Cost-effectiveness analysis of expectant vs active management for treatment of persistent pregnancies of unknown location.

BACKGROUND: Persistent pregnancies of unknown location are defined by abnormally trending serum human chorionic gonadotropin with nondiagnostic ultrasound. There is no consensus on optimal management. OBJECTIVE: This study aimed to assess the cost-effectiveness of 3 primary management strategies for persistent pregnancies of unknown location: (1) expectant management, (2) empirical 2-dose methotrexate, and (3) uterine evacuation followed by methotrexate, if indicated. STUDY DESIGN: This was a prospective economic evaluation performed concurrently with the Expectant versus Active Management for Treatment of Persistent Pregnancies of Unknown Location multicenter randomized trial that was conducted from July 2014 to June 2019. Participants were randomized 1:1:1 to expectant management, 2-dose methotrexate, or uterine evacuation. The analysis was from the healthcare sector perspective with a 6-week time horizon after randomization. Costs were expressed in 2018 US dollars. Effectiveness was measured in quality-adjusted life years and the rate of salpingectomy. Incremental cost-effectiveness ratios and cost-effectiveness acceptability curves were generated. Sensitivity analyses were performed to assess the robustness of the analysis. RESULTS: Methotrexate had the lowest mean cost ($875), followed by expectant management ($1085) and uterine evacuation ($1902) (P=.001). Expectant management had the highest mean quality-adjusted life years (0.1043), followed by methotrexate (0.1031) and uterine evacuation (0.0992) (P=.0001). The salpingectomy rate was higher for expectant management than for methotrexate (9.4% vs 1.2%, respectively; P=.02) and for expectant management than for uterine evacuation (9.4% vs 8.1%, respectively; P=.04). Uterine evacuation, with the highest costs and the lowest quality-adjusted life years, was dominated by both expectant management and methotrexate. In the base case analysis, expectant management was not cost-effective compared with methotrexate at a willingness to pay of $150,000 per quality-adjusted life year given an incremental cost-effectiveness ratio of $175,083 per quality-adjusted life year gained (95% confidence interval, -$1,666,825 to $2,676,375). Threshold analysis demonstrated that methotrexate administration would have to cost $214 (an increase of $16 or 8%) to favor expectant management. Moreover, expectant management would be favorable in lower-risk patient populations with rates of laparoscopic surgical management for ectopic pregnancy not exceeding 4% of pregnancies of unknown location. Based on the cost-effectiveness acceptability curves, the probability of expectant management being cost-effective compared with methotrexate at a willingness to pay of $150,000 per quality-adjusted life year gained was 50%. The results were dependent on the cost of surgical intervention and the expected rate of methotrexate failure. CONCLUSION: The management of pregnancies of unknown location with a 2-dose methotrexate protocol may be cost-effective compared with expectant management and uterine evacuation. Although uterine evacuation was dominated, expectant management vs methotrexate results were sensitive to modest changes in treatment costs of both methotrexate and surgical management.

The Menopause Transition: Signs, Symptoms, and Management Options.

CONTEXT: Menopause, the permanent cessation of menses, reflects oocyte depletion and loss of gonadal steroids. It is preceded by a transition state, the perimenopause, which is characterized by the gradual loss of oocytes, altered responsiveness to gonadal steroid feedback, wide hormonal fluctuations, and irregular menstrual patterns. The goal of this mini-review is to discuss the basic pathophysiology of the menopausal transition and the hormonal and nonhormonal management of clinicopathology attributed to it. EVIDENCE ACQUISITION: A Medline search of epidemiologic, population-based studies, and studies of reproductive physiology was conducted. A total of 758 publications were screened. EVIDENCE SYNTHESIS: The reproductive hormonal milieu of the menopausal transition precipitates bothersome vasomotor symptoms, mood disruption, temporary cognitive dysfunction, genitourinary symptoms, and other disease processes that reduce the quality of life of affected women. The endocrine tumult of the menopause transition also exposes racial and socioeconomic disparities in the onset, severity, and frequency of symptoms. Hormone therapy (HT) treatment can be effective for perimenopausal symptoms but its use has been stymied by concerns about health risks observed in postmenopausal HT users who are older than 60 and/or women who have been postmenopausal for greater than 10 years. CONCLUSIONS: The menopause transition is a disruptive process that can last for over a decade and causes symptoms in a majority of women. It is important for clinicians to recognize early signs and symptoms of the transition and be prepared to offer treatment to mitigate these symptoms. Many safe and effective options, including HT, are available.

