Menstrual Cycle as a Vital Sign
Regular menstrual cycles can indicate balanced hormone levels and reproductive health. In addition, regular cycles are associated with better bone density, cardiovascular health and mental well-being. Conversely, menstrual irregularities can indicate hormonal imbalances, gynecological diseases, or infections. Such irregularities include changes in cycle length, intensity of blood flow or other negative period-related changes, such as cramping – also called dysmenorrhea – or painful periods. These irregularities can signal underlying issues such as polycystic ovary syndrome, which can also be a precursor to diabetes, primary ovarian insufficiency or endometriosis. Irregular menstrual cycles can also lead to osteoporosis or indicate thyroid disease or reproductive organ abnormalities. In turn, these can affect fertility and overall quality of life. Stress, changes in weight or diet, certain medications, and other lifestyle factors can cause temporary changes in the menstrual cycle. For example, absent periods could flag problematic lifestyle factors, such as exercise-induced amenorrhea – meaning lack of periods – or eating disorders such as anorexia and bulimia. As cardiovascular disease is the leading cause of death in women worldwide, we will discuss further how menstrual experiences throughout the reproductive years and beyond can offer critical insights into a person’s well-being.
Emerging Risk Factor for Cardiovascular Disease
Cardiovascular disease is responsible for 35% of deaths in women each year – more than all cancers combined. It can affect women of any age. Yet, cardiovascular in women continues to be seriously understudied, under-recognised, under-diagnosed and under-treated. Variability in menstruation onset, cycles, and duration of phases has only recently been leveraged to explore risk for health outcomes and generate causal hypotheses linking ovarian hormones (estrogen and progesterone) to cardiovascular health and disease.
Regular menstrual cycle length, defined as cycle length between 22 and 34 days, throughout a woman’s reproductive life reflects normal functioning. However, about 20% of women experience long cycles or cycles of varying lengths. An analysis of data for more than 58,000 women over 12 years in the U.K. Biobank found that both short (less than 21 days) or long (more than 35 days) menstrual cycles were associated with the development of cardiovascular disease, heart attack or atrial fibrillation. Indeed, the fact that irregular menstrual cycle length was associated with a 40% higher risk of atrial fibrillation suggests that an irregular menstrual cycle throughout reproductive lifespan may be a previously unrecognized risk factor for atrial fibrillation over time.
It is well known that atrial fibrillation has a more significant impact on women’s morbidity and mortality. Compared to those without atrial fibrillation, women with atrial fibrillation have an approximately three-fold higher risk of suffering a cardiovascular disease-related event (i.e., hospitalization or death) related to arrhythmia. Men have a 1.8-fold higher risk than the general male population. Though significant progress has been made over the last 20 years, the diagnosis and management of atrial fibrillation remains an important clinical issue. Patients may be asymptomatic with insidious onset and the electrocardiograph (ECG) could be atypical in routine medical examinations. Nonspecific ECG changes are more common in women than in men—for example, estrogen-associated ECG changes mimicking ischemia. This may be exacerbated by incorrect placement of the ECG electrodes because of presumed signal reduction by breast tissue. It can potentially be mitigated by ensuring correct positioning using bone landmarks. This can help minimize inaccuracies in the ECG and prevent misdiagnosis.
As the McKinsey Health Institute highlight in The Sate of US women’s heart and health: A path to improved health and financial outcomes report, developing more knowledge around women and heart disease relies on a deeper understanding of biological differences. During the menstrual cycle, estrogen and progesterone levels naturally rise and fall. These changes affect the heart’s electrical activity, sometimes triggering heart palpitations just before or during the monthly period. Furthermore, women go through unique stages of life characterized by fluctuating levels of estrogen (such as puberty and menopause) and additional physiological stress on the body (such as pregnancy).
