Sex hormones and oxytocin augmentation strategies in schizophrenia: A quantitative review.
BACKGROUND
Sex differences in incidence, onset and course of schizophrenia suggest sex hormones play a protective role in the pathophysiology. Such a role is also proposed for oxytocin, another important regulator of reproduction function. Evidence on the efficacy of sex hormones and oxytocin in the treatment of schizophrenia is summarized.


METHODS
Double-blind, placebo-controlled, randomized studies were included, examining augmentation with estrogens, selective estrogen receptor modulators (SERMs), testosterone, dehydroepiandrosterone (DHEA), pregnenolone, and oxytocin. Outcome measures were total symptom severity, positive and negative symptom subscores, and cognition. In meta-analyses, combined weighted effect sizes (Hedges' g) per hormone were calculated.


RESULTS
Twenty-four studies were included, examining 1149 patients. Significant effects were found for estrogen action (k=10), regarding total symptoms (Hedges' g=0.63, p=0.001), positive (Hedges' g=0.42, p<0.001), and negative symptoms (Hedges' g=0.35, p=0.001). Subgroup analyses yielded significant results for estrogens in premenopausal women (k=6) for total, positive, and negative symptoms, and for the SERM raloxifene in postmenopausal women (k=3) for total and negative, but not positive symptoms. Testosterone augmentation in males (k=1) was beneficial only for negative symptoms (Hedges' g=0.82, p=0.027). No overall effects were found for DHEA (k=4), pregnenolone (k=4), and oxytocin (k=6). Results for cognition (k=12) were too diverse for meta-analyses, and inspection of these data showed no consistent benefit.


CONCLUSIONS
Estrogens and SERMs could be effective augmentation strategies in the treatment of women with schizophrenia, although potential side effects, partially associated with longer duration use, should be taken into account. Future trials are needed to study long-term effects and effects on cognition.
University Medical Center Utrecht, Brain Center Rudolf Magnus, Department of Psychiatry, PO Box 85500, 3508 GA Utrecht, The Netherlands. Electronic address: s.m.heringa@umcutrecht.nl.
Sophie M
SM
Heringa
University Medical Center Utrecht, Brain Center Rudolf Magnus, Department of Psychiatry, PO Box 85500, 3508 GA Utrecht, The Netherlands. Electronic address: m.j.h.begemann@umcutrecht.nl.
Marieke J H
MJ
Begemann
University Medical Center Utrecht, Department of Reproductive Medicine and Gynecology, PO Box 85500, 3508 GA Utrecht, The Netherlands. Electronic address: a.j.goverde@umcutrecht.nl.
Angelique J
AJ
Goverde
University Medical Center Utrecht, Brain Center Rudolf Magnus, Department of Psychiatry, PO Box 85500, 3508 GA Utrecht, The Netherlands. Electronic address: i.sommer@umcutrecht.nl.
Iris E C
IE
Sommer
D014150:Antipsychotic Agents / Q000627:therapeutic use*; D042341:Gonadal Hormones / Q000627:therapeutic use*; D020249:Hormone Replacement Therapy / Q000379:methods*; D006801:Humans; D010121:Oxytocin / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012559:Schizophrenia / Q000188:drug therapy*
D014150:Antipsychotic Agents; D042341:Gonadal Hormones; D010121:Oxytocin
Cognition; Meta-analysis; Oxytocin; Schizophrenia; Sex hormones; Treatment