A new review article from researchers at Universidade Estadual Paulista (Unesp) highlights the complex interplay between hormonal fluctuations and the female immune system-a relationship often elaborate by inconsistencies in research methodology. the study, published in Maturitas, underscores the need for more precise tracking of the menstrual cycle and hormonal phases in studies involving women, as simplified methods may yield inconclusive results.Researchers are now preparing follow-up studies in Brazil aimed at better understanding how exercise can potentially mitigate the effects of thes hormonal shifts on immunity and overall health.
Imunologia
Hormonal fluctuations impact women’s immunity, but exercise may help mitigate the effect
A review article published by researchers at Unesp suggests that hormonal shifts affect the immune system, but the extent of that impact is still being studied due to inconsistencies in research methods.
Imunologia
Hormonal fluctuations impact women’s immunity, but exercise may help mitigate the effect
A review article published by researchers at Unesp suggests that hormonal shifts affect the immune system, but the extent of that impact is still being studied due to inconsistencies in research methods.
Inconsistencies in methods used to control for sex hormones lead to diverse and inconclusive results, according to a researcher (image: Rawpixel.com/Freepik)
Maria Fernanda Ziegler | Agência FAPESP – Throughout a woman’s life, hormonal changes significantly influence the immune system. Fluctuations in estrogen and progesterone impact immune and inflammatory responses at a cellular level. For example, the days leading up to menstruation, known as the luteal phase, often see heightened inflammatory activity, while the decline in sex hormones during menopause promotes a pro-inflammatory state. Understanding these connections is crucial for addressing women’s health needs.
While knowledge of the relationship between hormonal fluctuations and the immune system has grown, scientists haven’t reached a consensus on the precise impact of the menstrual cycle, perimenopause, and menopause on immunity. A key reason for this uncertainty, according to a recent review, is the inadequate characterization of the menstrual cycle in many studies.
Researchers at the Universidade Estadual Paulista (Unesp) in Presidente Prudente investigated this issue in a review supported by FAPESP. They found that many studies rely on simplified methods, such as using mobile apps, to determine a woman’s phase in the menstrual cycle.
“According to the leading international guideline, simplified methods only tell us if a person is menstruating, and that’s not enough for scientific studies,” explains Barbara de Moura Antunes, the researcher who led the study. “A combination of methods is needed to identify whether someone is in the follicular, ovulatory, or luteal phase, as each stage involves variations in progesterone and estrogen—hormones with distinct implications for the immune system.”
This methodological gap, Antunes explains, has led to conflicting results in research on the topic. “The inconsistency and differences in methods used to control for sex hormones result in a wide range of outcomes, and consequently, inconclusive findings. This doesn’t fill gaps in knowledge; it simply creates more confusion and misinformation,” she says.
Antunes believes the lack of consensus stems from a historical issue: the insufficient inclusion of female-specific considerations in scientific studies. “For many years, clinical trials and animal experiments were conducted only on men or male animals. However, the female body experiences constant hormonal fluctuations, unlike the male body, which maintains more stable levels throughout life. Ignoring this dynamic compromises our understanding of women’s health,” she states.
The review article published in the journal Maturitas is opening new avenues of research to investigate this relationship and the impact of physical exercise throughout a woman’s life.
The research team is now preparing for a new phase: an original study with Brazilian women designed to address these gaps. “Does the level of physical activity or fitness, combined with hormonal fluctuations, impact the inflammatory response? Is there an ideal type of exercise when it comes to immunity? Should training variables be adjusted over time? What is the impact of these hormonal oscillations on sedentary, active, and trained women? These are all questions we intend to investigate to expand our understanding of the health of half the population,” the researcher told Agência FAPESP.
The research will be conducted in two phases. The first will analyze women of reproductive age (18 to 35 years), categorized by their cardiorespiratory fitness levels, to investigate how different phases of the menstrual cycle modulate the inflammatory response. The second phase will include women in pre-menopause, menopause, and post-menopause, also divided by fitness levels, to assess the effects of hormonal decline.
Antunes explains that current knowledge suggests that during a woman’s reproductive years, levels of estradiol (a specific type of estrogen) and progesterone fluctuate throughout the menstrual cycle, directly influencing the immune system. These hormonal fluctuations affect immune cells, such as monocytes and lymphocytes, which have receptors for sex hormones and consequently respond to this stimulation by producing cytokines—signaling proteins that regulate inflammation.
She notes that from menstruation to ovulation (the end of the follicular phase), estrogen levels are high and progesterone levels are low, promoting an anti-inflammatory response and improved physical and cognitive performance. However, during the luteal phase, preceding menstruation, the situation reverses: estrogen falls and progesterone rises, making the body more susceptible to inflammation, fatigue, and delayed muscle recovery.
Studies conducted by the group show that the follicular phase has a higher presence of anti-inflammatory and health-protective markers (such as IL-1ra and HDL-c), while the luteal phase is dominated by pro-inflammatory markers (such as TNF-α and IL-6).
“With aging, especially during menopause, there is a sharp decline in estradiol, which is associated with various health problems, such as cardiovascular disease, loss of muscle mass [sarcopenia], osteoporosis, and changes in lipid metabolism.”
The analyzed studies also showed that physical exercise, even without reversing the decline in estradiol, acts as a powerful tool to prevent and treat the negative effects of aging. “It improves the production of anti-inflammatory cytokines, strengthens muscles and bones, and helps maintain a woman’s overall health at all stages of life.”
The article Immunometabolic insights into women’s health across all ages can be read at: www.sciencedirect.com/science/article/abs/pii/S0378512225005274.
