Mental Health Awareness Month
Effects of Steroid Hormones in a Woman’s Brain: A Review
By: Dara Tolchin
Director’s Note: We continue our series on Mental Health Awareness with a review that explores the relationship between steroid hormones and the central nervous system. The research review was published in Frontiers in Public Health [1] by Del Río et al and summarized below by Dara Tolchin, who completed the FACTS elective as a medical student. The authors focused on the actions of hormones such as estrogen and progesterone upon signaling pathways to affect mood, behavior, and cognition. Hormonal balance is a key theme throughout the review, with clear implications for female cycle tracking. As Tolchin noted, assessing a woman’s ovulatory status through a modern method of charting and understanding steroid hormone fluctuations across the reproductive lifespan should be part of a holistic approach to address mental health concerns.
Introduction
Steroid hormones, including estrogen and progesterone, have a significant impact on a woman’s health and wellbeing throughout her life. This review article focused on the actions of these hormones within the central nervous system (CNS) and how they affect mood, behavior, and cognition. Estrogen and progesterone can be synthesized within the CNS and peripheral nervous system (PNS) and then cross the blood-brain barrier. When they enter neurons, they are either able to bind via the classical signaling pathway or at the mitochondria or endoplasmic reticulum. It has been shown that estrogen and progesterone act at synapses within the CNS containing various neurotransmitters, including glutamine, GABA, dopamine, and serotonin. The functions induced by these hormones at these synapses can affect a woman’s mood, behavior or cognition. Studies show when estradiol and progesterone levels are high during the menstrual cycle, women demonstrate improved verbal abilities. [1] Low estrogen and progesterone levels, on the other hand, are associated with noticeable spatial memory deficits that can be reversed with estrogen and progesterone treatment. [1] This review explains what those effects are, how the ovarian continuum can be understood in this context, and the action of exogenous synthetic hormones during adolescence and menopause. The purpose of this review is to discuss the importance of hormonal balance in a woman’s life.
“Studies show when estradiol and progesterone levels are high during the menstrual cycle, women demonstrate improved verbal abilities.”
Hormonal Production in a Woman’s Life
Throughout life, a woman goes through various stages of the ovarian continuum: she may have cycles with no ovarian activity, cycles with a luteinized unruptured follicle, and cycles with an adequate or deficient luteal phase. [1] Given the complexity of ovulatory function, it is important to consider which phase of the continuum a woman is in when evaluating her for mental health conditions or neurocognitive dysfunction. [1]
The FACTS elective teaches how a woman can chart her cycle and understand the potential hormonal disruptions she may be experiencing. Mood disorders can be treated with various mood stabilizers and/or antipsychotic medications. However, a woman’s ovulatory function is an aspect of her health that is often overlooked. The lecture on the Fifth Vital Sign emphasized that understanding a woman’s ovulatory function can aid in both diagnosis and treatment of underlying issues, including mental health concerns. This review also stresses that sentiment. Before treating a woman with a presumed mood disorder with mood-stabilizing medication, her ovulatory status should be assessed, as she may simply need hormonal stabilization. As discussed as a theme throughout the FACTS elective, the goal is to identify and treat the root cause instead of using other medications to simply mask symptoms.
“The lecture on the Fifth Vital Sign emphasized that understanding a woman’s ovulatory function can aid in both diagnosis and treatment of underlying issues, including mental health concerns.”
Hormonal Actions in the Female Brain
Estrogen and progesterone affect signaling pathways within a woman’s brain. In the CNS, these hormones activate anti-apoptotic signaling and increase cell/neuronal survival, regulate bioenergetic systems to help meet the metabolic demands of neural cells, and also regulate neurogenesis. [1] Progesterone has been shown to induce neural cell proliferation more consistently than estrogen. [1] Interestingly, these hormones do not have a synergistic effect but have a better response when given alone or in sequence. They also have varying functions at GABAergic, glutamatergic, dopaminergic, and serotonergic synapses.
Effects of Exogenous Synthetic Hormones in Behavior, Mood, and Cognition
The authors discussed the effect of exogenous synthetic estrogen and progesterone during adolescence and menopause. They cited a study from Denmark [4] published in JAMA Psychiatry in 2016 that found adolescents and women ages 15 to 34 who used hormonal contraception have increased rates of being diagnosed with depression. Among these women, levonorgestrel-only products were shown to have a higher rate of depression and a higher incidence of suicide attempts and actual suicide. [4] More research about the effects of oral contraceptives on behavior, mood, and cognition is critical. As discussed in the FACTS elective, young women can be taught how to chart their cycles and follow their ovulatory patterns using different fertility awareness-based methods (FABMs) to avoid pregnancy and prevent the often-detrimental side effects of synthetic hormones.
Del Río et al discussed hormone replacement therapy and potential benefits of estrogen during menopause; however, they cautioned against the use of unopposed estrogen for a long period of time. [1] During the initial stages of menopause, while a woman’s estrogen receptors are still sensitive to estrogen, estrogen replacement has been shown to help prevent neurocognitive decline, Alzheimer’s disease, and Parkinson’s disease. [1] Charting with FABMs can help a woman identify when she is in the perimenopausal phase. Recognizing this vital transition can help time the use of estrogen when needed, which may help prevent neurocognitive decline and improve quality of life.
“During the initial stages of menopause, while a woman’s estrogen receptors are still sensitive to estrogen, estrogen replacement has been shown to help prevent neurocognitive decline, Alzheimer’s disease, and Parkinson’s disease.”
Conclusion
This review stressed the importance of understanding the fluctuations of steroid hormones, specifically estrogen and progesterone, throughout a woman’s life and their effects on her brain. The effects of estrogen and progesterone on mood, behavior, and cognition should be further studied in patients with hormonal imbalances such as polycystic ovary syndrome (PCOS), hyperprolactinemia, hypothyroidism, and functional hypothalamic anovulation. These conditions may be identified and treated sooner by charting with FABMs, which can enhance a woman’s understanding of these hormonal fluctuations throughout her life.
References
[1] Del Río JP, Alliende MI, Molina N, Serrano FG, Molina S, Vigil P. Steroid Hormones and Their Action in Women’s Brains: The Importance of Hormonal Balance. Front Public Health. 2018;6:141. Published 2018 May 23. doi:10.3389/fpubh.2018.00141.
[2] Rupprecht R, Holsboer F. Neuroactive steroids: mechanisms of action and neuropsychopharmacological perspectives. Trends Neurosci. (1999)22:410–6. doi: 10.1016/S0166-2236(99)01399-5.
[3] Sisk CL, Zehr JL. Pubertal hormones organize the adolescent brain and behavior. Front Neuroendocrinol.(2005) 26:163–74. doi: 10.1016/j.yfrne.2005.10.003.
[4] Skovlund CW, Mørch LS, Kessing LV, Lidegaard Ø. Association of hormonal contraception with depression. JAMA Psychiatry (2016) 73:1154–62. doi: 10.1001/jamapsychiatry.2016.2387.
ABOUT THE AUTHOR
Dara Tolchin
Dara Tolchin is a fourth-year medical student at the Philadelphia College of Osteopathic Medicine in Philadelphia, PA. She is currently applying to internal medicine programs with hopes of specializing in endocrinology. She enrolled in the FACTS elective to gain better insight into women’s reproductive health and learn about fertility awareness-based methods. This information and resources will enable Tolchin to educate her patients about fertility and empower them to learn more about their reproductive health.
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