Adverse Effects Of Androgen Deprivation Therapy Research Articles

Balancing Hormone Therapy: Mitigating Adverse Effects of Androgen-Deprivation Therapy and Exploring Alternatives in Prostate Cancer Management.

Androgen-deprivation therapy (ADT) is well established as the standard of care in metastatic prostate cancer (PCa) management; however, ADT has significant adverse effects (AEs) that must be addressed. This review aims to highlight opportunities to mitigate AEs of ADT and explore alternatives in PCa management. Specifically, we discuss behavioral and pharmacologic strategies for mitigating ADT AEs as well as ADT-sparing approaches for hormone-sensitive and castration-resistant PCa. Equipped with effective mitigation strategies and possible alternatives, clinicians and researchers can optimize health-related quality of life for patients currently receiving ADT for PCa and consider treatments that spare patients from AEs of ADT.

Prevalence of Hand Joint Symptoms in Androgen Deprivation Therapy Among Japanese Patients with Prostate Cancer

Purpose: The current trends in favor of androgen deprivation therapy (ADT) for nonmetastatic prostate cancer at the stage of biochemical recurrence or increasing prostate-specific antigen levels raise the issue of exposing asymptomatic patients to potential adverse effects over the longer term. The aim of this study is to assess the hand joint symptoms caused by ADT in Japanese patients with prostate cancer. Materials and Methods: We retrospectively reviewed and performed a cross-sectional survey of hand joint symptoms in patients receiving ADT for prostate cancer. The results were compared with a control group of patients with prostate cancer that was hormone-naïve group. In total, there were 279 Japanese patients with prostate cancer, of whom 150 patients were ADT treated and 129 patients were hormone naïve. Patients completed a three-item self-administered questionnaire assessing the presence of hand joint symptoms that started or worsened after initiating ADT. Results: A statistically significant difference was found between the incidence rates of hand joint symptoms of both groups (P = 0.0056). There was a statistically significant difference in the incidence rates of hand joint pain (P = 0.0273). However, the incidence rates of hand numbness (P = 0.0576) and hand muscle weakness (P = 0.1098) between both groups were not significantly different. Conclusion: Our cross-sectional study demonstrated that patients receiving ADT for prostate cancer show significant hand joint symptoms compared to hormone-naïve patients. Consequently, for patients receiving ADT who suffer from hand joint symptoms, we must consider the adverse effects of ADT.

Degarelix versus luteinizing hormone-releasing hormone agonists for the treatment of prostate cancer

ABSTRACTIntroduction: Androgen deprivation therapy (ADT) is the mainstay for advanced, hormone-sensitive prostate cancer, and options include surgical castration, luteinizing hormone-releasing hormone (LHRH) agonist, and more recently, gonadotropin releasing hormone (GnRH) antagonist therapy. Our understanding of the mechanisms and adverse effects of ADT has increased substantially, including the class-specific adverse effects of ADT.Areas covered: This review will summarize the pharmacodynamic and pharmacokinetic properties of the GnRH antagonist degarelix and its role in the management of advanced prostate cancer, the clinical evidence supporting its regulatory approval, as well as potential benefits and disadvantages over traditional LHRH agonist therapy.Expert opinion: Degarelix represents a newer class of ADT that results in a rapid and reliable decline in serum testosterone, a quality that makes it particularly advantageous in men presenting with symptomatic, hormone-sensitive prostate cancer. Due to differences in mechanism of action, there is observational data suggesting a potential cardiovascular and even oncologic benefit over traditional LHRH agonist therapy. Further research is ongoing to more clearly define this potential benefit.

Adverse effects of ADT on cognitive function and dementia for men with prostate cancer: A meta-analysis and systematic review.

150 Background: Nearly 50% of men diagnosed with prostate cancer may receive treatment with some form of androgen deprivation therapy (ADT). While some side effects of ADT are well acknowledged, the specific impact of ADT on cognitive function is uncertain. Our objective was to perform a systematic review and meta-analysis assessing the impact of ADT on overall cognitive decline, and the risks of Alzheimers, Parkinson’s disease. Methods: Relevant studies were identified through search of English language articles indexed in PubMed Medline, PsycINFO, Cochrane Library and Web of Knowledge/Science. First, we assessed rates of cognitive decline in five cohorts from three studies. Second, we assessed rates of Alzheimer’s or Parkinson disease using three large retrospective studies. A pooled-analysis was conducted using a meta-analysis. Weighted averages were reported as odds ratios (OR) with 95% confidence intervals (CI) using RevMan and a DerSimonian and Laird random-effects model. The heterogeneity test was measured using the Q-Mantel-Haenszel ( P< 0.10 was considered of significant heterogeneity). Results: With respect to overall cognitive decline (defined as scoring 1.5 standard deviations [SD] in two or more objective cognitive tests), patients receiving ADT had higher odds of overall cognitive decline than patients with prostate cancer not treated with ADT or health controls (OR: 2.03, 95% CI: 1.42–2.90). Furthermore, men with a history of ADT for prostate cancer had higher odds of developing Alzheimer’s and Parkinson dementia compared to men with prostate cancer not treated with ADT (OR: 1.32, 95% CI: 1.27–1.37). Conclusions: Men receiving ADT for prostate cancer performed significantly worse on measures of overall cognitive function. Additionally, results from the three large observational trials included suggest men exposed to ADT for prostate cancer have higher rates of Parkinson/Alzheimer’s compared to men without ADT.

