Cortisol, estradiol-17β, and progesterone secretion within the first hour after awakening in women with regular menstrual cycles

Abstract

Cortisol concentration in both serum and saliva sharply increases and reaches a peak within the first hour after waking in the morning. This phenomenon is known as the cortisol awakening response (CAR) and is used as an index of hypothalamus-pituitary-adrenal (HPA) axis function. We examined whether ovarian steroid concentrations increased after awakening as with the CAR in the HPA axis. To do this, cortisol, estradiol-17β (E(2)), and progesterone (P(4)) concentrations were determined in saliva samples collected immediately upon awakening and 30 and 60 min after awakening in women with regular menstrual cycles and postmenopausal women. We found that both E(2) and P(4) concentrations increased during the post-awakening period in women with regular menstrual cycles, but these phenomena were not seen in any postmenopausal women. The area under the E(2) and P(4) curve from the time interval immediately after awakening to 60 min after awakening (i.e. E(2)auc and P(4)auc) in women with regular menstrual cycles were greater than those in the postmenopausal women. E(2) and P(4) secretory activity during the post-awakening period was influenced by the phase of the menstrual cycle. E(2)auc in the peri-ovulatory phase and P(4)auc in the early to mid-luteal phase were greater than in the menstrual phase. Meanwhile, cortisol secretory activity during the post-awakening period was not influenced by menstrual status or the phase of menstrual cycle. These findings indicate that, as with the CAR in the HPA axis function, ovarian steroidogenic activity increased after awakening and is closely associated with menstrual status and phase of menstrual cycle.

Figure 1

Changes in cortisol concentration within the first hour after awakening in women with regular menstrual cycles and postmenopausal women. Cortisol concentration at each examined time point is depicted in (A). The relative mean increase in cortisol concentration 30 and 60 min after awakening over the individual baseline (F-MnInc %) and the integrated cortisol concentration ranging from the time immediately upon awakening to 60 min after awakening (i.e. area under the cortisol curve with respect to baseline, Fauc) in each examined group are depicted in (B and C) respectively. Each data point in (A) and each bar in (B and C) represents mean±s.e.m.

Figure 2

Difference in estradiol-17β (E₂) concentrations within the first hour after awakening in women with regular menstrual cycles and postmenopausal women. E₂ concentration at each examined time point is depicted in (A). The relative mean increase in E₂ concentration 30 and 60 min after awakening over the individual baseline (E₂-MnInc %) and integrated E₂ concentration ranging from the time immediately upon awakening to 60 min after awakening (i.e. area under the E₂ curve with respect to baseline, E₂auc) are depicted in (B and C) respectively. Each data point in (A) and each bar in (B and C) represents mean±s.e.m. Asterisks denote the level of significance between both groups: **P<0·01; ***P<0·001 (by the Mann–Whitney test).

Figure 3

Difference in progesterone (P₄) concentration within the first hour after awakening in women with regular menstrual cycles and postmenopausal women. P₄ concentration at each examined time point is depicted in (A). The relative mean increase in P₄ concentration 30 and 60 min after awakening over the individual baseline (P₄-MnInc %) and integrated P₄ concentration ranging from the time immediately upon awakening to 60 min after awakening (i.e. area under the P₄ curve with respect to baseline, P₄auc) are depicted in (A and B) respectively. Each data point in (A) and each bar in (B and C) represents mean±s.e.m. Asterisks denote the level of significance between both groups: **P<0·01; ***P<0·001 (by the Mann–Whitney test).

Figure 4

Changes in cortisol, estradiol-17β, and progesterone (P₄) secretory activity throughout phases of the menstrual cycles in women with regular menstrual cycles. Cortisol (F), estradiol-17β (E₂), and P₄ secretory activity in each phase is presented in panels A–C respectively. The relative mean increases in steroid concentrations 30 and 60 min after awakening over the individual baseline (MnInc %) and the integrated steroid concentrations ranging from the time immediately upon awakening to 60 min after awakening (i.e. area under the curve (AUC) with respect to baseline) are depicted as mean±s.e.m. Bars with different Greek or Latin letters in each panel are significantly different from each other (P<0·05) by the Kruskal–Wallis test with Dunn's post-hoc test.