Hormonal treatment may trigger depression in men with prostate cancer

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. This leads researchers to suggest that patients receiving androgen deprivation therapy should be monitored for post-surgical depression. This is presented at the European Association of Urology congress in Barcelona.

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. Now a group of Danish researchers has shown that men who receive anti-hormonal treatment after a radical prostatectomy have an increased tendency to depression.

“The anti- hormonal treatment is given to control the growth of tumour cells” said lead researcher Dr Anne Sofie Friberg from the Rigshospitalet in Copenhagen. “Unfortunately, we have found that it is also associated with depression.”

The researchers examined medical records of 5,570 men from the Danish Prostate Cancer Registry. They found that 773 of these men were 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. The researchers also checked whether radiotherapy after radical prostatectomy was associated with depression, but these results were inconclusive.

Anne Sofie Friberg said:

“The treatment prevents the production of androgen hormones, like testosterone. We know from other studies that low testosterone can affect a man’s well-being, so it may be that limiting testosterone production might have the same effect, perhaps especially after a major stress such as cancer treatment.

It is important to note that compared to men without prostate cancer the patients treated with prostatectomy as a whole has 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.”

They note that the definition of depression – antidepressant prescriptions or referral to a psychiatric department for depression – is a possible limitation of the study (not all would have sought treatment, and sometimes anti-depressants are prescribed for other conditions). But the large numbers in the study means that the results are likely to be robust.

Commenting, EAU Adjunct Secretary General for Education, Prof Hendrik Van Poppel (University Hospitals of the KULeuven, Belgium) said:

“This is a large study which shows that prostate cancer treatment can spill over to cause other issues. We need to be aware of this potential. As urologists we have a responsibility to treat the whole patient, so this argues for a multi-disciplinary approach to treating prostate cancer, and underlines the value of following evidence-based guidelines to try to ensure that the patient receives comprehensive care”.

Mr Erik Briers MS PhD (patient member of the EAU guidelines committee on prostate cancer) said:

“This study is very relevant from the patient’s point of view; it again shows the importance of the holistic treatment of prostate cancer patients and in this treatment the importance of including psycho-oncology and socio psychology professionals. The care for prostate cancer patients does never stop, consequences can show up very late”.

Neither Professor Van Poppel nor Erik Briers were involved in this research, these are independent comments

This work was funded by the Danish Cancer Society and the Capital and Zealand Region of Denmark fund.

Conference abstract: The hazard of depression after radical prostatectomy – A nationwide registry-based study

Authors: Friberg A.S. 1 , Brasso K. 2 , Andersen E.W. 3 , Helgstrand J.T. 2 , Röder M.A. 2 , Johansen C. 1 , Dalton S.O. 4

1Rigshospitalet, Copenhagen University Hospital, Dept. of Oncology, Copenhagen, Denmark, 2Rigshospitalet, Copenhagen University Hospital, Copenhagen Prostate Cancer Center, Dept. of Urology, Copenhagen, Denmark, 3Danish Cancer Society Research Center, Dept. of Statistics and Pharmaco-epidemiology, Copenhagen, Denmark, 4Danish Cancer Society Research Center, Survivorship, Copenhagen, Denmark

Introduction & Objectives

Depression is a recognized late effect of cancer and may be a result of diagnosis, treatment, and/or symptoms. The contribution to the risk of depression of each of these factors remains unknown. Prostate cancer patients follow a range of different treatment paths and in this study we investigated the effect of either radiotherapy or androgen deprivation on the subsequent risk of depression in men treated with radical prostatectomy.

Materials & Methods

This is a nationwide population-based cohort study of all men who underwent radical prostatectomy in Denmark from 1998 to 2011. The study population was based on data from the Danish Prostate Cancer Registry (DaPCaR). Primary outcome was depression, defined as either a hospital contact for depression or redemption of a prescription of antidepressant medication. Information on primary outcome and covariates were obtained from nationwide Danish registries. The main variables of interest were radiotherapy and androgen deprivation therapy. Men were followed from date of surgery until depression or censoring. Time since surgery was used as underlying timescale in the analyses of data using Cox models with time-varying covariates and adjustment for the identified possible confounders age, calendar period, cohabitation status, income quintile and Charlson comorbidity index.

Results

The cohort consisted of 5570 men. During follow-up, 773 men had an event of depression. Compared to men not undergoing subsequent therapies we found that androgen deprivation therapy increased the risk of depression (HR 1.8 (95% CI 1.4 to 2.3), p<0.001), whereas salvage radiation without androgen deprivation therapy did not significantly increase the risk of depression (HR 1.3 (95% CI 1.0 to 1.6) p=0.07). The effect of the two treatments was additive (HR 2.22 (95% CI 1.75 to 2.81)) with no sign of interaction (p=0.85). The estimates were adjusted for age group at time of surgery, year of surgery, income quintile and cohabitation status. Further adjustment for Charlson comorbidity index did not change the estimates.

Conclusions

We found an increased hazard for depression in men who have undergone radical prostatectomy and subsequent androgen deprivation therapy was initiated. Treatment with radiotherapy did not increase the hazard to the same degree as androgen deprivation therapy, but had an additive effect on the hazard of depression. In perspective, men who have undergone radical prostatectomy and later receive treatment with androgen deprivation therapy may be in need of preventive measures to reduce the risk of depression and initiate treatment in time.