Families with children resulting from ART: psychosocial and financial implications.

STUDY QUESTION: What are the psychosocial and financial issues experienced among families with children 2-12 years of age conceived by ART? SUMMARY ANSWER: Our results suggest that families with children, 2-12 years of age, conceived via ART are doing well, although impacts were identified on parents of twins and higher-order multiples. WHAT IS KNOWN ALREADY: Multiple births have been associated with higher morbidity and mortality of children, as well as financial costs to families and society. STUDY DESIGN SIZE DURATION: This study was an assessment of familial response to birth of singletons, twins and higher order multiples at child's ages of 2-12. PARTICIPANTS/MATERIALS SETTING METHODS: Semi-structured interviews and surveys were conducted with mothers (n = 348) and fathers (n = 338) of singletons, twins and higher-order multiple gestations who received fertility services. MAIN RESULTS AND THE ROLE OF CHANCE: No significant differences were observed between the groups in domains of primary caregiving or parental separation/divorce. Impacts were identified on parent's ability to maintain employment. The revised 15-item scores of the Impact on Family Scale were significantly lower, reflecting more negative impacts, among families with twins (beta = -2.6, 95% confidence interval (CI), -4.7, -0.5, P = 0.014) and multiples (beta = -7.4, 95% CI, -10.4, -4.5, P < 0.001) than among families with singletons. Similarly, the Parenting Stress Index total scores were significantly lower among families with twins and multiples, indicating greater levels of stress, when compared to those with singletons. In addition, the Beck Depression Inventory total score were significantly higher for twins and multiples, and the Child Behaviour Checklist for ages 1.5-5 total problem score was significantly higher for twins when compared to singletons. LIMITATIONS REASONS FOR CAUTION: The study was limited to families who received fertility treatment and constitutes a population that was well educated and had higher incomes. Additionally, interview data was self-reported. STUDY FUNDING/COMPETING INTERESTS: This work was supported by National Institutes of Health (NIH)/Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) U10 HD39005 (to M.P.D.), U10 HD077680 (to K.R.H.), U10 HD077844 (to A.Z.), U10 HD077841 (to M.C.), U10 HD38992 (to R.S.L.), U10 HD27049 (to C.C.), U10 HD055925 (to H.Z.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NICHD or NIH.Dr Virginia Miller-no conflicts; Dr Michael P. Diamond-NIH Funding, AbbVie, Bayer and ObsEva Funding; Board of Directors and Stockholder for Advanced Reproductive Care; Dr Karl R. Hansen-Yale University/Reproductive Medicine Network/NICHD, Roche Diagnostics and Ferring International Pharmascience Center US funding; Dr Anne Steiner-NIH Funding; Dr Marcelle I. Cedars-no conflicts; Dr Richard Legro-consultant for Ogeda, Millendo, Kindex and Bayer; Ferring and Astra Zeneca funding; Dr Stephen A. Krawetz-no conflicts; Dr Christos Coutifaris-NIH Funding; Dr Hao Huang-no conflicts; Dr Nanette Santoro-no conflicts; Dr Heping Zhang-NIH Funding. TRIAL REGISTRATION NUMBER: N/A.

Comparison of sonohysterography to hysterosalpingogram for tubal patency assessment in a multicenter fertility treatment trial among women with polycystic ovary syndrome.

