In short: Hardly any hormone has such a bad reputation as testosterone – and hardly any is so poorly justified. The fear of prostate cancer dates back to a 1941 study whose crucial conclusion was based on a single patient. Later came the misinterpretation of a women's study and some methodologically weak studies on heart risk. With the TRAVERSE study of 2023, a large randomized study is now available. Why the stigma has nevertheless survived – and what it costs patients.
It all started in the late 1930s of the last century. Back then, the first testosterone preparations came on the market. After that, testosterone therapy lay dormant until the 1980s and 1990s – due to fears of prostate cancer, which have now been refuted.
This went so far that doctors were afraid to prescribe testosterone therapies. The result was paradoxical: More experience was gained in the doping sports world than in medicine. Whether bodybuilding, athletics, or combat sports – testosterone was more abused than needed by athletes.
How a hormone became a buzzword
Furthermore, testosterone is often used by the media to describe certain male behaviors or characters. When there was an exciting day on the stock market, you read phrases like: "Today there was a lot of testosterone on the stock market." Objectively speaking, this is nonsense. Unfortunately, the media are not always accurate in their reporting, but rather focused on clicks.
All this causes a lot of confusion – even among doctors. Testosterone is directly associated with bodybuilding, "toxic masculinity", and doping. All things that a doctor generally wants to have nothing to do with or be confronted with (Traish, 2017).
Everyone thinks they know something about testosterone. And usually, this limited knowledge is negative in nature.
The paradox that has arisen from this is all the greater. Because the testosterone level is associated with a remarkable range of conditions: diabetes mellitus, metabolic syndrome, obesity, osteoporosis, anemia, sexual dysfunction, infertility, cognitive decline, rheumatic diseases – and overall mortality. Compared to other laboratory values, the testosterone level thus combines an admittedly very broad range of significance.
Why is this hormone therefore largely left untouched by conventional medicine? A comparison with any other group of medications – antibiotics, antipyretics – quickly makes the difference clear. It is the bad image (Morgentaler, 2014). Not infrequently, the desire for a testosterone determination at the general practitioner's blood draw resembles a real odyssey.
The origin: one study, one patient
Testosterone suffered a very unfortunate timing in its history. It became known in the late 1930s. Initially, it was designated as a potent medication to treat hypogonadism. The effects were described as largely positive – until 1941.
In this year, Huggins and Hodges published their groundbreaking work on prostate cancer. They showed that a significant reduction in testosterone levels through castration or estrogen administration caused metastatic prostate cancers to regress – a discovery for which Huggins later received the Nobel Prize. In addition, they reported that the administration of exogenous testosterone caused the cancer to grow.
And this is exactly where the historical core of the problem lies: This second conclusion was based on the results of a single patient (Morgentaler, 2006).
Important is the distinction that was lost over decades: Huggins and Hodges studied men with already existing, metastatic prostate cancer. Their work says nothing about whether testosterone causes prostate cancer. However, exactly this confusion has become established as the prevailing opinion.
Numerous later studies found no progression under testosterone administration. In clinical studies, neither healthy men nor men with increased risk showed an increased rate of prostate cancer; longitudinal studies found no connection between serum testosterone levels and cancer risk, and men with low testosterone had no reduced risk. This apparent paradox is explained today by the saturation model: The maximum stimulation of the prostate tissue is already achieved at relatively low testosterone concentrations – beyond that, more testosterone no longer has any effect (Morgentaler, 2006).
The second blow: a women's study
In the late 1990s, there was an increasing awareness of anti- or quality-aging. It was increasingly believed that one should not necessarily become progressively frail and weaker in old age, but could also enjoy life to the fullest in old age. Testosterone was chosen as an effective medication within the framework of a growing awareness of "andropause" as a result of the "andropause". The enthusiasm for the hormone rose again.
In 2002, the most extensive randomized study on hormone replacement therapy in women to date was published: the Women's Health Initiative. It was the result of an increasing awareness of the previously subordinate role of women in clinical studies. The result yielded the headline that hormone replacement therapy was dangerous for women – an assessment that was significantly relativized in the context of later re-analyses (Cagnacci & Venier, 2019). As a result, an entire generation of women lost the opportunity for treatment of postmenopausal complaints.