Estrogen is believed to have a protective effect on the heart playing a role in regulating various metabolic functions, such as lipid levels (amounts of fat) in the blood, inflammatory markers (contributing to damage to vessel walls), and the coagulant system (affecting blood clot formation). Additionally, estrogen is believed to help relax and open up blood vessels throughout the body, allowing for better blood flow. The understanding of biological differences such as these has expanded, but major knowledge gaps still exist. With the increasing prevalence of cardiovascular in women, novel sex-related risk factors should be considered to guide its early prevention, diagnosis, and treatment in women across all stages of life.
These findings point out that women with menstrual cycle dysfunction might have adverse health consequences and highlight the importance of monitoring menstrual cycle characteristics throughout women’s reproductive life and beyond in the prevention of cardiovascular disease and atrial fibrillation among women. As ECG is not a reliable solution for monitoring cardiovascular disease in women, menstrual cycle monitoring with ECG may provide greater diagnostic accuracy as discussed in the next section.
Improve routine health data collection, diagnostics, and treatment algorithms
Accurate identification of high-risk individuals coupled with a successful preventive approach is the preferred strategy for the control of cardiovascular disease. Therefore, the reliability of an objective measurement, such as the ECG, assumes a greater role in the evaluation of the cardiac status. In cardiac medicine, the resting ECG has proved its value as a diagnostic tool for detecting heart disease. Apart from its use in the clinical context, and with the advent of at-home ECG monitoring, the ECG has been employed as a prognostic tool in apparently healthy subjects. The resting ECG permits us to suspect or diagnose a large number of cardiac disorders. Although ECG is widely available and is relatively inexpensive, the sensitivity and especially the specificity rates of the stress ECG are lower in women than in men. This is believed to be related both to the lower workloads achieved by women when corrected for age, and as mentioned earlier, the putative effect of estrogen on the ECG. Thus, women are 5 to 20 times more likely to have a false positive ECG than men. As a result of this lower specificity, the best diagnostic strategy for the detection of cardiovascular disease in women remains controversial.
Assessing menstrual cycle irregularity is an easily scalable tool that can be deployed in multiple health care settings to initiate further and repeated screening, and with further research may help reveal causal pathways. Today, there is increasing interest in tracking menstruation, with millions of people using period and ovulation tracking apps to monitor their monthly cycles. Although it may seem as though the menstrual cycle’s main role is to facilitate pregnancy, this is only part of its purpose. In fact, it is a cornerstone of overall health and well-being throughout the reproductive years and into the menopausal transition. However, continuous monitoring of ovarian hormone levels to provide accurate information in real time to inform ECG is more challenging.
OnaWave Medical’s core technology is a bio-signal – the electrical activity of the slow waves in the uterus recorded by uterine electromyogram (EMG), also known as electro-hysterogram (EHG), which is known to be representative of uterine contractility. Measuring changes in the slow wave activity of the uterus gives an objective measure of not only the regularity of the menstrual cycle but more personalised insight’s into an individual’s hormonal health (as the bio-signal changes in response to estrogen and progesterone). As this data is captured non-invasively using an at-home device capturing not only symptomatic data (cramping, bleeding intensity etc.) but also asymptomatic data (cycle length, hormonal changes as measured by uterine electrical activity etc.), it provides a potential avenue to augment and inform ECG data collection and diagnosis.
Effective guidelines and algorithms rely on a foundation of comprehensive data collection and a balanced representation of women across all age groups and health conditions. Collecting women-specific data in a standardized, easily digestible format should become routine. Learning about menstruation as a vital sign of health can generate personalised insights into not just cardiovascular health but overall health and wellbeing. After all, there is no shortage of data – the average person who menstruates experiences 450 periods in their lifetime. We just need to capture it and act on it.
Discover more about OnaWave Medical
OnaWave Medical are developing a digital biomarker-based risk-stratification platform and associated wearable solutions that can identify pelvic conditions, such as endometriosis, to support clinical decision-making and enhance the delivery of personalized care for the individual. This work is funded by the European Union under the European Innovation Council Transition program (Project EndoSolve).