PURPOSE: To compare saline infusion sonohysterography (SIS) versus hysterosalpingogram (HSG) for confirmation of tubal patency. METHODS: Secondary analysis of a randomized controlled trial, Pregnancy in Polycystic Ovary Syndrome II (PPCOS II). Seven hundred fifty infertile women (18-40 years old) with polycystic ovary syndrome (PCOS) were randomized to up to 5 cycles of letrozole or clomiphene citrate. Prior to enrollment, tubal patency was determined by HSG, the presence of free fluid in the pelvis on SIS, laparoscopy, or recent intrauterine pregnancy. Logistic regression was conducted in patients who ovulated with clinical pregnancy as the outcome and HSG or SIS as the key independent variable. RESULTS: Among women who ovulated, 414 (66.9%) had tubal patency confirmed by SIS and 187 (30.2%) had at least one tube patent on HSG. Multivariable analysis indicated that choice of HSG versus SIS did not have a significant relationship on likelihood of clinical pregnancy, after adjustment for treatment arm, BMI, duration of infertility, smoking, and education (OR 1.14, 95% CI 0.77, 1.67, P = 0.52). Ectopic pregnancy occurred more often in women who had tubal patency confirmed by HSG compared to SIS (2.8% versus 0.6%, P = 0.02). CONCLUSIONS: In this large cohort of women with PCOS, there was no significant difference in clinical pregnancy rate between women who had tubal patency confirmed by HSG versus SIS. SIS is an acceptable imaging modality for assessment of tubal patency in this population.

Menopause and exercise.

OBJECTIVE: Accumulating data suggest that regular physical exercise reduces mortality and extends the functional life span of men and women. This review seeks to describe the current state of the medical literature on this topic. METHODS: A narrative review of the current medical literature including randomized clinical trials and clinical guidelines that address the benefits of physical fitness and regular exercise on the health of midlife and postmenopausal women. RESULTS: Reduction and avoidance of obesity and its related comorbidities (hypertension, glucose intolerance, dyslipidemia, and heart disease) are one major benefit of exercise. However, long-term physical exercise is also associated with reduced rates of cancer, dementia and cognitive decline, adverse mood and anxiety symptoms, and reduction of osteoporosis, osteopenia, falls, and fractures. Beneficial physical activity includes exercise that will promote cardiovascular fitness (aerobic), muscle strength (resistance), flexibility (stretching), and balance (many of the preceding, and additional activities such as yoga). CONCLUSIONS: Given that it is unambiguously beneficial, inexpensive, and minimal risk, maintaining a healthy exercise regimen should be a goal for every participant to enhance lifelong wellness. Clinicians should use a number of behavioral strategies to support the physical fitness goals of their participants.

Assessment of multiple intrauterine gestations from ovarian stimulation (AMIGOS) trial: baseline characteristics.

OBJECTIVE: To identify baseline characteristics of women with unexplained infertility to determine whether treatment with an aromatase inhibitor will result in a lower rate of multiple gestations than current standard ovulation induction medications. DESIGN: Randomized, prospective clinical trial. SETTING: Multicenter university-based clinical practices. PATIENT(S): A total of 900 couples with unexplained infertility. INTERVENTION(S): Collection of baseline demographics, blood samples, and ultrasonographic assessments. MAIN OUTCOME MEASURE(S): Demographic, laboratory, imaging, and survey characteristics. RESULT(S): Demographic characteristics of women receiving clomiphene citrate (CC), letrozole, or gonadotropins for ovarian stimulation were very consistent. Their mean age was 32.2 ± 4.4 years and infertility duration was 34.7 ± 25.7 months, with 59% primary infertility. More than one-third of the women were current or past smokers. The mean body mass index (BMI) was 27 and mean antimüllerian hormone level was 2.6; only 11 women (1.3%) had antral follicle counts of <5. Similar observations were identified for hormonal profiles, ultrasound characterization of the ovaries, semen parameters, and quality of life assessments in both male and female partners. CONCLUSION(S): The cause of infertility in the couples recruited to this treatment trial is elusive, as the women were regularly ovulating and had evidence of good ovarian reserve both by basal FSH, antimüllerian hormone levels, and antral follicle counts; the male partners had normal semen parameters. The three treatment groups have common baseline characteristics, thereby providing comparable patient populations for testing the hypothesis that use of letrozole for ovarian stimulation can reduce the rates of multiples from that observed with gonadotropin and CC treatment. CLINICAL TRIAL REGISTRATION NUMBER: NCT 01044862.

Associations of testosterone and sex hormone binding globulin with adipose tissue hormones in midlife women.

