Maria E. Bleil

Race/ethnic disparities in reproductive age: An examination of ovarian reserve estimates across four race/ethnic groups of healthy, regularly-cycling women

OBJECTIVE To determine whether reproductive age, as indexed by a validated marker of ovarian reserve (antimüllerian hormone [AMH]), varies among women of different race/ethnic backgrounds. DESIGN Cross-sectional study. SETTING Community-based sample. PATIENT(S) Multiethnic sample of 947 (277 white, 237 African American, 220 Latina, and 213 Chinese) healthy and regularly cycling premenopausal women, ages 25-45. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) AMH level. RESULT(S) A multivariate model was fit examining race/ethnicity, covariates, nonlinear terms for age (age(2), age(3)), and body mass index (BMI(2), BMI(3)), and two-way interactions between race/ethnicity and each of the other predictor variables in relation to AMH. After backward elimination, significant effects included race/ethnicity (F = 8.45), age (F = 349.94), race/ethnicity-by-linear age interaction (F = 4.67), age(2) (F = 31.61), and BMI (F = 10.69). Inspection of the significant race/ethnicity-by-linear age interaction showed AMH levels were consistently lower among Latina women compared with white women across all ages, whereas AMH levels were lower among African American and Chinese women compared with the white women at younger and middle ages, respectively. The AMH levels were higher among African American compared with Latina and Chinese women at older ages. CONCLUSION(S) Although the results must be considered preliminary, the findings are twofold: African American women may have lower AMH levels at younger ages but experience less of a reduction in AMH with advancing age, and Latina and Chinese women compared with white women may have lower AMH levels, marking a lower ovarian reserve and a possibly increased risk for earlier menopause.

Does accelerated reproductive aging underlie premenopausal risk for cardiovascular disease

Objective The menopausal transition is associated with an increase in risk for cardiovascular disease; however, whether variability in reproductive aging relates to cardiovascular risk factors in the premenopausal period has not been studied. Methods In a multiethnic sample of 951 healthy, regularly cycling women aged 25 to 45 years (mean [SD] age, 35.2 [5.5] y), we examined antimüllerian hormone (AMH), a validated marker of ovarian reserve, in relation to the overall number of cardiometabolic risk factors, calculated as the sum of the five components of metabolic syndrome (triglycerides ≥150 mg/dL; high-density lipoprotein <50 mg/dL; homeostasis model assessment of insulin resistance ≥2.6; waist circumference equal to or higher than race-specific cutoff; and hypertensive [vs normotensive] status), and in relation to each of these risk factors individually. Results In age-adjusted models, results showed that the number of cardiometabolic risk factors was 52.1% higher among women with low versus high AMH levels and 46.0% higher among women with mid versus high AMH levels. In addition, results showed that low and mid levels of AMH (vs high) were associated with an increase in risk with respect to high-density lipoprotein (odds ratio [OR], 1.814; 95% CI, 1.211-2.718 and OR, 1.568; 95% CI, 1.083-2.269, respectively), waist circumference (OR, 2.012; 95% CI, 1.380-2.934 and OR, 1.881; 95% CI, 1.333-2.654, respectively), and hypertensive status (OR, 2.373; 95% CI, 1.095-5.143 and OR, 2.052; 95% CI, 0.976-4.314, respectively) outcomes. Associations, however, attenuated when body mass index was covaried (Ps > 0.05). Conclusions Cross-sectional evidence suggests that having a greater ovarian reserve is associated with having a healthier cardiometabolic risk factor profile. Future longitudinal studies are needed to determine whether this association may be mediated by body mass index.

Adverse childhood experiences and repeat induced abortion.

