Coffee and testosterone could help slow prostate cancer
The 2019 congress of the European Association of Urology (EAU), held from 15–19 March in Barcelona, saw scientists from all over the world share new insights into prostate cancer treatment.
For example, Japanese scientists led by Kanazawa University have identified compounds found in coffee which may inhibit the growth of prostate cancer. Their work has been published in the journal The Prostate.
Coffee is a complex mixture of compounds which has been shown to influence human health, and there is increasing evidence that drinking certain types of coffee is associated with a reduction in incidence of some cancers, including prostate cancers. With this in mind, researchers tested six compounds, naturally found in coffee, on the proliferation of human prostate cancers cells in vitro — cells which are resistant to common anticancer drugs such as Cabazitaxel.
They found that cells treated with kahweol acetate and cafestol — hydrocarbons naturally found in Arabica coffee — grew more slowly than controls. They then tested these compounds on prostate cancer cells which had been transplanted to mice. Four mice were controls, four were treated with kahweol acetate, four were treated with cafestol and four were treated with a combination of kahweol acetate and cafestol.
“We found that kahweol acetate and cafestol inhibited the growth of the cancer cells in mice, but the combination seemed to work synergistically, leading to a significantly slower tumour growth than in untreated mice,” said study leader Dr Hiroaki Iwamoto. “After 11 days, the untreated tumours had grown by around three-and-a-half times the original volume (342%), whereas the tumours in the mice treated with both compounds had grown by around just over one-and-a-half (167%) times the original size.
“This is a pilot study, so this work shows that the use of these compounds is scientifically feasible, but needs further investigation; it does not mean that the findings can yet be applied to humans. We also found the growth reduction in transplanted tumour cells, rather than in native tumour cells. What it does show is that these compounds appear to have an effect on drug-resistant prostate cancer cells in the right circumstances, and that they too need further investigation. We are currently considering how we might test these findings in a larger sample, and then in humans.”
“These are promising findings, but they should not make people change their coffee consumption,” added co-author Professor Atsushi Mizokami. “Coffee can have both positive and negative effects (for example, it can increase hypertension), so we need to find out more about the mechanisms behind these findings before we can think about clinical applications. However, if we can confirm these results, we may have candidates to treat drug-resistant prostate cancer.”
Meanwhile, a separate study saw US researchers reveal that testosterone replacement actually slows the recurrence of prostate cancer in low-risk patients, calling into question Huggins and Hodges’ research from 1941 that a reduction in testosterone was linked to a reduction in prostate cancer — research which won Huggins the 1966 Nobel Prize for Medicine. Since then, medicines which reduce testosterone levels have become a standard option for many patients.
But from the late 1990s onwards, doctors began to find that although men on long-term anti-testosterone treatments were not dying from prostate cancer, they were dying prematurely of cardiovascular disease. It seemed that although anti-testosterone therapies were treating the prostate cancer, the extremely low testosterone levels were significantly worsening metabolic complications such as elevated blood sugar, diabetes, elevated cholesterol, mid-abdomen visceral fat, etc, as well as causing a loss of sexual function. This led some doctors to suggest testosterone replacement in some low-risk men after radiation or surgical treatment.
Starting in 2008, a team of doctors from the University of California, Irvine began to carefully select patients for testosterone replacement after primary treatment of prostate cancer with robotic radical prostatectomy, in hopes of improving recovery of sexual function. The team worked with 834 patients undergoing radical prostatectomy, treating 152 low-risk patients with no evidence of disease with testosterone replacement therapy.
After a median of 3.1 years following surgery, the researchers tested the patients for biochemical recurrence of the cancer, as indicated by measurement of the prostate-specific antigen (PSA) levels. They found that the cancer had recurred in only approximately 5% of treated patients, whereas the cancer had recurred in 15% of the patients who did not receive testosterone. Overall, after accounting for differences between the groups, they found nearly a three-fold reduction by three years.
“This is not what we set out to prove, so it was a big surprise: not only did testosterone replacement not increase recurrence, but it actually lowered recurrence rates,” said study leader Professor Thomas Ahlering. “While the testosterone is not curing the cancer per se, it is slowing the growth of the cancer, giving an average of an extra 1.5 years before traces of cancer can be found. We already know that testosterone can help with physiological markers such as muscle mass, better cholesterol and triglyceride levels and increased sexual activity, so this seems to be a win-win.
“There have been smaller studies which have hinted that testosterone may not be risky for certain patient groups, but this is the largest such study ever conducted. We’re not suggesting that treatment methods be changed just yet, but this puts us at the stage where we need to question the taboo against testosterone use in prostate cancer therapy — especially for low-risk patients after radical prostatectomy.”
In fact, there may be an additional reason why anti-testosterone treatment should be reviewed. Another study presented at the congress, this time by Danish researchers, found that men who receive anti-hormonal treatment after having their prostate removed are 80% more likely to suffer from depression than men who don’t receive this treatment.
Increasingly, doctors are becoming aware that for many men, a cancer diagnosis and treatment leads to depression, with suicide rates seen rising disproportionately for those with urological cancers. Examining the medical records of 5570 men from the Danish Prostate Cancer Registry, researchers found that 773 had been treated for depression after surgery. They found that men treated with anti-hormonal medicines were 1.8 times more likely to suffer from depression than men who did not receive the additional treatment.
“We know from other studies that low testosterone can affect a man’s wellbeing, so it may be that limiting testosterone production might have the same effect, perhaps especially after a major stress such as cancer treatment,” said lead researcher Dr Anne Sofie Friberg from the Rigshospitalet in Copenhagen.
“It is important to note that compared to men without prostate cancer, the patients treated with prostatectomy as a whole had an increased risk of depression. After surgery, erectile dysfunction and urinary incontinence are frequent symptoms. In case of recurrence and hormonal treatment, these symptoms may worsen and, in addition, altered body image and loss of libido are common. These treatment effects are likely to increase the risk of depression. Also, low testosterone levels may directly affect mood centres of the brain.
“As many as 25% of men undergoing radical prostatectomy will relapse and may be offered hormonal treatment. These men appear to be at a higher risk of developing depression once hormonal treatment is introduced. The reason could be either a consequence of failing surgery, directly caused by the hormonal manipulation, or both.”
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