A preliminary evaluation of the TrueNTH androgen deprivation therapy educational program.

219 Background: Androgen deprivation therapy (ADT) is the most common systemic treatment for prostate cancer (PCa), but has many adverse effects that reduce patients’ quality of life and that of their partners. In 5 Canadian cities, we offer an educational program designed to help PCa patients and their partners manage ADT side effects as well as maintain a strong dyadic relationship despite changes that accompany ADT. Methods: Patients on or about to start ADT and their partners participate in a 1.5 hour educational session. Patients receive a copy of the 2014 book, Androgen Deprivation Therapy: An essential guide for men with prostate cancer and their partners (DEMOS Health, NY) which discusses how to manage ADT side effects and how to make effective lifestyle changes to maintain a good quality of life. To date, 358 patients and 220 partners have attended the ADT class. A subset (32%) of participants elected to complete questionnaires at baseline and again 2 to 3 months later to assess the program efficacy. Results: At the time of the ADT class, patients who have been on ADT for ≥ 2 months had more frequent side effects (e.g., hot flashes and breast tenderness), and were more bothered by hot flashes. They also reported worse self-efficacy for managing weight gain and diabetes than those who have been on ADT for < 2 months. However, at 2 to 3 months after the class, patients’ self-efficacy for managing ADT side effects improved, despite experiencing more side effects and more bother associated with those side effects. Notably, patients who were on ADT for a shorter duration (< 2 months), who have attended the class, had less bother associated with hot flashes and better self-efficacy for managing weight gain than those who had been on ADT longer before attending the class. Conclusions: The TrueNTH ADT Educational Program potentially dampens side effect bother and improves self-efficacy for two of the most troublesome adverse effects of ADT, hot flashes and weight gain respectively. The program is most beneficial when offered to patients just starting on ADT. Future analyses will focus on exercise behaviour and dyadic relationship to assess the program’s effectiveness in encouraging a healthy lifestyle and maintain strong dyadic bonds in the face of ADT.

Integrating diet and exercise into care of prostate cancer patients on androgen deprivation therapy.

Improved diagnosis and treatment regimens have resulted in greater longevity for men with prostate cancer. This has led to an increase in both androgen deprivation therapy (ADT) use and duration of exposure, and therefore to its associated adverse effects, such as sexual dysfunction, osteoporosis, reduced muscle mass, increased fat mass, and increased incidence of cardiovascular disease and type 2 diabetes. Given that the adverse effects of ADT are systemic, often debilitating, and difficult to treat, efforts continue in the development of new strategies for long-term management of prostate cancer. The PubMed database was searched to select trials, reviews, and meta-analyses in English using such search terms as “prostate cancer” and “androgen deprivation therapy”, “cardiovascular risk”, “lean body mass”, “exercise”, and “diet”. The initial searches produced 379 articles with dates 2005 or more recent. Articles published after 2004 were favored. This review utilizes the latest data to provide a status update on the effects of exercise and diet on patients with prostate cancer, focusing on ADT-associated side effects, and it discusses the evidence for such interventions. Since the evidence of large-scale trials in patients with prostate cancer is missing, and an extrapolation of supporting data to all patient subgroups cannot be provided, individualized risk assessments remain necessary before the initiation of exercise and diet programs. Exercise, diet, and nutritional supplementation interventions have the potential to provide effective, accessible, and relatively inexpensive strategies for mitigating ADT-associated toxicities without introducing additional adverse effects.

The adverse effects of androgen-deprivation therapy: Comparison between gonadotropin-releasing hormone agonists and orchiectomy in the SEER-Medicare population.

