Racial and Gender Disparities in Utilization of Outpatient Total Shoulder Arthroplasties.

BACKGROUND: Utilization in outpatient total shoulder arthroplasties (TSAs) has increased significantly in recent years. It remains largely unknown whether utilization of outpatient TSA differs across gender and racial groups. This study aimed to quantify racial and gender disparities both nationally and by geographic regions. METHODS: 168,504 TSAs were identified using Medicare fee-for-service (FFS) inpatient and outpatient claims data and beneficiary enrollment data from 2020 to 2022Q4. The percentage of outpatient cases, defined as cases discharged on the same day of surgery, was evaluated by racial and gender groups and by different census divisions. A multivariate logistics regression model controlling for patient socio-demographic information (white vs. non-white race, age, gender, and dual eligibility for both Medicare and Medicaid), hierarchical condition category (HCC) score, hospital characteristics, year fixed effects, and patient residency state fixed effects was performed. RESULTS: The TSA volume per 1000 beneficiaries was 2.3 for the White population compared to 0.8, 0.6 and 0.3 for the Black, Hispanic, and Asian population, respectively. A higher percentage of outpatient TSAs were in White patients (25.6%) compared to Black patients (20.4%) (p < 0.001). The Black TSA patients were also younger, more likely to be female, more likely to be dually eligible for Medicaid, and had higher HCC risk scores. After controlling for patient socio-demographic characteristics and hospital characteristics, the odds of receiving outpatient TSAs were 30% less for Black than the White group (OR 0.70). Variations were observed across different census divisions with South Atlantic (0.67, p < 0.01), East North Central (0.56, p < 0.001), and Middle Atlantic (0.36, p < 0.01) being the four regions observed with significant racial disparities. Statistically significant gender disparities were also found nationally and across regions, with an overall odds ratio of 0.75 (p < 0.001). DISCUSSION: Statistically significant racial and gender disparities were found nationally in outpatient TSAs, with Black patients having 30% (p < 0.001) fewer odds of receiving outpatient TSAs than white patients, and female patients with 25% (p < 0.001) fewer odds than male patients. Racial and gender disparities continue to be an issue for shoulder arthroplasties after the adoption of outpatient TSAs.

A Preoperative Risk Assessment Tool for Predicting Adverse Outcomes among Total Shoulder Arthroplasty Patients.

BACKGROUND: With the increased utilization of Total Shoulder Arthroplasty (TSA) in the outpatient setting, understanding the risk factors associated with complications and hospital readmissions becomes a more significant consideration. Prior developed assessment metrics in the literature either consisted of hard-to-implement tools or relied on postoperative data to guide decision-making. This study aimed to develop a preoperative risk assessment tool to help predict the risk of hospital readmission and other postoperative adverse outcomes. METHODS: We retrospectively evaluated the 2019-2022(Q2) Medicare fee-for-service inpatient and outpatient claims data to identify primary anatomic or reserve TSAs and to predict postoperative adverse outcomes within 90 days post-discharge, including all-cause hospital readmissions, postoperative complications, emergency room visits, and mortality. We screened 108 candidate predictors, including demographics, social determinants of health, TSA indications, prior 12-month hospital and skilled nursing home admissions, comorbidities measured by hierarchical conditional categories, and prior orthopedic device-related complications. We used two approaches to reduce the number of predictors based on 80% of the data: 1) the Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression and 2) the machine-learning-based cross-validation approach, with the resulting predictor sets being assessed in the remaining 20% of the data. A scoring system was created based on the final regression models' coefficients, and score cutoff points were determined for low, medium, and high-risk patients. RESULTS: A total of 208,634 TSA cases were included. There was a 6.8% hospital readmission rate with 11.2% of cases having at least one postoperative adverse outcome. Fifteen covariates were identified for predicting hospital readmission with the area under the curve (AUC) of 0.70, and 16 were selected to predict any adverse postoperative outcome (AUC=0.75). The LASSO and machine learning approaches had similar performance. Advanced age and a history of fracture due to orthopedic devices are among the top predictors of hospital readmissions and other adverse outcomes. The score range for hospital readmission and an adverse postoperative outcome was 0 to 48 and 0 to 79, respectively. The cutoff points for the low, medium, and high-risk categories are 0-9, 10-14, ≥15 for hospital readmissions, and 0-11, 12-16, ≥17 for the composite outcome. CONCLUSION: Based on Medicare fee-for-service claims data, this study presents a preoperative risk stratification tool to assess hospital readmission or adverse surgical outcomes following TSA. Further investigation is warranted to validate these tools in a variety of diverse demographic settings and improve their predictive performance.

