov (NCT04277975). Women undergoing isolated MUS by a Female Pelvic Medicine and Reconstructive Surgery physician at a Penn State Health hospital from June 1, 2020 to November 22, 2021 were offered enrollment into this prospective, randomized, open-label, non-inferiority clinical trial. Participants gave informed consent and were enrolled by a member of the study team. Allocation was concealed to patient and study personnel until randomization on the day of surgery. Preoperatively, all participants completed baseline demographic and pain surveys including CSI-9, PCS, and Likert pain score (scale 0-10). Participants were randomized to either receive a standard prescription of ten 5 mg tablets oxycodone provided preoperatively (standard) or opioid prescription provided only upon patient request postoperatively (restricted). Randomization was performed by the study team surgeon using the REDCap randomization module on the day of surgery. Following MUS, subjects completed a daily diary for 1 week, i.e., postoperative day (POD) 0 through 7. Within the dairy, subjects provided the following information: average daily pain score, opioid use and amount of opioid utilized, other forms of pain management, satisfaction with pain control, perception of the amount of opioid prescribed, and need for pain management hospital/clinic visits. The online Prescription Drug Monitoring Program (PDMP) was queried for all patients to determine if prescriptions for opioids were filled during the postoperative period. The primary outcome was average postoperative day 1 pain score and an a priori determined margin of non-inferiority was set at 2 points. Secondary outcomes included whether subject filled an opioid prescription (indicated by the online PDMP), opioid use (yes/no), satisfaction with pain control (on a scale of 1= "much worse" to 5= "much better" than expected), and how subjects felt about the amount of opioid prescribed (on a scale of 1="prescribed far more" to 3="prescribed the right amount" to 5="prescribed far less" opioid than needed). 82 participants underwent isolated MUS placement and met inclusion criteria; 40 were randomized to the standard arm and 42 to the restricted group. Within this manuscript, we detail the data obtained from this randomized clinical trial and the methods utilized.

Oil-based or saline contrast for sono-hysterosalpingography in infertile women: a pilot randomized controlled double blind trial.

Objective: To determine the feasibility, safety, and outcomes of an oil-based, iodinated contrast using office-based, ultrasound-imaged hysterosalpingography in women with infertility. Design: Randomized Controlled Double Blind Clinical Trial. Setting: Academic health center. Interventions: Tubal flushing with oil-based contrast medium (Lipiodol UF) versus saline. Main Outcome Measures: Ongoing pregnancy rate, pain, quality of life, and thyroid function. Results: Forty-eight patients (24 in each group) were analyzed. The groups were well-matched at baseline. Ongoing pregnancy was noted in 17% (4/24) of the oil-contrast group versus 37% (9/24) in the saline group. Saline group patients more frequently initiated infertility therapy in the six-month follow-up period (saline, 67% vs. oil, 33%), and no serious adverse events in either group. There were no differences in pain from the procedure between groups. There were no differences in thyroid function tests postprocedure between groups, but within the oil-contrast group, there was a slight increase in thyroid-stimulating hormone (post vs. preratio of geometric means: 1.18; 95% confidence interval [CI], 1.02-1.38) and decrease in Free T4 (postdifference vs. predifference in means: 0.08 ng/dL; 95% CI, -0.14 to -0.01). Immediately after the test, the physicians correctly guessed 79% of oil and 71% of saline randomization assignments, whereas patients correctly guessed 63% of oil and 38% of saline. Conclusions: This pilot study demonstrates the safety and feasibility of giving an oil-based contrast medium during ultrasound-imaged hysterosalpingography. Pregnancies were seen after oil-based administration, and this contrast is associated with minor thyroid function impairment.

Enhanced recovery for cesarean delivery leads to no difference in length of stay, decreased opioid use and lower infection rates.

