Progesterone-Enriched Oral Contraceptives Linked To Mood Disorders And Increased Risk Of Suicide!

Mental Health: In the intricate landscape of women's health, the use of oral contraceptives has long been a subject of discussion. Recent research conducted by the Netherlands Institute for Neuroscience has brought forth compelling evidence linking progesterone-enriched oral contraceptives to an increased risk of mood disorders and suicide. Led by Dr Lin Zhang under the guidance of Professor Dr Dick Swaab, this study not only explores the mechanisms underlying this connection but also advocates for a reevaluation of contraceptive recommendations, particularly for women with a history of depression or suicidal thoughts.


Progesterone-Enriched Oral Contraceptives Linked To Mood Disorders
And Increased Risk Of Suicide!

The Dual Role of Progesterone
Traditionally recognized for its pivotal role in the female reproductive system, progesterone is a hormone with a dual nature. Beyond its reproductive functions, progesterone also acts as a stress hormone, a facet often overlooked in discussions surrounding its impact on Mental Health. Dr Zhang's research, drawing from brain samples obtained through the Netherlands Brain Bank, unveils the stress-related dimension of progesterone, prompting a closer examination of how this hormone influences the brain, particularly in the context of depression and suicide risk.
 
The Infundibular Nucleus - A Key Player
Within the intricate structure of the human brain, the infundibular nucleus in the hypothalamus emerges as a critical focal point in Dr Zhang's investigation. This region is identified as the primary site where progesterone exerts its influence. Through meticulous analysis, an intriguing correlation is unveiled - in individuals with depression who tragically succumbed to suicide, an increased number of cells producing an opiate-like substance were observed. Significantly, this elevation is directly linked to the presence of progesterone receptors, paving the way for a deeper understanding of the mechanisms that may contribute to heightened suicidal risk.
 
Progesterone and the Opioid System
Dr Swaab elucidates the connection between progesterone and the brain's opioid system, shedding light on the potential pathways through which progesterone could elevate the risk of suicide. The activation of the opioid system, triggered by an increase in progesterone, emerges as a significant factor in the heightened susceptibility to suicidal behaviors. The interplay between progesterone and the opioid system becomes a crucial element in the complex web of factors contributing to mental health challenges.
 
Cell Division in the Aged Population
One notable observation from Dr Zhang's research is the indication of cell division in the infundibular nucleus of the aged population. This observation sparks a debate among neuroscientists, as the generation of newborn neurons in the adult human brain, especially in the elderly, remains a topic of ongoing discussion. The potential implications of cell division in the aged infundibular nucleus add a layer of complexity to the understanding of brain function and aging.
 
Clinical Implications and Risk Evaluation
As the use of progestogen-containing drugs, commonly prescribed for contraception and menopausal complaints, comes under scrutiny, clinical implications come to the forefront. While clinical research suggests that the suicide risk is minimal in drugs containing natural progesterone, concerns are raised regarding the synthetic form of progesterone present in certain contraceptives, known for its increased potency. Gynecologists, being at the forefront of women's health, have begun incorporating this knowledge into their standard practice by screening patients for depression and suicidal risk before prescribing progestogen-containing contraceptives. However, this cautionary approach is yet to be universally adopted by general practitioners.
 
Mapping Progesterone Receptor Distribution
Delving deeper into the anatomical aspects, the study systematically examines the distribution of progesterone receptors in the human hypothalamus in relation to age and sex. The findings reveal a concentration of progesterone receptors in specific hypothalamic nuclei, shedding light on the diverse functions these receptors mediate, including anxiety and stress response, neurogenesis, circadian rhythm, and more. This widespread distribution raises intriguing questions about how progesterone, whether originating peripherally or produced locally in the brain, might impact various neuroendocrine regulators.
 
Peering into Neuropeptides and Neurotransmitters
The study not only explores the role of progesterone receptors but also delves into the dynamics of neuropeptides, specifically pro-opiomelanocortin (POMC) and neuropeptide Y (NPY), within the infundibular nucleus. POMC+ neurons, known for their involvement in depressive-like behavior regulation, showed an increase in suicide completers with mood disorders. The co-expression of progesterone receptors in these neurons suggests a direct link between progesterone and suicidal tendencies. On the other hand, a sharp reduction in NPY+ neurons in patients with mood disorders adds another layer to the understanding of the molecular basis of psychopathology in suicide.
 
Sex Differences and Hormonal Influences
The research brings attention to sex differences in the reduction of NPY+ neurons in the infundibular nucleus, uncovering potential hormonal influences on mental health. Notably, only males with mood disorders exhibited fewer NPY+ neurons. This observation aligns with previous studies indicating that NPY expression in the infundibular nucleus is activated by testosterone only in male animals. The intricate interplay between hormones, neurochemicals, and mental health underscores the need for gender-specific considerations in understanding and addressing mood disorders.
 
Conclusion
In conclusion, the research conducted by the Netherlands Institute for Neuroscience significantly advances our understanding of the complex relationship between progesterone-enriched contraceptives, mood disorders, and suicide risk. The identified mechanisms involving the infundibular nucleus, progesterone receptors, and neuropeptides provide a foundation for further exploration and potential interventions in women's mental health. The call to action extends to medical professionals, urging them to integrate this knowledge into their practice, emphasizing personalized contraceptive recommendations and mental health assessments for women with a history of depression or suicidal thoughts. As scientific inquiry delves deeper into the intricate intersections of hormones, neural circuits, and mental health, this research stands as a beacon, guiding conversations and strategies for women's holistic well-being.
 
The study findings were published in the peer reviewed journal:
Acta Neuropathologica Communications.
 
https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-024-01733-y
 
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