How testosterone went from prostate cancer villain to potential ally

For more than 80 years, men have been told that testosterone helps prostate cancer grow. But a very different picture has emerged over the past two decades.

The prostate is a small gland that sits just below the bladder. Its job is to produce the fluid that helps transport sperm, and it relies heavily on testosterone to do so. In fact, the prostate is one of the body parts most affected by testosterone.

All prostate cells, whether healthy or cancerous, contain androgen receptors. These are the molecular switches that initiate testosterone’s action inside cells. When testosterone binds to these receptors, it helps the prostate grow and function normally.

This close hormonal control is important, but it also sets the stage for one of the most enduring assumptions in men’s health: because testosterone stimulates normal prostate growth, it must also stimulate cancer growth.

This belief rested largely on the Nobel prize-winning research of Charles Huggins in the 1940s. He found that prostate cancer shrank when testosterone levels were lowered and accelerated when testosterone was added, via injections.

Lowering testosterone levels, known as androgen deprivation therapy, became the standard treatment for advanced prostate cancer. It still is. Removing testosterone often shrinks tumours, slows disease progression and improves survival.

This belief became deeply embedded in medical practice, shaping decades of caution around testosterone replacement therapy for hypogonadism (testosterone deficienecy) because of fears it could trigger or drive prostate cancer.

Changing the narrative

In the early 1990s, Harvard urologist and testosterone pioneer Abraham Morgentaler began to challenge this view. He pointed out that some of the early research relied heavily on the response of just one patient.

In his clinic, he saw that men with very low testosterone still developed prostate cancer that was often more aggressive, while men receiving testosterone therapy did not show the expected rise in cancer rates.

This led to the proposal of the “saturation model”, which suggests that prostate tissue is sensitive to testosterone only at very low levels. Once androgen receptors are saturated, additional testosterone has little further effect.

At the same time, it was being shown that chronically low testosterone was associated with more aggressive prostate cancer, further challenging the idea that low testosterone is inherently protective.

Recent medical studies now show that testosterone treatment is safe. In multiple high-quality studies, testosterone therapy in men with low testosterone levels does not increase the risk of prostate cancer compared to men who didn’t receive the treatment. New long-term research even suggests that men whose testosterone levels are properly restored and monitored by doctors may actually have lower cancer rates.

But what about men who already have prostate cancer? This is where the discussion often becomes confused. For men with active prostate cancer, particularly early-stage disease, lowering testosterone remains an effective treatment. So how can this paradox exist with evidence that normal testosterone levels are not harmful?

The answer lies in how prostate cells react to different amounts of testosterone. When testosterone levels are very low, cancer cells can adjust by finding new ways to grow and survive. They become super-sensitive to any testosterone signals they can detect.

This is why many men eventually develop castration-resistant prostate cancer, where the disease progresses and can become more aggressive despite near-zero testosterone. Higher levels of testosterone may push these cancer cells into a more stable, slower growth state and, in some situations, may even destabilise them, promoting cell death.

Striking reversal

This discovery has led to a surprising change in treatment. In carefully chosen patients who are closely watched by doctors, testosterone is now being given back after prostate cancer treatment without increasing the chance of the cancer returning.

Even more surprisingly, doctors are testing a new approach in certain men with prostate cancer called bipolar androgen therapy, which switches testosterone levels between very low and very high. The idea is to use testosterone itself as a weapon to confuse and kill cancer cells that have learned to survive without it.

This is one of the most striking reversals in modern cancer treatment. Testosterone has shifted from a presumed villain feared to ignite prostate cancer, to a hormone whose effects are more complex than once believed, and even a possible ally in the fight against prostate cancer.

This evolution is finally reaching medical practice and drug regulation. On December 10, just one month after the US Food and Drug Administration (FDA) announced the removal of black-box warnings from oestrogen products, the FDA organised an expert panel to consider whether longstanding warnings around testosterone use are similarly out of date. A large part of these discussions is about prostate safety and reflects how far the evidence has shifted.

None of this means testosterone replacement therapy – for men with low testosterone levels – is completely without risk. Men starting treatment should still get proper medical checks, have their prostate monitored regularly, and make decisions after talking things through with their doctor.

But the science has changed. The old belief that testosterone therapy increases prostate cancer or makes it worse is no longer backed up by modern research.

For men who genuinely have low testosterone, this change is important. It can remove unnecessary obstacles to getting care and gives them more safe, science-backed treatment options, which helps improve men’s health overall.

Daniel Kelly does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.