OBJECTIVE: The primary objective of this study was to report surgical outcomes for cesarean delivery (CD) patients following the implementation of an Enhanced Recovery after Surgery (ERAS) pathway based on the ERAS Society recommendations. The primary outcome for which the study was powered was the length of stay (LOS). METHODS: This IRB-approved cohort study was conducted at a single tertiary-care labor and delivery unit and utilized a pre-post intervention design. Our ERAS for CD protocol was designed using the ERAS Society recommendations and implemented globally for every patient admitted to the labor and delivery unit including both scheduled and unscheduled cases. The study was designed to have at least 85% power to detect a 6-h difference in length of stay (LOS) between the pre-intervention and post-intervention cohorts, assuming a standard deviation of 18 h. A total of 339 records were included for data analysis, 170 in the pre-intervention cohort and 169 in the post-intervention cohort. To assess the difference between groups with respect to the primary outcome of LOS, linear regression was used with and without adjusting for covariates. Differences in dichotomous secondary outcomes were assessed using binary logistic regression. Differences in continuous secondary outcomes were assessed via a two-sample t-test or Wilcoxon rank sum test. Individual components of protocol adherence were compared using chi-square tests. RESULTS: Mean LOS was 80.5 ± 22.9 h and 82.3 ± 28.0 h, pre- and post-intervention respectively. There was no difference in LOS between the 2 cohorts (difference of means = 1.8 h; 95% confidence interval (CI): (-3.7, 7.3); p = .51). Cesarean procedure infection decreased from 11.8% pre-intervention to 5.3% post-intervention, corresponding to a 58% decrease in odds of cesarean procedure infection (odds ratio (OR)=0.42; 95% CI: (0.19, 0.96); p = .04). Inpatient opioid use also significantly decreased in the post-intervention cohort with a median MME per 12 h-period of 5.1 (25th percentile = 2.2, 75th percentile = 7.8) pre-intervention and 3.3 (25th percentile = 1.0, 75th percentile = 7.6) post-intervention (p = .04). CONCLUSION: The results of this study support the implementation of an ERAS for CD protocol based on ERAS Society recommendations as evidenced by the statistically significant decrease observed in both procedure-related infection rates and inpatient opioid use. We did not find a significant difference in LOS, which leaves room for further investigation into factors that impact LOS after CD.

Opioid use after cesarean: a cohort study comparing combined versus separate oxycodone and acetaminophen regimens.

OBJECTIVE: To determine whether an inpatient post-cesarean analgesic regimen which separated oxycodone and acetaminophen resulted in less inpatient opioid use, when compared to a regimen using combination medications containing both acetaminophen and oxycodone in a cohort including patients of all gestational ages, acuity levels, and modes of operative anesthesia. METHODS: This is a retrospective cohort study which was conducted at a single tertiary care center Labor and Delivery unit. Data were collected via retrospective chart review, and a total of 170 records were examined with a final N = 150. Inclusion criteria were all patients over the age of 18, and >23.0 weeks gestational age, who had a singleton or twin cesarean delivery regardless of their mode of operative anesthesia and whether or not they received intrathecal opioid at time of delivery. Exclusion criteria were pregnancies of higher-level multiples (triplets or greater), prolonged intensive care unit (ICU) stay, and patients who received both combination oxycodone-acetaminophen and separately administered oxycodone. For analysis patients were classified into two groups: the "Combined Medication" group representing patients who received combination oxycodone-acetaminophen medication only (n = 83) and the "Separate Medication" group representing patients who received oxycodone and acetaminophen separately (n = 67). Differences between the groups with respect to opioid use and acetaminophen use were assessed. RESULTS: The primary outcome was inpatient opioid medication use per 12-h period in intravenous morphine mg equivalents (MME). Patients received an average of 4.6 ± 3.5 MME IV morphine per 12 h in the Separate Medication group and 5.7 ± 3.7 MME IV morphine per 12 h in the Combined Medication group. When controlled for several covariates, the Separate Medication group took significantly fewer MME per 12-h period (mean difference = -1.2, 95% CI: (-2.3, -0.1), p = .04). There was no appreciable difference in acetaminophen utilization between groups. CONCLUSIONS: An analgesic regimen where oxycodone is ordered separately from acetaminophen is associated with reduced inpatient opioid medication use in patients of all gestational ages, acuity levels, and modes of operative anesthesia.