OBJECTIVE: Regulators of adipose tissue hormones remain incompletely understood, but may include sex hormones. As adipose tissue hormones have been shown to contribute to numerous metabolic and cardiovascular disorders, understanding their regulation in midlife women is of clinical importance. Therefore, we assessed the associations between testosterone (T) and sex hormone binding globulin (SHBG) with leptin, high molecular weight (HMW) adiponectin, and the soluble form of the leptin receptor (sOB-R) in healthy midlife women. DESIGN AND METHODS: Cross-sectional analyses were performed using data from 1,881 midlife women (average age 52.6 (±2.7) years) attending the sixth Annual follow-up visit of the multiethnic Study of Women's Health Across the Nation. RESULTS: T was weakly negatively associated with both HMW adiponectin and sOB-R (r = -0.12 and r = -0.10, respectively; P < 0.001 for both), and positively associated with leptin (r = 0.17; P < 0.001). SHBG was more strongly and positively associated with both HMW adiponectin and sOB-R (r = 0.29 and r = 0.24, respectively; P < 0.001 for both), and more strongly and negatively associated with leptin (r = -0.27; P < 0.001). Adjustment for fat mass, insulin resistance, or waist circumference only partially diminished associations with HMW adiponectin and sOB-R, but attenuated associations with leptin. In conclusion, in these midlife women, lower SHBG values, and to a lesser extent, higher T levels, were associated with lower, or less favorable, levels of adiponectin and sOB-R, independent of fat mass. CONCLUSIONS: These data suggest that variation in these adipose hormones resulting from lower SHBG levels, and possibly, though less likely, greater androgenicity, may contribute to susceptibility for metabolic and cardiovascular outcomes during midlife in women.

Assessment of luteal function in the vervet monkey as a means to develop a model for obesity-related reproductive phenotype.

The objective of the current study was to characterize luteal function in vervet monkeys. Urine from 12 adult female vervets housed at an academic research center was collected for 10 weeks from single-caged monkeys in order to assess evidence of luteal activity (ELA) as determined by urinary excretion of pregnanediol glucuronide (Pdg) and estrone conjugates (E1c). Dual energy X-ray absorptiometry (DXA) was performed on the monkeys to assess body composition, bone density, and fat mass. Menstrual cyclicity was determined using records of vaginal bleeding. ELA was observed in 9 monkeys and was characterized by a late follicular rise in E1c followed by a progressive increase in Pdg excretion. Mean menstrual cycle length was 26.7 ± 3.8 days and the average day of luteal transition was 14 ± 1.8. Three monkeys without ELA had a clearly defined E1c rise (mean 12-fold from nadir) followed by an E1c drop that was not accompanied by Pdg rise and coincided with vaginal bleeding. Among the 9 ELA monkeys, excretion of E1c tended to negatively associate with fat mass, although this finding did not reach statistical significance (r = -0.61, p = 0.08). Similar to women, vervet monkeys experience an increase in E1c late in the follicular phase of the menstrual cycle which is followed by a subsequent luteal Pdg peak. Assessment of urinary reproductive hormones allows for identification of cardinal menstrual cycle events; thus, the similarity of vervet cycles to human menstrual cycles makes them a useful model for obesity-related human reproductive impairment.

The SWAN song: Study of Women's Health Across the Nation's recurring themes.

Reproductive health can be a reflection of overall health. It follows that abnormalities of reproductive milestones may be a manifestation of unhealthy aging. Since 1994, the Study of Women's Health Across the Nation (SWAN) has assessed how menopause and the process of that transition may affect future health. Themes have emerged from SWAN associating patterns of hormones and symptoms with metabolic status.The nature of these relationships vary as women traverse the menopause and ovarian hormone production ceases. This review describes these cross-cutting themes and their possible meaning for the health of the mid-life woman.

Assessing comprehension of clinical research.