304 Background: Androgen-deprivation therapy (ADT) through surgical castration is equally effective as medical castration in controlling prostate cancer (PCa). However, the adverse effect profiles of both ADT groups have never been compared. Our objective was to provide a comparative effectiveness analysis of the adverse effects of gonadotropin-releasing hormone agonists (GnRHa) vs. bilateral orchiectomy in a homogeneous population. Methods: A total of 3295 men with metastatic PCa aged ≥ 66 years old, treated with GnRHa or bilateral orchiectomy between 1995 and 2009 were identified. Multivariable competing-risks regression models were performed, with the adjustment of all-cause mortality and treatment propensity score. Secondary analyses examined the effect of increasing duration of GnRHa treatment, and expenditures. Our main examined measures were: [1] any fractures, [2] peripheral arterial disease, [3] venous thromboembolism, [4] cardiac-related complications, [5] diabetes mellitus, [6] cognitive disorders, and [7] total expenditures. Results: In adjusted analyses, orchiectomy was associated with significantly lower risks of any fracture (HR: 0.80, 95% CI: 0.65–0.97), peripheral arterial disease (HR: 0.70, 95% CI: 0.53–0.92), and cardiac-related complications (HR: 0.82, 95% CI: 0.69–0.97) compared to those treated with GnRHa. No statistically significant difference was noted between orchiectomy and GnRHa for diabetes and cognitive disorders. When compared to individuals treated for ≥ 35 months with GnRHa, the increased risk for GnRHa compared to orchiectomy was noted for fractures, peripheral arterial disease, venous thromboembolism, cardiac-related complications, and diabetes mellitus (HR: 1.69, 2.19, 1.60, 1.62, and 1.36, respectively, all P≤ 0.04). No difference with respect to total expenditures was observed between GnRHa and orchiectomy (odds ratio [OR]: 1.21, 95% CI: 0.92–1.58). Conclusions: GnRHa was associated with higher risks in 3/7 examined adverse effects: any fractures, peripheral arterial disease rates, and cardiac-related complications.

Association between weight gain and sarcopenic obesity in patients treated with androgen deprivation therapy.

189 Background: Weight gain in response to androgen deprivation therapy (ADT) can be a marker for adverse effects of ADT. However, a concomitant decrease in lean mass in response to ADT may decrease the utility of weight gain in terms of sarcopenia. Therefore, the goal of the present study was to analyze the relationship among weight gain, obesity, and sarcopenia in patients undergoing ADT. Methods: Patients with prostate cancer who were hormone-naïve and scheduled to receive long-term ADT were recruited between 2011 and 2013. Body weight and results from blood tests of lipid and glucose metabolism were recorded every 3 months during 1 year of ADT. Computed tomography (CT) was performed to measure areas of subcutaneous and visceral fat and the psoas muscle before and after 1-year of ADT. ADT was limited to a luteinizing hormone-releasing hormone agonist with or without bicalutamide. Results: CT was performed in 72 patients before and after 1 year of ADT. Median age was 74 years (49-83). Median prostate-specific antigen before ADT was 21.9 ng/ml (0.3-3316). Clinical stage was B (43.1%), C (26.4%), and D (29.2%). Mean increase in weight was 2.7% after 1 year of ADT. Mean increase in the area of subcutaneous and visceral fat was 31.3% and 20.7%, respectively. Mean change in the area of the psoas muscle was -8.4%. When patients were divided into two groups according to weight change during 1 year of ADT (Group A (n = 34): weight gain < 3.0%, Group B (n = 38): weight gain ≥ 3.0%), an increase in subcutaneous and visceral fat was significantly more frequent in Group B, whereas the frequency of a decrease in psoas muscle area was not significantly different between the two groups (Group A: -9.5%, Group B: -7.5%, P = 0.11). Pearson correlation coefficients showed a moderate relationship between weight gain and fat accumulation (r = 0.44-0.52), but little relationship between weight gain and a decrease in psoas muscle area (r = 0.18). Conclusions: Fat accumulation tended to increase in patients who gained weight during ADT, whereas a decrease in psoas muscle area was not related to weight change. Sarcopenia could occur despite weight change during ADT. Clinical trial information: UMIN000018478.

Targeting muscle signaling pathways to minimize adverse effects of androgen deprivation.

Androgen deprivation therapy (ADT) is a highly effective treatment used in ∼30% of men with prostate cancer. Adverse effects of ADT on muscle are significant with consistent losses in muscle mass. However, effects of ADT on muscle strength and physical function, of most relevance to the patient, are less well understood. This is in part due to the fact that muscle effects of ADT at the cellular, genetic and protein level, critical to the understanding of the pathophysiology of sarcopenia, have come into focus only recently. This review highlights the complexity of androgen-dependent signaling in muscle with an emphasis on recent findings in the regulation of muscle growth and muscle atrophy pathways. Furthermore, the effects of ADT and testosterone on skeletal muscle histology, gene expression and protein transcription are discussed. A better mechanistic understanding of the regulation of muscle mass and function by androgens should not only pave the way for developing targeted promyogenic interventions for men with prostate cancer receiving ADT but also may have wider implications for age-associated sarcopenia in the general population.

