Testosterone Is a Metabolic Marker — The Symptom We're Treating as the Disease

Let me give you the analogy I use to think about this, because it's how I like to remember it.

Imagine you're sitting in your office, and you feel cold. Now, the first thing you don't think is, "the thermostat's broken." You don't think the HVAC has failed, or the ducts are blocked. You think about the environment. Has someone left the window open? Has my daughter messed with the thermostat? Am I dressed warmly enough? Am I moving around, or have I been sitting still for two hours? Maybe I'm getting sick. All these things go into how you feel about the temperature, and the first thing you don't reach for is that something is broken in the system.

That's how I want you to think about a low testosterone number. The number on the lab report is the temperature in the room. Most of the time, the thermostat is fine. The system is working. The environment is the problem. And if you don't look at the environment first, you are going to spend a lot of money replacing a thermostat that was never broken.

So the idea here is that testosterone, in the vast majority of men with low levels, is not a disease. It's a metabolic marker. It tells us how healthy our metabolism is. And if we treat the number without addressing the metabolism underneath it, we are not practicing longevity medicine. We're practicing symptom suppression, and there are real downstream consequences to that.

A medical condition with a market

Needless to say, social media has taken a huge interest in our testosterone levels. Everyone is talking about it. If you look at the venture funding into TRT-related companies, it's grown exponentially over the last several years. The number of unique web domains specific to testosterone replacement has grown the same way. It's a hockey stick.

And unfortunately, what's come along with that growth is a lot of muddied messaging. You hear, "Aging decreases testosterone, so probably all of us should be on testosterone." You hear that "all that matters is that you have testosterone in your system." And in my experience, it's never that simple.

There was an interesting analysis presented at the 2024 Annual Fall Scientific Meeting of the Sexual Medicine Society of North America. They looked at the top fifty testosterone videos on social media. Seventy-two percent of those were created by companies looking to make money on testosterone. Four out of fifty mentioned that the evidence for testosterone improving cognition is inconclusive. Zero discussed the long-term impact on fertility. And out of twenty-two unique content creators, only one was a physician. The rest had financial interests in selling tests, supplements, or clinic services.

I want to be clear. I'm not anti-TRT. There's a population of men for whom testosterone replacement is appropriate, sometimes necessary. But that population is a lot smaller than the wellness industry would have you believe, and the work of figuring out who actually belongs in it is more involved than a single morning lab and a symptom checklist.

What aging actually does to testosterone

If you ask the average man why his testosterone is low, he'll tell you, "I'm getting older." And almost always, that's wrong. There are a few studies worth knowing about.

The first is Sartorius and colleagues, published in Clinical Endocrinology, 2012. They looked at 325 men aged 40 to 97 who self-reported very good health and had no chronic disease. In that group — healthy aging men — total testosterone declined at about 0.4 percent per year. So a healthy 80-year-old in their cohort had testosterone levels that really weren't that different from a healthy 40-year-old. Over a forty-year stretch, you're talking about a sixteen-percent drop. That's clinically negligible.

Contrast that with Travison and colleagues, published in the Journal of Clinical Endocrinology and Metabolism in 2007. They looked at population-level testosterone in unselected American men, using NHANES data, and they found that testosterone in the general male population fell about seventeen percent between 1987 and 2004. But here's the important part. That decline was independent of age. A fifty-year-old in 2004 had lower testosterone than a fifty-year-old in 1987. So this is a generational decline, not a biological one. Something about the modern environment is driving down androgen production at every age. The leading suspects are obesity, sedentary behavior, sleep loss, and exposure to endocrine-disrupting chemicals.

The third study is the European Male Aging Study (EMAS) — Wu and colleagues, New England Journal of Medicine, 2010. They asked, of 3,369 men aged 40 to 79, how many actually have symptomatic late-onset hypogonadism, meaning low testosterone plus the clinical syndrome? The answer was 2.1 percent. And the cases were driven by obesity and comorbid disease, not by age.

