Doctor of Philosophy

dissertationCaffeinated and fructose-rich beverages are widely consumed among women of reproductive age but their association with reproductive hormones is not well understood, due in part to inadequate exposure assessment. Our objectives were to 1) assess the relationship between caffeine and fructose intake and reproductive hormones in healthy premenopausal women, evaluating potential effect modification by race; and 2) determine the validity of the Food Frequency Questionnaire (FFQ) for measuring monthly caffeinated beverage intake compared to multiple 24-hour dietary recalls (24HDR). The BioCycle Study (2005-2007) prospective cohort (n=259) included women, ages 18-44, who were followed for 2 menstrual cycles, providing fasting blood specimens at up to 8 visits per cycle, 4 24HDRs per cycle, and an FFQ at the end of each cycle. Caffeine intake ≥200 mg/day was inversely associated with free estradiol (E2) concentrations among white women (β=-0.15 [95% confidence interval (CI): -0.26, - 0.05] and positively associated among Asian women (β=0.61 [95% CI: 0.31, 0.92] after taking into account potential confounders. Women who consumed more added sugar than an average American woman (≥ 73.2 grams/day) or above the 66th percentile in fructose intake (≥ 41.5 grams/day) had elevated free E2 concentrations compared to women who consumed less. Women who consumed ≥1 cup/day of sweetened soda had elevated free E2 (β=0.15 [95% CI: 0.06, 0.24]. Neither artificially sweetened soda intake nor fruit juice iv intake ≥1 cup/day was significantly associated with reproductive hormones. Caffeine intake reported in the FFQ was greater than that reported in the 24HDRs (mean=114.1 versus 92.6 mg/day; P=0.006) despite high correlation (r=0.80, P<0.001) and moderate agreement (kappa=0.56, 95% CI: 0.42-0.70). In summary, moderate caffeine consumption was associated with reduced E2 among white women and elevated E2 among Asian women. Added sugars, total fructose, and sweetened soda were associated with elevated E2 among all races. Further research on the association between caffeine, caffeinated beverage components and reproductive hormones, and whether these relationships differ by race, is warranted. Additionally, although caffeine exposures are highly correlated, absolute intakes differ significantly between measurement tools, highlighting the importance of considering potential misclassification of caffeine exposure when conducting women's health epidemiologic studies

Characteristics of the Menstrual Cycle After Discontinuation of Oral Contraceptives

Background: Menstrual cycle function may continue to be altered after discontinuation of oral contraceptives (OC). Few studies have been published on the effects of recent OC use on menstrual cycle parameters; none have examined characteristics of the menstrual flow or the quality of cervical mucus. The purpose of this retrospective matched cohort study is to assess biomarkers of the menstrual cycle after discontinuation of OCs. Methods: Among a sample of women who daily recorded observations of menstrual cycle biomarkers, 70 women who had recently discontinued OCs were randomly matched by age and parity with 70 women who had not used OCs for at least 1 year. Outcomes investigated included overall cycle length, length of the luteal phase, estimated day of ovulation, duration of menstrual flow, menstrual intensity, and mucus score. Differences between recent OC users and controls were assessed using random effects modeling. Results: Recent OC users had statistically significantly lower scores for mucus quality for cycles 1 and 2. Additionally, OC users had a later estimated day of ovulation that was statistically significant in cycle 2 and a decreased intensity of menstrual flow that was significant in the first four cycles (difference = −0.48 days). In random effects modeling, all these parameters were significantly different for the first six cycles combined. Conclusions: Menstrual cycle biomarkers are altered for at least two cycles after discontinuation of OCs, and this may help explain the temporary decrease in fecundity associated with recent OC use

Perceived Stress, Reproductive Hormones, and Ovulatory Function: A Prospective Cohort Study

Stress has been shown to suppress ovulation in experimental models, but its effect on human reproduction at the population level is unclear

Interrater and Intrarater Reliability in the Diagnosis and Staging of Endometriosis

OBJECTIVE: To estimate the interrater and intrarater reliability of endometriosis diagnosis and severity of disease among gynecologic surgeons viewing operative digital images. METHODS: The study population comprised a random sample (n = 148 [36%]) of women who participated in the Endometriosis: Natural History, Diagnosis and Outcomes study. Four academic expert and four local, specialized expert surgeons reviewed the images, diagnosed the presence or absence of endometriosis for each woman, and rated severity using the revised American Society for Reproductive Medicine (ASRM) criteria. Interrater-level and intrarater-level agreement were calculated for both endometriosis diagnosis and staging. RESULTS: The interrater reliability for endometriosis diagnosis among the eight surgeons was substantial: Fleiss kappa = 0.69 (95% confidence interval [CI] 0.64-0.74). Surgeons agreed on revised ASRM endometriosis staging criteria after experienced assessment in a majority of cases (mean 61%, range 52-75%) with moderate interrater reliability: Fleiss kappa = 0.44 (95% CI 0.41-0.47). The intrarater reliability for experienced assessment compared with computer-assisted revised ASRM staging was almost perfect (mean weighted kappa = 0.95, range 0.89-0.99). CONCLUSION: Substantial reliability was found for revised ASRM endometriosis diagnosis, whereas moderate reliability was observed for staging. Almost perfect reliability was observed for surgeons' rating of disease severity compared with computerized-assisted, checklist-based staging. Findings suggest that reliability in endometriosis diagnosis is not greatly altered by location or composition of surgeons, supporting the conduct of multisite studies or compilation of endometriosis data across clinical centers. Although surgeons appear to be skilled at assessing endometriosis stage intuitively, how staging of disease burden correlates with clinical outcomes remains to be developed. (Obstet Gynecol 2012; 120: 104-12) DOI:10.1097/AOG. 0b013e31825bc6cfKeywords: Population, American Fertility Society, System, Interobserver variability, Intraobserver, Classification, Reproducibility, Adhesions, Laparoscopy, Agreemen