Five-Year Mortality Rates Following Elective Shoulder Arthroplasty and Shoulder Arthroplasty for Fracture in Patients Over Age 65.

Background: To effectively counsel patients prior to shoulder arthroplasty, surgeons should understand the overall life trajectory and life expectancy of patients in the context of the patient's shoulder pathology and medical comorbidities. Such an understanding can influence both operative and nonoperative decision-making and implant choices. This study evaluated 5-year mortality following shoulder arthroplasty in patients ≥65 years old and identified associated risk factors. Methods: We utilized Centers for Medicare & Medicaid Services Fee-for-Service inpatient and outpatient claims data to investigate the 5-year mortality rate following shoulder arthroplasty procedures performed from 2014 to 2016. The impact of patient demographics, including fracture diagnosis, year fixed effects, and state fixed effects; patient comorbidities; and hospital-level characteristics on 5-year mortality rates were assessed with use of a Cox proportional hazards regression model. A p value of <0.05 was considered significant. Results: A total of 108,667 shoulder arthroplasty cases (96,104 nonfracture and 12,563 fracture) were examined. The cohort was 62.7% female and 5.8% non-White and had a mean age at surgery of 74.3 years. The mean 5-year mortality rate was 16.6% across all shoulder arthroplasty cases, 14.9% for nonfracture cases, and 29.9% for fracture cases. The trend toward higher mortality in the fracture group compared with the nonfracture group was sustained throughout the 5-year postoperative period, with a fracture diagnosis being associated with a hazard ratio of 1.63 for mortality (p < 0.001). Medical comorbidities were associated with an increased risk of mortality, with liver disease bearing the highest hazard ratio (3.07; p < 0.001), followed by chronic kidney disease (2.59; p < 0.001), chronic obstructive pulmonary disease (1.92; p < 0.001), and congestive heart failure (1.90; p < 0.001). Conclusions: The mean 5-year mortality following shoulder arthroplasty was 16.6%. Patients with a fracture diagnosis had a significantly higher 5-year mortality risk (29.9%) than those with a nonfracture diagnosis (14.9%). Medical comorbidities had the greatest impact on mortality risk, with chronic liver and kidney disease being the most noteworthy. This novel longer-term data can help with patient education and risk stratification prior to undergoing shoulder replacement. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Trends in the Adoption of Outpatient Joint Arthroplasties and Patient Risk: A Retrospective Analysis of 2019 to 2021 Medicare Claims Data.

INTRODUCTION: Total joint arthroplasties (TJAs) have recently been shifting toward outpatient arthroplasty. This study aims to explore recent trends in outpatient total joint arthroplasty (TJA) procedures and examine whether patients with a higher comorbidity burden are undergoing outpatient arthroplasty. METHODS: Medicare fee-for-service claims were screened for patients who underwent total hip, knee, or shoulder arthroplasty procedures between January 2019 and December 2022. The procedure was considered to be outpatient if the patient was discharged on the same date of the procedure. The Hierarchical Condition Category Score (HCC) and the Charlson Comorbidity Index (CCI) scores were used to assess patient comorbidity burden. Patient adverse outcomes included all-cause hospital readmission, mortality, and postoperative complications. Logistic regression analyses were used to evaluate if higher HCC/CCI scores were associated with adverse patient outcomes. RESULTS: A total of 69,520, 116,411, and 41,922 respective total knee, hip, and shoulder arthroplasties were identified, respectively. Despite earlier removal from the inpatient-only list, outpatient knee and hip surgical volume did not markedly increase until the pandemic started. By 2022Q4, 16%, 23%, and 36% of hip, knee, and shoulder arthroplasties were discharged on the same day of surgery, respectively. Both HCC and CCI risk scores in outpatients increased over time (P < 0.001). DISCUSSION: TJA procedures are shifting toward outpatient surgery over time, largely driven by the COVID-19 pandemic. TJA outpatients' HCC and CCI risk scores increased over this same period, and additional research to determine the effects of this should be pursued. LEVEL OF EVIDENCE: Level III, therapeutic retrospective cohort study.

