Impact of Sex on CV Adaptations to Exercise: Key Points

Petek BJ, Chung EH, Kim JH, et al.
Impact of Sex on Cardiovascular Adaptations to Exercise: JACC Review Topic of the Week. J Am Coll Cardiol 2023;82:1030-1038.

The following are key points to remember from a review about the impact of sex on cardiovascular (CV) adaptations to exercise:

  1. Exercise is associated with CV adaptations, which differ by sex and are observed for both athletes and the general population. This review by Petek et al., examines the effect of sex on CV adaptations and outcomes, including the impact of sex hormones on exercise performance. This review also outlines critical areas in need of further research.
  2. Knowledge gaps stem from underrepresentation of female participants in athletic-based research, despite significant increases in the number of female athletes. In particular, preparticipation screening of athletes is unequally distributed in competitive sports.
  3. Exercise training is associated with CV remodeling. Female athletes have smaller absolute left ventricular (LV) and right ventricular (RV) cavity dimensions as well as smaller LV wall thickness, and LV mass compared to males. However, when indexing to body surface area, female athletes no longer have smaller LV and RV cavity sizes versus male athletes, but still have smaller average LV mass. Overall, it appears that female hearts do not necessarily remodel ‘less’ but rather differently in response to exercise by incompletely understood mechanisms. Decreased peak exercise systolic blood pressure (BP) in female athletes may impart a diminished pressure load on the heart and induce less hypertrophy relative to chamber enlargement. Alternatively, higher testosterone levels in males may lead to more LV hypertrophy.
  4. In general, females have shorter QRS intervals and lower QRS voltage on electrocardiography (ECG) compared to males. Although data on athletes that compares sexes are limited, it is likely that differences in chest size, breast tissue, and cardiac size are contributors to ECG patterns, which appear less remodeled in female athletes. Although female athletes exhibit fewer training-related ECG changes, they are three times more likely to have “abnormal” anterior T-wave inversions than males.
  5. Female athletes have a lower risk of sudden cardiac death compared to males, which is a similar finding in the general population. Male athletes appear to be predisposed to the development of coronary artery calcium (CAC) that is not observed in female athletes. The lack of excess CAC in female master athletes may be due to estrogen-mediated protection from coronary artery disease over midlife exercise exposure. Male master athletes also have a higher prevalence of myocardial fibrosis on cardiac magnetic resonance imaging. Possible mechanisms for less fibrosis in females include lower exercise BP and lower testosterone, given testosterone potentiates myocardial inflammation.
  6. While moderate physical activity is associated with a reduced incidence of atrial fibrillation (AF) in both sexes, high doses of vigorous physical activity have been associated with a three- to five-fold increase in AF in males, which is not seen in females. However, female athletes with a large lifetime exercise exposure may be underrepresented among available studies.
  7. Male athletes typically outperform female athletes by 10-35% starting around puberty. Lower testosterone in female athletes is associated with several differences in the CV determinants of exercise performance. Relevant to endurance sport, peak oxygen uptake is lower in females even accounting for smaller body size and is related to females’ lower exercise stroke volume, blood volume, and hemoglobin. Females’ muscle fiber composition and metabolism confer higher fatigue resistance and better short-term recovery.
  8. The impact of variation in estradiol and progesterone over the menstrual cycle or the different phases of oral contraceptive pills (OCPs) on exercise performance is incompletely understood. Existing studies suggest that exercise performance is not substantially impacted by the menstrual or OCP phase, and that use of OCPs overall has at most trivial detrimental impact.
  9. The use of exogenous testosterone and other androgens has been most extensively studied in males, but this also appears to improve lean mass and exercise performance in females. Higher endogenous androgens in female athletes also appear to be associated with better performance in several specific exercise disciplines.
  10. Emerging data suggest that several years of gender-affirming hormonal therapy (GAHT) in transgender females results in declines in running speed and muscular strength, but both typically remain higher than in cisgender females. The effect of GAHT on performance among transgender males is not well-defined.

Clinical Topics: Arrhythmias and Clinical EP, Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Prevention, Sports and Exercise Cardiology, Atherosclerotic Disease (CAD/PAD), SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure, Exercise

Keywords: Androgens, Athletes, Atrial Fibrillation, Blood Pressure, Contraceptive Agents, Coronary Artery Disease, Death, Sudden, Cardiac, Electrocardiography, Estrogens, Exercise, Fibrosis, Heart Failure, Hemoglobins, Hypertrophy, Left Ventricular, Inflammation, Menstrual Cycle, Primary Prevention, Progesterone, Puberty, Ventricular Remodeling, Sports, Testosterone, Transgender Persons, Women

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