Exacerbation of Psychosis During the Perimenstrual Phase of the Menstrual Cycle: Systematic Review and Meta-analysis

Abstract

Psychotic disorders can be exacerbated by the hormonal changes associated with childbirth, but the extent to which exacerbations occur with the menstrual cycle is unclear. We addressed this issue by conducting a systematic review. Embase, Medline, and PsychINFO databases were searched for studies that measured exacerbations of psychotic disorders in relation to the menstrual cycle. We extracted exacerbation measure, definition of menstrual cycle phase, and measurement of menstrual cycle phase. Standard incidence ratios were calculated for the perimenstrual phase based on the observed admissions during this phase divided by the expected number of admissions if the menstrual cycle had no effect. Random effects models were used to examine pooled rates of psychiatric admission in the perimenstrual phase. Nineteen studies, comprising 1193 participants were eligible for inclusion. Eleven studies examined psychiatric admission rates, 5 examined symptoms scores, 2 examined self-reported exacerbation, and 1 examined both admission rates and symptom scores. A random effects model demonstrated the rate of admissions during the perimenstrual phase was 1.48 times higher than expected (95% CI: 1.31–1.67), with no significant heterogeneity detected. Four of six symptom score studies reported perimenstrual worsening, but lack of consistency in timepoints precluded meta-analysis. Two studies examining self-reported menstrual exacerbations reported prevalences ranging from 20% to 32.4%. Psychiatric admission rates are significantly higher than expected during the perimenstrual phase. There is some evidence that a worsening of psychotic symptoms also occurs during this phase, but further research with more precise measurement of the menstrual cycle and symptomatology is required.

Schizophrenia and Sex Hormones: What Is the Link?

“…Psychiatric admission rates are higher than expected during the perimenstrual phase. This is in agreement with the observation that a worsening of psychotic symptoms occurs during this phase ( 45 ). Most of the studies about the menstrual cycle and psychotic symptoms lack measurements of hormonal fluctuations throughout the menstrual cycle.…”

Estrogens in schizophrenia: progress, current challenges and opportunities

“…On a clinical level, psychotic vulnerability is increased in women during low estrogenic periods (e.g. in the premenstrual cycle phase or after menopause) [ 55 , 56 ▪ ]. Simultaneously with the menopausal drop of estrogen levels, both prevalence and relapse rates of psychosis rise, whereas psychotic symptoms decrease when estrogen levels are high, for example during pregnancy [ 57 – 60 ].…”

“…Since estrogens raise the availability of antipsychotics, premenopausal women require lower antipsychotic dosages [ 91 ]. However, considering that psychotic symptoms increase during low estrogenic phases of the menstrual cycle [ 32 , 87 ▪ , 92 ], younger women can benefit from slight increases in antipsychotic doses during these phases, to prevent monthly exacerbations in their illness [ 56 ▪ ]. For women who are sensitive to these monthly symptom increases, oral estrogenic contraceptives may be helpful.…”

Gaps or links between hormonal therapy and schizophrenia? (Review)

“…Studies on human induced pluripotent cells (iPSC) also demonstrated positive effects of estradiol-17β. The results of a study performed in 2018 showed its ability to increase the expression of synaptic protein in iPSC-neurons in patients diagnosed with schizophrenia to a similar level found in iPSC-neurons of healthy people (19).…”