Trends and outcomes of outpatient total shoulder arthroplasty after its removal from CMS's inpatient-only list.

BACKGROUND: In January 2021, the US Medicare program approved reimbursement of outpatient total shoulder arthroplasties (TSA), including anatomic and reverse TSAs. It remains unclear whether shifting TSAs from the inpatient to outpatient setting has affected clinical outcomes. Herein, we describe the rate of outpatient TSA growth and compare inpatient and outpatient TSA complications, readmissions, and mortality. METHODS: Medicare fee-for-service claims for 2019-2022Q1 were analyzed to identify the trends in outpatient TSAs and to compare 90-day postoperative complications, all-cause hospital readmissions, and mortality between outpatients and inpatients. Outpatient cases were defined as those discharged on the same day of the surgery. To reduce the COVID-19 pandemic's impact and selection bias, we excluded 2020Q2-Q4 data and used propensity scores to match 2021-2022Q1 outpatients with inpatients from the same period (the primary analysis) and from 2019-2020Q1 (the secondary analysis), respectively. We performed both propensity score-matched and -weighted multivariate analyses to compare outcomes between the two groups. Covariates included sociodemographics, preoperative diagnosis, comorbid conditions, the Hierarchical Condition Category risk score, prior year hospital/skilled nursing home admissions, annual surgeon volume, and hospital characteristics. RESULTS: Nationally, the proportion of outpatient TSAs increased from 3% (619) in 2019Q1 to 22% (3456) in 2021Q1 and 38% (6778) in 2022Q1. A total of 55,166 cases were identified for the primary analysis (14,540 outpatients and 40,576 inpatients). Overall, glenohumeral osteoarthritis was the most common indication for surgery (70.8%), followed by rotator cuff pathology (14.6%). The unadjusted rates of complications (1.3 vs 2.4%, P < .001), readmissions (3.7 vs 6.1%, P < .001), and mortality (0.2 vs 0.4%, P = .024) were significantly lower among outpatient TSAs than inpatient TSAs. Using 1:1 nearest matching, 12,703 patient pairs were identified. Propensity score-matched multivariate analyses showed similar rates of postoperative complications, hospital readmissions, and mortality between outpatients and inpatients. Propensity score-weighted multivariate analyses resulted in similar conclusions. The secondary analysis showed a lower hospital readmission rate in outpatients (odds ratio: 0.8, P < .001). CONCLUSIONS: There has been accelerated growth in outpatient TSAs since 2019. Outpatient and inpatient TSAs have similar rates of postoperative complication, hospital readmission, and mortality.

Higher Surgeon Volume is Associated With a Lower Rate of Subsequent Revision Procedures After Total Shoulder Arthroplasty: A National Analysis.

