Until recently, clinical research almost entirely ignored changes in heart rate throughout the menstrual cycle. Since hormonal fluctuations could influence study outcomes, females of reproductive age have been excluded from cardiovascular research. But over the past few years, with the understanding that male and female physiology is different, preliminary research presents fascinating insights on the relationship between the menstrual cycle and various physical and emotional phenomena.
The hormone estrogen protects the female heart through several mechanisms, the best known of which is through enhanced flexibility and a relaxation of the blood vessels. We also know that among females of menopausal age, who experience reduced estrogen levels, there is an increased incidence of cardiovascular morbidity, nearly equal to that among males. But hormonal influence is not limited only to estrogen. The female endocrine system also includes progesterone, LH, FSH, testosterone, and aldosterone.
The effect of hormonal fluctuations throughout the menstrual cycle on the heart
Evidence increasingly suggests that the heart responds to hormonal fluctuations that take place throughout the month among females of reproductive age. To understand the relationship between the menstrual cycle and the heart’s electrical activity, we first need to understand some basic terminology:
The menstrual cycle is divided into two phases: the follicular phase and the luteal phase. The follicular phase begins with menstruation and ends in ovulation, while the luteal phase begins with ovulation and ends with menstruation. The follicular phase is characterized by high estrogen levels (specifically estradiol, one form of estrogen) and low progesterone levels. After ovulation, the beginning of the luteal phase is marked by a decline in estrogen and spike in progesterone. At the end of the luteal phase progesterone levels drop while estrogen levels remain low, and menstruation occurs.
The well-established and common electrocardiogram test, or ECG, provides information on the physiological state of the heart. One of the ECG’s most important components is the QT interval, which indicates the time between when the heart’s ventricles begin to contract and when they relax, the action that pumps blood from the heart to elsewhere in the body. A short QT interval is typically associated with high heart rate, risk of arrhythmia, and even risk of cardiac arrest, while a long QT interval is tied to a low heart rate and arrhythmia.
Several studies have demonstrated a lengthening of the QT interval and a lower heart rate during the follicular phase, which is characterized by high estrogen levels. However, during the luteal phase, which is characterized by high progesterone levels, the QT interval was shown to shorten. The prevailing hypothesis, then, is that estrogen lengthens the QT interval while progesterone as well as testosterone shorten it. An older study even shows that most incidences of arrhythmia among women with occur during the luteal phase. Studies suggest that females of reproductive age should have ECGs on the days between ovulation and menstruation—at the time when the progesterone levels in their blood are high and the estrogen low. The chance to detect an arrhythmia grows during that time. And yet, the risk of torsades de pointes arrhythmia in women with a longer QT interval increases during the follicular phase or post-partum.
Males are not immune to the influence of sex hormones on heart rate, either. Aldosterone, a steroid hormone that affects the body’s electrolyte balance and blood pressure, can also cause a change in heart rate, and lengthen the QT interval among both females and males. FHS, too, appears to slow the heart rate by lengthening the QT interval among both sexes.
The scientific explanation for sex hormones’ effect on heart rate is tied to the expression of ion channels in the ventricles as well as the increased production of nitric oxide, which relaxes the heart muscle. Estrogen reduces the heart rate by suppressing the expression of calcium channels in the heart, and by impacting the activity of the autonomic nervous system. Progesterone affects fluid and electrolyte balance in the body, raising blood pressure through the renin-angiotensin system and indirectly increasing the heart rate.
The effect of hormones on heart rate does not necessarily depend on the concentration of one hormone or another in the blood. Rather, it depends on the ratios and interactions between them; in particular, estrogen, progesterone, FSH, and aldosterone. It appears that hormonal fluctuations—increases and decreases in levels of different hormones—also play a key role.
As we can see, many questions remain unanswered. For instance, what quantitative ratios between hormones elevate the risk of arrhythmia? What role does the nervous system, which shapes the heart, play, and how is it influenced by progesterone and estrogen? Are changes in the emotional state throughout the menstrual cycle the product of shifts in heart activity, or a factor influencing that activity?
Ultimately, the exclusion of females of reproductive age from heart studies has left us with more questions than answers. With that, studies have been published in recent years that shed light on this mystery. The relationship between estrogen and progesterone levels in the blood and heart rate, identified by those studies, calls for several changes and updates in the way medicine treats females of reproductive age in matters related to their heart health:
- ECG’s can be scheduled in coordination with the phase of the menstrual cycle, with preference to the luteal phase (between ovulation and menstruation), where incidences of arrhythmias are higher.
- Understanding the pathophysiology of hormonal processes can explain females’ increased sensitivity to cardiological drugs, and presents new, estrogen- or progesterone-based treatment opportunities.
- When prescribing medications, the influence of progesterone and estrogen on heart rate and on a shortened QT interval must be considered.
- While females of reproductive age constitute a third of the global population, the medical community still does not fully know the influence of sex hormones and the menstrual cycle on heart activity. For their sake, there is a moral obligation to include members of this group in any relevant research.
Inbal Mandler is a medical student in Ben Gurion University of the Negev
