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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.

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 

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] 

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

Does Menopause Occurring Later In Life Lead To Better Vascular Health?

Julia Palka
February 2025

Menopause is the dreaded cycle of hormonal imbalance, hot flashes, and discomfort. Women of all ages know it will manifest in various stages, with different symptoms and degrees of abruptness. However, first, we must all face the monthly gift of menstruation, but new findings show that if your body’s natural clock is a little late to the initial onset of menopausal symptoms (55 or older), you may have a significantly decreased risk of cardiovascular events!

According to newly published research from the University of Colorado at Boulder, Women who go through menopause at later ages in life have healthier blood vessels than women who go through it earlier. The research, published in the American Heart Association journal Circulation Research¹ arrived just in time for February, which is Women’s Heart Health Month. The findings can help pave the way to new research and advancements in therapies and treatments aimed at reducing heart disease, the leading cause of death in women.

The new insights show that females who stop menstruating at 55 or older are suggested to have a significantly lower risk of heart attacks and cardiovascular events during their postmenopausal years over women who stop menstruation below 55 years of age. To support this claim, studies write that women 55 or older are actually 20% less likely to develop ailments like heart disease than those 54 and younger. Sanna Darvish, a PhD candidate in the Department of Integrative Physiology at the University of Colorado at Boulder is part of a study assessing the vascular health of 92 women and how well their brachial artery dilates with increased blood flow. Darvish and her colleagues also measured the women’s mitochondrial health in relation to the cells lining the women’s blood vessels. The mitochondria, which is considered the powerhouse of energy in the human body, helped the researchers determine what molecules were present in the women’s blood streams.

The study proved that all the postmenopausal women had significantly worse function in their arteries than women who had not yet experienced menopause³. This is because, as women age, they produce less nitric oxide, a chemical compound that helps prevent plaque build up and stiffness as it dilates the blood vessels. The mitochondria in the cells lining the blood vessels also become more dysfunctional with age and generate free radicals; highly reactive and unstable molecules produced naturally by the human body. 

When women go through menopause, the age related decline in cardiovascular health is accelerated. However, the 10% of women who experience a late onset of menopausal symptoms are seemingly less affected by this predicament. Darvish’s study found that vascular function was only 24% worse in the women who experienced menopause later in life compared to the premenopausal women. In contrast those in the normal onset stage had a 51% decline in vascular health. The differences between the groups occurred 5 years or more after the women went through menopause, where remarkably the late onset group had a reported  44% better vascular function than the normal onset group. 

The success of maintaining better vascular health in the late onset group was linked to the women’s better functioning of mitochondria, which decreased the amount of free radicals produced. The circulating blood in the late onset group also generated more favorable levels of different lipid metabolites in their blood. Darvash and her team will next study how early onset menopause might impact heart health and how certain nutritional supplements marketed as targeting free radicals in the blood vessels may reduce heart disease in women at higher risks. Future research is still necessary to solidify the gaps between the studies currently published, and how and if all women will experience the same prognosis. John Hopkins Medicine says;  If cardiovascular disease runs strongly in the family, it’s also important that you see a cardiologist to further assess the likelihood of having cardiovascular disease and to optimize treatment. ² In summary, the important research provided from the University of Colorado at Boulder suggests that women who experience menopause at 55 or older have healthier blood vessels and a 20% lower risk of heart disease compared to those with earlier menopause. This is linked to better mitochondrial function, reduced free radicals, and improved vascular health, highlighting potential new avenues for cardiovascular disease prevention in women. 

References:

Darvish, S., et al. (2025). Preservation of vascular endothelial function in late-onset postmenopausal women. Circulation Research. https://doi.org/10.1161/circresaha.124.325639

Hopkins Medicine. (n.d.). Menopause and the cardiovascular system. Retrieved February 14, 2025, from https://www.hopkinsmedicine.org/health/conditions-and-diseases/menopause-and-the-cardiovascular-system#:~:text=Plus%2C%20studies%20that%20have%20followed,normal%20age%20(around%2050)

News-Medical. (2025, February 4). Late menopause linked to better vascular health in women. News-Medical. Retrieved from https://www.news-medical.net/news/20250204/Late-menopause-linked-to-better-vascular-health-in-women.aspx

Understanding Organ Prolapse: Causes, Symptoms, and Treatment 

Steven Shin
February 2025

Pregnancy is thought of as a joyful experience, but for some women, it can bring life-threatening health challenges. One of the challenges is Peripartum Cardiomyopathy (PPCM), a form of heart failure that occurs during the final stages of pregnancy or in the postpartum period.¹ Recent research has revealed new information in the diagnosis, treatment, and management of PPCM to help women worldwide. 