BACKGROUND: Studies assessing the relationship between surgeon volume and outcomes have shown mixed results, depending on the specific procedure analyzed. This volume relationship has not been well studied in patients undergoing total shoulder arthroplasty (TSA), but it should be, because this procedure is common, expensive, and potentially morbid. QUESTIONS/PURPOSES: We performed this study to assess the association between increasing surgeon volume and decreasing rate of revision at 2 years for (1) anatomic TSA (aTSA) and (2) reverse TSA (rTSA) in the United States. METHODS: In this retrospective study, we used Centers for Medicare and Medicaid Services (CMS) fee-for-service inpatient and outpatient data from 2015 to 2021 to study the association between annual surgeon aTSA and rTSA volume and 2-year revision shoulder procedures after the initial surgery. The CMS database was chosen for this study because it is a national sample and can be used to follow patients over time. We included patients with Diagnosis-related Group code 483 and Current Procedural Terminology code 23472 for TSA (these codes include both aTSA and rTSA). We used International Classification of Diseases, Tenth Revision, procedural codes. Patients who underwent shoulder arthroplasty for fracture (10% [17,524 of 173,242]) were excluded. We studied the variables associated with the subsequent procedure rate through a generalized linear model, controlling for confounders such as patient age, comorbidity risk score, surgeon and hospital volume, surgeon graduation year, hospital size and teaching status, assuming a binomial distribution with the dependent variable being whether an episode had at least one subsequent procedure within 2 years. The regression was fitted with standard errors clustered at the hospital level, combining all TSAs and within the aTSA and rTSA groups, respectively. Hospital and surgeon yearly volumes were calculated by including all TSAs, primary procedure and subsequent, during the study period. Other hospital-level and surgeon-level characteristics were obtained through public files from the CMS. The CMS Hierarchical Condition Category risk score was controlled because it is a measure reflecting the expected future health costs for each patient based on the patient's demographics and chronic illnesses. We then converted regression coefficients to the percentage change in the odds of having a subsequent procedure. RESULTS: After controlling for confounding variables including patient age, comorbidity risk score, surgeon and hospital volume, surgeon graduation year, and hospital size and teaching status, we found that an annual surgeon volume of ≥ 10 aTSAs was associated with a 27% decreased odds of revision within 2 years (95% confidence interval 13% to 39%; p < 0.001), while surgeon volume of ≥ 29 aTSAs was associated with a 33% decreased odds of revision within 2 years (95% CI 18% to 45%; p < 0.001) compared with a volume of fewer than four aTSAs per year. Annual surgeon volume of ≥ 29 rTSAs was associated with a 26% decreased odds of revision within 2 years (95% CI 9% to 39%; p < 0.001). CONCLUSION: Surgeons should consider modalities such as virtual planning software, templating, or enhanced surgeon training to aid lower-volume surgeons who perform aTSA and rTSA. More research is needed to assess the value of these modalities and their relationship with the rates of subsequent revision. LEVEL OF EVIDENCE: Level III, therapeutic study.

Impact of the COVID-19 pandemic on shoulder arthroplasty: surgical trends and postoperative care pathway analysis.

BACKGROUND: COVID-19 triggered disruption in the conventional care pathways for many orthopedic procedures. The current study aims to quantify the impact of the COVID-19 pandemic on shoulder arthroplasty hospital surgical volume, trends in surgical case distribution, length of hospitalization, posthospital disposition, and 30-day readmission rates. METHODS: This study queried all Medicare (100% sample) fee-for-service beneficiaries who underwent a shoulder arthroplasty procedure (Diagnosis-Related Group code 483, Current Procedural Terminology code 23472) from January 1, 2019, to December 18, 2020. Fracture cases were separated from nonfracture cases, which were further subdivided into anatomic or reverse arthroplasty. Volume per 1000 Medicare beneficiaries was calculated from April to December 2020 and compared to the same months in 2019. Length of stay (LOS), discharged-home rate, and 30-day readmission for the same period were obtained. The yearly difference adjusted for age, sex, race (white vs. nonwhite), Centers for Medicare & Medicaid Services Hierarchical Condition Category risk score, month fixed effects, and Core-Based Statistical Area fixed effects, with standard errors clustered at the provider level, was calculated using a multivariate analysis (P < .05). RESULTS: A total of 49,412 and 41,554 total shoulder arthroplasty (TSA) cases were observed April through December for 2019 and 2020, respectively. There was an overall decrease in shoulder arthroplasty volume per 1000 Medicare beneficiaries by 14% (19% reduction in anatomic TSA, 13% reduction in reverse shoulder arthroplasty, and 3% reduction in fracture cases). LOS for all shoulder arthroplasty cases decreased by 16% (-0.27 days, P < .001) when adjusted for confounders. There was a 5% increase in the discharged-home rate (88.0% to 92.7%, P < .001), which was most prominent in fracture cases, with a 20% increase in discharged-home cases (65.0% to 73.4%, P < .001). There was no significant change in 30-day hospital readmission rates overall (P = .20) or when broken down by individual procedures. CONCLUSIONS: There was an overall decrease in shoulder arthroplasty volume per 1000 Medicare beneficiaries by 14% during the COVID-19 pandemic. A decrease in LOS and increase in the discharged-home rates was also observed with no significant change in 30-day hospital readmission, indicating that a shift toward an outpatient surgical model can be performed safely and efficiently and has the potential to provide value.

