Heart Health

Matters of the heart — female sex hormones and cardiovascular health | by Luzia Trobinger | Nov, 2021

My heart was too big for my body, so I let it go
Anis Mojgani

Thought about your heart health lately? Chances are that if you’re fit, young and healthy, the answer isno’. As with most things that are essential, we only learn to appreciate what our heart does for us when it’s already too late. When it comes to heart health though, leaving it too late may spell disaster.

Given its central role in physiological functioning, it is no surprise that the heart has also found its way into everyday language: To take heart, to be heartless, to suffer heartbreak — it almost sounds as if we feel more through our hearts than through our brains. Arguably, this is quite natural: When we are stressed, scared or excited, one of the first things we notice is a change in our heart beat. This is more tangible than the release of hormones and neurotransmitters (although, technically, the change in heart beat is caused by these substances) because we can feel and intuitively understand it.

So what does any of this have to do with women’s health and female sex hormones? Well, we’re about to find out.

Tracking heart beats

Before we can start talking about sex differences in heart functioning, we need to take a look at how this is measured in the first place. One of the most important ways of assessing how well the heart is doing its job is the Electrocardiogram, or ECG. Like the name suggests, the ECG picks up the electrical activity associated with heart beats. More precisely, it offers a way of tracking changes in the electrical potentials of cardiac cells that spread through the heart in a wave-like manner as it contracts (Becker, 2006).

Figure 1: The ECG waveform. Image source: Zheng et al., 2020

The ECG waveform consists of a series of negative and positive inflections, which are labelled using the letters P to U. This waveform allows clinicians to visually track how the wave of potential changes moves through the different areas of the heart as it contracts. The inflections themselves and the time intervals between them represent important clinical markers that provide insight into heart health and functioning. Interestingly, some of these markers are known to exhibit sex-specific differences. For instance, the R-R interval — that is, the time between successive R peaks — tends to be shorter in women. In other words, women tend to have higher resting heart rates than men. The T wave is also known to exhibit sex-specific differences in terms of both shape and timing. Finally, the duration of the QT interval, which represents ventricular activation and recovery, differs between the sexes (Ravens, 2018, Macfarlane, 2018). Among these differences, the QT interval in particular has received a great deal of attention from researchers and clinicians due to its association with irregular heartbeats (cardiac arrhythmias). In the next section, we’re going to take a closer look at this association and its significance in the context of sex-specific approaches to treatment.

The QT interval — your heart as a beating drum

Although the reasons for sex-specific differences in QT intervals are not completely understood yet, there are many clues that suggest sex hormones might be involved. Firstly, QT interval differences do not manifest until after puberty, which is associated with a surge in sex hormones. At this point in development, the QT interval of males shortens, which has been linked increasing testosterone levels. In adulthood, sex differences gradually become less pronounced as the drop in testosterone in males causes the QT interval to lengthen again (Vink et al., 2018). The role of female sex hormones on the other hand is less clear due to the complex interaction between oestrogen and progesterone. While animal studies have shown that oestrogen leads to a lengthening of the QT interval (Sedlak et al., 2012), human studies do not necessarily support this finding. As levels of sex hormones vary throughout the menstrual cycle, researchers have also studied whether these changes affect the duration of QT intervals. The results are somewhat mixed, with most studies indicating that in healthy females, no clear QT interval differences exist across the different menstrual cycle phases. However, those studies that have found differences report shorter QT interval duration in the second as compared to the first half of the cycle (Burke et al., 1997, Endres et al., 2004).

While the above may be interesting, it might be difficult to see how any of this is crucial for heart health. In most cases, it probably isn’t, but problems can arise when the QT interval is prolonged beyond what is considered normal. This might occur with pre-existing genetic conditions, such as ‘Long QT Syndrome’ (LQTS)(Engelstein, 2003), or as a result of taking prescription drugs (Li et al., 2013). In such cases, women may be greater risk of developing dangerous cardiac arrhythmias such as ‘Torsade de Pointes’, which can lead to ventricular fibrillation, fainting and sudden death (Cohagan and Brandis, 2021).

