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

Abstract

BackgroundCortisol 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.MethodologyWe 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.SignificanceThe observed trend suggests that studies including cycling women should account for day dependent variation in cortisol in cycles with long follicular and luteal phases.

Menstrual Cycle Phase Modulates Emotional Conflict Processing in Women with and without Premenstrual Syndrome (PMS) – A Pilot Study

“…Finally, cortisol levels represent only one aspect of HPA axis function and inter-individual cortisol differences are considerable [54]. To obtain a valid assessment of baseline cortisol levels across the menstrual cycle, Nepomnaschy et al suggest collecting 10–14 samples at multiple times in a longitudinal design [55]. We acknowledge this by limiting our interpretation to the within-group change of cortisol in the PMS group and conclude that this preliminary finding is of exploratory nature and needs further investigation in a larger sample following an assessment protocol as suggested by Nepomnaschy and colleagues [55].…”

A longitudinal evaluation of the relationship between first morning urinary and salivary cortisol

“…Although cortisol levels can be assessed in a variety of matrices, urine and saliva are favored over other matrices such as cerebrospinal fluid or serum, especially in studies based on naturalistic, longitudinal designs involving the collection of multiple biospecimens per participant (Gatti and De Palo, ; Nepomnaschy et al, ; Papacosta and Nassis, ; Plenis and Baczek, ; Wedekind et al, ). Urine and saliva present several advantages including less‐invasive, simpler and less‐onerous collection protocols than other matrices.…”

Home ovulation tests and stress in women trying to conceive: a randomized controlled trial

“…Both are useful tools for measuring baseline information and in evaluating change over time while qualitative techniques are useful in exploring common themes arising from in-depth discussions. Cortisol is a well-established biomarker associated with increased levels of stress (Miki and Sudo, 1998; Nicolson, 2008; Nepomnaschy et al , 2011), and there are several psychological questionnaires that are well-validated and commonly used for observing both specific and non-specific stress in clinical settings. All three of these measures were incorporated into this randomized, controlled study.…”