OBJECTIVE The objective of the study was to characterize the backgrounds of women who have repeat abortions. STUDY DESIGN In a cross-sectional study of 259 women (mean age, 35.2 ± 5.6 years), the relation between adverse experiences in childhood and risk of having 2 or more abortions vs 0 or 1 abortion was examined. Self-reported adverse events occurring between the ages of 0 and 12 years were summed. RESULTS Independent of confounding factors, women who experienced more abuse, personal safety, and total adverse events in childhood were more likely to have 2 or more abortions vs 0 abortions (odds ratio [OR], 2.56; 95% confidence interval [CI], 1.15-5.71; OR, 2.74; 95% CI, 1.29-5.82; and OR, 1.59; 95% CI, 1.21-2.09, respectively) and vs 1 abortion (OR, 5.83; 95% CI, 1.71-19.89; OR, 2.23; 95% CI, 1.03-4.81; and OR, 1.37; 95% CI, 1.04-1.81, respectively). Women who experienced more family disruption events in childhood were more likely to have 2 or more abortions vs 0 abortions (OR, 1.75; 95% CI, 1.14-2.69) but not vs 1 abortion (OR, 1.16; 95% CI, 0.79-1.70). CONCLUSION Women who have repeat abortions are more likely to have experienced childhood adversity than those having 0 or 1 abortion.

Prevalence and predictors of major depressive disorder for fertility treatment patients and their partners

OBJECTIVE To examine the prevalence and predictors of major depressive disorder (MDD) for women and their partners during the course of fertility treatment. DESIGN Prospective cohort study during an 18-month period. Participants completed interviews and questionnaires at baseline and at 4, 10, and 18 months of follow-up. SETTING Five community and academic fertility practices. PATIENT(S) A total of 174 women and 144 of their male partners who did not have a successful child-related outcome during the time frame of the study. INTERVENTION(S) No interventions administered. MAIN OUTCOME MEASURE(S) The MDD was assessed using the Composite International Diagnostic Interview Major Depression module, a structured diagnostic interview. Additional variables were assessed with self-report questionnaire measures. RESULT(S) Of the women 39.1% and of the men 15.3% met the criteria for MDD during the 18-month course of the study. A binary logistic covariate-adjusted model showed that, for both women and men, past MDD was a significant predictor of MDD during treatment. Past MDD further predicted significant risk for MDD during treatment after controlling for other well-established risk factors (i.e., baseline levels of depression, anxiety, and partner support). CONCLUSION(S) The MDD was highly prevalent for fertility treatment patients and their partners. Past MDD predicted risk for MDD during treatment, and it contributed to MDD risk more than other commonly assessed risk factors. This suggests that patients and their partners would benefit from being routinely assessed for a history of MDD before the start of treatment to best direct psychosocial support and interventions to those most in need.

Childhood adversity and pubertal timing: understanding the origins of adulthood cardiovascular risk.

OBJECTIVE To determine whether greater childhood adversity relates to younger menarcheal age; whether younger menarcheal age relates to increased CVD risk; and whether greater childhood adversity relates to increased CVD risk, directly or indirectly (mediated by menarcheal age). METHODS Among 650 pre-menopausal women (ages 25-45; M=34.9[5.6]), SEM was performed to estimate relations between childhood adversity, menarcheal age, and CVD risk. RESULTS Results supported a covariate-adjusted model (RMSEA=0.035; CFI=0.983) in which greater childhood adversity was related to younger menarcheal age (β=-.13, p<.01) and younger menarcheal age was related to greater CVD risk (β=-.18, p<.05). Direct and indirect effects of childhood adversity on CVD risk were non-significant. Re-evaluation of the same model with additional covariate-adjustment for adulthood body composition showed the relation between menarcheal age and CVD risk attenuated (β=-.03, p=.376). CONCLUSIONS Cross-sectional evidence suggests family-related adversity experiences in childhood confer risk for earlier menarche which, in turn, relates to increased CVD risk in adulthood, possibly via post-pubertal body size.

Depressive Symptomatology, Psychological Stress, and Ovarian Reserve: A Role for Psychological Factors in Ovarian Aging?

