Category: Science

The Luteal Lowdown: Hormones, Mood, and the Science of Cycles

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The Luteal Lowdown: Hormones, Mood, and the Science of Cycles

Asmita Adya
March 2025

The time between ovulation and menstruation, known as the luteal phase, is often marked by emotional variability and instability in menstruating individuals. Feelings of negative affect, physical discomfort, and general malaise commonly plague individuals as the uterine lining thickens in preparation for pregnancy or, if fertilization does not occur, menstruation.

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The Biological Basis

During ovulation, the hypothalamus secretes a surge of gonadotropin-releasing hormone (GnRH) to the pituitary gland. In response, the anterior pituitary gland releases luteinizing hormone (LH), which stimulates the gonads, leading to the luteal phase. During this phase, progesterone reaches its peak concentration. Prior to this, during the follicular phase, the anterior pituitary secretes follicle-stimulating hormone (FSH), which leads to a peak in estradiol levels. Estrogen, an ovarian hormone critical to well-being, plays a key role in mood regulation. Low estrogen levels have been implicated in increased vulnerability to depression and impaired emotional regulation. Thus, during the luteal phase, when estrogen levels decline, studies have shown that women exhibit more frequent negative affect and a heightened stress response [1]. Additionally, estradiol contributes to reward processing, as it has a stimulatory, activational effect and interacts with dopamine [2].

However, this raises the question: does the likelihood of experiencing negative affect stem solely from decreased estrogen, or does progesterone itself play a direct role? The lack of conclusive clinical evidence remains a significant barrier to answering this question.

The Implications of Hormonal Contraceptives

Hormonal contraceptives and their effects may serve as a clue. In the 1960s, ‘the pill’ revolutionized hormonal contraception in the United States. The pill typically contains ethinyl estradiol or mestranol (synthetic estrogen) and progestin (synthetic progesterone), though some formulations are progestin-only. The androgenic properties of different progestins vary, ranging from strongly anti-androgenic to strongly androgenic. The typical dose ranges from 0.1 to 3.0 mg per pill.

Although the exact mechanism of action is not fully understood, hormonal contraceptives are thought to “mimic pregnancy.” During pregnancy, endogenous estrogen and progesterone levels rise, exerting negative feedback on hypothalamic GnRH secretion. Similarly, contraceptives prevent pregnancy by mimicking these negative feedback effects. Exogenous hormones from the pill inhibit GnRH release, thereby suppressing FSH and LH secretion from the anterior pituitary. As a result, follicular development is inhibited due to reduced FSH, and ovulation does not occur due to the absence of an LH surge. While the extent of hormonal suppression varies by contraceptive formulation, this chronic suppression prevents pregnancy. Women using hormonal contraceptives typically have endogenous hormone concentrations equivalent to or lower than those observed in the early follicular phase of naturally cycling women. Although hormone levels usually return to baseline within months after discontinuation, some studies suggest lower levels persist for years [3].

Why does this matter? Women who use hormonal contraceptives often report negative side effects such as mood changes, diminished libido, and exacerbation of underlying psychiatric conditions [4]. Furthermore, contraceptives have been implicated in structural and functional changes in brain regions involved in affective and reward processing [5]. These effects highlight the profound impact of exogenous hormone manipulation. Since many contraceptive methods rely on progestin as a primary component, it is plausible that progesterone plays a key role in negative affect, though further research is needed to establish a definitive correlation.

Plausible Physical and Mental Effects

Possible physical and mental effects of elevated progesterone include fatigue, negative affect, and mood fluctuations [6]. These effects can impair emotional and physical functioning and exacerbate underlying psychiatric conditions. These hormonal fluctuations occur independently of individual control; menstruation follows its cyclical course, only ceasing at menopause. So, never dismiss a woman as “too hormonal”—she is simply functioning as nature intended.

References 

[1] Albert, K. M., & Newhouse, P. A. (2019). Estrogen, stress, and depression: Cognitive and biological interactions. Annual Review of Clinical Psychology, 15, 399–423. https://doi.org/10.1146/annurev-clinpsy-050718-095557.

[2] Beltz, A. M., & Moser, J. S. (Year). Ovarian hormones: A long overlooked but critical contributor to cognitive brain structures and function. Annals of the New York Academy of Sciences, Special Issue: The Year in Cognitive Neuroscience.

