Urologic Oncology: Seminars and Original Investigations
Original articleClinical—prostatePsychological distress in men with prostate cancer receiving adjuvant androgen-deprivation therapy☆,1
Introduction
Androgen-deprivation therapy (ADT) is the mainstay of treatment for prostate cancer patients with metastatic disease [1]. In prospective randomized clinical trials, ADT was found to be effective in reducing the risk of recurrence in high-risk men undergoing radical prostatectomy [2] and in improving overall survival in high-risk men after radiation therapy [3]. Although increasingly prescribed in apparently healthy men with a long life expectancy, the potential benefits of ADT still need to be carefully weighed against the risks of long-term toxicity.
Several studies have shown that ADT has long-term side effects, including cardiovascular diseases, diabetes, anemia, bone fractures, obesity, metabolic syndrome, and decreased lean body-mass [4], all of which can diminish quality of life [5], [6], [7]. Furthermore, ADT can also have neuropsychiatric effects including depression.
Low testosterone levels may, in fact, alter serotonin neurotransmission [8], negatively affecting mood as demonstrated in animal models [9]. Also, testosterone deficiency may decrease cerebral perfusion in the brain regions involved in memory, reasoning, judgment, and emotions [10], leading to a deterioration in mental and overall well-being [11], [12].
Studies in elderly subjects and non-cancer patients have reported a clear association between testosterone levels and depressive symptoms [13]: lower testosterone levels in older men have been associated with more depressive symptoms [14], [15], which seem to disappear with testosterone hormone treatment [16], [17]. Besides contributing to the onset of depressive disorders, decreased testosterone blood levels can cause breast tenderness and loss of penile length or volume. These changes, together with unwanted weight gain, lead to a worsening of self body image perception [18].
Low circulating testosterone levels are associated with diminished sleep efficiency and fewer rapid eye movement (REM) sleep episodes with altered REM sleep latency [19]. In a large study on prostate cancer patients treated with radical prostatectomy, androgen blockade-related symptoms were associated with a significantly higher likelihood of insomnia syndrome [20]. As insomnia and worsened body image perception are both notoriously linked to depression [21], [22], [23], [24], they can concur in the development of depressive symptoms associated with low testosterone levels.
These premises notwithstanding, study results on depression in prostate cancer patients undergoing ADT remain controversial: one pilot study found major depressive disorder in a high percent of prostate cancer patients under ADT [25], whereas a large population-based analysis of depressive and cognitive symptoms in patients with prostate cancer failed to show a higher prevalence of depressive symptoms in ADT-treated patients vs. non-treated patients after adjusting for age, comorbidities, and disease stage [26].
The present study was designed to investigate the frequency of depression and other contributory physical and psychological distresses, such as quality of life deterioration, worsening of self body image perception, and sleep disorders, in a group of consecutive prostate cancer patients referred for ADT as adjuvant therapy after loco-regional treatment as compared with a group of prostate cancer patients referred for follow up only.
Section snippets
Subjects
From March to May 2007, consecutive patients either under adjuvant ADT or included in a follow-up program after loco-regional treatment of localized prostate cancer were recruited at the Prostate Cancer Unit, San Luigi Hospital, Orbassano, Italy.
Eligibility criteria were: (1) histologically confirmed diagnosis of prostate cancer; (2) previous loco-regional treatment of primary tumor (prostatectomy or 3D conformational radiotherapy); (3) absence of metastatic disease; (4) at least 6 months
Patient characteristics
The study population was 103 patients, 49 (47.6%) of whom had undergone hormone therapy with LH-RH analogues and 54 (52.4%) had not (control group). The control group included 47 low-risk and 2 high-risk patients who had undergone radical prostatectomy and 5 low-risk patients treated with radiation therapy, who declined the recommended hormone therapy due to fear of impotence.
