Psychotic Symptoms May Worsen During Perimenstrual Phase of the Menstrual Cycle

Worsening psychotic symptoms around the time of menstruation support the estrogen protection hypothesis.

Women with psychotic disorders may experience worsening symptoms during the perimenstrual phase of the menstrual cycle, according to meta-analysis results published in Schizophrenia Bulletin. These findings support the estrogen protection hypothesis, which asserts that lower estrogen levels can worsen or precipitate psychosis.

Investigators conducted a systematic review of Medline, Embase, PsychINFO, and PubMed for published studies that examined the relationship between the menstrual cycle and exacerbation of any psychotic disorder. Psychiatric hospital admissions, psychiatric symptom scale scores, and self-report symptom severity were considered metrics of psychotic symptom exacerbation. Researchers standardized calculations to a 28-day menstrual cycle where day 24 through day 5 represented the “perimenstrual” phase. Standard incident ratios were calculated for the perimenstrual phase by dividing the observed number of psychiatric admissions during this phase by the number of expected admissions if the menstrual cycle had no effect. Random effects models were used to examine pooled rates of psychiatric admission in the perimenstrual phase. Data were extracted independently by 2 researchers and tested for bias; disagreements were resolved with a senior researcher.

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A total of 19 studies comprising 1193 participants were selected for inclusion. As exacerbation measures, 11 studies examined psychiatric admission rates, 5 examined psychiatric symptom scores, 2 examined self-reported exacerbations, and 1 examined both admission rates and symptom scores. Per the random effects model, the rate of admissions during the perimenstrual phase was 1.48 times greater than expected (95% CI, 1.31-1.67). No significant heterogeneity was detected between studies used for this calculation. Of the 6 studies reporting psychiatric symptom scores, 4 indicated worsening symptoms during the perimenstrual phase, while 2 reported no effect. The 2 studies examining self-reported data indicated perimenstrual worsening in 20% to 32.4% of patients. However, the quality of these 2 studies was low: neither used a validated measurement of menstrual cycle or exacerbation.

These data demonstrate a significant increase in psychiatric admission during the perimenstrual phase for women with a psychotic disorder. However, psychiatric admission rates may not capture all events of psychotic symptom worsening.

“Further research is needed to characterize the effect of the menstrual cycle on the symptomatology of psychosis, whether there is a subgroup of women who individually have a strong correlation between psychotic symptoms and menstrual cycles, and whether this subgroup is amenable to intervention in the form of hormonal therapy,” investigators concluded.

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Reilly TJ, Sagnay de la Bastida VC, Joyce DW, Cullen AE, McGuire P. Exacerbation of psychosis during the perimenstrual phase of the menstrual cycle: systematic review and meta-analysis [published online May 9, 2019]. Schizophr Bull. doi:10.1093/schbul/sbz030

This article originally appeared on Psychiatry Advisor