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Originally published as JCO Early Release 10.1200/JCO.2009.23.5663 on August 3 2009 © 2009 American Society of Clinical Oncology.
Risk of Depressive Events in Long-Term Surviving Patients Affected by Hormone-Related Cancer According to Time After DiagnosisMedical Oncology, Department of Clinical and Biological Sciences, "San Luigi Gonzaga" Medical School, University of Torino, Torino, Italy
Psychiatry, Department of Clinical and Biological Sciences, "San Luigi Gonzaga" Medical School, University of Torino, Torino, Italy
Medical Oncology, Department of Clinical and Biological Sciences, "San Luigi Gonzaga" Medical School, University of Torino, Torino, Italy
Psychiatry, Department of Clinical and Biological Sciences, "San Luigi Gonzaga" Medical School, University of Torino, Torino, Italy
Medical Oncology, Department of Clinical and Biological Sciences, "San Luigi Gonzaga" Medical School, University of Torino, Torino, Italy
Psychiatry, Department of Clinical and Biological Sciences, "San Luigi Gonzaga" Medical School, University of Torino, Torino, Italy
Medical Oncology, Department of Clinical and Biological Sciences, "San Luigi Gonzaga" Medical School, University of Torino, Torino, Italy To the Editor: Depressive disorders consistently worsen the quality of life of long-term surviving patients with cancer. These adverse events are a direct consequence of the diagnosis of malignant disease and/or the antineoplastic treatment administered. The potentiality of antineoplastic treatment to induce depression should be carefully considered in the treatment decision making process, but this issue has been relatively neglected by oncologists. Dalton et al1 investigated the rates of hospitalization for depression in a population-based cohort of more than 600,000 adults with cancer who were observed for up to 30 years. Their results showed an increased risk for depression in the first year after cancer diagnosis compared with that of the general population, with decreasing but still significant excess risk throughout subsequent follow-up years. This trend was found in most cancers at most sites, albeit with some variations. Interestingly, a consistent increased risk of depressive symptoms persisted for 10 or more years after diagnosis in both men and women with hormone-related cancers. However, it must be outlined that a divergent pattern between sexes was observed. The relative risk of depression development in women, in fact, decreased from the first year of follow-up onward but still remained elevated from years 2 to 10 and consistently decreased afterward. On the contrary, in men with hormone-related cancers, the risk of depression showed a decreasing trend from the first to fourth years of follow-up, with a subsequent new increase that reached its maximum after year 10. Dalton et al1 did not provide any explanation on the long-lasting persistence of high incidence of major depressive disorders in patients with hormone-dependent malignant disease; neither did they discuss the different patterns according to sex. The long-term effects of antineoplastic treatment in long-term surviving patients with breast cancer have been repeatedly studied and could be responsible at least in part for the persisting high incidence of depressive disorders. Most patients, in fact, undergo adjuvant treatment after diagnosis, and if a patient is eligible for hormone therapy, this treatment is usually prescribed for 5 years. Chemotherapy and hormone therapy administered in the adjuvant setting lead to vasomotor symptoms, weight gain, and musculoskeletal, genitourinary, and cognitive complaints. It is of note that these side effects have been found to have different distributions according to age. Compared with older women, younger women are at higher risk of weight gain, causing unhappiness with their bodies, and sexual impairment resulting from fear of reduced sexual attractiveness, reduced sexual desire, vaginal discharge, and dyspareunia.2 These features may contribute to a higher risk of depressive symptoms in younger women as opposed to their counterparts. As far as men with prostate cancer are concerned, the association between androgen deprivation therapy and major episodes of depression has been demonstrated in a pilot study.3 Similar to what happens in women, the mechanisms underlying this association may include loss of sexual potency, fatigue, and cognitive impairment,4 as well as changes in body composition, which lead to deterioration of patients' perceptions of their bodies.5 Moreover, a direct correlation between testosterone levels and depressive symptoms has been proven in a cross-sectional study6 of 856 community-dwelling older men; this study showed that depression was inversely associated with bioavailable testosterone, independent of age, weight change, and physical activity. Although lower levels of testosterone in older men have been associated with more depressive symptoms,7,8 these symptoms seem to disappear with testosterone hormone treatment.9,10 A majority of patients with prostate cancer initially receive radical prostatectomy without any adjuvant treatment. Hormone therapy is frequently introduced at the time of serologic or clinical disease progression, which may occur a few years later and may contribute to the new rise in frequency of depressive symptoms observed by Dalton et al1 from the fifth year onward. However, high-risk and older patients preferably receive radiation therapy instead of surgery after diagnosis, and this treatment is usually delivered in association with hormone therapy. Early hormone therapy in these patients may account for the persistence of low to moderate increased risk of depression from the second to fifth years. To support these hypotheses, we believe it would be interesting if Dalton et al1 were to stratify the risk of major depressive disorders over time in patients with hormone-related cancers according to age and whether these patients were receiving concomitant hormone treatment. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES
1. Dalton SO, Laursen TM, Ross L, et al: Risk for hospitalization with depression after a cancer diagnosis: A nationwide, population-based study of cancer patients in Denmark from 1973 to 2003. J Clin Oncol 27:1440–1445, 2009. 2. Ganz PA, Greendale GA, Petersen L, et al: Breast cancer in younger women: Reproductive and late health effects of treatment. J Clin Oncol 21:4184–4193, 2003. 3. Pirl WF, Siegel GI, Goode MJ, et al: Depression in men receiving androgen deprivation therapy for prostate cancer: A pilot study. Psychooncology 11:518–523, 2002.[CrossRef][Medline] 4. Joly F, Alibhai SM, Galica JT, 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 176:2443–2447, 2006.[CrossRef][Medline] 5. Berruti A, Dogliotti L, Terrone C, et al: 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 167:2361–2367, 2002.[CrossRef][Medline] 6. Barrett-Connor E, Von Mühlen DG, Kritz-Silverstein D: Bioavailable testosterone and depressed mood in older men: The Rancho Bernardo study. J Clin Endocrinol Metab 84:573–577, 1999. 7. Seidman SN, Araujo AB, Roose SP, et al: Testosterone level, androgen receptor polymorphism, and depressive symptoms in middle-aged men. Biol Psychiatry 50:371–376, 2001.[CrossRef][Medline] 8. Schweiger U, Deuschle M, Weber B, et al: Testosterone, gonadotropin, and cortisol secretion in male patients with major depression. Psychosom Med 61:292–296, 1999. 9. Wang C, Alexander G, Berman N, et al: Testosterone replacement therapy improves mood inhypogonadal men: A clinical research center study. J Clin Endocrinol Metab 81:3578–3583, 1996.[Abstract] 10. Perry PJ, Yates WR, Williams RD, et al: Testosterone therapy in late-life major depression in males. J Clin Psychiatry 63:1096–1101, 2002.[Medline]
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Copyright © 2009 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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