As inflammation is a known risk factor for atherosclerosis and CVD, there has been interest in exploring the effects of testosterone on inflammation. Adiponectin is an adipocytokine of which the levels are inversely related to cardiovascular risk. Increased stimulation of leptin receptors on Leydig cells can attenuate LH stimulation and thus lower testosterone production.86 The use of aromatase inhibitors or DHT has resulted in the attenuation of the hormone's beneficial effects, indicating an important role of E2. Men who watch sexually explicit films also report increased motivation and competitiveness, and decreased exhaustion. Men who watch a sexually explicit movie have an average increase of 35% in testosterone, peaking at 60–90 minutes after the end of the film, but no increase is seen in men who watch sexually neutral films. In non-human primates, it may be that testosterone in puberty stimulates sexual arousal, which allows the primate to increasingly seek out sexual experiences with females and thus creates a sexual preference for females. Sexual arousal and masturbation in women produce small increases in testosterone concentrations. 2020 guidelines from the American College of Physicians support the discussion of testosterone treatment in adult men with age-related low levels of testosterone who have sexual dysfunction. It is unclear if the use of testosterone for low levels due to aging is beneficial or harmful. In September 2024, an international European Group of Experts in the Field of TTh (European Expert Panel for Testosterone Research PaTeR) convened in London to discuss and draft this position statement on the TRAVERSE study and its impact. A secondary CV end point was the first occurrence of any component of the composite of primary end point and coronary revascularization. The TRAVERSE trial offered critical insights into the CV safety of TTh for men with hypogonadism. Participants received either placebo or T gel (a 1.62% gel), titrated to maintain physiological serum T levels (350–750 ng/dL) for a mean of 22 months. TRAVERSE enrolled 5246, 45–80‐year‐old men (mean age 63.3 years; 47% older than 65 years of age) with functional hypogonadism as above mentioned. It employed a large‐scale, randomized, double‐blind, placebo‐controlled approach.7 Enrolling men with clinically confirmed hypogonadism, the trial aimed to assess the incidence of MACE—including myocardial infarction, stroke, and CV death—over an extended follow‐up. The TRAVERSE trial stands as a landmark study in TTh, particularly concerning CV safety. Some biological effects of testosterone may result from its aromatization to estradiol and subsequent interaction with the estrogen receptor. Testosterone (T) is the principal male sex hormone, secreted primarily by the testes and transported in the blood by the carrier protein, sex-hormone binding globulin (SHBG). Testosterone replacement therapy (TRT) has been shown to improve myocardial ischemia in men with CAD, improve exercise capacity in patients with CHF, and improve serum glucose levels, HbA1c, and insulin resistance in men with diabetes and prediabetes. Studies have reported a reduced CV risk with higher endogenous T concentration, improvement of known CV risk factors with T therapy, and reduced mortality in T-deficient men who underwent T replacement therapy versus untreated men. In the randomized, placebo-controlled T4DM trial involving men with dysglycemia, testosterone treatment on a background of lifestyle intervention reduced risk of type 2 diabetes mellitus after 2 years. In contrast, normalization of circulating T levels with transdermal TRT did not affect HDL-c levels in older, hypogonadal men . The HDL-c lowering effect appears variable with age, dose, and route of T administration and it is most striking with high-dose, oral therapy. Notably, substantial decreases in HDL-c concentrations have mainly been demonstrated with supraphysiologic doses of androgens administered to young men and the use of anabolic androgens among athletes . Nonetheless, this HDL-c lowering effect has raised concern regarding the cardiovascular safety of TRT. However, the authors did not observe an association between T concentrations and HDL-c or LDL-c levels.
