Child Mortality, Hypothalamic-Pituitary-Adrenal Axis Activity and Cellular Aging in Mothers

Psychological challenges, including traumatic events, have been hypothesized to increase the age-related pace of biological aging. Here we test the hypothesis that psychological challenges can affect the pace of telomere attrition, a marker of cellular aging, using data from an ongoing longitudinal-cohort study of Kaqchikel Mayan women living in a population with a high frequency of child mortality, a traumatic life event. Specifically, we evaluate the associations between child mortality, maternal telomere length and the mothers’ hypothalamic-pituitary-adrenal axis (HPAA), or stress axis, activity. Child mortality data were collected in 2000 and 2013. HPAA activity was assessed by quantifying cortisol levels in first morning urinary specimens collected every other day for seven weeks in 2013. Telomere length (TL) was quantified using qPCR in 55 women from buccal specimens collected in 2013. Results: Shorter TL with increasing age was only observed in women who experienced child mortality (p = 0.015). Women with higher average basal cortisol (p = 0.007) and greater within-individual variation (standard deviation) in basal cortisol (p = 0.053) presented shorter TL. Non-parametric bootstrapping to estimate mediation effects suggests that HPAA activity mediates the effect of child mortality on TL. Our results are, thus, consistent with the hypothesis that traumatic events can influence cellular aging and that HPAA activity may play a mediatory role. Future large-scale longitudinal studies are necessary to confirm our results and further explore the role of the HPAA in cellular aging, as well as to advance our understanding of the underlying mechanisms involved

Is Cortisol Excretion Independent of Menstrual Cycle Day? A Longitudinal Evaluation of First Morning Urinary Specimens

Background Cortisol is frequently used as a marker of physiologic stress levels. Using cortisol for that purpose, however, requires a thorough understanding of its normal longitudinal variability. The current understanding of longitudinal variability of basal cortisol secretion in women is very limited. It is often assumed, for example, that basal cortisol profiles do not vary across the menstrual cycle. This is a critical assumption: if cortisol were to follow a time dependent pattern during the menstrual cycle, then ignoring this cyclic variation could lead to erroneous imputation of physiologic stress. Yet, the assumption that basal cortisol levels are stable across the menstrual cycle rests on partial and contradictory evidence. Here we conduct a thorough test of that assumption using data collected for up to a year from 25 women living in rural Guatemala. Methodology We apply a linear mixed model to describe longitudinal first morning urinary cortisol profiles, accounting for differences in both mean and standard deviation of cortisol among women. To that aim we evaluate the fit of two alternative models. The first model assumes that cortisol does not vary with menstrual cycle day. The second assumes that cortisol mean varies across the menstrual cycle. Menstrual cycles are aligned on ovulation day (day 0). Follicular days are assigned negative numbers and luteal days positive numbers. When we compared Models 1 and 2 restricting our analysis to days between −14 (follicular) and day 14 (luteal) then day of the menstrual cycle did not emerge as a predictor of urinary cortisol levels (p-value >0.05). Yet, when we extended our analyses beyond that central 28-day-period then day of the menstrual cycle become a statistically significant predictor of cortisol levels. Significance The observed trend suggests that studies including cycling women should account for day dependent variation in cortisol in cycles with long follicular and luteal phases

Stress and female reproduction in a rural Mayan population.

The goal of this dissertation is to identify the stressors faced daily by Kaqchikel Mayan women living in a rural community in Guatemala and investigate the association between stress and reproductive function among these women. The second chapter examines the relationship between self-reported concerns and urinary cortisol levels (a physiological stress marker). The third evaluates the link between daily variations in cortisol levels and fluctuations in the reproductive hormones: estrogen, progestins, luteinizing hormone, and follicle stimulating hormone during the menstrual cycle. The fourth chapter analyzes the association between maternal cortisol levels during the placentation period (first 3 weeks of gestation) and pregnancy fate. Daily Concerns reported by the participants included health problems affecting them and their relatives, inter-personal conflicts, work overloads, and economic problems, among others. These concerns were as a group a statistically significant predictor of increases in urinary cortisol levels (p = 0.03). Independently from those results, variations in cortisol levels were used to assess the combined effects of energetic, health, and psychosocial stressors faced by participants in their daily lives. Cortisol increases were significantly associated with untimely increases in the gonadotrophins throughout the menstrual cycle, with increased progestin levels during the follicular phase, and with low progestin and estrogen levels during the middle of the luteal phase (all p-values p = 0.03). These results are consistent with the hypotheses that stress can lead to the suppression of reproductive processes. The evolutionary hypothesis that motivated this research and the significance and implications of these results within that theoretical framework are discussed.Ph.D.Health and Environmental SciencesPhysical anthropologyPhysiological psychologyPsychologyPublic healthSocial SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/125172/2/3186714.pd

Stress, immune function, and women's reproduction

Only 23% of women will begin a successful pregnancy during the first menstrual cycle in their attempt to conceive.(1) A large number of these failed reproductive attempts are attributed to a broad set of pathologies, but across studies an important proportion of unsuccessful cycles is consistently left unexplained. Stress has become a commonly cited factor when discussing unexplained reproductive failures. Early research on the effect of stress on reproduction was plagued with methodological problems and lacked a solid theoretical framework. However, recent experimental, clinical and population-based research provides new evidence and suggests novel biological mechanisms, which merit a fresh evaluation of the purported association. Here we briefly review the latest advancements in the study of the interplay between stress, the immune system and women’s reproduction, discuss a proposed evolutionary origin for their relationship and examine the biological pathways that may mediate the connection between these three systems

Social and Biological Transgenerational Underpinnings of Adolescent Pregnancy

Adolescent pregnancy (occurring < age 20) is considered a public health problem that creates and perpetuates inequities, affecting not only women, but societies as a whole globally. The efficacy of current approaches to reduce its prevalence is limited. Most existing interventions focus on outcomes without identifying or addressing upstream social and biological causes. Current rhetoric revolves around the need to change girls’ individual behaviours during adolescence and puberty. Yet, emerging evidence suggests risk for adolescent pregnancy may be influenced by exposures taking place much earlier during development, starting as early as gametogenesis. Furthermore, pregnancy risks are determined by complex interactions between socio-structural and ecological factors including housing and food security, family structure, and gender-based power dynamics. To explore these interactions, we merge three complimentary theoretical frameworks: “Eco-Social”, “Life History” and “Developmental Origins of Health and Disease”. We use our new lens to discuss social and biological determinants of two key developmental milestones associated with age at first birth: age at girls’ first menstrual bleed (menarche) and age at first sexual intercourse (coitarche). Our review of the literature suggests that promoting stable and safe environments starting at conception (including improving economic and social equity, in addition to gender-based power dynamics) is paramount to effectively curbing adolescent pregnancy rates. Adolescent pregnancy exacerbates and perpetuates social inequities within and across generations. As such, reducing it should be considered a key priority for public health and social change agenda

NPCRA comparing Maya, Malagasy [16], and industrial United States participants.

NPCRA comparing Maya, Malagasy [16], and industrial United States participants.</p

Descriptive statistics: Mean (SD) and statistical tests for gender differences in circadian rhythm.

Descriptive statistics: Mean (SD) and statistical tests for gender differences in circadian rhythm.</p

Results from linear regression models predicting interdaily stability and intradaily variability between Maya and MIDUS cohorts.

Significance codes: * p (CSV)</p