Interpretation
The observed progressive increase in cortisol levels during pregnancy is consistent with previous evidence of increased maternal mean cortisol level from about gestational week 25 - 28 as assessed by monthly measurement of cortisol in saliva 32. Our present data indicate a slightly earlier increase of cortisol concentrations during pregnancy compared to previous studies as we found increased cortisol levels as early as gestational weeks 18- 21 16. This echoes the benefit of using HCC which reflects the average cortisol concentrations over extended periods of time. The previously established transient increase in cortisol levels associated with labour and the subsequent decrease during the subsequent four days33-34 was not evident in our results. This was expected, as each measurement covers one month which makes short-lived fluctuations difficult to measure using hair extracts, and the hair sample taken during labour also included one week before until three weeks after childbirth. Hence, the elevation of cortisol associated with labour was probably outweighed by the downswing in cortisol in the first three postpartum weeks, in agreement with prior findings33, 35. In our study, the cortisol levels at the first three months postpartum remained slightly higher than in the second trimester, consistent with earlier reports of prolonged cortisol elevation for two to three postpartum months 36-38. This is in accordance with the reported suppressed dexamethasone test up to six weeks postpartum and blunted ACTH response to CRH up to 12 weeks postpartum 39 suggesting a slow restoration of the HPA system functions. It seems possible that ACTH has a role in the observed slow normalisation of cortisol level postpartum.
The present finding of higher cortisol levels among primiparous women in line with prior reports may reflect these women’s worries, anxiety and stress about the upcoming labour 21-22, 40-42. It is notable that the tendency for slowly escalating cortisol levels observed between weeks 14 and 25 is broken thereafter in multiparae, and the cortisol level becomes lower in the third month before childbirth, and then increases again following the same pattern as for primiparae but remaining lower. The explanation for this could be a more rapid inhibition of the mothers´ hypothalamic secretion of CRH by the placenta CRH secondary to adaptive processes during the longstanding inhibition during previous pregnancies. The influence of parity on the cortisol level vanished directly after the childbirth and remained that way, consistent with previous observations on salivary cortisol levels22.
The postpartum cortisol levels, were not related to those in the former part of the second trimester but rather to those from about GW 18 until childbirth, a period when the placenta CRH is becoming more dominant in the regulation of the rising cortisol level 32. This suggests that the HPA-axis has not fully normalised in the first three postpartum months but is still under the influence of pregnancy-related HPA alterations.
Taken together, the results suggest that the HPA axis may respond differently to the placenta production of cortisol in multiparae. One explanation could be that the negative feedback system is more prepared and suppresses the cortisol production of the adrenal cortex quicker and more effectively secondary to the initiation of cortisol placenta production. Such a theory would not only explain the lower concentration of cortisol in multiparae but also the lack of association between cortisol levels in GW 14 -17 and the levels found in the periods when placenta production has started. Similarly, in primiparae, the concentrations are dominated for longer by the woman’s own secretion, thereby explaining the closely related monthly cortisol levels of the second trimester and the lack of relation to the levels found in the third trimester.
Conclusion
Monthly measurements of HCC appear to closely mirror the activity of the HPA-axis during pregnancy. Increasing cortisol concentrations were found during pregnancy, with a decrease three months prior to childbirth in multiparae. The results suggest a quicker suppression of the hypothalamic CRH production by placenta CRH in multiparous women.