The effects of menstrual cycle phase and oral contraceptive use on the acute immune response to physical exercise

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Abstract

The immune response to acute exercise is essential to provide defence against external pathogens, modulate physiological processes during exercise and guide tissue regeneration and adaptation post exercise. This exercise-induced immune response is dependent on a variety of factors including mode, intensity and duration of exercise, as well as health, sex and hormonal milieu. The profile of sex hormones particularly fluctuates in women, depending for example on menstrual cycle phase or oral contraceptive use. As oestrogen and progesterone are known to exert immunomodulatory activity, it has been suggested that variations in these hormones could impact basal immune status as well as exercise-induced immune responses in women. Unfortunately, results of changes in immune responses throughout the menstrual cycle and with oral contraceptive use have been somewhat conflicting, likely also due to methodological differences. Therefore, the aim of this thesis was to analyse differences in immune and inflammatory parameters between menstrual cycle and oral contraceptive phases at rest and in response to acute exercise.
Two systematic reviews and meta-analyses were performed, which analysed the differences in immune parameters between the follicular and luteal phase of the menstrual cycle (review I) or between oral contraceptive users and naturally cycling women (review II) at rest and in response to acute exercise. Additionally, two acute strength interventions with strength trained women were performed according to the recommended guidelines for menstrual cycle and oral contraceptive testing. Differences in the response of leukocyte subpopulations (intervention II, 24 women) and cytokines (intervention I, 21 women) were compared between various cycle phases: early follicular, late follicular and mid-luteal phase of naturally cycling women and the pill-free interval and pill-active phase of oral contraceptive users.
At rest, the analysis of studies found within review I revealed higher numbers of leukocytes and innate immune cells (monocytes, granulocytes, neutrophils), as well as higher leptin concentrations in the luteal phase compared to the follicular phase. When comparing results of studies analysing oral contraceptive users to naturally cycling women (review II), higher numbers of lymphocytes, higher CRP concentrations and lower cell adhesion molecule concentrations were found in the former group at rest. Other immune parameters, such as adaptive immune cells (T and B cells), cytokines and chemokines mostly showed no difference between cycle phases or between oral contraceptive users and naturally cycling women.
In response to acute exercise, the systematic reviews suggested a potentially stronger pro-inflammatory response in the luteal phase compared to the follicular phase after running exercise (review I) and revealed mainly no differences in the immune response between oral contraceptive users and naturally cycling women (review II). Conversely, the analysis of the immune response in the acute strength interventions showed somewhat differing results. In intervention II, no differences were found in the response of any of the measured cell populations between
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menstrual cycle phases. In contrast, in oral contraceptive users, the increase of total lymphocytes, NK cells, T cell and Tc cells was significantly attenuated in the pill-free interval compared to the pill-active phase. Furthermore, oral contraceptive users showed reduced concentrations of Th1 cells directly after acute strength exercise, which were significantly different from the increases observed in naturally cycling women. Additionally, differences in the response of cytokines between oral contraceptive users in the pill-free interval and naturally cycling women in the early follicular phase were found in intervention I. Concentrations of IL-1ra increased directly after exercise and returned to baseline at 24 h after exercise only in oral contraceptive users. Furthermore, at 24 h after acute strength exercise, oral contraceptive users in the pill-free interval showed reduced concentrations of IL-1β compared to naturally cycling women in the early follicular phase.
In summary, the results of this present thesis revealed some significant differences in basal immune status between menstrual cycle phases and oral contraceptive users. Women in the luteal phase showed increased numbers of leukocytes, innate immune cells and higher leptin concentrations, while oral contraceptive users showed higher lymphocyte numbers and CRP concentrations compared to non-users. In response to acute strength exercise, the results of this thesis showed that compared to endogenous hormonal fluctuations, the use and fluctuations of exogenous hormones in oral contraceptive users had a stronger effect on the exercise-induced immune response. No differences were found in changes of leukocytes between menstrual cycle phases, while an attenuation of exercise-induced increases of lymphocyte subpopulations in the pill-free interval compared to the pill-active phase was observed. Additionally, IL-1β concentrations and Th1 cell numbers were decreased in response to acute strength exercise in oral contraceptive users compared to naturally cycling women. In conclusion, these results could indicate a reduced pro-inflammatory and Th1 type response to acute strength exercise in oral contraceptive users. Whether these differences affect muscle regenerative and proliferative processes, as well as long-term training adaptations remains to be investigated.
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Original languageEnglish
Place of PublicationKöln
PublisherDeutsche Sporthochschule Köln
Number of pages226
Publication statusPublished - 2023

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