Anatomic Total Shoulder Arthroplasty: Component Size Prediction with 3-Dimensional Pre-Operative Digital Planning.

Background: The rate, complexity, and cost of total shoulder arthroplasty (TSA) continues to grow. Technology has advanced pre-operative templating. Reducing cost of TSA has positive impact for the patient, manufacturer, and hospital. The aim of this study was to evaluate the accuracy of implant size selection based on 3-D templating. Our hypothesis was that pre-operative templating would enable accurate implant prediction within one size. Methods: Multicenter retrospective study of anatomic TSAs templated utilizing 3-D virtual planning technology. This program uses computed tomography (CT) scans allowing the surgeon to predict component sizes of the glenoid and humeral head and stem. Pre-operative templated implant size were compared to actual implant size at the time of surgery. Primary data analysis utilized unweighted Cohen's Kappa test. Results: 111 TSAs were analyzed from five surgeons. Pre-operative templated glenoid sizes were within one size of actual implant in 99% and exactly matched in 89%. For patients requiring a posterior glenoid augment (n = 14), 100% of implants were within one size of the template and 93% matched exactly. For stemless humeral components (n = 87) implanted, 98% matched the pre-operative template within one size with 79% exactly matched. For stemmed components (n = 24), 88% of cases were within one size of the preoperative plan and exactly matching in 83%. Humeral head diameter matched within one size of the pre-operative template in 84% of cases and exactly matched in 72%. Conclusion: Pre-operative 3-D templating for TSAs can accurately predict glenoid and humeral component size. This study sets the groundwork for utilization of pre-operative 3-D templating as a potential method to reduce overall TSA costs by managing cost of implants, reducing inventory needs, and improving surgical efficiency.

Worsening Arthroplasty Utilization With Widening Racial Variance During the COVID-19 Pandemic.

BACKGROUND: Elective arthroplasty surgery in the United States came to a near-complete halt in the spring of 2019 as a response to the COVID-19 pandemic. Racial disparity has been a long-term concern in healthcare with increased focus during the pandemic. The purpose of this study is to evaluate the effects of COVID-19 and race on arthroplasty utilization trends during the pandemic. METHODS: We used 2019 and 2020 Center for Medicare and Medicaid Service fee-for-service claims data to compare arthroplasty volumes prior to and during the COVID-19 pandemic. We compared overall arthroplasty utilization rates between 2019 and 2020 and then sought to determine the effect of race and COVID-19, both independently and combined. RESULTS: There was a decrease in primary total knee arthroplasty (-28%), primary total hip arthroplasty (-14%), primary total hip arthroplasty for fracture (-2%), and revision arthroplasty (-14%) utilization between 2019 and 2020. The highest decrease in overall arthroplasty utilization was in the Hispanic population (34% decrease vs 19% decrease in the White population). We found that a non-White patient was 39.9% (P < .001) less likely to receive a total joint arthroplasty prior to COVID-19. The COVID-19 pandemic further exacerbated the pre-existing racial differences in arthroplasty utilization by decreasing the probability of receiving a total joint arthroplasty for non-White patient by another 12.9% (P < .001). CONCLUSION: We found an overall decreased utilization rate of arthroplasty during the COVID-19 pandemic with further decrease noted in all non-White populations. This raises significant concern for worsening racial disparity in arthroplasty caused by the ongoing pandemic.

The National Trend in Arthroplasty Surgery Location and the Economic Impact on Surgeons, Hospitals and ASCs.

