SAN FRANCISCO — Adjunctive estrogen may be effective in reducing symptoms in women with

schizophrenia and offers a potential new treatment option, new research suggests.

Elise Turner, MD, and Viviana Alvarez Toro, MD

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.

"Natural Antipsychotic"

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.

Furthermore, previous research suggests overall estrogen levels are typically lower in women with
schizophrenia compared with their counterparts without the disorder.

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.
Dose-Dependent Relationship

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.

"Timely, Important"

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."

Previous research has shown that estrogen has been associated with an elevated risk of cancer and can
increase blood pressure.

The investigators and Malaspina have disclosed no relevant financial relationships.

American Psychiatric Association (APA) 2019: P2-2. Presented May 18, 2019.

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