Evidence for increased cardiovascular events in the fathers but not mothers of women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a familial syndrome, associated with multiple cardiovascular disease (CVD) risk factors. Thus, parents of affected women may have a higher prevalence of CVD events than the general population. METHODS: PCOS probands (n = 410) and their participating parents (n = 180 fathers and 211 mothers) were queried for CVD events in themselves and non-participating family members. In order to include the family CVD history of all parents, agreement between the proband and parental reports of CVD events was assessed. Estimated 10-year coronary heart disease (CHD) risk was calculated using the Framingham risk calculator. The National Health and Nutrition Examination Survey (NHANES) 2001-2002 database was used to generate gender, age and body mass index-relevant population parameters of CVD prevalence in the USA population. RESULTS: Ninety-eight percent of the parents' self-reporting of CVD events agreed with the proband's report of parental heart attack history [Kappa = 0.82; 95% CI: (0.69, 0.94)] and 99% with parental stroke history [Kappa = 0.79; 95% CI: (0.62, 0.97)]. Fathers of women with PCOS had a higher prevalence of heart attack and stroke compared with the reference NHANES population (heart attack: 11.1 versus 5.3%, P < 0.0001; stroke: 3.0 versus 1.0%, P = 0.002). Fathers of women with PCOS had an elevated 10-year risk for CHD (11.5 versus 9.9% in NHANES, P = 0.03). No statistically significant increased prevalence of CVD events or 10-year risk was noted in probands or mothers. CONCLUSIONS: Fathers, and not mothers, may be disproportionately burdened with CVD in PCOS families. The strengths of this study include the size of our cohort, the consistent phenotyping and the validation of proband's reporting of parental CVD events.

Opioid Prescribing and Utilization Following Isolated Mid-Urethral Sling.

INTRODUCTION: Overprescribing by providers is a leading contributor to the opioid crisis. Despite available information regarding the role that physician prescribing plays in the community availability of opioids, guidelines for the management of acute pain remain sparse. This project aims to evaluate opioid prescribing, opioid usage patterns, and postoperative pain control in patients undergoing isolated mid-urethral sling (MUS) placement. METHODS: Patients who underwent isolated MUS placement from March 19, 2019 through March 19, 2020 were contacted by telephone in May 2020 and asked a series of questions examining opioid usage, postoperative pain, what they did with unused opioids, and whether they had received education on disposal techniques. A chart review was utilized to determine the amount of opioid prescribed, the presence of any operative complications, and medical and demographic characteristics of subjects. RESULTS: A total of 53 subjects met inclusion criteria, of which 31 participated in a phone interview. Of the 53 subjects, 54.7% received a postoperative opioid prescription, and all but two of these subjects filled their prescription. Of the interviewed subjects, only 66.6% who filled a prescription reported using opioids Fifty percent (n=6) of patients that required oxycodone reported use of four tablets (30 morphine milligram equivalents (MMEs)) or less and used for 1-2 days postoperatively. No patient reported using opioids beyond five days. Only 22.2% reported receiving instruction on opioid disposal, and 16.7% returned unused opioids to a disposal center. 87.1% of subjects rated postoperative pain as "better" or "much better" than expected. CONCLUSION: Patients undergoing isolated MUS placement require limited amounts of postoperative opioids, if any are needed at all, to achieve satisfactory pain control. Excess prescribed opioids, along with inadequate patient education on proper disposal techniques, may contribute towards opioids that are at risk of diversion for nonmedical use.

Lifestyle modifications alone or combined with hormonal contraceptives improve sexual dysfunction in women with polycystic ovary syndrome.

OBJECTIVE: To describe the prevalence of female sexual dysfunction in a well-defined polycystic ovary syndrome (PCOS) population, and to assess the impact of common PCOS treatments on sexual function. DESIGN: Secondary analysis of a randomized controlled trial, oral contraceptive pills and weight loss in PCOS. SETTING: Two academic medical centers. PATIENTS: Women with PCOS (N = 114) defined by the Rotterdam criteria. INTERVENTIONS: Continuous oral contraceptive pill (OCP) or intensive lifestyle modification (Lifestyle) or the combination (Combined) for 16 weeks. MAIN OUTCOME MEASURES: Change in Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-Revised (FSDS-R) scores after 16 weeks. RESULTS: There was no change in total FSFI or FSDS-R score in any treatment group; however, an increase in the FSFI desire domain subscore was observed in the Lifestyle and Combined treatments, indicating improved sexual desire over the 16-week period. Overall, 33 participants (28.9%) met criteria for sexual dysfunction by FSFI criteria (baseline score ≤26.55). Among this group, FSFI score improved after 16 weeks of Lifestyle and Combined treatments. There was no change in prevalence of sexual dysfunction in treatment groups at 16 weeks. Use of OCPs did not alter FSFI scores. CONCLUSION(S): Female sexual dysfunction is highly prevalent among women with PCOS. Our findings suggest that common treatments for PCOS, including intensive lifestyle modification and the combination of intensive lifestyle modification and OCPs, have the potential to improve sexual function in these women; the mechanism for these improvements is likely multifactorial. CLINICAL TRIAL REGISTRATION NUMBER: NCT00704912.