BACKGROUND: We sought to understand the magnitude of the shift in care settings (hospital inpatient, hospital outpatient, or ambulatory surgery center) for primary total joint arthroplasty (TJA) and its economic impact on surgeons and hospitals. METHODS: We measured the shift in care settings for primary TJAs using national 100% sample Medicare fee-for-service (FFS) claims data from January 2017 through March 2021. We also measured the percent of case being discharged the same day over time. We calculated the national average hospital payment rate by setting and the weighted average hospital payment rates based on the mix of inpatient and outpatient cases over time. We compared average facility and physician payment rate changes over time across common types of surgeries. RESULTS: By the first quarter of 2021, 29% of Medicare FFS primary TJAs were performed hospital inpatient (down from 100% in 2017), 64% were performed hospital outpatient, and about 7% in an ambulatory surgery center. The percent of hospital-based primary TJAs that were discharged the same day increased from less than 2% in the first quarter of 2018 to over 18% in the first quarter of 2021. Medicare increased its payment rates for both inpatient and outpatient TJAs, which offset the impact of TJAs shifting from being performed inpatient to outpatient. The average Medicare payment rates for TJAs declined by more than they did for most other major procedures. CONCLUSION: There was a significant shift in care setting from hospital inpatient to hospital outpatient for Medicare primary TJAs. This shift led to lower average TJA payment rates to hospitals; however, the impact was attenuated due to the increasing Medicare reimbursement rates in each setting, particularly for outpatient cases.

An Examination of the Adoption of Outpatient Total Knee Arthroplasty Since 2018.

BACKGROUND: The Centers for Medicare and Medicaid Services removed total knee arthroplasties (TKAs) from the inpatient-only (IPO) list on January 1, 2018, which meant that TKAs could be performed on a hospital outpatient basis. We examined the following: (1) the national rate of adoption of outpatient TKAs over time, (2) how adoption varied across hospitals, and (3) whether adoption of outpatient TKAs has positively or negatively impacted 90-day TKA readmission rates. METHODS: We used national patient-level Medicare Fee-for-Service Part A claims data (100% sample) from January 2017 through June 2019 to look at the quarterly trend in percent of TKAs performed as outpatient, and the distribution in this percentage across hospitals in the country. We ran a case-level regression to understand whether inpatient vs outpatient coding status relates to 90-day readmission rates. RESULTS: In 2017 prior to the removal of TKAs from the IPO list, 0.2% were performed as outpatient. In the first quarter (Q1 2018) after the rule change, 24.9% were performed as outpatient, and by the second quarter of 2019, 36.4% were performed as outpatient. These rates varied widely across hospitals from 0% (10th and 25th percentiles) to 78% (90th percentile) from January 2018 through March 2019. There was no difference in readmission rates for same-day discharges, but outpatient cases discharged after one or more nights in the hospital had statistically lower readmissions than inpatient cases. CONCLUSION: There was a rapid increase in the adoption of hospital outpatient TKAs following their removal from the Medicare IPO, which has resulted in lower readmission rates, and so adoption is likely to continue.

The modulator of nongenomic actions of the estrogen receptor (MNAR) regulates transcription-independent androgen receptor-mediated signaling: evidence that MNAR participates in G protein-regulated meiosis in Xenopus laevis oocytes.

Classical steroid receptors mediate many transcription-independent (nongenomic) steroid responses in vitro, including activation of Src and G proteins. Estrogen-triggered activation of Src can be regulated by the modulator of nongenomic actions of the estrogen receptor (MNAR), which binds to estrogen receptors and Src to create a signaling complex. In contrast, the mechanisms regulating steroid-induced G protein activation are not known, nor are the physiologic responses mediated by MNAR. These studies demonstrate that MNAR regulates the biologically relevant process of meiosis in Xenopus laevis oocytes. MNAR was located throughout oocytes, and reduction of its expression by RNA interference markedly enhanced testosterone-triggered maturation and activation of MAPK. Additionally, Xenopus MNAR augmented androgen receptor (AR)-mediated transcription in CV1 cells through activation of Src. MNAR and AR coimmunoprecipitated as a complex involving the LXXLL-rich segment of MNAR and the ligand binding domain of AR. MNAR and Gbeta also precipitated together, with the same region of MNAR being important for this interaction. Finally, reduction of MNAR expression decreased Gbetagamma-mediated signaling in oocytes. MNAR therefore appears to participate in maintaining meiotic arrest, perhaps by directly enhancing Gbetagamma-mediated inhibition of meiosis. Androgen binding to AR might then release this inhibition, allowing maturation to occur. Thus, MNAR may augment multiple nongenomic signals, depending upon the context and cell type in which it is expressed.

