IPM Take
Low testosterone in a young man can easily become a hormone story. The new evidence suggests it may sometimes be better understood as a metabolic one.
Researchers studying men aged 18 to 35 found that lower total testosterone and sex hormone-binding globulin, or SHBG, clustered with several familiar cardiovascular risk factors, including larger waist circumference, higher BMI, higher triglycerides, higher blood pressure and lower HDL cholesterol.
But the relationship is not straightforward enough to justify turning testosterone into another cardiovascular screening biomarker, and certainly not into a reason to prescribe testosterone for prevention.
Once researchers adjusted for age, BMI and waist circumference, many of the associations weakened. Total testosterone remained independently associated with HDL cholesterol, while SHBG remained associated with HDL and blood pressure. Calculated free testosterone showed no independent association with the metabolic variables included in those adjusted models.
That pattern points directly toward the central problem: obesity may lower testosterone and SHBG, while low testosterone may also contribute to adverse body composition. Cross-sectional data cannot tell which direction dominates.
For policy and clinical practice, that ambiguity matters.
A low testosterone result may still be useful, not because it independently predicts a heart attack or proves endocrine disease, but because it could prompt clinicians to look harder for abdominal obesity, dyslipidaemia, hypertension, insulin resistance and other modifiable risks that can begin accumulating decades before cardiovascular disease becomes visible.
The important message is not “treat the testosterone.”
It is “do not let a low testosterone result distract from the metabolic picture around it.”
Executive Summary
Researchers at Federico II University of Naples examined the relationship between androgenic profile and metabolic cardiovascular risk in a single-centre cohort of 659 men aged 18 to 35 years.
The study assessed total testosterone, SHBG and calculated free testosterone alongside weight, BMI, waist circumference, fasting glucose, lipids and blood pressure.
Across progressively higher total testosterone levels, BMI, waist circumference, obesity prevalence, triglycerides and diastolic blood pressure generally fell, while HDL cholesterol increased. Higher SHBG showed a similar pattern, with lower weight, BMI, waist circumference, triglycerides and blood pressure and higher HDL.
The researchers also used 12 nmol/L, or approximately 350 ng/dL, as a threshold for biochemical testosterone deficiency. Overall, 16.8% of the cohort fell at or below that threshold.
Men in this lower-testosterone group had a mean BMI of 25.9 kg/m² compared with 24.2 kg/m² among men above the threshold and a mean waist circumference of 91.9 cm versus 86.4 cm. Generalised obesity was present in 14.4% versus 3.7%, while abdominal obesity was present in 13.9% versus 4.9%.
The relationship also ran in the opposite direction. Among men classified as overweight or obese, 24.6% had testosterone at or below the study threshold compared with 13.9% of normal-weight men.
However, the study measured exposure and risk factors at essentially the same point in time. It therefore cannot determine whether lower testosterone contributed to adverse metabolic health, whether excess adiposity suppressed testosterone, or whether both processes were operating simultaneously.
The study also did not diagnose clinical hypogonadism. Testosterone deficiency was based on a single morning total testosterone measurement without repeated biochemical confirmation or systematic assessment of sexual and other symptoms, which remain essential to the clinical diagnosis.
Why it matters
- HTA bodies: The findings reinforce the distinction between an associated biomarker and a validated intervention target. Low testosterone may help identify a metabolically higher-risk phenotype, but this study provides no evidence that testosterone testing improves cardiovascular outcomes or that testosterone replacement prevents cardiometabolic disease in young men. Any future risk-stratification strategy would need prospective evidence showing incremental value over conventional measures such as BMI, waist circumference, lipids, glucose and blood pressure.
- Payers: Expanding testosterone testing without clear clinical indications could increase diagnosis and treatment without demonstrating cardiovascular benefit. A more defensible pathway may be to use genuinely low results as a trigger for broader metabolic assessment where clinically appropriate, while avoiding unnecessary treatment of isolated biochemical findings.
- Industry / innovation partners: Men’s health, obesity and metabolic medicine are increasingly converging. Diagnostic platforms that combine hormone measurements with metabolic phenotyping may have potential, but the evidence argues against reducing risk to a single testosterone threshold. Future tools will need to distinguish endocrine disease from reversible metabolic suppression and show that better classification actually changes management.
Testosterone is usually discussed as a reproductive or sexual hormone, but in a young man with obesity, high triglycerides and rising blood pressure, a low result may be telling a much broader story.
That is the possibility raised by a new Italian study examining androgenic and cardiometabolic health in 659 men aged between 18 and 35. Instead of asking only whether testosterone fell below a diagnostic threshold, researchers looked across the hormonal spectrum and compared total testosterone, SHBG and calculated free testosterone with the metabolic characteristics that often begin quietly accumulating long before cardiovascular disease becomes clinically apparent.
The pattern was striking in its consistency. Men with lower total testosterone tended to have higher body weight, higher BMI, larger waist circumference, higher triglycerides and higher systolic blood pressure, while HDL cholesterol tended to be lower. SHBG showed a similar relationship, with lower concentrations accompanying less favourable weight, waist, blood pressure and lipid measures.
At first glance, that might make testosterone look like an early cardiovascular risk marker.
The reality is more complicated, because many of those same metabolic abnormalities can themselves alter the androgenic profile.
Obesity, particularly visceral obesity, is known to affect the hormonal environment in men. Insulin resistance can reduce SHBG production, which in turn lowers measured total testosterone, while inflammatory signalling, leptin resistance and changes in oestrogen metabolism may also suppress the hypothalamic-pituitary-gonadal axis. A young man with central obesity may therefore have lower testosterone partly because of the metabolic state the blood test appears to predict.
