A systematic literature review conducted by investigators at the University of Maryland in Baltimore showed the addition of estrogen reduced schizophrenia symptoms in a dose-dependent, and statistically significant, manner compared with stand-alone antipsychotic treatment.
“Our review suggests estrogen has a significant effect in terms or improving psychotic symptoms, so I think this finding is very encouraging and that it needs to be explored further in additional studies,” study investigator Viviana Alvarez Toro, MD, told Medscape Medical News.
The findings were presented here at the American Psychiatric Association (APA) 2019 annual meeting.
Schizophrenia affects about 1% of the population and previous research shows that although the prevalence of schizophrenia is similar in men and women, it often presents differently between the sexes.
Alvarez Toro and co-investigator Elise Turner, MD, both residents at the University of Maryland/Sheppard Pratt Psychiatry Residency Program, Baltimore, note that young women typically develop symptoms 3 to 4 years later than their male counterparts and that symptoms in women can develop at times of hormonal flux, including during the post-partum or post-menopausal periods.
Earlier studies also suggest estrogen enhances dopamine antagonists in animal models and may serve as a “natural antipsychotic agent” that may explain symptom differences between men and women, the investigators note.
The researchers also point out that estrogen may play a protective role in neuronal injury by promoting neurogenesis and re-myelination.
Based on these data, Alvarez Toro and colleagues conducted a systematic review to examine the effects of adjunctive estrogen in adult women and compared it to stand-alone treatments with antipsychotics — the current standard of care.
For the review, only randomized controlled trials (RCTs) were selected. The final analysis was based on six RCTs with a total of 426 adult women diagnosed with schizophrenia using DSM criteria.
These trials were also limited to studies that used evidenced-based scales, such as the Positive and Negative Syndrome Scale (PANSS) or Brief Psychiatric Rating Scale (BPRS), to measure positive and negative symptoms of schizophrenia.
The study‘s primary outcome of interest was reduction of positive and negative symptoms of schizophrenia as measured by the PANSS and the BPRS symptoms scales.
The investigators found that all of the studies that measured symptoms using PANSS showed statistically significant reductions in total scores for women treated with estrogen compared with women treated solely with an antipsychotic.
The review also showed that as estrogen doses increased, there was a larger reduction in total PANSS scores. The single study that measured symptoms using the BPRS showed a non-statistically significant trend toward reductions in total scores for participants treated with estrogen compared with those treated with antipsychotic monotherapy.
Overall, said Alvarez Toro, estrogen as an adjunctive treatment for women with schizophrenia appears to reduce positive and negative symptoms in a dose-dependent manner. While there are no clinical implications at this point, Alvarez Toro added that the findings definitely warrant further study in larger and diverse populations.
Commenting on the findings for Medscape Medical News, Dolores Malaspina, MD, described the research as “timely and important.”
“It is consistently observed that psychiatric symptoms can emerge in the premenstrual period and this includes positive and negative psychiatric symptoms in women with schizophrenia,” said Malaspina, professor of psychiatry, neuroscience, and genetics and genomic sciences, Icahn School of Medicine at Mount Sinai in New York.
In addition, Malaspina noted that dysregulated gonadal hormones are a common feature of the disease apart from treatment. She also pointed out that estrogen and the stress hormone cortisol have an inverse relationship and that stress is commonly elevated in women with schizophrenia, which, in turn, reduces estrogen levels.
Malaspina said that estrogen may be an important adjunctive treatment for some women. However, she added, “estrogen treatment is not without its own cautions.”
The investigators and Malaspina have disclosed no relevant financial relationships.
American Psychiatric Association (APA) 2019: P2-2. Presented May 18, 2019.