Unfortunately, this credo was simultaneously transferred to male hormone replacement therapy. Endocrinologists increasingly distanced themselves from hormone replacement therapies even within the framework of andropause – although the study had examined neither men nor testosterone.
The third blow: the cardiovascular debate of the 2010s
It continued just as negatively. In the early 2010s, several studies appeared that linked testosterone with an increased cardiovascular risk. These publications made negative headlines, so testosterone once again suffered media criticism.
Upon closer inspection, however, these studies differ considerably in their significance – and this differentiation is more important than a blanket judgment:
The TOM study by Basaria and colleagues (2010) was a randomized, placebo-controlled study that was stopped prematurely. However, it only included 209 men with an average age of 74 years, all of whom had mobility impairments and a high rate of pre-existing conditions. The authors themselves pointed out that the small size and the very specific population do not allow for further conclusions about the safety of testosterone therapy.
The work of Vigen and colleagues (2013), on the other hand, was a retrospective cohort study of veterans after coronary angiography – thus, an observational study, with all known weaknesses. It also had to be corrected after the discovery of data errors.
The work of Finkle and colleagues (2014) was also an analysis of prescription data, not a controlled study.
One cannot therefore lump these studies together. What unites them is not their design, but their media impact.
Where the evidence stands today
In 2023, the study that the field had long awaited was published with TRAVERSE: a multicenter, randomized, double-blind, and placebo-controlled study of 5,246 men between 45 and 80 years with symptoms of hypogonadism, two testosterone values below 300 ng/dl, and existing or imminent cardiovascular disease.
The result: The primary cardiovascular endpoint – cardiovascular death, non-fatal heart attack, or non-fatal stroke – occurred in 7.0 percent in the testosterone group and in 7.3 percent in the placebo group. The hazard ratio was 0.96 (95% confidence interval 0.78–1.17), thus achieving the pre-defined non-inferiority (Lincoff et al., 2023).
Thus, the central concern of the 2010s is dispelled. However, to complete the picture, TRAVERSE found higher rates of atrial fibrillation, acute kidney failure, and pulmonary embolisms in the testosterone group. TRAVERSE thus shows that guideline-compliant testosterone therapy is cardiovascularly acceptable in proven deficiency – not that it is without consequences. It remains a therapy to be monitored by a doctor with control intervals, not a lifestyle preparation.
Where conventional medicine reaches its limits
For the treatment of cancer, heart attacks, diabetes mellitus, transplants, or strokes – i.e., serious, life-threatening illnesses – modern medicine is excellently suited.
In young to middle-aged men who objectively appear perfectly healthy, but still feel weak, listless, and generally worse than they actually should, however, almost any approach of our conventional medicine often fails. And I write this as a conventional medical doctor who always strives to be familiar with current guidelines.
Exactly in this gap lies the topic of hormone status – and exactly there the stigma has its most concrete effect. Not as an abstract debate, but as an unrequested laboratory value.
This expressly does not mean that testosterone would be the answer to every exhaustion. The symptoms of testosterone deficiency are non-specific and overlap with sleep apnea, thyroid diseases, iron deficiency, and depression. It simply means that the question should be asked and the value determined – result-open, in the morning between 7 and 11 a.m., and in case of an abnormal finding, confirmed by a second measurement.
For listening:
- #26 – Testosterone: Doping vs. Therapy | Dr. Regalbuto on Men's Health
- #79 – The Truth About TRT, Peptides & Co. | Dr. Regalbuto on Men's Health
Conclusion
The bad image of testosterone rests on three historical events: a conclusion from 1941 that was based on a single patient; a women's study from 2002 whose result was transferred to men without verification; and a series of methodologically very different studies from the 2010s that were lumped together in the media.
None of these three points withstands a review today. With TRAVERSE, a large randomized study has been available since 2023 that dispels the central safety concern – without therefore making the therapy trivial.
What remains is a simple demand: testosterone should be treated like any other laboratory value. Determined when the symptoms fit. Interpreted in context. And treated if a deficiency exists.
