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Now, new research has confirmed testosterone replacement therapy doesn’t increase the risk of heart attack or stroke. For years, physicians debated testosterone replacement therapy’s impact on cardiovascular health. No definitive statement can be made regarding the effects of testosterone replacement therapy on the levels of either LDL or HDL cholesterol.11 Lower-than-normal testosterone levels typically only cause symptoms in males.
A relatively small number of men experience immediate side effects of testosterone supplementation, such as acne, disturbed breathing while sleeping (worsening sleep apnea), breast swelling or tenderness, or swelling in the ankles. Men can often feel a big difference when they stop therapy because their body's testosterone production has not yet recovered. General fatigue and malaise has so many other causes, and when most men get a blood test, the result is a normal testosterone level.
Contrasting with the female menopause, the male ‘andropause' often results in rather non-specific symptoms, including reduced libido, fatigue, weakness, depression, dry skin and poor concentration, symptoms which are often regarded simply as a natural part of the aging process. Similar results were found more recently in men receiving oestrogens for treatment of prostatic carcinoma.14, 15 The effects of sex hormones are, therefore, gender-specific and their roles are more sophisticated than first perceived. "Despite some of the unknowns, what we know for sure is that low T can be a warning sign for heart disease."
However, none of the individual prostate-related adverse events significantly differed between groups, including incident prostate cancer, which showed no difference between the TRT group and placebo.34 In 2016, Boyle et al. reported results of a meta-analysis on prostate cancer in TRT trials. The TRT group had a significantly greater incidence of all prostate-related adverse events, with a pooled odds ratio of 1.78 (95% CI, 1.07–2.95). In this study, fat biopsies were also used to show that the expression of insulin-signaling genes (IR-ß, IRS-1, AKT-2, and GLUT 4) was lower in men with TD and diabetes. Although T was shown to significantly improve exercise capacity, none of the studies found a significant change in LVEF, although NYHA class was shown to improve in two of the studies. Toma et al. performed a meta-analysis of these studies and discovered that there was a net pooled improvement of 0.52 standard deviations in exercise capacity among those who received TRT. Given emerging evidence from basic-science models, it is reasonable to assume that TRT positively affects the exercise capacity of CHF patients via a peripheral mechanism, such as promoting increased type I muscle fiber proliferation.27 Four authors have investigated the effects of TRT on exercise capacity in men with CHF. The evidence regarding the association between baseline T levels and lipid subfractions is conflicting; therefore, there is no clear consensus among the numerous authors who have investigated this association.
The next challenge in this interesting field of work will be to perform large randomized controlled trials of testosterone replacement in men with coronary artery disease. More importantly, once hypogonadism is diagnosed, replacement therapy has a beneficial anti-ischaemic effect, along with beneficial effects on lipids, glucose metabolism, inflammatory cytokine profiles, lean body mass, blood clotting profiles and patient well-being. However, to our knowledge, there is no evidence supporting a causative role of testosterone supplementation on the levels in the physiological normal range, with the risk of developing prostate cancer.

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