Reproductive Psychiatry is Still Psychiatry
For a psychiatrist with scientific aspirations, ethical commitments to gender equality, and the lived experience of physical womanhood, characterizing any mental illness as an effect of reproductive hormone activity is fraught with peril. Since hormonal flux is normal in all females, attributing any mental problems to “hormones” encourages the idea that being female, relative to male, is itself disorder. Old terms like “hysteria” “puerperal insanity” and “involutional melancholia,” initially coined to characterize mental illnesses in women, have been carefully excised from diagnostic nosology, for good and ill (Hirschbein, 2009). Other terms like “post-partum (or perinatal) depression,” have been expanded to include men, though the pathophysiology involved must differ from that of women with similar criterion symptoms. Striving for gender neutrality may paradoxically harm women by directing attention away from conditions where hormonal factors play a role or could improve treatment.
An editorial and article in the most recent American Journal of Psychiatry (Reilly and McCutcheon 2024; Brand et al, 2024) suggests that it is time re-examine both old theories and new scruples about the role of reproductive hormones in serious mental illness. Researchers have long noted that schizophrenic spectrum disorders (SSD) begin later in females than in males and follow a different course. As women age, they may respond less well to antipsychotic medication and show increased risk of relapse, compared both to younger women and to men. These observations have supported speculation that female reproductive hormones have a neuroprotective effect and that their natural decline may exacerbate SSDs and other presumed neurological conditions.
Acting on this hypothesis, a group of Finnish scientists, themselves mostly women (Brand et al, 2024), examined 20 years of records 3,488 women identified hospitalized with an SSD when between 42 and 60 years of age, from a wider cohort of 30,785 women who received prescriptions for menopausal hormone therapy (MHT) as prescribed in Finland. The women took MHT for varying periods of time, beginning at varying ages. Overall, the use of any MHT was associated with a 16% reduction in the women’s risk for relapse of their SSD as measured by psychiatric hospitalization. This reduction appeared in women who began MHT before the age of 56 and was not seen in women who initiated MHT later than that.
These results should not surprise anyone who has looked carefully at the results of the Women’s Health Initiative Study (WHI) (Manson al, 2024). The WHI showed that estrogen/progesterone therapy does not prevent cardiovascular disease or dementia and increases risk for stroke and heart attack when given to women in their sixties and seventies, that is, ten or more years after menopause. This result was very influential in discouraging the automatic prescription of estrogen/progesterone to women of every age, again showing that the events of women’s reproductive life cycle are not themselves diseases requiring treatment.
However, the hormones administered in the WHI differed from today’s estrogen progesterone regimens, the doses were high, and effects on other conditions were not the primary outcome measures. In subsequent years, estrogens and progesterone that more closely resemble naturally occurring hormones have become available. These compounds have been somewhat useful and present little risk in women on either side of menopause who become or have been depressed, especially when they also experience characteristic menopausal symptoms (poor sleep, hot flashes) (Manson et al 2024). This report suggests that female reproductive hormones may indeed play a role in the management of serious mental illness as well. While this finding does not apply to all or even most women, the relative safety and tolerability of hormone therapy could be an important addition to available therapies.
Practicing reproductive psychiatry is a hopeful vocation based on the joy of seeing even seriously distressed younger women often achieve full recovery. Still, as psychiatrists we should be eager to apply our knowledge to help the many other women we have been trained to treat. Further study of the role of estrogen and progesterone in the treatment of SSDs should be a priority. Reducing suffering and disability and lowering the burdens of treatment is a mandate for psychiatrists treating people at every stage of life.
Brand, Bodyl. A., Sommer, Iris. E., Gangadin, Shiral et al (2024). Real-World Effectiveness of Menopausal Hormone Therapy in Preventing Relapse in Women With Schizophrenia or Schizoaffective Disorder. The American Journal of Psychiatry, 181(10), 893–900.
Hirshein, Laura. D. (2009). Gender, Age, and Diagnosis: The Rise and Fall of Involutional Melancholia in American Psychiatry, 1900–1980. Bulletin of the History of Medicine, 83(4), 710–745.
Manson, J. E., Crandall, C. J., Rossouw, J. E. et al . (2024). The Women’s Health Initiative Randomized Trials and Clinical Practice: A Review. JAMA : The Journal of the American Medical Association, 331(20), 1748–1760.
Reilly, Thomas. J., & McCutcheon, Robert. A. (2024). Menopausal Hormone Therapy for Women with Schizophrenia: What’s Stopping Us? The American Journal of Psychiatry, 181(10), 854–855.
By: Dr. Julia Frank, The International Marcé Society Communications Committee