Is there a relationship between estrogen serum level and symptom severity throughout the menstrual cycle of patients with schizophrenia?

Shahin Akhondzadeh, Kamran Mokhberi, Homayoun Amini, Bagher Larijani, Ladan Kashani, Ladan Hashemi, Ali-Akbar Nejatisafa and Ahmad-Reza Shafaei

Background: Sex differences in terms of age at onset, symptom expression and course of illness have consistently been demonstrated in patients with schizophrenia. Some studies have reported that schizophrenic symptoms are exacerbated during the premenstrual phase when the blood estrogen level is low. Nevertheless, the results are controversial. We hypothesized that higher levels of estrogen would be associated with a decreased severity of illness in women with schizophrenia. To that end, we examined the relation of gonadal hormone levels to severity of symptoms in 30 women with chronic schizophrenia. Methods: Patients were 30 female in-patients who met Diagnostic and Statistical Manual of Mental Disorders IV criteria for chronic schizophrenia, aged between 20 and 40 years. All patients received a fixed dose of risperidone (6 mg/day) throughout the study and were assessed over one complete menstrual cycle following 1 month’s hospitalization. During the second month they were assessed from the first day of menstrual flow to the onset of the next menstrual flow period. A trained resident of psychiatry who was blind to the patients’ cycle phase, used the Positive and Negative Syndrome Scale (PANSS) to rate patients. They rated each patient four times during the menstrual cycle: on the third day of menstruation when estrogen and progesterone levels are low; on the tenth day of menstruation when the estrogen level is rising; on the 13th day of menstruation when estrogen level is high (preovulatory peak); and on the 21st day of menstruation (midluteal) when progesterone level is high. Serum levels of estrogen, progesterone and prolactin were measured on the same days. Results: A repeated-measures analysis of variance showed a significant change in the serum level of estrogen and progesterone. Post hoc Tukey comparisons of the estrogen and progesterone serum levels on day 3 with days 10, 13 and 21, revealed a significant increase (p < 0.001). In addition, a repeated-measures analysis of variance showed significant changes on the PANSS total scores and all its subscales including positive, negative and general psychopathology. Regarding PANSS total scores and all its subscales, post hoc comparisons of day 3 with the scores on days 10 and 13 by means of the Tukey procedure revealed a significant reduction from day 3 (p < 0.001). Conclusion: Although more systematic research is needed to understand the etiology of the sex difference in schizophrenia, the present data add to a growing body of research suggesting that estrogen has an important role in the brain and higher estrogen levels in female patients with schizophrenia may be associated with better outcome. Moreover, exacerbation of symptoms during the premenstrual period supports the role of reproductive hormones in schizophrenia.