Effects of Oral Contraception and Lifestyle Modification on Incretins and TGF-ß Superfamily Hormones in PCOS.

OBJECTIVE: To examine the effects of common treatments for polycystic ovary syndrome (PCOS) on a panel of hormones (reproductive/metabolic). DESIGN: Secondary analysis of blood from a randomized controlled trial of three 16-week preconception interventions designed to improve PCOS-related abnormalities: continuous oral contraceptive pills (OCPs, N = 34 subjects), intensive lifestyle modification (Lifestyle, N = 31), or a combination of both (Combined, N = 29). MATERIALS AND METHODS: Post-treatment levels of activin A and B, inhibin B, and follistatin (FST), as well as Insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 2 (IGFBP-2), glucagon, glucagon-like peptide 1 (GLP-1) and 2, and oxyntomodulin were compared to baseline, and the change from baseline in these parameters were correlated with outcomes. RESULTS: Oral contraceptive pill use was associated with a significant suppression in activin A, inhibin A, and anti-mullerian hormone (AMH), but a significant increase in FST. IGF-1, IGFBP-2, glucagon, and GLP-2 levels were significantly decreased. Oxyntomodulin was profoundly suppressed by OCPs (ratio of geometric means: 0.09, 95% confidence interval [CI]: 0.05, 0.18, P < 0.001). None of the analytes were significantly affected by Lifestyle, whereas the effects of Combined were similar to OCPs alone, although attenuated. Oxyntomodulin was significantly positively associated with the change in total ovarian volume (rs = 0.27; 95% CI: 0.03, 0.48; P = 0.03) and insulin sensitivity index (rs = 0.48; 95% CI: 0.27, 0.64; P < 0.001), and it was inversely correlated with change in area under the curve (AUC) glucose [rs = -0.38; 95% CI: -0.57, -0.16; P = 0.001]. None of the hormonal changes were associated with live birth, only Activin A was associated with ovulation (risk ratio per 1 ng/mL increase in change in Activin A: 6.0 [2.2, 16.2]; P < 0.001). CONCLUSIONS: In women with PCOS, OCPs (and not Lifestyle) affect a wide variety of reproductive/metabolic hormones, but their treatment response does not correlate with live birth.

Corneal transplantation at Tenwek Hospital, Kenya, East Africa: Analysis of outcomes and associated patient socioeconomic characteristics.

PURPOSE: To review the graft survival rate, visual outcomes, and patient demographics of primary penetrating keratoplasty performed at Tenwek Hospital, a mission hospital in rural Kenya. METHODS: A retrospective review was performed of the clinical records of patients who underwent primary penetrating keratoplasty for optical purposes from January 2012 to October 2014. The graft survival rates were constructed using the Kaplan-Meier method, and the effect of clinical and socioeconomic characteristics on time to graft failure were examined using Cox regression models. RESULTS: 118 patients met the inclusion criteria. The most common indication for surgery was keratoconus (66.1%), followed by corneal scar (22.0%). Despite all patients giving a verbal commitment to do so, 40 patients (33.9%) failed to make it to followup one year postoperatively. Graft survival at one year, inclusive of all indications, was 85.8%. Of the different indications, keratoconus had the highest one-year graft survival rate of 89.9%. Compared to the preoperative uncorrected visual acuity, 85.3% achieved an improvement at one year. Compared to patients who had completed college or university, the risk of developing graft failure was 4.7 times higher among patients with less education (P = 0.01). CONCLUSIONS: Corneal transplantation at Tenwek Hospital can be performed with a reasonable chance of success at one year, particularly in cases of keratoconus and in patients with higher educational backgrounds. Adherence to followup recommendations proves to be a challenge in this patient population. Additional studies of larger patient populations with longer follow up periods in similar settings may be helpful in informing appropriate patient selection and maximizing successful outcomes of corneal transplantation in low-resource settings.

Mindfulness-Based Stress Reduction in Women with Overweight or Obesity: A Randomized Clinical Trial.

