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. 2024 Oct 1;181(10):893-900.
doi: 10.1176/appi.ajp.20230850. Epub 2024 Sep 12.

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

Bodyl A Brand  1 , Iris E Sommer  1 , Shiral S Gangadin  1 , Antti Tanskanen  1 , Jari Tiihonen  1 , Heidi Taipale  1
Affiliations

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

Bodyl A Brand et al. Am J Psychiatry. .

Abstract

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.

Keywords: Epidemiology; Hormonal Therapy; Psychopharmacology; Schizophrenia Spectrum and Other Psychotic Disorders; Women.

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Conflict of interest statement

Dr. Taipale, Dr. Tanskanen, and Prof. Tiihonen have participated in research projects funded by grants from Janssen-Cilag and Eli Lilly to their employing institution. Prof. Tiihonen has been a consultant/advisor to and has received honoraria from: Eli Lilly, Evidera, Janssen-Cilag, Lundbeck, Orion, Otsuka, Mediuutiset, Sidera, and Sunovion. Dr. Taipale reports personal fees from Gedeon Richter, Janssen, Lundbeck and Otsuka. Dr. Sommer has received speaker fees from Otsuka and a charity grant from Janssen unrelated to this project. The remaining authors report no financial relationships with commercial interests.

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