BACKGROUND: Comprehension and retention of study-related concepts by research subjects are understudied, particularly in certain areas of women's health such as menopausal hormone therapy (MHT). METHODS: In a multi-center trial of MHT, a 9-item participant comprehension questionnaire (PCQ) tested knowledge of key concerns relating to MHT at two study sites. The PCQ was administered at baseline. At study site1, PCQ was re-administered to assess information retention months later. Multivariable analyses assessed predictors of participant comprehension after adjusting for age, race, education, annual family income (AFI), menopausal symptoms and study site. RESULTS: 151 participants (n = 89 at site I, n = 62 at site II) completed the PCQ at baseline; 71 participants from site I completed the follow-up PCQ. Participant comprehension at baseline was influenced by age, marital status, education, symptom of dyspareunia, season of enrollment and AFI<$40,000. Significant improvement in correct responses was observed at follow-up compared to baseline (p = 0.02); season and low AFI<$20,000 were predictive of likelihood for correctly answering <5/9 at follow up. CONCLUSION: Assessing participant comprehension of research-related concepts using a PCQ identifies a need for ongoing reinforcement of relevant details, especially in symptomatic early menopausal women of lower education and income. Improved participant comprehension at follow up is reassuring and reflects success of the research team in communicating study-related concepts to participants enrolled in longitudinal studies.

Decision trees for identifying predictors of treatment effectiveness in clinical trials and its application to ovulation in a study of women with polycystic ovary syndrome.

BACKGROUND: Double-blind, randomized clinical trials are the preferred approach to demonstrating the effectiveness of one treatment against another. The comparison is, however, made on the average group effects. While patients and clinicians have always struggled to understand why patients respond differently to the same treatment, and while much hope has been held for the nascent field of predictive biomarkers (e.g. genetic markers), there is still much utility in exploring whether it is possible to estimate treatment efficacy based on demographic and baseline variables. METHODS: The pregnancy in polycystic ovary syndrome (PPCOS) study was a prospective, multi-center, randomized clinical trial comparing three ovulation induction regimens: clomiphene citrate (CC), metformin and the combination of the two. There were 446 women who ovulated in response to the treatments among the entire 626 participants. In this report, we focus on the 418 women who received CC (alone or combined with metformin) to determine if readily available baseline physical characteristics and/or easily obtainable baseline measures could be used to distinguish treatment effectiveness in stimulating ovulation. We used a recursive partitioning technique and developed a node-splitting rule to build decision tree models that reflected within-node and within-treatment responses. RESULTS: Overall, the combination of CC plus metformin resulted in an increased incidence of ovulation compared with CC alone. This is particularly so in women with relatively larger left ovarian volumes (≥ 19.5 cubic cm), and a left ovarian volume <19.5 cubic cm was related to treatment outcomes for all subsequent nodes. Women who were older, who had higher baseline insulin, higher waist-to-hip circumference ratio or higher sex hormone-binding globulin levels had better ovulatory rates with CC alone than with the combination of CC plus metformin. CONCLUSIONS: Polycystic ovary syndrome (PCOS) is a phenotypically diverse condition. Both baseline laboratory and clinical parameters can predict the ovulatory response in women with PCOS undergoing ovulation induction. Without a priori hypotheses with regard to any predictors, the observation regarding left ovary volume is novel and worthy of further investigation and validation.

Simple tools for assessment of ovarian reserve (OR): individual ovarian dimensions are reliable predictors of OR.

OBJECTIVE: To determine the association between individual ovarian dimensions, advancing age, and declining ovarian reserve (OR) in an infertile population. DESIGN: An ongoing prospective observational study. SETTING: Academic infertility practice. PATIENT(S): Sixty-nine premenopausal women presenting for the evaluation and management of infertility. INTERVENTION(S): Transvaginal ultrasound assessment of the ovarian dimensions (length, width, and overall diameter in cm) and evaluation of the OR status by measuring serum levels of FSH and E(2) in the early follicular phase of the menstrual cycle. MAIN OUTCOME MEASURE(S): Relationship of the individual ovarian dimensions to age (years) and OR (reflected by historical maximal FSH levels). RESULT(S): A statistically significant decrease in three ovarian size parameters accompanied advancing age (ovarian width, r = -0.30; ovarian length, r = -0.24; and the mean overall ovarian diameter, r = -0.30). Levels of FSH demonstrated a significant and linear correlation with age (r = 0.39). Increasing levels of FSH (and hence declining OR) were associated with statistically significant declines in the mean ovarian width (r = -0.39), length (r = -0.38), and overall mean ovarian diameter (r = -.42), Patients with a known diagnosis of diminished OR demonstrated significantly reduced ovarian dimensions compared with patients with other infertility etiologies. Multivariate linear regression analysis confirmed individual ovarian measurements (width, length, and overall diameter) as independent predictors of OR (FSH levels) after adjusting for parameters that are known to influence ovarian size, i.e., age, smoking status, body mass index, and anovulation history. Ovarian width emerged as the strongest predictor of OR (largest beta coefficient and hence the strongest association with OR status), compared with ovarian length and the mean ovarian diameter. CONCLUSION(S): Single ovarian dimensions are reliable predictors of advancing age and declining OR status in premenopausal infertile women. The magnitude of this association is most robust for the ovarian width.