Effects of metformin on body mass index, menstrual cyclicity, and ovulation induction in women with polycystic ovary syndrome.

OBJECTIVE: Metformin has been used as a treatment in many studies of the infertility associated with polycystic ovary syndrome (PCOS). We will review the literature on this topic as it specifically relates to changes in body mass index (BMI), improvement in menstrual cyclicity, and effects on ovulation and pregnancy rates. DESIGN: Review of studies addressing biochemical and clinical changes in women with PCOS on metformin. MAIN OUTCOME MEASURE(S): Changes in BMI, menstrual cyclicity, ovulation rate, and pregnancy rate. RESULT(S): Metformin has been shown to produce small but significant reductions in BMI. Multiple observational studies have confirmed an improvement in menstrual cyclicity with metformin therapy. The studies addressing the concomitant use of metformin with clomiphene citrate initially predicted great success, but these have been followed by more modest results. There is little data in the literature concerning the use of metformin and hMGs. CONCLUSION(S): Some (but not all) women with PCOS have improvements in their menstrual cycles while on metformin. The data supporting the use of metformin in ovulation induction with clomiphene citrate and hMG remain to be confirmed by large, randomized, prospective studies.

Effect of rosiglitazone on spontaneous and clomiphene citrate-induced ovulation in women with polycystic ovary syndrome.

OBJECTIVE: In women suffering from polycystic ovary syndrome (PCOS), correction of hyperinsulinemia results enhances spontaneous ovulation or alternatively, the responsiveness to ovulation induction agents such as clomiphene citrate (CC). We investigated the effect of rosiglitazone maleate on ovulation induction in overweight and obese, CC-resistant women with PCOS. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: Academic reproductive endocrinology clinic. PATIENT(S): Overweight and obese women with clinical and laboratory manifestations of PCOS who desired pregnancy and were resistant to CC. INTERVENTION(S): Twenty-five women were randomized into two treatment groups. Subjects in Group I (n = 12) were randomized to receive rosiglitazone 4 mg b.i.d. with a placebo on cycle days 5-9. Group II (n = 13) was randomized to receive rosiglitazone 4 mg b.i.d. with CC on cycle days 5-9. The duration of the study was 2 months. MAIN OUTCOME MEASURE(S): The primary outcome was ovulation as defined by luteal serum progesterone greater than 5 ng/dL assessed on days 21, 24, and 28 of the cycle. Secondary outcomes were pregnancy and changes in insulin sensitivity, serum lipoproteins, and androgens. RESULT(S): Overall, 14 of 25 (56%) women, who were previously resistant to CC, successfully ovulated. In subjects taking rosiglitazone alone (Group I), 4 of 12 (33%) subjects ovulated compared with 10 of 13 (77%) women randomized to rosiglitazone with CC (Group II) (P=.04, Fisher's exact). One subject in Group I became pregnant, resulting in one uncomplicated live birth; two subjects in Group II conceived, with one successful live birth and one first trimester, spontaneous abortion. For all subjects, fasting insulin declined from 29.4 +/- 13.8 microU/mL to 17.3 +/- 7.8 microU/mL after rosiglitazone (P=.003, paired t-test). Although mean levels of total testosterone (T) and dehydroepiandrosterone sulfate (DHEAS) did not decline significantly, sex hormone-binding globulin (SHBG) did increase from 0.7 +/- 0.3 microg/dL to 1.0 +/- 0.3 microg/dL after rosiglitazone therapy (P=.001, paired t test). There was also a decrease in luteinizing hormone (LH) from 9.4 +/- 6.3 mU/mL to 7.2 +/- 3.7 mU/mL (P=.01). Lipoproteins including total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides did not change. CONCLUSIONS: Short-term rosiglitazone therapy enhances both spontaneous and clomiphene-induced ovulation in overweight and obese women with PCOS. Rosiglitazone therapy improves insulin sensitivity and decreases hyperandrogenemia primarily through increases in SHBG.