[3] Taylor, C. M., Pritschet, L., & Jacobs, E. G. (2021). The scientific body of knowledge – whose body does it serve? A spotlight on oral contraceptives and women’s health factors in neuroimaging. Frontiers in Neuroendocrinology, 60, 100874. https://doi.org/10.1016/j.yfrne.2020.100874

[4] Martell, S., Marini, C., Kondas, C. A., & Deutch, A. B. (2023). Psychological side effects of hormonal contraception: A disconnect between patients and providers. Journal of Women’s Health, 32(1), 45-53. https://doi.org/10.1089/jwh.2022.0467

[5] Brønnick, M. K., Økland, I., Graugaard, C., & Brønnick, K. K. (2020). The effects of hormonal contraceptives on the brain: A systematic review of neuroimaging studies. Frontiers in Psychology, 11, Article 556577. https://doi.org/10.3389/fpsyg.2020.556577

[6] Standeven, L. R., McEvoy, K. O., & Osborne, L. M. (2020). Progesterone, reproduction, and psychiatric illness. Best Practice & Research Clinical Obstetrics & Gynaecology, 69, 108–126. https://doi.org/10.1016/j.bpobgyn.2020.06.001

Exercise Arises as a Key Strategy to Reduce Falls in Polypharmacy for Elderly Women 

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Exercise Arises as a Key Strategy to Reduce Falls in Polypharmacy for Elderly Women 

Steven Shin
March 2025

Among the elderly, a condition known as polypharmacy became one of the most significant public health concerns. Recent research by the University of Eastern Finland and Kuopio University Hospital has highlighted the effectiveness of structured exercise in reducing fall risks in elderly women.[3] The study underscores the importance of incorporating physical activity into healthcare strategies aimed at fall prevention. 

The Impact of Polypharmacy on Physical Function 

Polypharmacy, the concurrent use of four or more medications, has been linked to deteriorating physical fitness and an increased risk of falls.[3] As older adults frequently require multiple medications to manage chronic conditions, this association is concerning. However, while previous studies have suggested a direct correlation between polypharmacy and higher fall risks, the recent findings challenge this notion by demonstrating that targeted exercise programs can mitigate these risks.[2] 

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The Kuopio Fall Prevention Study: A Game-Changer 

The study analyzed data from the Kuopio Fall Prevention Study, a randomized controlled trial involving 914 women with a median age of 76.5 years. Participants were randomly assigned to either an exercise group or a control group. The exercise program consisted of twice-weekly guided exercise sessions, including tai chi and circuit training, for the first six months. Afterward, participants were granted free access to the city’s recreational sports facilities for an additional six months.[3] Fitness assessments were conducted at baseline, one year, and two years into the study. Medication use was tracked through self-reported questionnaires, and falls were monitored for approximately two years via biweekly SMS queries.[3] 

The results of the study were compelling. Among participants with polypharmacy, those engaged in the exercise intervention exhibited a 29% lower risk of falls compared to the control group taking zero to one medications.[1] Additionally, while 1,380 falls were recorded during the study period—739 of which resulted in injury or pain and 63 in fractures—polypharmacy did not increase the likelihood of falls in the control group.[3] Moreover, fitness tests revealed that participants using zero to one medications generally performed better than those with polypharmacy. However, individuals with the poorest physical fitness at the outset of the study

benefited the most from the intervention.[2] This finding suggests that physical activity can significantly enhance functional ability, even among those with limited mobility. 

Patient Outcomes and Future Directions 

The study’s findings reinforce the need to integrate structured exercise programs into standard geriatric care. Healthcare professionals should actively encourage physical activity, particularly for elderly patients managing multiple medications. The benefits of tai chi and circuit training extend beyond fall prevention; they contribute to improved balance, strength, and overall quality of life.[4] 

Additionally, previous research has linked polypharmacy to reduced physical function, further emphasizing the importance of targeted exercise interventions. For example, a systematic review  found a reciprocal relationship between polypharmacy and diminished physical performance in older adults. Similarly, findings from the Medical Research Council National Survey of Health and Development indicated that polypharmacy at ages 60 to 69 was associated with poorer cognitive and physical capabilities, even when accounting for chronic disease burden.[1] 

Given the significant benefits demonstrated by the Kuopio Fall Prevention Study, exercise should be a cornerstone of fall prevention strategies for elderly individuals, particularly those with polypharmacy. Encouraging participation in structured physical activity programs may not only reduce fall risk but also enhance overall physical well-being. Future research should continue exploring how tailored interventions can further optimize outcomes for older adults managing multiple medications. 