OBJECTIVE: To evaluate the feasibility and cardiometabolic effects of mindfulness-based stress reduction (MBSR) in women with overweight or obesity. METHODS: Eighty-six women with BMI ≥ 25 kg/m2 were randomized to 8 weeks of MBSR or health education and followed for 16 weeks. The primary outcome was the Toronto Mindfulness Scale. Secondary outcomes included the Perceived Stress Scale-10, fasting glucose, and blood pressure. RESULTS: Compared to health education, the MBSR group demonstrated significantly improved mindfulness at 8 weeks (mean change from baseline, 4.5 vs. -1.0; P = 0.03) and significantly decreased perceived stress at 16 weeks (-3.6 vs. -1.3, P = 0.01). In the MBSR group, there were significant reductions in fasting glucose at 8 weeks (-8.9 mg/dL, P = 0.02) and at 16 weeks (-9.3 mg/dL, P = 0.02) compared to baseline. Fasting glucose did not significantly improve in the health education group. There were no significant changes in blood pressure, weight, or insulin resistance in the MBSR group. CONCLUSIONS: In women with overweight or obesity, MBSR significantly reduces stress and may have beneficial effects on glucose. Future studies demonstrating long-term cardiometabolic benefits of MBSR will be key for establishing MBSR as an effective tool in the management of obesity.

Normal Pubertal Development in Daughters of Women With PCOS: A Controlled Study.

Context: Daughters of women with polycystic ovary syndrome (PCOS) are thought to be at increased risk for developing stigmata of the syndrome, but the ontogeny during puberty is uncertain. Objective: We phenotyped daughters (n = 76) of mothers with PCOS and daughters (n = 80) from control mothers for reproductive and metabolic parameters characteristic of PCOS. Design, Setting, and Participants: We performed a matched case/control study at Penn State Hershey Medical Center that included non-Hispanic, white girls 4 to 17 years old. Intervention: We obtained birth history, biometric, ovarian ultrasounds, whole-body dual-energy X-ray absorptiometry scan for body composition, 2-hour glucose challenged salivary insulin levels, and two timed urinary collections (12 hours overnight and 3 hours in the morning) for gonadotropins and sex steroids. Main Outcome Measures: We measured integrated urinary levels of adrenal (dehydroepiandrosterone sulfate) and ovarian [testosterone (TT)] steroids. Other endpoints included integrated salivary insulin levels and urinary luteinizing hormone levels. Results: There were no differences in detection rates or mean levels for gonadotropins and sex steroids in timed urinary collections between PCOS daughters and control daughters, nor were there differences in integrated salivary insulin levels. Results showed that 69% of Tanner 4/5 PCOS daughters vs 31% of control daughters had hirsutism defined as a Ferriman-Gallwey score >8 (P = 0.04). There were no differences in body composition as determined by dual-energy X-ray absorptiometry between groups in the three major body contents (i.e., bone, lean body mass, and fat) or in ovarian volume between groups. Conclusions: Matched for pubertal stage, PCOS daughters have similar levels of urinary androgens and gonadotropins as well as glucose-challenged salivary insulin levels.

Weight Loss and Lowering Androgens Predict Improvements in Health-Related Quality of Life in Women With PCOS.

CONTEXT: Polycystic ovary syndrome (PCOS) is associated with reduced health-related quality of life (HRQOL) and increased prevalence of depressive and anxiety disorders. The impact of PCOS-specific treatments on these co-morbidities is unclear. OBJECTIVE: To assess the impact of weight loss and decreasing hyperandrogenism on HRQOL and mood and anxiety disorders in women with PCOS. DESIGN/SETTING/PARTICIPANTS: A secondary analysis of a randomized controlled trial (OWL-PCOS) of preconception treatment conducted at two academic centers in women (age, 18-40 years; body mass index, 27-42 kg/m(2)) with PCOS defined by Rotterdam criteria. INTERVENTION: Continuous oral contraceptive pill (OCP) or intensive lifestyle intervention or the combination (Combined) for 16 weeks. MAIN OUTCOME MEASURE(S): Changes in HRQOL assessed by PCOSQ and SF-36 and prevalence of depression and anxiety disorder assessed by PRIME-MD PHQ. RESULTS: The lowest scores were noted on the general health domain of the SF-36 and the weight and infertility domains on the PCOSQ. All three interventions resulted in significant improvement in the general health score on the SF-36. Both the OCP and Combined groups showed improvements in all domains of the PCOSQ (P < .01) compared to baseline scores. The Combined group had significant improvements in the weight, body hair, and infertility domains compared to a single treatment group (P < .05). In a linear regression model, change in weight correlated with improvements in the weight domain (P < .001) and physical well-being (P < .02), change in T correlated with improvements in the hair domain (P < .001), and change in both weight and T correlated with the infertility (P < .001) and menstrual domains (P < .05). CONCLUSIONS: Both weight loss and OCP use result in significant improvements in several physical and mental domains related to quality of life, depressive symptoms, and anxiety disorders, and combined therapies offer further benefits in overweight/obese women with PCOS.

