The role of health anxiety in the experience of perceived stress across the menstrual cycle.

Background: Hormonal variation throughout the menstrual cycle influences physiological and psychological symptoms, although not for all women. Individual differences in health anxiety (HA) might help to explain the differences in physiological and psychological symptoms and perceived stress observed across women. Design: We examined the moderating role of HA in the relation between menstrual phase and premenstrual symptom severity and perceived stress. Methods: A total of 38 women completed visits in both late luteal and follicular phases, with visit order randomized. Menstrual phase was verified using day-count, a luteinizing hormone test, and progesterone assay. Results: Linear mixed models revealed that women experienced more premenstrual symptoms during the late luteal phase vs. the follicular phase; however, HA did not moderate this effect. There was a significant HA × menstrual cycle phase interaction for perceived stress. During the late luteal phase, women with higher HA reported greater perceived stress compared to women with lower HA. In the follicular phase, women with higher and lower HA reported similar levels of perceived stress. Conclusion: Higher levels of HA may play a role in the experience of perceived stress in specific phases of the menstrual cycle.

PTSD in women is associated with a block in conversion of progesterone to the GABAergic neurosteroids allopregnanolone and pregnanolone measured in plasma.

There is a need to identify new and more effective treatments for posttraumatic stress disorder (PTSD). Allopregnanolone and its stereoisomer pregnanolone (together termed ALLO) are metabolites of progesterone that positively and allosterically modulate GABA effects at GABAA receptors, thereby reducing anxiety and depression. Previous research revealed that women with PTSD had low cerebrospinal fluid (CSF) ALLO levels and a low ratio of ALLO to the allopregnanolone precursor 5α-DHP, consistent with deficient activity of the ALLO synthetic enzyme 3α-hydroxysteroid dehydrogenase (3α-HSD). The current study examined ALLO and the ratio of ALLO to 5α-DHP in plasma at rest and in response to psychophysiological stressors in trauma-exposed, medication-free women with and without PTSD. Participants were examined twice in random order during the early follicular phase (eFP) and mid-luteal phase (mLP) of the menstrual cycle. Plasma neurosteroids were measured using gas chromatography-mass spectrometry. Results indicate that the ALLO to 5α-DHP ratio in plasma increases between the eFP and mLP. In addition, women with PTSD have a lower ratio of ALLO to 5α-DHP than trauma-exposed healthy women, as well as blunted increases in this ratio in response to a moderately stressful laboratory procedure, i.e., differential fear conditioning, across the menstrual cycle. Clinically feasible testing for 3α-HSD dysfunction is critical to translating this line of research into clinical care. Measurement of this ratio in plasma could facilitate patient stratification in clinical treatment trials, as well as precision medicine targeting of treatments that address ALLO synthesis deficits in women with PTSD.