Perceived stress, reproductive hormones, and ovulatory function: a prospective cohort study

Background Stress has been shown to suppress ovulation in experimental models, but its effect on human reproduction at the population level is unclear. Methods Healthy women (n=259), aged 18–44 years from Western New York, were followed for two menstrual cycles (2005–2007). Women completed daily perceived stress assessments, a 4-item Perceived Stress Scale (PSS-4) up to four times each cycle, and a 14-item PSS at baseline. Mixed model analyses were used to assess effects of stress on log reproductive hormone concentrations and sporadic anovulation. Results High versus low daily stress was associated with lower estradiol (-9.5%; 95% confidence interval (CI)= -15.6% to -3.0%), free estradiol (-10.4% [-16.5% to -3.9%]), and LH (-14.8% = [-21.3% to -7.7%]), and higher FSH (6.2% [2.0% to 10.5%]) after adjusting for age, race, percent body fat, depression score, and time-varying hormones and vigorous exercise. High versus low daily stress was also associated with lower luteal progesterone (-10.4% [-19.7% to -0.10%]) and higher odds of anovulation (adjusted OR = 2.2 [95% CI=1.0 to 4.7]). For each unit increase in daily stress level, women had a 70% higher odds of an anovulatory episode (OR=1.7 [1.1 to 2.4]). Similar but attenuated results were found for the association between the PSS-4 and reproductive hormones, while null findings were found for the baseline PSS. Conclusion Daily perceived stress does appear to interfere with menstrual cycle function among women with no known reproductive disorders, warranting further research to explore potential population-level impacts and causal biologic mechanisms

Women\u27s Reproductive History Before the Diagnosis of Incident Endometriosis

BACKGROUND: Endometriosis is a gynecologic disease reported to be associated with infertility and, possibly, adverse pregnancy outcomes. While considerable research focuses on pregnancy outcomes following diagnosis and/or treatment, few data actually describe women\u27s reproductive history before diagnosis for a more complete understanding of endometriosis and reproduction. MATERIALS AND METHODS: The study sample comprised 473 women (aged 18-44 years) undergoing laparoscopies or laparotomies, irrespective of surgical indication at 14 clinical sites, during the period 2007-2009. Upon enrollment and before surgery, women were queried about pregnancy intentions and the time required to become pregnant for planned pregnancies. Endometriosis was defined as surgically visualized disease. Using discrete time survival analysis, we estimated fecundability odds ratios (FORs) and 95% confidence intervals (CIs) to assess time to pregnancy (TTP) after adjusting for potential confounders (age, body composition, cigarette smoking, site). Generalized estimating equations accounted for multiple pregnancy attempts per woman. FORs \u3c1.0 denote a longer TTP or diminished fecundity. RESULTS: Approximately 66% and 69% of women with and without endometriosis, respectively, reported having a planned pregnancy before surgery, respectively. After adjustment, an endometriosis diagnosis was associated with ≈29% reduction in fecundity or a longer TTP across all pregnancy-trying attempts (adjusted FOR = 0.71; 95% CI 0.46-1.10). While FORs were consistently \u3c1.0, irrespective of endometriosis staging, CIs included 1. CONCLUSIONS: Women with endometriosis had a longer TTP than unaffected women, irrespective of disease severity, although the findings did not achieve significance. Prior reproductive history may be informative for predicting fecundity and pregnancy outcomes following diagnosis/treatment

Polycystic ovary syndrome and postpartum depression among Hispanics and non-Hispanics: a population-based studyAJOG Global Reports at a Glance