Benefit of Delayed Fertility Therapy With Preconception Weight Loss Over Immediate Therapy in Obese Women With PCOS.

CONTEXT: In overweight/obese women with polycystic ovary syndrome (PCOS), the relative benefit of delaying infertility treatment to lose weight vs seeking immediate treatment is unknown. OBJECTIVE: We compared the results of two, multicenter, concurrent clinical trials treating infertility in women with PCOS. DESIGN, SETTING, AND PARTICIPANTS: This was a secondary analysis of two randomized trials conducted at academic health centers studying women 18-40 years of age who were overweight/obese and infertile with PCOS. INTERVENTION: We compared immediate treatment with clomiphene from the Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) trial (N = 187) to delayed treatment with clomiphene after preconception treatment with continuous oral contraceptives, lifestyle modification (Lifestyle: including caloric restriction, antiobesity medication, behavioral modification, and exercise) or the combination of both (combined) from the Treatment of Hyperandrogenism Versus Insulin Resistance in Infertile Polycystic Ovary Syndrome (OWL PCOS) trial (N = 142). MAIN OUTCOME MEASURES: Live birth, pregnancy loss, and ovulation were measured. RESULTS: In PPCOS II, after four cycles of clomiphene, the cumulative per-cycle ovulation rate was 44.7% (277/619) and the cumulative live birth rate was 10.2% (19/187), nearly identical to that after oral contraceptive pretreatment in the OWL PCOS trial (ovulation 45% [67/149] and live birth: 8.5% [4/47]). In comparison, deferred clomiphene treatment preceded by lifestyle and combined treatment in OWL PCOS offered a significantly better cumulative ovulation rate compared to immediate treatment with clomiphene. (Lifestyle: 62.0% [80/129]; risk ratio compared to PPCOS II = 1.4; 95% confidence interval [CI], 1.1-1.7; P = .003; combined: 64.3% [83/129]; risk ratio compared to PPCOS II = 1.4; 95% CI, 1.2-1.8; P < .001 and a significantly better live birth rate lifestyle: 25.0% [12/48]; risk ratio compared to PPCOS II = 2.5; 95% CI, 1.3-4.7; P = .01 and combined: 25.5% [12/47]; risk ratio compared to PPCOS II = 2.5; 95% CI, 1.3-4.8; P = .01). CONCLUSIONS: These data show the benefit of improved ovulation and live birth with delayed infertility treatment with clomiphene citrate when preceded by lifestyle modification with weight loss compared with immediate treatment. Pretreatment with oral contraceptives likely has little effect on the ovulation and live birth rate compared with immediate treatment.

Mindfulness-based stress reduction for overweight/obese women with and without polycystic ovary syndrome: design and methods of a pilot randomized controlled trial.

INTRODUCTION: Mindfulness-based stress reduction (MBSR) may be beneficial for overweight/obese women, including women with polycystic ovary syndrome (PCOS), as it has been shown to reduce psychological distress and improve quality of life in other patient populations. Preliminary studies suggest that MBSR may also have salutary effects on blood pressure and blood glucose. This paper describes the design and methods of an ongoing pilot randomized controlled trial evaluating the feasibility and effects of MBSR in PCOS and non-PCOS women who are overweight or obese (NCT01464398). METHODS AND DESIGN: Eighty six (86) women with body mass index ≥ 25 kg/m(2), including 31 women with PCOS, have been randomized to 8 weeks of MBSR or health education control, and followed for 16 weeks. The primary outcome is mindfulness assessed with the Toronto Mindfulness Scale. Secondary outcomes include measures of blood pressure, blood glucose, quality of life, anxiety and depression. DISCUSSION: Our overall hypothesis is that MBSR will increase mindfulness and ultimately lead to favorable changes in blood pressure, blood glucose, psychological distress and quality of life in PCOS and non-PCOS women. This would support the integration of MBSR with conventional medical treatments to reduce psychological distress, cardiovascular disease and diabetes in PCOS and non-PCOS women who are overweight or obese.

