A negative view of testosterone’s impact on cardiovascular disease comes from the observation that high-density lipoprotein (HDL) cholesterol levels decrease in patients on oral testosterone therapy, or when taken in supraphysiological doses by athletes (29,30). Human observational studies, however, have shown no associations between high testosterone levels and coronary artery disease, and testosterone has been shown to dilate the coronary arteries both in vitro and in vivo. Measuring testosterone levels in populations, while useful, is different from measuring hypogonadal symptoms. In this review, hypogonadism will be used as a general term to refer to any state characterised by low blood testosterone levels. A key consideration for any physician is to understand the clinical significance of low testosterone levels and how hypogonadal men are likely to benefit from testosterone replacement therapy.
With such a high prevalence, hypogonadism is a candidate for the most common complication of male type 2 diabetes. However, clinicians have often not related low testosterone concentrations to clinical hypogonadism. In fact, those with low testosterone were 40% more likely to die (all-cause mortality) than those with higher levels.
Before making any decision, you need comprehensive bloodwork — not just total testosterone. The quality-of-life impact of severely low testosterone — depression, fatigue, loss of muscle mass, cognitive decline, sexual dysfunction — is too significant to leave unaddressed for philosophical reasons. Primary hypogonadism — where the testicles themselves are damaged or dysfunctional — won’t respond adequately to stimulation approaches. Once you introduce exogenous testosterone, your hypothalamic-pituitary-gonadal (HPG) axis recognizes the external supply and downregulates its own production.
This is known as hypogonadotropic hypogonadism because there are low levels of hormones. Healthcare providers consider testosterone levels below 300 nanograms per deciliter (ng/dL) as low in adults. Low testosterone (male hypogonadism) is a condition in which your testicles don’t produce enough testosterone. It is therefore surprising that young men are evaluated for testosterone deficiency with the same cutoff of 300 ng/dL that was developed from samples of older men. If your LH is low-normal with low testosterone, there’s significant room for improvement through HPG axis stimulation. The panel should include total testosterone, free testosterone (calculated or measured by equilibrium dialysis), SHBG, LH, FSH, estradiol, DHEA-S, prolactin, thyroid panel (TSH, free T3, free T4), CBC (hematocrit and hemoglobin), and a metabolic panel.
But hormone replacement therapy helps improve sex drive, symptoms of depression and energy levels. Most males with symptoms of low testosterone don’t have a problem with their pituitary glands or testicles. Primary hypogonadism happens when your testicles aren’t making normal levels of testosterone. Providers call it male hypogonadism when you have symptoms along with these low levels. Accordingly, age-specific normative values and cutoffs should be integrated into the evaluation of young men presenting with testosterone deficiency. Age-specific cutoffs for low testosterone levels were 409, 413, 359, 352, and 350 ng/dL, respectively.