DESPR Office of the Director (OD)

Stress and Female Fecundity

The overarching research goal is to understand the impact of stress as measured by two salivary biomarkers on female fecundity and fertility as measured by menstruation, time-to-pregnancy, pregnancy loss, and the secondary sex ratio.

• Women with higher salivary alpha-amylase concentrations, a biomarker of stress via the sympathetic medullar pathway, had a reduced probability of conception (fecundity odds ratio=0.85; 95% confidence interval 0.67, 1.09) after adjusting for the couples' ages, intercourse frequency, and alcohol consumption. Stress significantly reduced the probability of conception each day during the fertile window.
  Buck Louis GM, Lum K, Sundaram R, Chen Z, Kim S, Lynch CD, Schisterman EF, Pyper C. Stress reduces conception probabilities across the fertile window: evidence in support of relaxation. Fertility and Sterility 2011; 95(7):2184-2189. PMID: 20688324

LIFE Study

The overarching research goal of the LIFE Study is to understand the relation between environmental (non-genetic) exposures and couple fecundity in the context of lifestyle factors important for human fecundity and fertility.

• Couples planning pregnancies can be recruited from targeted study populations for participation in intensive prospective cohort studies, but sampling frameworks need to be large to accommodate the relatively low percentage of planners at any one point in time.
  Buck Louis GM, Schisterman EF, Sweeney AM, Wilcosky TC, Gore-Langton R, Lynch CD, Barr DD, Schrader SM, Kim S, Chen Z, Sundaram R. Designing prospective cohort studies for assessing reproductive and developmental toxicity during sensitive windows of human reproduction and development — the LIFE Study. Paediatric and Perinatal Epidemiology 2011; 25: 413-424. PMID: 21819423
• Preconception blood concentrations of heavy metals were significantly associated with reduced couple fecundity as measured by a longer time required for couples to become pregnant. Female partners’ blood cadmium concentrations reduced fecundity as measured by fecundability odds ratios <1 (FOR=0.78; 95% CI 0.63, 0.97), as did male partners’ blood lead concentrations (FOR=0.85; 95% CI 0.73, 0.98). When jointly modeling couples’ metal exposures, only male lead concentration significantly reduced the FOR (0.82; 95% CI 0.68, 0.97), though the FOR remained <1 for female cadmium (0.80; 95% CI 0.64, 1.00). This prospective couple based cohort with longitudinal capture of time to pregnancy is suggestive of cadmium and lead’s reproductive toxicity at environmentally relevant concentrations.
  Buck Louis, Sundaram R, Schisterman EF, Sweeney AM, Lynch CD, Gore-Langton RE, Chen Z, Kim S, Caldwell K, Boyd Barr D. Heavy metals and couple fecundity, the LIFE Study. Chemosphere 2012; 87:1201-1207. PMID: 22309709

ENDO Study

The overarching research goal of the ENDO Study is to understand the relation between environmental influences and female fecundity, as measured by gynecologic health and diseases such as endometriosis and fibroids.

• Two cohorts of reproductive age women were recruited and enrolled in the study to estimate the incidence of endometriosis and risks factors associated with diagnosis. The two cohorts included an operative cohort comprising women seeking medical clinical care and undergoing surgery, and a population cohort comprising women not seeking care but residing within the geographic area served by participating clinical facilities. The incidence of surgically visualized endometriosis, which is considered the gold standard, in the operative cohort was 41%. However, incidence varied by diagnostic criteria: 0.7% for only histology and 7% for only MRI. The incidence of magnetic resonance imaging (MRI) diagnosed endometriosis in the population cohort was 11%. These findings suggest that a sizable percentage of asymptomatic women may have endometriosis, and that women seeking clinical care may represent only the tip of the iceberg of affected women at the population level.
  Buck Louis GM, Hediger ML, Peterson CM, Croughan M, Sundaram R, Stanford J, Chen Z, Fujimoto V, Varner M, Giudice L. Incidence of endometriosis by study population and diagnostic method: the ENDO study. Fertility and Sterility 2011; 96(2):360-365. PMID: 21719000
• Two persistent organochlorine environmental pesticides were associated with an increased odds of an endometriosis diagnosis. Specifically in the operative cohort, ?-hexachlorocyclohexane (?-HCH) was positively associated with endometriosis (per 1-SD increase in log-transformed ?-HCH: adjusted OR (AOR) = 1.27; 95% CI: 1.01, 1.59), while ß-HCH was the only significant predictor in the population cohort (per 1-SD increase in log-transformed ß-HCH: AOR = 1.72; 95% CI: 1.09, 2.72). These findings are consistent with other persistent environmental and hormonally active chemicals being associated with an endometriosis diagnosis.
  Buck Louis GM, Chen Z, Peterson CM, Hediger ML, Croughan MS, Sundaram R, Stanford JB, Varner MW, Fujimoto VY, Giudice LC, Trumble A, Parsons PJ, Kannan K. Persistent lipophilic environmental chemicals and endometriosis: The ENDO Study, 2007-2009. Environmental Health Perspectives 2012; 120(6):811-816. PMID: 22417635
• The relation between UV filters (sunscreen components) measured in urine and the odds of an endometriosis diagnosis were assessed for five BP derivatives: 2-hydroxy-4-methoxybenzophenone (2OH-4MeO-BP), 2,4-ihydroxybenzophenone (2,4OH-BP), 2,2'-dihydroxy-4-methoxybenzophenone (2,2'OH-4MeO-BP), 2,2',4,4'-tetrahydroxybenzophenone (2,2',4,4'OH-BP), and 4-hydroxybenzophenone (4OH-BP). The only significant association was observed for 2,4OH-BP and the odds of an endometriosis diagnosis in the operative cohort (OR = 1.19; 95% CI = 1.01, 1.41). The findings await corroboration, given this first reported study focusing on BP filters and endometriosis. The estrogenic properties of 2,4OH-BP in relation to development of endometriosis await mechanistic research.
  Kunisue T, Chen Z, Buck Louis GM, Sundaram R, Hediger ML, Sun L, Kannan K. Urinary concentrations of benzophenone-type UV filters and endometriosis, the ENDO Study. Environmental Science and Technology 2012; 46:4624-4632. PMID: 22417702