Testosterone replacement therapy (TRT) is used to treat men with low testosterone levels. Choosing the right method depends on each person's health, how their body responds to testosterone, and their risk for heart problems. Gels and patches offer more even hormone levels and may carry a lower risk of heart-related symptoms. Similar to injections, this may stimulate the heart, increase metabolism, and raise the heart rate in some people. High doses from overabsorption can still lead to increased heart rate, though this is less common than with injections. The sharp rise in testosterone can sometimes cause an increase in heart rate, especially during the peak. After an injection, testosterone levels in the blood can rise quickly. This is because existing estrogen levels do not prohibit testosterone levels from rising if you are taking HRT, meaning someone can still get the desired physical and emotional changes from T without an estrogen blocker. Masculinizing HRT usually consists of taking a form of testosterone therapy, the most common of which is an injectable synthetic form of the hormone called testosterone cypionate. Monitoring changes in HRV over time is a great way to not only improve your health but also a novel response when on testosterone replacement therapy. This improved autonomic function reduces cardiovascular risk by fostering a more resilient and adaptable heart. TRT boosts HRV by normalizing testosterone levels, enhancing the balance between the body's stress and relaxation responses. It is believed that TRT may improve HRV levels by directly enhancing cardiovascular health in addition to changes in the autonomic nervous system. In a clinical trial, men were provided 250mg of testosterone replacement therapy (TRT) for 9 weeks, and HRV was assessed with a 24-hour Holter monitor. Cumulative incidence did not differ between the 2 groups.47 These studies led the American Health Association, the American Cancer Society, and the American Urological Association48 to issue a joint statement in 2010, declaring it to be "appropriate to state that there may be a relation between ADT and cardiovascular risk." Soon after, the FDA also mandated the addition of warnings of increased risk of diabetes and CVD as a result of GnRH agonist use in men with prostate cancer.49 The effects of the artificial lowering of testosterone levels by ADT on an individual's overall health has also been studied extensively. Adequately powered randomized clinical trials designed to assess cardiovascular events are required to definitively determine the effect of testosterone therapy on cardiovascular risk. In contrast to these studies, others have reported a protective effect of testosterone therapy on cardiovascular health. The indication of an association between testosterone therapy and risk for adverse cardiovascular events prompted the US Food and Drug Administration (FDA) to issue a safety warning on testosterone therapy for older men, which was followed by a reduction in testosterone prescriptions.30 The safety warning cautioned against the use of testosterone therapy for aging-related decline and reinforced the current approval of testosterone products for hypogonadal men only.30 However, it is important to note that the methodology and reliability of the aforementioned studies have since been questioned. All participants had previous experience with aerobic (9.1 ± 3.4 years) and resistance training (5.9 ± 3.4 years). Eight recreationally active men and women ages 18–35 were recruited for participation in the present study. Currently, the relationship between the ANS and hormonal balance throughout a multimodality exercise program such as high-intensity functional training (HIFT) is not well understood (11). Due to the complex integration of these systems, to date, no single definitive marker can accurately quantify the fitness and fatigue responses to training (4, 6). As the ANS and HPA work in tandem to respond to disrupted homeostatic processes, measuring stress responses from exercise training via the highly coordinated and interconnected ANS and HPA pathways (45, 48). Exercise-induced hormonal responses are controlled by the hypothalamic-pituitary adrenal axis (HPA), a key regulator of homeostasis, which responds to stress by triggering a series of endocrine changes resulting in the release of testosterone (T) and cortisol (C) (26). Recently, there has been accumulating evidence indicating that sex hormones may have a significant impact on the cardiac rhythm. Given the correlation of physical activity with various cardiovascular risk factors, it is unclear whether any observed associations with testosterone level are directly or indirectly mediated by one or more of the risk factors. The relationship between physical activity and testosterone levels is still unclear. As inflammation is a known risk factor for atherosclerosis and CVD, there has been interest in exploring the effects of testosterone on inflammation. These effects depend on the person’s age, health, and how testosterone is given. Thicker blood can raise blood pressure and may increase the risk of blood clots. TRT is a hormone therapy used to treat low testosterone in men with confirmed hypogonadism. Missing data were treated using pairwise (i.e., available case) analyses and the resulting number of observations for each specific analysis is reported in the results section. A model comparison approach was employed using the Akaike Information Criterion (AIC) goodness-of-fit metric to identify an alternative model that best explained the data for each relationship of interest (25). Additionally, participants were asked to not engage in any exercise training outside of the intervention. All training days included an instructor-led warm-up; a brief movement preparation period, daily workout, and a cool-down lasting a total of approximately one hour in duration. Specific details of the structure and components of each daily training session can be found in Table A1 within the previously published work by Crawford et al. (8). All training sessions were conducted as group exercise within the Functional Intensity Training Laboratory (FIT Lab) at Kansas State University. Among these, sex hormones, and particularly testosterone, seem to play an important role in arrhythmogenesis. Preclinical studies showed that pretreatment with testosterone of rat hearts exposed to ischemia decreased arrhythmias, as effectively as it was the case after estradiol administration (47). This is in line with increasing evidence suggesting that the differences exerted by sex hormones may not be uniform across the heart. Certain changes can help lower the chance of heart problems and reduce symptoms like a fast heartbeat. There are several steps that can help reduce risks and improve safety for patients using TRT. Doctors make these decisions based on individual health history, test results, and how the person feels. If someone notices a fast or irregular heartbeat after starting TRT, a doctor may recommend further heart testing. These tools help doctors track how the body responds to testosterone. After starting therapy, it is important to continue monitoring.
