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But recent studies suggest it’s not just about symptoms. That’s called testosterone deficiency (sometimes called hypogonadism).2 This is normal, but in some men, the drop becomes steep enough to trigger symptoms like low libido, fatigue, muscle loss, and irritability. Only a small amount (around 1–2%) circulates as "free testosterone," which is the form that’s active and available to your body’s tissues, including the heart and blood vessels.2 In the bloodstream, most testosterone is bound to a protein called SHBG (sex hormone-binding globulin).
There are no large long-term, placebo-controlled, randomized clinical trials to provide definitive conclusions about TRT and CV risk.
What's more, testosterone plays other important roles in health and disease that may surprise you. Another unanswered question regards the possible role for screening men with coronary artery disease for hypogonadism. About half the group had a history of cardiovascular disease and the rest had significant cardiovascular risk factors. The first was the concern that it might promote coronary heart disease and acute coronary syndromes. Historically, there have been two main concerns regarding testosterone therapy in middle aged and older men.
For women, testosterone therapy has a much narrower evidence-based use case, and treatment should remain within the female physiologic range rather than approach male-style replacement targets (Mulhall et al., Journal of Urology, 2018; Davis et al., Journal of Sexual Medicine, 2019). For men, replacement therapy is meant to restore testosterone into a normal physiologic range in the setting of confirmed deficiency. Late-onset male hypogonadism happens when the decline in testosterone levels is linked to general aging and/or age-related conditions, particularly obesity and Type 2 diabetes. Classical male hypogonadism is when low testosterone levels are due to an underlying medical condition or damage to your testicles, pituitary gland or hypothalamus. To allow the therapy to take full effect, healthcare providers typically wait 30 days after you start TRT to check your testosterone levels.
Emerging evidence indicates that congestive heart failure (CHF) is more than just a syndrome affecting a failing heart. Additional research is needed to further evaluate the association between low T levels and CAD severity. In their 2013 review, Oskui and colleagues reported on evidence suggesting that men with lower levels of endogenous T are more likely to develop CAD during their lifetimes.11 The severity of CAD has also been investigated as a function of serum T concentrations. Populations at high risk for TD include men with CHF, type 2 diabetes, obesity, chronic obstructive pulmonary disorder, HIV, and chronic opioid use.7 However, there is no specific value that reliably distinguishes men who experience signs and symptoms of TD from those who do not nor those who will likely respond to treatment. Only 1% to 2% of testosterone circulates in blood as unbound "free" testosterone, but this fraction exhibits the most potent biological activity.
However, the wisdom and effectiveness of testosterone treatment to improve sexual function or cognitive function among postmenopausal women is unclear. As a result, there is some controversy about which men should be treated with supplemental testosterone. Testosterone may stimulate the prostate gland and prostate cancer to grow. The most common example is probably prostate cancer. There are times when low testosterone is not such a bad thing. For example, problem with function of pituitary gland or adrenal glands may lead to reduced testosterone production.
Coronary heart disease is the biggest underlying cause of heart failure in the Western world. The risk of death was greater for men in the lowest baseline quartile of both total and bioavailable testosterone compared with those in the highest quartile. More modern studies have been more consistent in design and definition, especially when the primary hypothesis was related to the question of the link between testosterone blood level and CAD. Some studies measured total testosterone level, others used free or bioavailable testosterone or used calculated free-androgen index.
Despite some heterogeneity, the majority of studies that investigated androgen levels in men with coronary disease, showed that testosterone levels were significantly lower in men with coronary disease than in matched controls. Moreover, androgen replacement therapy has positive effects on coronary risk factor profile and acts as a vasodilator demonstrating potential, because it is an anti-ischaemic agent. This means that the same behaviors that help support normal testosterone levels also promote a healthier heart. Dr. Nasir points out that only men who need the therapy should be considered for it, but it's also important to understand a man's risk of heart disease before prescribing testosterone therapy. More evidence is needed to clearly define the link between low T and heart disease, but most cardiologists agree that taking steps to keep testosterone levels healthy is important for promoting good heart health. In fact, in one study of men with heart failure, those with low testosterone had a higher risk of dying than those with normal levels.1
A recently published meta-analysis of 19 prospective studies40 investigated some of the previously found heterogeneity in the results and design of studies in this area. It is possible to measure bioavailable testosterone by the method of Tremblay and Dube,41 but the assay is labour-intensive and time-consuming and, as such, is mainly restricted to the research laboratory. It could be argued that bioavailable testosterone quantification would provide a more accurate measurement. Testosterone circulates partly bound to albumin (weakly) and partly bound to sex hormone binding globulin (strongly) and only a small fraction is free. The authors concluded that low testosterone may act as an early warning sign for the development of the metabolic syndrome, and provide an opportunity for early (primary) intervention.38