ObjectiveThe aim of this study was to examine psychological factors in relation to antral follicle count (AFC), a marker of ovarian reserve, in a multiethnic sample of 683 premenopausal women in the Ovarian Aging (OVA) Study. MethodsIn cross-sectional analyses, linear regression was performed to determine whether AFC decline across women varied over levels of depression as well as depression in combination with psychological stress. The total and subscale scores of the Center for Epidemiological Studies Depression Scale were used to measure depression, and the Perceived Stress Scale was used to measure psychological stress. ResultsAfter covariate adjustment, the two-way interaction of age × positive affect and the three-way interaction of age × positive affect × stress were related to AFC (b = 0.047, P = 0.036; b = 0.012, P = 0.099, respectively). In stratified analyses, stress was related to AFC in women with low positive affect (b = –0.070, P = 0.021) but not in women with high positive affect (b = 0.018, P = 0.54). AFC decline across women was progressively higher in women with low positive affect who reported low (–0.747 follicles/year), mid (–0.920 follicles/year), and high (–1.112 follicles/year) levels of stress. Results examining the Center for Epidemiological Studies Depression Scale total and remaining subscale scores were all nonsignificant (P values > 0.05). ConclusionsCross-sectional evidence suggests that (1) women with low positive affect may experience accelerated AFC decline and (2) low positive affect may be a vulnerability factor, or, alternatively, high positive affect may be a protective factor, in moderating the negative effects of psychological stress on AFC decline.

Psychological stress and reproductive aging among pre-menopausal women

BACKGROUND Life history models suggest that biological preparation for current versus longer term reproduction is favored in environments of adversity. In this context, we present a model of reproductive aging in which environmental adversity is proposed to increase the number of growing follicles at the cost of hastening the depletion of the ovarian reserve over time. We evaluated this model by examining psychological stress in relation to reproductive aging indexed by antral follicle count (AFC), a marker of total ovarian reserve. We hypothesized that stress would be related to (i) higher AFC in younger women, reflecting greater reproductive readiness as well as (ii) greater AFC loss across women, reflecting more accelerated reproductive aging. METHODS In a multi-ethnic, community sample of 979 participants [ages 25-45 (mean (standard deviation) = 35.2 (5.5)); 27.5% Caucasian] in the Ovarian Aging study, an investigation of the correlates of reproductive aging, the interaction of age-x-stress was assessed in relation to AFC to determine whether AFC and AFC loss varied across women experiencing differing levels of stress. Stress was assessed by the perceived stress scale and AFC was assessed by summing the total number of antral follicles visible by transvaginal ultrasound. RESULTS In linear regression examining AFC as the dependent variable, covariates (race/ethnicity, socio-economic status, menarcheal age, hormone-containing medication for birth control, parity, cigarette smoking, bodymass index, waist-to-hip ratio) and age were entered on step 1, stress on step 2 and the interaction term (age-x-stress) on step 3. On step 3, significant main effects showed that older age was related to lower AFC (b = -0.882, P = 0.000) and greater stress was related to higher AFC (b = 0.545, P = 0.005). Follow-up analyses showed that the main effect of stress on AFC was present in the younger women only. A significant interaction term (b = -0.036, P = 0.031) showed the relationship between age and AFC varied as function of stress. When the sample was divided into tertiles of stress, the average follicle loss was -0.781, -0.842 and -0.994 follicles/year in the low-, mid- and high-stress groups, respectively. CONCLUSIONS Psychological stress was related to higher AFC among younger women and greater AFC decline across women, suggesting that greater stress may enhance reproductive readiness in the short term at the cost of accelerating reproductive aging in the long term. Findings are preliminary, however, due to the cross-sectional nature of the current study.

Disruptions in ovarian function are related to depression and cardiometabolic risk during premenopause.