Randomized Controlled Trial of Preconception Interventions in Infertile Women With Polycystic Ovary Syndrome.

CONTEXT: Lifestyle modification is recommended in women with polycystic ovary syndrome (PCOS) prior to conception but there are few randomized trials to support its implementation or benefit. OBJECTIVE: This study aimed to determine the relative efficacy of preconception intervention on reproductive and metabolic abnormalities in overweight/obese women with PCOS. DESIGN, SETTING, AND PARTICIPANTS: This was a randomized controlled trial of preconception and infertility treatment at Academic Health Centers in women with infertility due to PCOS, age 18-40 y and body mass index 27-42 kg/m(2). INTERVENTION: Women were randomly assigned to receive either 16 weeks of 1) continuous oral contraceptive pills (OCPs) (ethinyl estradiol 20 mcg/1 mg norethindrone acetate) ("OCP"); 2) lifestyle modification consisting of caloric restriction with meal replacements, weight loss medication (either sibutramine, or orlistat), and increased physical activity to promote a 7% weight loss ("Lifestyle"); or 3) combined treatment with both OCP and lifestyle modification ("Combined"). After preconception intervention, women underwent standardized ovulation induction with clomiphene citrate and timed intercourse for four cycles. Pregnancies were followed with trimester visits until delivery. MAIN OUTCOME MEASURES: Weight, ovulation, and live birth were measured. RESULTS: We consented 216 and randomly assigned 149 women (Lifestyle: n = 50; OCP: n = 49; Combined: n = 50). We achieved significant weight loss with both Lifestyle (mean weight loss, -6.2%; 95% confidence interval (CI), -7.4--5.0; and Combined (mean weight loss, -6.4%; 95% CI, -7.6--5.2) compared with baseline and OCP (both P < .001). There was a significant increase in the prevalence of metabolic syndrome at the end of preconception treatment compared with baseline within OCP (odds ratio [OR, 2.47; 95% CI, 1.42-4.27) whereas no change in metabolic syndrome was detected in the Lifestyle (OR, 1.18; 95% CI, 0.63-2.19) or Combined (OR, 0.72; 95% CI, 0.44-1.17) groups. Cumulative ovulation rates were superior after weight loss: OCP, 46%; Lifestyle, 60%; and Combined, 67% (P < .05). Live birth rates were OCP, 12%; Lifestyle, 26%; and Combined, 24% (P = .13). CONCLUSIONS: A preconception weight loss intervention eliminates the adverse metabolic oral contraceptive effects and, compared with oral contraceptive pretreatment, leads to higher ovulation rates.

High-dose vitamin D supplementation and measures of insulin sensitivity in polycystic ovary syndrome: a randomized, controlled pilot trial.

OBJECTIVE: To determine the effects of high-dose vitamin D on insulin sensitivity in polycystic ovary syndrome (PCOS). DESIGN: Randomized, placebo-controlled trial. SETTING: Academic medical center. PATIENT(S): Twenty-eight women with PCOS. INTERVENTION(S): Vitamin D3, 12,000 IU, or placebo daily for 12 weeks. MAIN OUTCOME MEASURE(S): The primary outcome was quantitative insulin sensitivity check index. Secondary outcomes included glucose and insulin levels during a 75-g oral glucose tolerance test and blood pressure. RESULT(S): Twenty-two women completed the study. Compared with placebo, vitamin D significantly increased 25-hydroxyvitamin D (mean [95% confidence interval] in vitamin D group 20.1 [15.7 to 24.5] ng/mL at baseline and 65.7 [52.3 to 79.2] ng/mL at 12 weeks; placebo 22.5 [18.1 to 26.8] ng/mL at baseline and 23.8 [10.4 to 37.2] ng/mL at 12 weeks). There were no significant differences in quantitative insulin sensitivity check index and other measures of insulin sensitivity; however, we observed trends toward lower 2-hour insulin and lower 2-hour glucose. We also observed a protective effect of vitamin D on blood pressure. CONCLUSION(S): In women with PCOS, insulin sensitivity was unchanged with high-dose vitamin D, but there was a trend toward decreased 2-hour insulin and a protective effect on blood pressure. CLINICAL TRIAL REGISTRATION NUMBER: NCT00907153.