Put those three studies together and the picture is fundamentally different from the cultural narrative. Healthy men, more or less, don't lose meaningful amounts of testosterone with age. The population-wide decline is a function of metabolic deterioration. And true age-related hypogonadism, in the absence of comorbidity, is pretty rare. So when a forty-eight-year-old man walks in with a total testosterone of 320 and gets told, "Your levels are low for your age, you should consider TRT" — that framing is not medically accurate. His levels are not low for his age. His levels are low because his metabolism is sick.

The physiology — why visceral fat is the problem

To understand why, we have to spend a little time on the physiology. I'm not going to ask you to memorize anything. The point is just to see how the system works.

The system that regulates testosterone is what we call the H-P-G axis — hypothalamic-pituitary-gonadal. The hypothalamus releases gonadotropin-releasing hormone in pulses. That signal goes to the pituitary, which releases luteinizing hormone (LH) and follicle-stimulating hormone (FSH). LH travels down to the Leydig cells of the testes and tells them to produce testosterone. Some of that testosterone gets converted to estradiol by an enzyme called aromatase, and the estradiol loops back up to the brain, telling it there's enough testosterone — slow down. That's the negative feedback. This is the thermostat: a finely tuned, dynamic system that adjusts to keep testosterone where it needs to be.

So if your number comes back low, the question is: what is the system reading from the environment that's telling it to dial down? The biggest environmental factor — by far — is visceral adiposity. There are two types of fat in the body. Subcutaneous fat sits under the skin, on the arms, legs, and backside — the part you can pinch. Visceral fat sits inside the abdominal wall, wrapping the liver, the pancreas, the intestines. These two fats look different under a microscope, behave differently, and have very different effects on the body. Subcutaneous fat is mostly a quiet storage depot. Visceral fat is a hormonally active, pro-inflammatory endocrine organ.

And visceral fat suppresses testosterone in essentially three ways. First, it converts testosterone to estradiol — visceral adipose tissue has high levels of aromatase, so more visceral fat means more aromatization, more estradiol, and a stronger "dial it down" signal to the brain. Second, it disrupts leptin signaling, and we need functional leptin signaling for the brain to release GnRH in a normal, pulsatile rhythm. Third, inflammation — visceral fat secretes cytokines (interleukin-6, TNF-alpha, resistin) that suppress gonadotropin release at the pituitary and impair the Leydig cells directly.

And then layer in insulin resistance, which travels with visceral fat. When tissues become insulin resistant, the brain, pituitary, and testes essentially think there's no food available, and they go into starvation mode. In starvation mode, the body's job is not to reproduce — so it dials down testosterone. Once you're in this state, low testosterone reinforces it: less lean mass, more visceral fat, less energy to exercise, worse sleep — and testosterone is made at night, so poor sleep means less production. The whole cycle deepens itself. We call this functional hypogonadotropic hypogonadism, and the important thing about it is that it's reversible — but only if you fix what's actually driving it.

Does low testosterone actually shorten lives?

This is the longevity question, and it's a good one. If you look at the large cohort studies — Khaw in EPIC-Norfolk (Circulation 2007); Laughlin in the Rancho Bernardo cohort (JCEM 2008); Yeap in the Health In Men Study (JCEM 2014); Araujo's meta-analysis (JCEM 2011) — the signal is consistent. Men in the lowest quartile of testosterone, generally below about 250 ng/dL, have higher all-cause mortality. That's real.

But the question is, is the low testosterone causing the higher mortality, or is it a marker of the disease that's causing the higher mortality? The cleanest way to answer that is to take men with low testosterone, give them testosterone, and see if the mortality risk improves. That's exactly what TRAVERSE did. Published in the New England Journal of Medicine in 2023, it enrolled over 5,000 men with low testosterone and elevated cardiovascular risk, randomized them to transdermal testosterone or placebo, and followed them for major adverse cardiovascular events. TRT did not reduce cardiovascular events. It did not reduce mortality. It did, however, modestly increase the rates of atrial fibrillation, pulmonary embolism, and acute kidney injury.