ObjectiveThe aim of this study was to evaluate the extent to which mild disruptions in ovarian function, indexed by changes in menstrual cycle length, may relate to cardiometabolic and psychological health in premenopausal women. MethodsAmong 804 healthy, regularly cycling women (aged 25-45 y; mean [SD] age, 35.5 [5.5] y), patterns of any change (shortening, lengthening, or increased variability) versus no change in menstrual cycle length were examined in relation to a composite of cardiometabolic risk and individual risk factors (high-density lipoprotein, triglycerides, waist circumference, glucose, and hypertensive status), as well as in relation to depression indicators (Center for Epidemiological Studies Depression Scale score ≥16 [yes/no], lifetime depression diagnosis [yes/no], and lifetime antidepressant medication use [yes/no]). Models were also explored to test whether changes in menstrual cycle length mediated relations between depression history and cardiometabolic risk. ResultsIn covariate-adjusted models compared with no change, any change in menstrual cycle length was associated with higher cardiometabolic risk composite scores and lower high-density lipoprotein (P < 0.05). In addition, compared with no change, any change in menstrual cycle length was associated with a Center for Epidemiological Studies Depression Scale score of 16 or higher, having received a depression diagnosis, and having used antidepressant medications (P < 0.05). In exploratory analyses, any change in menstrual cycle length partially mediated the relation between depression history and cardiometabolic risk (b = 0.152, P = 0.040), which attenuated (b = 0.129, P = 0.083) when any change in menstrual cycle length was covaried. ConclusionsFindings suggest that disruptions in ovarian function, marked by subtle changes in menstrual cycle length, may relate to aspects of cardiometabolic and psychological health among healthy, premenopausal women.

Addressing the needs of fertility treatment patients and their partners: are they informed of and do they receive mental health services?

OBJECTIVE To determine the extent to which fertility patients and partners received mental health services (MHS) and were provided with information about MHS by their fertility clinics, and whether the use of MHS, or the provision of information about MHS by fertility clinics, was targeted to the most distressed individuals. DESIGN Prospective longitudinal cohort study. SETTING Five fertility practices. PATIENT(S) A total of 352 women and 274 men seeking treatment for infertility. INTERVENTION(S) No interventions administered. MAIN OUTCOME MEASURE(S) Depression, anxiety, and MHS information provision and use. RESULT(S) We found that 56.5% of women and 32.1% of men scored in the clinical range for depressive symptomatology at one or more assessments and that 75.9% of women and 60.6% of men scored in the clinical range for anxiety symptomatology at one or more assessments. Depression and anxiety were higher for women and men who remained infertile compared with those who were successful. Overall, 21% of women and 11.3% of men reported that they had received MHS, and 26.7% of women and 24.1% of men reported that a fertility clinic made information available to them about MHS. Women and men who reported significant depressive or anxiety symptoms, even those with prolonged symptoms, were no more likely than other patients to have received information about MHS. CONCLUSION(S) Psychological distress is common during fertility treatment, but most patients and partners do not receive and are not referred for MHS. Furthermore, MHS use and referral is not targeted to those at high risk for serious psychological distress. More attention needs to be given to the mental health needs of our patients and their partners.

Beverages contribute extra calories to meals and daily energy intake in overweight and obese women

Caloric beverages may promote obesity by yielding energy without producing satiety, but prior laboratory and intervention studies are inconclusive. This study examined whether the diets of free-living overweight and obese women show evidence that calories from beverages are offset by reductions in solid food within individual eating occasions and across entire days. Eighty-two women weighed and recorded all consumed foods and beverages for seven days. Beverages were coded as high-calorie (≥ 0.165 kcal/g) or low-calorie (<0.165 kcal/g), and total energy intake and energy intake from solid food were calculated for each eating occasion and day. In covariate-adjusted models, energy intake from solid food did not differ between eating occasions that included high-calorie or low-calorie beverages and those with no reported beverage. Energy intake from solid food was also unrelated to the number of high-calorie or low-calorie beverages consumed per day. On average, eating occasions that included a high-calorie beverage were 169 kcal higher in total energy than those with no reported beverage, and 195 kcal higher in total energy than those that included a low-calorie beverage. Each high-calorie beverage consumed per day contributed an additional 147 kcal to womens daily energy intake, whereas low-calorie beverage intake was unrelated to daily energy intake. Beverages contributed to total energy intake in a near-additive fashion among free-living overweight and obese women, suggesting a need to develop more effective interventions to reduce caloric beverage intake in the context of weight management, and to potentially reexamine dietary guidelines.