Could the menstrual cycle be used to tailor treatments for PTSD?

Lower estradiol levels were linked to more symptoms of post-traumatic stress disorder (PTSD) in women with a history of trauma at the start of their monthly menstrual cycles, according to a small multi-method study.

Specifically, a lower estradiol level was associated with a higher number of total traumatic symptoms (r_s = -0.36, P= 0.023), more recurrent symptoms (r_s = -0.32, P= 0.046), and more avoidance symptoms (r_s = -0.40, P= 0.010) which were also more severe (r_s = -0.34, P= 0.034), reported Jenna Rieder, PhD, of Thomas Jefferson University in Philadelphia, and colleagues from Psychological trauma: theory, research, practice and policy.

These findings were consistent with previous research, which found links between lower estradiol levels and increased activation of limbic areas of the brain, greater fear reactions, and the presence of intrusive memories.

Throughout the menstrual cycle, the overall severity of PTSD symptoms – measured by 10-day Momentary Ecological Assessments (EMAs) and the PTSD checklist for DSM-5 – decreased during each period, from phases early to late folliculars (b = -0.39, SE= 0.19, P= 0.039).

Notably, the severity of negative cognition / mood (b = -0.19, SE= 0.08, P= 0.012) and symptoms of excitement (b = -0.14, SE= 0.07, P= 0.043) also decreased during the cycle. However, the severity of the re-experience and avoidance did not change from the day of the cycle (b = -0.06, SE= 0.05, P= 0.195; b = -0.01, SE= 0.02, P= 0.694, respectively).

The small but diverse sample at the heart of the study included 40 women aged 18 to 33 (mean age 21.9), all of whom had had a traumatic experience. Eight participants (20%) met the criteria for a provisional diagnosis of PTSD.

Participants were also expected to have natural and regular menstrual cycles; the use of hormonal contraceptives, the fact of being pregnant or having a historically irregular period all fell under exclusion criteria.

“When in the cycle you assess, women can really affect whether they meet the diagnostic criteria for PTSD, especially for people who are right at the border,” Rieder said in a press release. “And that can have real practical implications, say, for someone who is a veteran and entitled to benefits or for health insurance purposes.”

In the study, the women participated in an initial lab visit, followed by a 10-day EMA that covered the early and late follicular phases of their menstrual cycles.

The laboratory visit included a clinical interview to check for the presence of trauma exposure and to assess symptoms of PTSD and other potential psychiatric disorders. Exposure to trauma in this setting was measured using Criterion A of the clinician-administered PTSD scale for the DSM-5, which includes exposure to actual or threatened death, serious injury, and to sexual violence through direct or indirect exposure, among others.

Participants also provided saliva samples at three different times during the laboratory visit: at the start of the visit (which was used as a baseline measurement), immediately after the description of the traumatic event during each maintenance and 20 minutes after the second sample. With these samples, Rieder and his colleagues measured salivary alpha-amylase (a surrogate marker of sympathetic nervous system function), cortisol levels, and estradiol levels.

The EMA period of the study was conducted over 10 days, covering the early follicular phase (lower estradiol) and the late follicular phase (higher estradiol) of the menstrual cycle. Participants completed five-point questionnaires daily – as soon as they woke up, before falling asleep, and at three varying times of the day – using a phone provided to them.

Rieder and his team also confirmed the increase in estradiol during the EMA portion by collecting two home saliva samples on the first and last days of the EMA; progesterone was also measured in these samples, to verify that participants were staying in the follicular phase of their cycles.

Participants rated their current affect on a scale of 1 to 9, with 1 being “extremely unpleasant”, 5 being “neutral” and 9 being “extremely pleasant”. Arousal was also rated on the same numerical scale, where 1 was “extremely unstimulated or activated”, 5 was “moderately stimulated or activated” and 9 was “extremely stimulated or activated”.

One of the main limitations of this study, the authors acknowledged, was that laboratory visits were not scheduled in accordance with a phase of the participants’ menstrual cycles, unlike the EMA portion of the study; thus, they were not able to directly test the effects of cycle phase on stress reactivity. Another limitation, they noted, was that their research did not focus specifically on female cyclists who have been clinically diagnosed with PTSD.

“Clinicians working with PTSD populations could gather information about clients’ recent menstrual cycles to predict when clients might have more frequent aversive daily experiences, including symptoms,” wrote Rieder and colleagues. “[They] could also potentially tailor treatments and schedule interventions at specific times in the menstrual cycle. “

“The degree to which certain treatments might be more effective during certain menstrual phases is an exciting avenue for future clinical trials,” they concluded.