Assessment of the proliferative status of epithelial cell types in the endometrium of young and menopausal transition women.

BACKGROUND: We determined protein and mRNA expressions of markers of normal human endometrial proliferation and hypothesized that dysregulation of the endometrial response to estradiol (E(2)) and progesterone would be observed in the older menopausal transition (MT) women compared with mid-reproductive age (MRA) controls. METHODS: Endometrial biopsies were prospectively obtained from MRA and MT non-randomized healthy volunteers during proliferative (+/- exogenous E(2)) and secretory (MRA only) menstrual cycle phases. mRNA and/or nuclear protein expressions of proliferative markers (MKI67, PCNA and MCM2), cell-cycle regulators (cyclins A1, E1 and D1 and cyclin dependent kinase Inhibitor B; CCNA1, CCNE1, CCND1 and CDKN1B) and sex-steroid receptors [estrogen receptor (ER) and progesterone receptor (PR)] were assessed in endometrial lumen, gland and stroma. RESULTS: MRA women had significantly higher proliferative than secretory expression of MKI67, PCNA, MCM2, CCNA1, CCNE1, ESR1 and PGR in lumen and gland (minimal stromal changes), whereas CDKN1B protein expression was higher during the secretory phase. E(2)-treatment of MT women led to relatively less MKI67 glandular protein expression compared with MRA women; no other age-related differences were observed. CONCLUSION: Although the MT does not appear to alter the proliferative cell phenotype of endometrial epithelium and stroma, the data suggest that prior to the MT, age is associated with a decrease in some proliferative markers and steroid receptor expression status within different endometrial cell types.

Helping midlife women predict the onset of the final menses: SWAN, the Study of Women's Health Across the Nation.

OBJECTIVE: Women approaching menopause often ask their doctors, "When are my periods going to end?" The objective of this study was to predict time to the final menstrual period (FMP). DESIGN: This multiethnic, observational cohort study, the Study of Women's Health Across the Nation, has been ongoing since 1996. Data collected from seven annual study visits were used. The community-based cohort from seven national sites included 3,302 white, African American, Hispanic, Chinese, and Japanese women aged 42 to 52 years at baseline with a uterus and at least one ovary, who were not pregnant or taking reproductive hormones, and had at least one menstrual period within the past 3 months at baseline. The time to the FMP was defined retrospectively after 12 months of amenorrhea. Uni- and multivariable Cox proportional hazard models, hazard ratios (HRs), and 95% CIs were computed for variables of interest. RESULTS: A total of 2,662 women, of whom 706 had an observed FMP, were included. Age, menstrual cycles that had become farther apart (HR = 2.56, 95% CI = 1.94-3.39) or more variable (HR = 1.79, 95% CI = 1.45-2.21), and current smoking (HR = 1.68, 95% CI = 1.35-2.08) were all associated with shorter time to the FMP. Higher (log) follicle-stimulating hormone (HR = 2.32, 95% CI = 2.02-2.67) was related to a shorter time to the FMP, but the highest estradiol category (>or=100 pg/mL [367 pmol/L]) was associated with an earlier onset of the FMP (HR = 2.16, 95% CI = 1.63-2.89). The number of vasomotor symptoms was related to an earlier FMP, whereas higher physical activity and educational levels were associated with a later FMP. CONCLUSIONS: Age, menstrual cycle recall, smoking status, and hormone measurements can be used to estimate when the FMP will occur, allowing for more precise estimates for older midlife women: in the most extreme cases, ie, age 54, high estradiol level, current smoking, and high follicle-stimulating hormone level, the FMP can be estimated to within 1 year.