If the low testosterone were causally driving the mortality signal, you would expect replacement to bend that curve. It didn't. The most parsimonious interpretation is that low testosterone in these cohorts is a marker for the underlying metabolic and cardiovascular disease — and treating the marker doesn't treat the disease. This is consistent with the T-Trials (NEJM 2016): some modest improvements in sexual function, some bone density and anemia benefits, but no meaningful effect on cognition, vitality, or physical function. Nothing close to what the wellness marketing implies.

What to actually do

So what does a rigorous workup look like? Three things.

First, get the right tests. Total testosterone alone isn't enough. We need to characterize the entire H-P-G axis and the metabolic state around it: total testosterone, free testosterone, estradiol, SHBG, LH, and FSH. LH and FSH tell us whether the problem is primary (the testes have failed) or secondary (the brain is no longer sending the signal). The vast majority of cases are secondary, with low or low-normal LH, which tells you immediately the problem is upstream. Then we need a metabolic panel — fasting insulin, fasting glucose, hemoglobin A1c, triglycerides — and ideally a DEXA scan to quantify visceral fat directly. You can have a normal BMI and still have a lot of visceral fat.

Second, get the right diagnosis. A man with low testosterone, low-normal LH, low SHBG, elevated fasting insulin, an A1c in the prediabetic range, and visceral fat above the threshold on his DEXA has functional hypogonadotropic hypogonadism secondary to metabolic syndrome. That's a fundamentally different clinical picture from a man with low testosterone and a high LH, which would point to actual testicular failure. Different diagnoses, different treatments.

Third, get the right treatment. For the metabolic phenotype — the vast majority — the highest-yield interventions are not pharmacologic. They're lifestyle. Sustained caloric deficit with weight loss can raise total testosterone by 50 to 200 ng/dL. In severely obese men, bariatric surgery raises it by about 233 on average. Resistance training over months adds 58 to 144. High-intensity interval training adds another 40 to 70. Sleep optimization — getting from five hours up to seven or eight — adds 40 to 60. Vitamin D, if you're deficient, adds about 78. Zinc, if you're deficient, adds 100 to 200 — but if you're already replete, supplementing won't give you anything.

And with the advent of GLP-1 agonists, this whole landscape has shifted. I was talking to a patient a few months ago who'd been on a GLP-1 for a long time, lost about fifty pounds, and we rechecked his testosterone. He'd gone from the low 400s into the low 600s — about a fifty percent increase — taking no testosterone at all. Just by losing the weight, the system corrected itself. That is what fixing the environment looks like.

This is where testosterone replacement can have a role, and I want to be honest about it. In a man who is so deep in the metabolic rut that he can't generate the energy to exercise, can't sleep, can't make progress on the lifestyle side, supplemental testosterone can be a bridge — giving him the energy and muscle response to start moving, and then you peel it off as the metabolism corrects. That's a legitimate use. It's not the typical use.

The typical use looks like this. A forty-two-year-old man, asymptomatic or mildly symptomatic, gets a total testosterone of 320, gets prescribed testosterone, and is never told that the medication will shut down his LH and FSH in a dose-dependent way. He's not told that his sperm count will drop in ten to twelve weeks, and that roughly ten percent of men never recover sperm production after they stop. He's not told that TRT doesn't consistently reduce visceral fat, or that all the benefits evaporate within months of stopping. And, per TRAVERSE, he's not told about the modest but real signal for atrial fibrillation, venous thromboembolism, and acute kidney injury. He feels better — and that's the most insidious part — because it decreases the incentive to fix the underlying problem. The thermostat is reading the right number. The window is still open. The metabolism is still sick.

Key takeaways

• Get the right tests. Beyond total testosterone, characterize the full H-P-G axis (free testosterone, estradiol, SHBG, LH, FSH) and the metabolic state around it.
• Get the right diagnosis. Find the driver. The vast majority of the time, the driver is metabolic — functional hypogonadism secondary to visceral fat and insulin resistance.
• Get the right treatment. Address the cause first with lifestyle and weight loss; treat the symptom with replacement only when genuinely warranted. An abnormal lab value is often the leaf, not the root.