References 

[1] Corbett, A., Stevens, T., Aarsland, D., Day, S., & Ballard, C. (2018). Systematic review of polypharmacy and cognitive impairment in older adults. Journal of the American Geriatrics Society, 66(6), 1071-1080. https://doi.org/10.1111/jgs.15374 

[2] Gutiérrez-Valencia, M., Aldaz-Herce, P., Lacalle-Fabo, E., Larrayoz-Sola, B., Martínez-Velilla, N., & Fernández de Retana-Marín, A. (2018). Relationship between polypharmacy and functional capacity in older adults: A systematic review. Aging & Disease, 9(6), 1014-1022. https://doi.org/10.14336/AD.2018.0611 

[3] Vilpunaho, T., Kröger, H., Honkanen, R., Koivumaa-Honkanen, H., Sirola, J., Kuvaja-Köllner, V., … & Rikkonen, T. (2019). Randomised controlled trial (RCT) study design for a large-scale municipal fall prevention exercise programme in community-living older

women: study protocol for the Kuopio Fall Prevention Study (KFPS). BMJ open, 9(6), e028716. https://doi.org/10.1136/bmjopen-2018-028716 [4] Sherrington, C., Fairhall, N. J., Wallbank, G. K., Tiedemann, A., Michaleff, Z. A., Howard, K., & Clemson, L. (2017). Exercise for preventing falls in older people living in the community: An abridged Cochrane systematic review. British Journal of Sports Medicine, 51(24), 1750-1758. https://doi.org/10.1136/bjsports-2017-098425

Fertility Preservation: What is oocyte cryopreservation and why has it increased in popularity?   

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Fertility Preservation: What is oocyte cryopreservation and why has it increased in popularity?   

Chaimaa Riad
February 2025

What is Oocyte Cryopreservation?

Oocyte cryopreservation is also known as egg freezing. This is a procedure in which a woman’s eggs are retrieved, frozen and stored to preserve her ability to conceive later in life, while she is still of reproductive age.[1] The eggs are specifically extracted from the body before their fertilization. Once they are ready to be used, the eggs undergo a thawing process to be transferred into the uterus and become fertilized for pregnancy.[1] Oocyte cryopreservation is considered a form of preventative healthcare.[2]

The first successful pregnancy recorded via egg freezing was in 1986. [3] Oocyte cryopreservation began to combat possible infertility in women with medical conditions like cancer, in which chemotherapy and pelvic radiation could damage their reproductive organs, or autoimmune conditions such as systemic lupus erythematosus. [4] However, there has been a large increase in the number of egg freezing procedures in the last six years for more social reasons. An increasing number of women have decided to do this procedure for financial, professional, or simply personal reasons. Studies have shown that many women believed that becoming pregnant before 35 would negatively impact their careers. [5] Women have been especially inclined to do this procedure with improvements in medical technology and even the use of AI in improving the freezing and thawing process for optimal fertilization. [4]

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There are multiple risks of oocyte cryopreservation. Short-term adverse effects include general symptoms such as nausea, headache, irritability, chest pain, pelvic pain, and oliguria (decreased urine output). [2] Additionally, there are increased risks that come with assisted reproductive techniques (ART), which include preterm birth. This is one of the more severe risks, which also carries the potential risk of cerebral palsy. [5] Furthermore, women who undergo oocyte cryopreservation are more likely to be older. As women age, the complications of pregnancy, such as preeclampsia, gestational diabetes, ectopic pregnancy, and the need for a cesarean section tend to increase. [5]

It is also important to consider both the emotional and financial impacts of this procedure on women. This process is invasive and often requires women to undergo multiple cycles of egg freezing.[3] These procedures can cost anywhere between $5,000-$10,000 per cycle. [4]

It is crucial for women to connect to a team of specialists who can thoroughly explain the benefits, drawbacks, and risks of the procedure. Additionally, counselors are essential to support women throughout the process. [2] In essence, egg freezing allows women the opportunity to have more flexibility in their family planning. There are ongoing advancements in reproductive medicine that will allow women to preserve fertility based on their own timeline. The most crucial factors to consider when deciding to freeze eggs would be the financial and emotional costs, as well as the possible risks, both long term and short term.

References:

[1] Egg freezing. UCLA Health. (n.d.). https://www.uclahealth.org/medical-services/obgyn/fertility/egg-freezing

[2] Katsani, D., Paraschou, N., Panagouli, E., Tsarna, E., Sergentanis, T. N., Vlahos, N., & Tsitsika, A. (2024, January 10). Social Egg freezing-a trend or modern reality?. Journal of clinical medicine. https://pmc.ncbi.nlm.nih.gov/articles/PMC10816669/

[3] Walker, Z., Lanes, A., & Ginsburg, E. (2022, January 7). Oocyte cryopreservation review: Outcomes of medical oocyte cryopreservation and planned oocyte cryopreservation – reproductive biology and endocrinology. BioMed Central. https://rbej.biomedcentral.com/articles/10.1186/s12958-021-00884-0

[4] Dimitriadis, I., (2024, February 20). Freezing Eggs: Advances in Fertility Treatment. Mass General Brigham. https://www.massgeneralbrigham.org/en/about/newsroom/articles/what-is-cryopreservation#:~:text=In%201984%2C%20the%20first%20baby,longer%20considered%20an%20experimental%20procedure. 

