Real-World Effectiveness of Menopausal Hormone Therapy in Preventing Relapse in Women With Schizophrenia or Schizoaffective Disorder

OBJECTIVE: Antipsychotic effectiveness in preventing relapse declines around menopausal age in women with schizophrenia or schizoaffective disorder (SSD). It is not known whether systemic menopausal hormone therapy (MHT) can help to prevent psychosis relapse. METHODS: A within-subject study design was used to study the effectiveness of MHT in preventing relapse in a Finnish nationwide cohort of women with SSD between 40 and 62 years of age who used MHT during follow-up (1994-2017). Hazard ratios adjusted for age and psychotropic drug use were calculated for psychosis relapse as main outcome and any psychiatric hospitalization as secondary outcome. RESULTS: The study population comprised 3,488 women using MHT. Use of MHT was associated with a 16% lower relapse risk (adjusted hazard ratio [aHR]=0.84, 95% CI=0.78-0.90) when compared to non-use. Stratified by age, MHT was associated with decreased relapse risks when used between ages 40-49 (aHR=0.86, 95% CI=0.78-0.95) and ages 50-55 (aHR=0.74, 95% CI=0.66-0.83), but not between ages 56-62 (aHR=1.11, 95% CI=0.91-1.37). Similar effectiveness was found for estrogen alone or combined with fixed or sequential progestogens (aHRs between 0.79 and 0.86), transdermal and oral formulations (aHRs 0.75-0.87), and for most specific formulations (aHRs 0.75-0.85), except tibolone (aHR=1.04, 95% CI=0.75-1.44) and formulations with dydrogesterone (aHR=1.05, 95% CI=0.85-1.30). Similar results were observed with any psychiatric hospitalization as outcome measure. CONCLUSIONS: The findings underscore the potential value of MHT in preventing psychosis relapse among women with SSD of menopausal age. These findings translate clinical evidence on the neuroprotective effects of estrogens to real-world settings, encompassing a group of women for whom current antipsychotic treatment options may be insufficient.