The relationship may also operate in the other direction. Testosterone has roles in maintaining muscle mass, adipose-tissue biology and metabolic function, meaning persistent deficiency could theoretically contribute to worsening body composition and insulin sensitivity.
Rather than a simple one-way pathway, researchers increasingly describe a potentially self-reinforcing loop in which visceral adiposity contributes to lower testosterone and lower testosterone may make adverse body composition harder to reverse.
The new study captures that relationship at a single moment, which means it cannot determine where the cycle started.
That limitation becomes particularly important when the researchers divided participants according to the study’s biochemical testosterone threshold.
Using total testosterone of 12 nmol/L or lower, 111 of the 659 men, or 16.8%, were classified as having biochemical testosterone deficiency. Their metabolic profile differed noticeably from that of men above the threshold.
Average waist circumference was more than five centimetres larger. Mean BMI was higher, triglycerides were higher and HDL cholesterol was lower. Generalised obesity was almost four times as common, affecting 14.4% of men in the lower-testosterone group compared with 3.7% of those with testosterone above the cut-off. Abdominal obesity was also more frequent, at 13.9% versus 4.9%.
The reverse analysis told much the same story. Among men who were overweight or obese, almost one quarter had testosterone at or below 12 nmol/L, compared with around 14% of normal-weight participants.
This bidirectional pattern is arguably more important than the threshold itself because it warns against an easy clinical interpretation.
A young man with obesity and low testosterone does not automatically have a primary testosterone disorder that needs hormone replacement. His metabolic condition may be contributing substantially to the biochemical result.
That is why the distinction between low testosterone and hypogonadism matters.
The study used one morning testosterone measurement and did not systematically assess the sexual symptoms and other clinical features required to diagnose male hypogonadism. Current European guidance continues to treat testosterone concentration as only one component of diagnosis. Testing should be standardised, performed in the morning and fasting, and a low result must be interpreted alongside symptoms, repeat biochemical confirmation and, where appropriate, SHBG and calculated free testosterone.
This matters particularly in younger men because labelling a single low value as hypogonadism can lead rapidly toward treatment discussions that have consequences for fertility, long-term monitoring and medicalisation.
The study itself offers no evidence that such treatment would prevent cardiovascular disease.
In fact, the adjusted analysis makes a simpler interpretation of testosterone even less convincing.
When researchers accounted for age, BMI and waist circumference, total testosterone remained independently associated with HDL cholesterol, but many of its other crude relationships with metabolic measures were no longer independently significant. SHBG retained independent associations with HDL cholesterol and both systolic and diastolic blood pressure. Calculated free testosterone did not show an independent association with the cardiometabolic variables in those models.
That is an important detail because it suggests that part of the apparent testosterone-risk relationship may be explained by adiposity itself.
It also makes SHBG particularly interesting.
SHBG is sometimes treated as little more than the transport protein needed to interpret testosterone results, yet its relationship with metabolic health has attracted increasing attention. Insulin resistance and obesity can suppress SHBG, meaning a low concentration may contain metabolic information even when the clinical question began as an endocrine one.
That still does not turn SHBG into a cardiovascular screening test.
The correlations reported in the study were generally modest, and conventional cardiovascular measurements remain far easier to interpret. A clinician does not need a testosterone assay to discover that a patient has a large waist circumference, elevated blood pressure or high triglycerides.
The potential value lies elsewhere.
A young man may seek medical care because of fatigue, reduced libido, sexual symptoms, fertility concerns or a testosterone result obtained elsewhere, while his cardiovascular risk is not the reason for the appointment at all. In that context, an adverse androgenic profile could become an opportunity to look beyond the presenting complaint.
Blood pressure can be checked. Lipids and glucose can be assessed where appropriate. Waist circumference, weight, smoking, sleep, physical activity and other metabolic risks can enter the conversation.
For a population often underrepresented in preventive healthcare, that opportunity could matter.
Young men frequently have a low estimated short-term cardiovascular risk simply because age dominates traditional risk calculators. That can create false reassurance while obesity, hypertension and dyslipidaemia accumulate over years. The new study does not establish testosterone as the answer to that problem, but it does reinforce the idea that reproductive and metabolic health should not be treated as separate clinical worlds.
It also intersects with another increasingly prominent debate: whether the growth of testosterone testing and testosterone therapy risks turning metabolic disease into a hormonal diagnosis.
The data offer a strong reason for caution.
If visceral adiposity can suppress testosterone, then treating only the laboratory value without addressing weight, blood pressure, lipids and metabolic health risks targeting one downstream feature while leaving the broader problem intact.
Conversely, assuming that every low result is simply a consequence of obesity could also miss genuine endocrine disease.
The useful clinical response lies between those extremes and requires proper diagnostic work rather than a single number.
Prospective research is now needed to establish whether androgenic changes precede metabolic deterioration in young men, whether improving metabolic health normalises testosterone and SHBG, and whether adding these hormone measures to conventional risk assessment improves prediction sufficiently to change care.
Until then, the findings are better viewed as a signal of interconnected physiology than as a new treatment algorithm.
A testosterone result may begin in an andrology clinic, but the health story around it can extend into obesity, lipids, blood pressure and future cardiovascular risk.
The lesson from this study is not that young men with low testosterone need more testosterone. It is that they may need clinicians to look beyond the hormone and ask what else the body is signalling.