[5] Varlas, V. N., Bors, R. G., Albu, D., Penes, O. N., Nasui, B. A., Mehedintu, C., & Pop, A. L. (2021, July 30). Social freezing: Pressing pause on fertility. International journal of environmental research and public health. https://pmc.ncbi.nlm.nih.gov/articles/PMC8345795/

Understanding the Gender Differences in Post-Traumatic Stress Disorder 

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Understanding the Gender Differences in Post-Traumatic Stress Disorder 

Helena Huynh
October 2024

Post-Traumatic Stress Disorder (PTSD) is a debilitating mental health condition typically following exposure to a traumatic event, with symptoms impacting day-to-day functioning, causing the person to re-experience their traumatic event, and affecting overall cognition and mood.[1] According to the World Health Organization, over half of the global population–a shocking 70% of people–will experience a potentially traumatic event in their lives, with a minority of that population (5.6%) going on to develop PTSD.[2] However, women are much more likely to develop PTSD, with lifetime prevalence rates being almost three times as frequent for women than for men.[3] Why does this happen? 

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Types of Trauma 

Women are much more likely to experience high-impact trauma, including sexual-related trauma and sexual assault. The CDC National Intimate Partner and Sexual Violence Survey conducted in 2010 found that 18.3% of women in the United States experienced rape at some point in their lives.[3] That equates to an alarming rate of about 1 in 5 women. Exposure to sexual violence are associated with higher rates of PTSD.[2] Additionally, women are also more likely to experience sexual abuse at younger ages compared to men.[3] Trauma in early childhood has a strong impact on overall neurobiological development[4] and also serves as a risk factor increasing the likelihood of developing PTSD.[1] 

Physiological Responses 

Prior research has found several differences when it comes to psychobiological reactions to PTSD[4]. For one, hormonal responses can potentially play a role in regulating trauma responses. The hypothalamic-pituitary-adrenal (HPA) axis, a neuroendocrine system within the body that regulates responses to stress, has been found to be more sensitive to stress and trauma. Additionally, studies have found that testosterone may possibly work to reduce HPA reactivity.[5] On top of that, studies have found that women with PTSD are more likely to experience a reduced fear-extinction during the mid-luteal phase of their menstrual cycle, when oestradiol and progesterone levels are lowest.[5] These hormones are related to cognitive-emotional processes relating to PTSD, and in trauma-exposed women without PTSD, researchers actually found the opposite result.[5]

Understanding PTSD Symptoms and Comorbidities 

When it comes to PTSD symptom expression, males and females tend to experience PTSD in a similar way.[3] A study found that male and female veterans were about equally likely to report different PTSD symptoms on the PTSD Checklist[3], a self-report measure looking at PTSD symptoms. However, when it comes to comorbidities, women are much more likely to experience internalizing disorders, including mood and anxiety-related disorders. Men, on the other hand, were much more likely to experience externalizing disorders, including substance abuse.[3] 

Overall, previous research has established a number of differences in the development and prevalence of PTSD in males and females. Given that much of the early research surrounding our knowledge of PTSD revolves around male war veterans[3], we must continue adding to the literature. Increasing our understanding of why these gender differences develop can inform targeted interventions to ultimately help those who need it. 

References 

[1] U.S. Department of Health and Human Services. (n.d.). Post-Traumatic Stress Disorder. National Institute of Mental Health. 

https://www.nimh.nih.gov/health/publications/post-traumatic-stress-disorder-ptsd

[2] World Health Organization. (2024, May 27). Post-traumatic stress disorder. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/post-traumatic-stress-disorder 

[3] Vogt, D. (2007, January 1). Va.gov: Veterans Affairs. Research on Women, Trauma and PTSD. https://www.ptsd.va.gov/professional/treat/specific/ptsd_research_women.asp#four 

[4] Olff, M. (2017). Sex and gender differences in post-traumatic stress disorder: An update. European Journal of Psychotraumatology, 8(sup4). 

https://doi.org/10.1080/20008198.2017.1351204

[5] Christiansen, D. M., & Berke, E. T. (2020). Gender- and sex-based contributors to sex differences in PTSD. Current Psychiatry Reports, 22(4). 

https://doi.org/10.1007/s11920-020-1140-y