Cortisol awakening response is blunted and pain perception is increased during menses in cyclic women

The incidence of menstrual symptoms is reported to be as high as 90% in cyclic women. These symptoms, including anxiety and pain, might be associated with cortisol, as its receptors are widely distributed in the brain areas associated with behavior. Therefore, the current study aimed to assess the cortisol awakening response (CAR) throughout the menstrual cycle and correlate it with pain perception and trait anxiety.

CAR was assessed by measuring salivary cortisol at 0, 15, 30, and 60min following awakening in the same women (n=59, age 22.2±0.37years) at various stages of the menstrual cycle (menses, midcycle, luteal and premenstrual phases). Progesterone and estradiol concentrations were also determined in saliva samples to assess cyclic changes. Self-reported pain, trait anxiety, and menstrual symptoms were assessed by visual analog scale (VAS), state-trait anxiety inventory (STAI-T), and the Daily Record of Severity of Problems (DRSP), respectively.

Estradiol was significantly elevated during the midcycle period and remained high during the early luteal phase (p<0.05). Progesterone was increased during the luteal phase (p<0.05). Post-awakening cortisol values increased during midcycle, luteal phase, and premenstrual phase (p<0.05, classical CAR), but not during the menses (p>0.05, blunted or flat CAR). Positive and significant correlations were found between cortisol and estradiol (R²=0.322; p=0.000), cortisol and progesterone (R²=0.156; p=0.000), and estradiol and progesterone (R²=0.349; p=0.001). Premenstrual symptom scores were higher in the menses and premenstrual phases than in the midcycle and luteal phases (p<0.001). Pain perception was the highest during the menses followed by the premenstrual phase (p<0.01).

CAR was blunted during the menses, suggesting that cortisol might play a phase-specific role in the regulation of the cycle. Additionally, premenstrual symptoms, including pain, were more severe when ovarian steroid levels reduced (i.e., menses and the premenstrual phase).