Table 1 summarizes the patient characteristics. The patients referred for adjuvant hormone therapy were slightly older,
Discussion
Androgen-deprivation therapy is increasingly administered for early stages of prostate cancer, exposing men to prolonged periods of treatment. In light of these trends, concerns have been raised about the toxic effects of ADT. Physicians are aware of the metabolic and physical toxicity of ADT, but relatively scarce attention has been paid to its psychological side effects. Both hypogonadism and testosterone deprivation have been associated with depressive disorders in non-neoplastic men [13],
Conclusion
The present study provides evidence that ADT is associated with depression, worsening in quality of life and altered body image perception, and sleep disturbances. These results extend the impact of ADT into the psychological domain beyond the already available data on its metabolic and physical toxicity, and reinforce the notion that prescribing ADT in apparently healthy men with a longer life expectancy needs to be carefully weighed against the risks of its long-term side effects.
References (40)
- et al.
EAU guidelines on prostate cancer
Eur Urol
(2008) - et al.
Androgen suppression plus radiation versus radiation alone for patients with D1 (pN+) adenocarcinoma of the prostate (results based on a national prospective randomized trial, RTOG 85–31)Radiation Therapy Oncology Group
Int J Radiat Oncol Biol Phis
(1997) - et al.
Impact of androgen deprivation therapy on physical and cognitive function, as well as quality of life of patients with nonmetastatic prostate cancer
J Urol
(2006) - et al.
Androgen actions on central serotonin neurotransmission: Relevance for mood, mental state, and memory
Behav Brain Res
(1999) - et al.
The effects of testosterone on sleep-disordered breathing in men: Its bidirectional interaction with erectile function
Sleep Med Rev
(2008) - et al.
Sleep and depression—results from psychobiological studies: An overview
Biol Psychol
(2001) - et al.
National Comprehensive Cancer Network guidelines for the management of prostate cancer
Urology
(2003) - et al.
Measuring quality of life in men with prostate cancer using the Functional Assessment of Cancer Therapy-Prostate instrument
Urology
(1997) - et al.
A body image scale for use with cancer patients
Eur J Cancer
(2001) - et al.
The Pittsburgh Sleep Quality Index: A new instrument for psychiatric practice and research
Psychiatry Res
(1989)
Changes in bone mineral density, lean body mass, and fat content as measured by dual energy X-ray absorptiometry in patients with prostate cancer without apparent bone metastases given androgen deprivation therapy
J Urol
Epidemiology of comorbid coronary artery disease and depression
Biol Psychiatry
Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer
N Engl J Med
Complications of androgen deprivation therapy for prostate cancer
Curr Opin Urol
Quality of life following localized prostate cancer treated initially with androgen deprivation therapy or no therapy
J Natl Cancer Inst
Quality of life in prostate cancer taking androgen deprivation therapy
J Am Geriatr Soc
Oestrogen and testosterone modulate the firing activity of dorsal raphe nucleus serotonergic neurones in both male and female rats
J Neuroendocrinol
Testosterone treatment enhances regional brain perfusion in hypogonadal men
J Clin Endocrinol Metab
Altered cognitive function in men treated for prostate cancer with luteinizing hormone releasing hormone analogues and cyproterone acetate: A randomized controlled trial
BJU Int
Androgen deprivation and cognition in prostate cancer
Br J Cancer
Cited by (54)
Anxiety, depression and urological cancer outcomes: A systematic review
2021, Urologic Oncology: Seminars and Original InvestigationsEffects of Exercise During Radiation Therapy on Physical Function and Treatment-Related Side Effects in Men With Prostate Cancer: A Systematic Review and Meta-Analysis
2021, International Journal of Radiation Oncology Biology PhysicsAndrogen Deprivation Therapy for Prostate Cancer: Focus on Cognitive Function and Mood
2024, Medicina (Lithuania)
- ☆
The authors acknowledge Regione Piemonte–Settore Ricerca Finalizzata for supporting this study.
- 1
Presented in part at the 23rd Annual Congress of the European Association of Urology, Milan, Italy, March 26-29, 2008.