Contributed article by Alessia Squinteri
Think back to the most prolonged stressful situation you’ve faced - do you remember how you felt when it finally ended? To illustrate this concept more tangibly, consider the enduring stressors imposed by the COVID-19 pandemic and its associated lockdowns - a collective experience shared by all[1]. It is now widely recognised that even under identical stressful conditions, individuals exhibit different stress responses. Furthermore, severe and prolonged stress responses can potentially lead to tissue damage and disease [2].
Investigating the impact of gender bias on stress effects raises intriguing questions. To delve into this topic, let’s first briefly review what stress is in a biological context. Stress, in essence, is the body’s rapid and adaptive reaction to a perceived threat to homeostasis, a mechanism vital for the survival of both humans and other mammals [3]. When the brain identifies a challenging situation, it triggers the activation of the hypothalamus–pituitary–adrenal (HPA) axis. This system orchestrates a series of physiological changes collectively known as the 'fight-or-flight' response. The amygdala, a crucial brain structure, detects stressors and signals the HPA axis to initiate the response. Subsequently, the hypothalamus communicates with the pituitary gland, which releases hormones acting as messengers in the stress-response system. These hormones travel from the brain to the adrenal glands, located on top of the kidneys, and prompt them to release cortisol, the primary stress hormone, into the body [4]. Cortisol plays a crucial role in priming the body for action during stressful situations. It sharpens cognitive clarity, channels energy toward essential muscles, and accelerates heart rate and breathing. Once released, cortisol raises glucose levels in the bloodstream, increases the brain’s glucose utilisation, and boosts the availability of substances necessary for tissue repair.
However, as cortisol's primary function is to prepare the body for a 'fight,' it also temporarily suppresses certain non-essential functions such as immune responses, digestion, growth and reproduction [5]. Going back to the COVID-19 pandemic and the associated lockdown, it has been observed that women experienced a higher incidence of anxiety and depression disorders, potentially affecting their ovulatory cycles. Chronic stress can lead to functional hypothalamic amenorrhea (FHA), a condition where stress disrupts the normal menstrual cycle[1]. FHA is primarily linked to impaired pulsatile gonadotropin releasing hormone (GnRH) secretion. This abnormality leads to reduced luteinizing hormone (LH) and follicle-stimulating hormone (FSH) pulses, resulting in the absence of LH surges during the menstrual cycle, impaired follicular development, anovulation, and low serum estradiol levels [6]. In essence, when cortisol levels rise due to chronic stress, the release of reproductive hormones is inhibited, signalling to a woman's body that it is too stressed for pregnancy [7].
FHA therefore has far-reaching consequences for women's health, most notably infertility. However, the sustained low-estrogen levels that characterise FHA can also increase the risk of cardiovascular disease (CVD), the leading cause of death among women, and adversely affect musculoskeletal tissue health [6]. It is important to note that FHA isn't solely triggered by extreme events like pandemics. Conditions such as eating disorders, excessive exercise, emotional distress, inadequate sleep, or a combination of these factors can also lead to FHA. Stress factors also seem to influence the risk of dysmenorrhea (i.e. painful menstruation). Research by Wang et al. (2004) describes how stress from the preceding month may affect the frequency of dysmenorrhea in the subsequent period, particularly in individuals with a history of this condition [8]. Furthermore, prolonged stress, among other factors, can lead to vaginal bleeding unrelated to the regular menstrual cycle (i.e. spotting) [9]. These effects, however, represent just the tip of the iceberg. Hormonal imbalances resulting from stress can give rise to mood swings, decreased libido, insomnia, and unexplained weight gain [9], deeply impacting women's psychological well-being.
Let’s focus on the positive side! While it’s impossible to completely eliminate stress from our lives, the field of femtech offers numerous innovative solutions to help women handle these challenging moments. One such solution is Moonai [10], a mobile app designed to alleviate both physical and mental menstrual pain using neuroscience and sounds therapy, providing a hormone-friendly solution. Hyivy Health [11] is pioneering a holistic pelvic rehabilitation system, catering to women experiencing pelvic health issues throughout their lives (and they are “...currently recruiting patients for focus groups and testing to ensure we create a product that works for you – not one that will just sit in a drawer!”). Bloume Health [12] provides a digital, evidence-based care platform for women dealing with persistent pelvic pain. They employ a biopsychosocial approach, a clinically validated method that considers mental health, physical health and social circumstances to manage pelvic pain. Another noteworthy solution is Hormona [13], which offers personalized, data-driven assistance. By tracking symptoms, the app is able to provide tailored tips,advice, and valuable insights into hormonal health.
References
1. Vigil P, Meléndez J, Soto H, Petkovic G, Bernal YA, Molina S. "Chronic Stress and Ovulatory Dysfunction: Implications in Times of COVID-19." *Front Glob Womens Health*. 2022 May 23;3:866104. [DOI: 10.3389/fgwh.2022.866104] [PMID: 35677754] [PMCID: PMC9168655].
2. Schneiderman N, Ironson G, Siegel SD. "Stress and health: psychological, behavioral, and biological determinants." *Annu Rev Clin Psychol*. 2005;1:607-28. [DOI: 10.1146/annurev.clinpsy.1.102803.144141] [PMID: 17716101] [PMCID: PMC2568977].
3. Harvard Health Publishing. "Understanding the Stress Response." [Online] Available at: [https://www.health.harvard.edu/staying-healthy/understanding-the-stress-response]
4. Frontiers for Young Minds. [https://kids.frontiersin.org/articles/10.3389/frym.2017.00071#ref1a]
5. Mayo Clinic. "Stress Management." [Online] Available at: [https://www.mayoclinic.org/healthy-lifestyle/stress-management/in-depth/stress/art-20046037]
6. Podfigurna A, Meczekalski B. "Functional Hypothalamic Amenorrhea: A Stress-Based Disease." *Endocrines*. 2021, 2, 203-211. [DOI: 10.3390/endocrines2030020]
7. Innie [https://www.inne.io/]
9. Wang L, Wang X, Wang W, et al. "Stress and dysmenorrhoea: a population-based prospective study." *Occupational and Environmental Medicine*. 2004;61:1021-1026.
9. Regain. "Can Stress Cause Spotting?" [Online] Available at: [https://www.regain.us/advice/general/can-stress-cause-spotting/]
10. Moon AI. [https://www.moonai.app/]
11. Hyivy. [https://hyivy.com/]
12. Bloume Health. [https://www.bloumehealth.com/]
13. Hormona. [https://www.hormona.io/]
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