Background: Gender differences in schizophrenia have been recognized for a long time and it has been widely accepted that sex
steroid hormones, especially estradiol, are strongly attributed to this fact. Two hypotheses regarding estradiol action in psychoses
gained special research attention – the estrogen protection hypothesis and hypoestrogenism hypothesis. A growing number of studies
have shown benefits in augmenting antipsychotic treatment with estrogens or selective estrogen receptor modulators (SERM).
Methods: This review is focused on the role of selective estrogen receptor modulators in the treatment of schizophrenic patients.
In order to achieve this result PubMed was searched using the following terms: schizophrenia, raloxifene, humans. We reviewed only
randomized, placebo-controlled studies.
Results: Raloxifene, a selective estrogen receptor modulator was identified as useful to improve negative, positive, and general
psychopathological symptoms, and also cognitive functions. All reviewed studies indicated improvement in at least one studied
domain. Augmentation with raloxifene was found to be a beneficial treatment strategy for chronic schizophrenia both in female and
male patients, however potential side effects (a small increase in the risk of venous thromboembolism and endometrial cancer)
should be carefully considered.
Conclusions: SERMs could be an effective augmentation strategy in the treatment of both men women with schizophrenia,
although further research efforts are needed to study potential long-term side effects