The menopause transition.

The menopause transition is a period of life during which a series of dynamic changes in physiology are taking place. There seems to be a transient increase in symptoms of many types, which are occasionally severe. There is a disproportionate burden of morbidity that seems to accrue to women of high body mass index and low socioeconomic status. Moreover, there are ethnic differences in hormones and symptoms that may reflect either basic biologic variation in hormone receptors and actions or the different social milieu that women in different ethnic groups experience. Current medical management of the perimenopause should include screen-ing for general health maintenance, avoidance of weight gain, and a holistic approach to symptoms.

Ethnic differences in insulin sensitivity and beta-cell function in premenopausal or early perimenopausal women without diabetes: the Study of Women's Health Across the Nation (SWAN).

OBJECTIVE: To assess differences in insulin sensitivity and beta-cell function between nondiabetic premenopausal or early perimenopausal non-Hispanic white women and African American, Chinese American, Japanese American, and non-Mexican-American Latino women. RESEARCH DESIGN AND METHODS: Homeostasis model assessments (HOMAs) of insulin sensitivity (HOMA%S) and beta-cell function (HOMA%beta) were used. Stepwise multivariable ethnic-specific ANCOVA models were used to compare HOMA%S and HOMA%beta between non-Hispanic whites and each of the four ethnic groups. RESULTS: HOMA%S was lower in African Americans, Chinese Americans, and Japanese Americans when compared with non-Hispanic white women after correcting for waist circumference, presence of impaired fasting glucose, and site. Significant differences persisted only between African Americans and non-Hispanic whites after inclusion of triglycerides in the model. Triglycerides indirectly corrected for the differences in HOMA%S in the other two groups. There were no differences in HOMA%S between the non-Mexican-American Latinos and the non-Hispanic whites. Japanese Americans and Chinese Americans had lower HOMA%beta than non-Hispanic whites, whereas African Americans had higher HOMA%beta than non-Hispanic whites after correcting for confounders. HOMA%beta was similar between non-Mexican-American Latinos and non-Hispanic whites. CONCLUSIONS: These data suggest that type 2 diabetes prevention strategies for African-American women should initially target decreased insulin sensitivity, whereas strategies for Japanese-American and Chinese-American women may initially need to target both decreased insulin sensitivity and beta-cell function. Previous studies of Mexican-American populations may not apply to non-Mexican-American Latino women.

Reproductive hormones in the early menopausal transition: relationship to ethnicity, body size, and menopausal status.

We measured serum reproductive hormone concentrations in a community-based, multiethnic population of premenopausal and early perimenopausal women to determine whether there are ethnic differences in hormones that can be explained by host factors. We studied 2930 participants in the Study of Women's Health Across the Nation who were aged 42-52 yr and self-identified as African-American (27.6%), Caucasian (47.1%), Chinese (7.4%), Hispanic (8.8%), or Japanese (9.0%) at 7 clinical sites. Outcome measures from this baseline assessment of a longitudinal study were serum estradiol (E2), FSH, testosterone (T), dehydroepiandrosterone sulfate, and SHBG concentrations and calculated estimates of free steroid availability, free testosterone index, and free E2 index from serum collected primarily in the early follicular phase of a spontaneous menstrual cycle. The primary explanatory variables were race/ethnicity, menopausal status, age, body mass index, day of the cycle, smoking, alcohol use, and physical activity. Chinese women had lower unadjusted E2 and SHBG levels, and Hispanic women had lower unadjusted T levels than other ethnic groups. Unadjusted serum FSH levels did not differ by race/ethnicity. E2 levels adjusted for host characteristics, particularly body size, did not differ by race/ethnicity. Adjusted FSH levels were higher, and adjusted T levels were lower in African-American and Hispanic women. Serum E2 and FSH concentrations were highly variable. Serum FSH levels, but no other hormone concentrations, were positively correlated with menopausal status. Serum dehydroepiandrosterone sulfate levels were negatively correlated with age, but not menopausal status. All hormone concentrations were significantly correlated with body mass index. We conclude that serum sex steroid, FSH, and SHBG levels vary by ethnicity, but are highly confounded by ethnic disparities in body size.