BACKGROUND: Women with polycystic ovary syndrome experience increased health complications during and after pregnancy, including a higher prevalence of postpartum depression. Although previous research has found that Hispanic women with polycystic ovary syndrome experience heightened hyperandrogenism and metabolic effects compared with non-Hispanic women, it is unknown whether they experience other polycystic ovary syndrome–related comorbidities, such as postpartum depression, to a greater degree than their non-Hispanic counterparts. OBJECTIVE: This study aimed to determine the associations among a self-reported prepregnancy diagnosis of polycystic ovary syndrome, polycystic ovary syndrome symptoms (irregular menstruation, hirsutism, and acne), and postpartum depression among a national sample of at-risk women and evaluated the potential effect modification by Hispanic ethnicity. STUDY DESIGN: The study population included 52,267 postpartum (2–6 months) women who completed the US Pregnancy Risk Assessment Monitoring System Phase 8 questionnaire (2016–2018). Data from US states that captured self-reported polycystic ovary syndrome symptoms in the 3 months before pregnancy (n=17 states) were used. Moreover, we performed a subanalysis restricted to data from the Utah Pregnancy Risk Assessment Monitoring System Phase 8 questionnaire (2016–2019; n=5814), as it was the only state that considered self-reported polycystic ovary syndrome symptoms during this period. Postpartum depressed mood and anhedonia, the postpartum depression outcome measurements, were assessed via the following questions, respectively: (1) “Since your new baby was born, how often have you felt down, depressed, or hopeless?” and (2) “Since your new baby was born, how often have you had little interest or little pleasure in doing things you usually enjoyed?” In addition, postpartum depressed mood and anhedonia were assessed separately and as a combined variable. Here, weighted adjusted prevalence ratios and 95% confidence intervals were used to assess the association between polycystic ovary syndrome and postpartum depressed mood and anhedonia among Hispanic women and non-Hispanic women while taking into account preconception sociodemographics, lifestyle, and health history confounding factors. RESULTS: The national study population was composed of 16.8% of Hispanic ethnicity, with 11.4% Hispanic women and 17.1% non-Hispanic women reporting prepregnancy polycystic ovary syndrome symptoms. The study found no association between women reporting prepregnancy polycystic ovary syndrome vs women without polycystic ovary syndrome and the prevalence of postpartum depressed mood and/or anhedonia. Moreover, the results were null when we stratified by Hispanic ethnicity. The Utah study population was composed of 15.5% of women of Hispanic ethnicity, with 5.8% of Hispanic women and 7.4% of non-Hispanic women reporting prepregnancy polycystic ovary syndrome. Symptom-based polycystic ovary syndrome (having irregular menstruation with hirsutism or irregular menstruation with acne), compared with having regular menstruation in the Utah sample, was associated with a 1.54 higher adjusted prevalence ratio (95% confidence interval, 1.14–2.09) for postpartum depressed mood and anhedonia. Stratified analyses by ethnicity indicated a 2- to 5-fold higher prevalence of postpartum depression with symptom-based polycystic ovary syndrome for Hispanic women and a 1.5-fold higher prevalence for non-Hispanic women. CONCLUSION: In this US population-based study, a self-reported prepregnancy diagnosis of polycystic ovary syndrome was not associated with postpartum depression. However, self-reported polycystic ovary syndrome symptoms, including irregular menstruation and acne and/or hirsutism, were associated with a higher probability of postpartum depression, most prominently for Hispanic women. Our findings suggested that capturing polycystic ovary syndrome symptoms among at-risk women may be important for identifying associations with postpartum depression and potentially other comorbidities

Adiposity and Endometriosis Severity and Typology

STUDY OBJECTIVE: Prior research has collectively shown that endometriosis is inversely related to women\u27s adiposity. The aim of this study was to assess whether this inverse relationship holds true by disease severity and typology. DESIGN: Cross-sectional study among women with no prior diagnosis of endometriosis. SETTING: Fourteen clinical centers in Salt Lake City, UT, and San Francisco, CA. PATIENTS: A total of 495 women (of which 473 were analyzed), aged 18-44 years, were enrolled in the operative cohort of the Endometriosis, Natural History, Diagnosis, and Outcomes (ENDO) Study. INTERVENTIONS: Gynecologic laparoscopy/laparotomy regardless of clinical indication. MEASUREMENTS AND MAIN RESULTS: Participants underwent anthropometric assessments, body composition measurements, and evaluations of body fat distribution ratios before surgery. Surgeons completed a standardized operative report immediately after surgery to capture revised American Society for Reproductive Medicine staging (I-IV) and typology of disease (superficial endometriosis [SE], ovarian endometrioma [OE], and deep infiltrating endometriosis [DIE]). Linear mixed models, taking into account within-clinical-center correlation, were used to generate least square means (95% confidence intervals) to assess differences in adiposity measures by endometriosis stage (no endometriosis, I-IV) and typology (no endometriosis, SE, DIE, OE, OE + DIE) adjusting for age, race/ethnicity, and parity. Although most confidence intervals were wide and overlapping, 3 general impressions emerged: (1) women with incident endometriosis had the lowest anthropometric/body composition indicators compared with those without incident endometriosis, (2) women with stage I or IV endometriosis had lower indicators compared with women with stage II or III, and (3) women with OE and/or DIE tended to have the lowest indicators, whereas women with SE had the highest indicators. CONCLUSION: Our research highlights that the relationship between women\u27s adiposity and endometriosis severity and typology may be more complicated than prior research indicates