The ten eligible studies were observational and analytical studies published between 2019 and 2024. Figure 1 shows the selection procedure for eligible studies and the reasons for exclusion. After screening, ten studies were deemed appropriate for qualitative analysis. We evaluated the quality of the included studies using the Newcastle–Ottawa scale (Ottawa Hospital Research Institute, 2024). We performed qualitative analyses and comparisons without conducting quantitative analyses because statistical analyses and presentations differed across the studies. Intracellular Ca2+ dysregulation also is implicated in the pathogenesis of diseases such as myocardial ischemia and arrhythmias , where a decrease in testosterone may influence disease expression. For example, the observation that contractions and Ca2+ transients decline in low-testosterone states may promote heart failure with reduced ejection fraction . The idea that testosterone regulates the cardiac action potential and Ca2+ homeostasis at the level of the individual heart cell has a number of important clinical implications. Second, the amount of SR Ca2+ available for release is reduced by GDX, and the magnitude of Ca2+ sparks may decline. However, the optimal amount of testosterone is far from clear. As a result, there is some controversy about which men should be treated with supplemental testosterone. Although testosterone may make prostate cancer grow, it is not clear that testosterone treatment actually causes cancer. Men taking testosterone replacement must be carefully monitored for prostate cancer. Testosterone may stimulate the prostate gland and prostate cancer to grow. There are times when low testosterone is not such a bad thing. Affected women may experience low libido, reduced bone strength, poor concentration or depression. Therefore, the role of androgens in regulating the intestinal barrier and microenvironment may affect and govern the gut microbiome. This is consistent with the findings of Matsushita et al. (2022b), who discovered a more significant number of gut microbes in the high-testosterone group than in the low-testosterone group. Furthermore, some studies have reported only phyla rather than specific microbiome species (Jie et al., 2021; Matsushita et al., 2022b; Shin et al., 2019). Several microbiome types were consistently reported across studies, such as the phylums Bacteroidetes and Firmicutes (Jie et al., 2021; Koliada et al., 2021; Matsushita et al., 2022b; Mayneris-Perxachs et al., 2020; Shin et al., 2019; Wilmanski et al., 2019). All the included studies had different microbiomes and statistical outputs; therefore, we could not continue the quantitative analysis or meta-analysis. The prevalence of the gut microbiome may be influenced by comorbidities, obesity, dietary patterns, and lifestyle factors. Koliada et al. (2021) reported similar findings, in which the type and number of specific microbiomes differed between men and women. These findings suggest that testosterone increases inward Ca2+ currents and that this effect is attenuated by GDX. In support of this, peak L- and T-type Ca2+ currents are enhanced in neonatal rat cardiomyocytes chronically exposed to testosterone (24–30 h in culture), an effect blocked by the nuclear androgen receptor antagonist, flutamide 92,93. However, a few studies have investigated the effect of GDX on L-type Ca2+ current (ICa-L), as shown in Table 3. There is general agreement that GDX has no effect on transient outward current (ITO), steady state K+ current (ISS) and inward rectifier K+ current (IK1), or on the expression of proteins or mRNA levels linked to these currents 38,74.
