How often have women been told by their doctor that their menstrual cycle symptoms are simply "normal"? For many, this answer is unsatisfying, and according to Dr. Mirjam Kruijt, it reflects a deeper issue: we lack a scientific framework to define what normal truly means for women.
Dr. Mirjam Kruijt, a postdoctoral researcher with a background in clinical chemistry and a focus on endocrinology, works to improve laboratory diagnostics for women. She studies how hormonal measurements can better reflect the biological realities of women’s lives, centering her research on the question: what are ‘normal’ lab values for women across different life phases?
A gap in women’s health research
Despite women making up half the population, there is still little research into women’s health and the specific changes that occur during different life stages. For much of their lives, women experience cyclical hormonal fluctuations of estrogens, progesterone, and other hormones that control the menstrual cycle. Yet, many questions about this stage of life remain unanswered.
As Mirjam notes, “It is striking how little we know about women’s health, and specifically, menstrual cycles. The broader impact of hormonal fluctuations on daily life is often underestimated.” Much of what is known is based on relatively small studies.
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The importance of women-specific reference intervals
Reference intervals define what is considered normal in blood tests and guide diagnoses and treatment. Traditionally, these intervals are established by grouping populations by sex and age. However, age-based groupings for women rarely capture the profound hormonal shifts across their reproductive life, and women’s hormonal changes and life stages are often overlooked.
To address this, Mirjam and Prof. Annemieke Heijboer are developing women-specific reference intervals, especially for hormones involved in the menstrual cycle. While cycle-phase-specific reference intervals exist for some hormones like estradiol, many hormonally driven markers lack tailored standards. “Women differ biologically from men in fundamental ways. Hormonal status does not align strictly with chronological age, so stratifying by age might work for men but often falls short for women.”
Without tailored standards, women may be told their symptoms are normal or dismissed, not because they are necessarily healthy, but because the scientific framework to interpret their results is incomplete.
The challenge of menstrual cycles in research
A main challenge is the menstrual cycle itself. Hormone levels such as estrogen and progesterone can fluctuate significantly. “We know the menstrual cycle is different for every woman, and even for the same woman, each cycle can be different. But as far as I know, there aren’t any studies yet that really look at those differences within one woman.” This variability makes it difficult to define a single normal range. Designing studies around menstrual cycles is complex and requires frequent sampling, with uncertainty about whether patterns are consistent across cycles. “This is difficult to investigate because the study protocol is hard to design; you need many measurement points.” Yet, as Mirjam notes,
If we never start [studying it], we will never fully understand the menstrual cycle."
To capture these hormonal dynamics, she uses liquid chromatography-mass spectrometry (LC-MS), a highly sensitive measurement technique, instead of traditional immunoassays commonly used in clinical labs. While immunoassays are practical, they lack the precision to detect subtle hormonal differences relevant to women's health. LC-MS can detect very small changes in concentration, making previously invisible differences measurable.
From the lab to everyday life
Understanding the basic physiology of the menstrual cycle is only the first step. As Mirjam points out, “next to studying medication effects or disease interactions, it is also important to study the basic physiology of the cycle itself, which is often overlooked these days.” Establishing reliable, women-specific reference intervals creates a foundation for more precise diagnostics and treatment strategies.
In the long term, Mirjam aims for research in women to reflect biological reality. “Women-sensitive research means not only including women in studies, but also properly accounting for the biological variables specific to women.” This requires tools that can accurately determine where a woman is in her cycle, enabling studies that reflect biological reality rather than defaulting to age-specific categories.
She also highlights broader societal implications. Beyond the clinic, workplaces and daily schedules could be better designed with the hormonal realities of the menstrual cycle and menopause in mind — for instance, by considering how energy levels, concentration, or physical symptoms fluctuate across the month. “It would be valuable if daily life, like work, will be better aligned with the menstrual cycle and menopause.” Building strong scientific evidence around these fluctuations is essential to inform policies that acknowledge and accommodate women's hormonal biology, rather than expecting a one-size-fits-all standard of productivity and performance.
Authors
Barbara Verhaar
Núria Farràs Solé
Rosalie Martens