What is PPCM? 

PPCM affects approximately 1 in 1,500 to 2,000 pregnancies globally with nonspecific symptoms like shortness of breath, exhaustion, and swelling¹. Crucial interventions or treatment are delayed because these symptoms are often dismissed as normal parts of pregnancy. In PPCM, the heart’s left ventricle weakens and impairs its function. While early treatment results in recovery, undiagnosed or untreated PPCM can lead to persistent heart failure or death³. 

Research showed that the hormone prolactin, commonly associated with breastfeeding, plays a significant role in PPCM. In affected women, prolactin is broken down into a harmful material that damages blood vessels and leads to heart failure. Researchers at the Hannover Medical  School found that the drug bromocriptine which is traditionally used to suppress lactation can block this harmful effect and promote heart recovery when used for heart failure therapy³. The safety and efficacy of bromocriptine showed that it can significantly improve maternal cardiac health without increasing the risk of complications such as blood clots². A study based on a global PPCM registry of 500+ patients supports bromocriptine as a recommended treatment for PPCM². 

New Hope for Subsequent Pregnancies 

Historically, women recovering from PPCM were advised against future pregnancies due to the high risk of relapse or worsening heart function. However, new research suggests a more optimistic outlook. A study based on data from the Global PPCM Registry found that even women with mild residual heart failure could safely carry another pregnancy under medical  supervision². 

This represents a major shift that allows women to expand their families without undue fear. Key to this success is interdisciplinary care by cardiologists, obstetricians, and maternal-fetal medicine specialists who ensure both mother and child are monitored closely¹.

PPCM’s impact is not uniform across the globe. A 20-year population study emphasized significant disparities in PPCM incidence and discussed higher rates reported in Black populations compared to White populations¹. These findings underscore the urgent need for targeted healthcare strategies and awareness campaigns in disproportionately affected communities. 

Access to specialized care also varies widely between high-income and low-income regions. In many low-resource settings, limited awareness means that PPCM often goes undetected until it progresses to a critical stage³. International registries and collaborations are vital in bridging this gap by providing data and resources to improve diagnosis and treatment worldwide³. 

Patient Outcomes and Future Directions 

A study published in the Journal of the American Heart Association reported that 6% of PPCM  patients die within six months of diagnosis, with 42% of these deaths attributed to heart failure and 30% to sudden cardiac arrest³. However, timely diagnosis and intervention can significantly reduce these figures. Advanced imaging techniques, the use of cardiac biomarkers, and continued research into genetic predispositions are important steps to improve outcomes¹. 

Additionally, researchers are exploring how to predict PPCM risk in future pregnancies more accurately. Early identification of at-risk women could allow for tailored monitoring and preventative therapies that potentially reduce the burden of this condition². Thanks to research and the dedication of specialized care teams, women diagnosed with PPCM now have access to better treatments and a brighter future. From innovative therapies like bromocriptine to improved management of subsequent pregnancies, advancements in PPCM care are empowering women to navigate motherhood against all odds. Despite the challenges, with early diagnosis and interdisciplinary care, affected women can embrace both recovery and the possibility of growing their families. 

Reference 

[1] Arany, Z., & Elkayam, U. (2016). Peripartum cardiomyopathy. Circulation, 133(14), 1397– 1409. https://doi.org/10.1161/CIRCULATIONAHA.116.018094 

[2] Sliwa, K., Bauersachs, J., van der Meer, P., Petrie, M. C., Hilfiker-Kleiner, D., Hamdan, R.,  & Seferovic, P. (2025). Pregnancies in women after peripartum cardiomyopathy: The global  European Society of Cardiology EuroObservational Research Programme Peri-Partum  Cardiomyopathy Registry. European Heart Journal. https://doi.org/10.1093/eurheartj/ehaf006

[3] Van der Meer, P., Sliwa, K., Bauersachs, J., Hilfiker-Kleiner, D., & Petrie, M. C. (2024).  Bromocriptine treatment and outcomes in peripartum cardiomyopathy: The EORP PPCM  registry. European Heart Journal. https://doi.org/10.1093/eurheartj/ehae559

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]

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/