From changing beats to broken hearts — octopus fishing and stress

Another heart condition that seems to affect females more frequently than males is Takotsubo cardiomyopathy, also known as ‘broken heart syndrome’.

Figure 2: Source: Original image by Bilal Saeed, M.D., University of Toledo Medical Center, Toledo, Ohio (A), and Satoshi Kurisu, M.D., Hiroshima City Hospital, Hiroshima, Japan (B), via: https://www.health.harvard.edu/heart-health/takotsubo-cardiomyopathy-broken-heart-syndrome

The condition’s name stems from the characteristic temporary ‘ballooning’ of the heart it causes, which renders its shape similar to that of traditional Japanese octopus fishing containers. The reason why it is also referred to as ‘broken heart syndrome’ may be even more obvious: Takotsubo cardiomyopathy is believed to be triggered by strong emotional or physical stressors (Amin et al., 2020). What is particularly interesting about this disease in a women’s health context is that it predominantly affects post-menopausal women. Since oestrogen has protective effects on heart health, this may be associated with the drop in levels of this hormone following menopause (Kuo et al., 2010, Pelliccia et al., 2017).

Conclusions

So, there you have it — a very brief journey into heart health, from a women’s health perspective. Perhaps I’ve scared you, just a bit? If you’re off now to get an ECG, that’s probably not a bad idea — we could all benefit from being a bit more conscious of what our heart does for us, and how to keep it in tip-top shape. Just don’t let it stress you to the point where it starts resembling a Japanese octopus trap.

References

AMIN, H. Z., AMIN, L. Z. & PRADIPTA, A. 2020. Takotsubo Cardiomyopathy: A Brief Review. J Med Life, 13, 3–7.

BECKER, D. E. 2006. Fundamentals of electrocardiography interpretation. Anesth Prog, 53, 53–63; quiz 64.

BURKE, J. H., EHLERT, F. A., KRUSE, J. T., PARKER, M. A., GOLDBERGER, J. J. & KADISH, A. H. 1997. Gender-specific differences in the QT interval and the effect of autonomic tone and menstrual cycle in healthy adults. Am J Cardiol, 79, 178–81.

COHAGAN, B. & BRANDIS, D. 2021. Torsade de Pointes. StatPearls. Treasure Island (FL).

ENDRES, S., MAYUGA, K. A., CRISTOFARO, A., TANEJA, T., GOLDBERGER, J. J. & KADISH, A. H. 2004. Menstrual cycle and ST height. Ann Noninvasive Electrocardiol, 9, 121–6.

ENGELSTEIN, E. D. 2003. Long QT syndrome: a preventable cause of sudden death in women. Curr Womens Health Rep, 3, 126–34.

KUO, B. T., CHOUBEY, R. & NOVARO, G. M. 2010. Reduced estrogen in menopause may predispose women to takotsubo cardiomyopathy. Gend Med, 7, 71–7.

LI, G., CHENG, G., WU, J., ZHOU, X., LIU, P. & SUN, C. 2013. Drug-induced long QT syndrome in women. Adv Ther, 30, 793–802.

MACFARLANE, P. W. 2018. The Influence of Age and Sex on the Electrocardiogram. Adv Exp Med Biol, 1065, 93–106.

PELLICCIA, F., KASKI, J. C., CREA, F. & CAMICI, P. G. 2017. Pathophysiology of Takotsubo Syndrome. Circulation, 135, 2426–2441.

RAVENS, U. 2018. Sex differences in cardiac electrophysiology. Can J Physiol Pharmacol, 96, 985–990.

SEDLAK, T., SHUFELT, C., IRIBARREN, C. & MERZ, C. N. 2012. Sex hormones and the QT interval: a review. J Womens Health (Larchmt), 21, 933–41.

VINK, A. S., CLUR, S. B., WILDE, A. A. M. & BLOM, N. A. 2018. Effect of age and gender on the QTc-interval in healthy individuals and patients with long-QT syndrome. Trends Cardiovasc Med, 28, 64–75.

ZHENG, J., ZHANG, J., DANIOKO, S., YAO, H., GUO, H. & RAKOVSKI, C. 2020. A 12-lead electrocardiogram database for arrhythmia research covering more than 10,000 patients. Sci Data, 7, 48.


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