Experience with androgen deprivation therapy for prostate cancer in Japan and future perspectives.

Novel anti-androgens and androgen biosynthesis inhibitors have been developed to treat castration-resistant prostate cancer. However, knowledge of androgen deprivation therapy (ADT) has not been developed in the criticism, including information regarding the adverse effects of hormonal therapy. We hypothesize that there are ethnic differences in the efficacy and adverse effects of ADT; therefore, this review summarizes the experience of ADT, mainly in Japan. A risk stratification instrument, the Japan Cancer of the Prostate Risk Assessment (J-CAPRA) score, was developed based on the Japan Study Group of Prostate Cancer registry, which is a large, multicenter, population-based database. It revealed that clinical outcomes were substantially better for males treated with ADT in Japan compared with those in the United States. Moreover, there were small survival differences in patients with localized and locally advanced cancer who received local therapy and primary ADT in another Japanese cohort study. In terms of adverse effects, including bone loss and cardiovascular risk, ADT appears to be better tolerated in Japanese populations than in Western cohorts. An ongoing randomized controlled trial of a trimodality treatment comprising brachytherapy, external beam radiation therapy, and neoadjuvant with or without adjuvant ADT in patients with localized high-risk prostate cancer will provide novel insights regarding adjuvant ADT. As a future perspective, the optimal selection of the type of primary ADT, including combining androgen blockade and novel hormonal compounds, adjusted according to each patient's clinicopathological background, may provide better clinical outcomes in patients with advanced prostate cancer.

Adverse effects of androgen-deprivation therapy in prostate cancer and their management.

To provide an up-to-date summary of current literature on the management of adverse effects of androgen-deprivation therapy (ADT). All relevant medical literature on men with prostate cancer treated with ADT from 2005 to 2014, and older relevant papers, were reviewed. Recent health advisory statements from the Australian government, societies and advocacy groups have been incorporated to the document. There are numerous adverse effects of ADT that require pro-active prevention and treatment. Ranging from cardiovascular disease, diabetes and osteoporosis, to depression, cognitive decline and sexual dysfunction, the range of adverse effects is wide. Baseline assessment, monitoring, prevention and consultation from a multidisciplinary team are important in minimising the harm from ADT. This review provides a series of practical recommendations to assist with managing the adverse effects of ADT.

Synergistic action of image-guided radiotherapy and androgen deprivation therapy.

The combined use of androgen deprivation therapy (ADT) and image-guided radiotherapy (IGRT) can improve overall survival in aggressive, localized prostate cancer. However, owing to the adverse effects of prolonged ADT, it is imperative to identify the patients who would benefit from this combined-modality therapy relative to the use of IGRT alone. Opportunities exist for more personalized approaches in treating aggressive, locally advanced prostate cancer. Biomarkers--such as disseminated tumour cells, circulating tumour cells, genomic signatures and molecular imaging techniques--could identify the patients who are at greatest risk for systemic metastases and who would benefit from the addition of systemic ADT. By contrast, when biomarkers of systemic disease are not present, treatment could proceed using local IGRT alone. The choice of drug, treatment duration and timing of ADT relative to IGRT could be predicated on these personalized approaches to prostate cancer medicine. These novel treatment intensification and reduction strategies could result in improved prostate-cancer-specific survival and overall survival, without incurring the added expense of metabolic syndrome and other adverse effects of ADT in all patients.

Low rate of bone density testing in men receiving androgen deprivation therapy

Low rate of bone density testing in men receiving androgen deprivation therapy

Muscle function, physical performance and body composition changes in men with prostate cancer undergoing androgen deprivation therapy

Prostate cancer (PCa) is the most common visceral malignancy in men with androgen deprivation therapy (ADT) the preferred therapy to suppress testosterone production and hence tumor growth. Despite its effectiveness in lowering testosterone, ADT is associated with side effects including loss of muscle mass, diminished muscle strength, decrements in physical performance, earlier fatigue and declining quality of life. This review reports a survey of the literature with a focus on changes in muscle strength, physical function and body composition, due to short-term and long-term ADT. Studies in these areas are sparse, especially well-controlled, prospective randomized trials. Cross-sectional and longitudinal data (up to 2 years) for men with PCa treated with ADT as well as patients with PCa not receiving ADT and age-matched healthy men are presented when available. Based on limited longitudinal data, the adverse effects of ADT on muscle function, physical performance and body composition occur shortly after the onset of ADT and tend to persist and worsen over time. Exercise training is a safe and effective intervention for mitigating these changes and initial guidelines for exercise program design for men with PCa have been published by the American College of Sports Medicine. Disparities in study duration, types of studies and other patient-specific variables such as time since diagnosis, cancer stage and comorbidities may all affect an understanding of the influence of ADT on health, physical performance and mortality.

Andropause Syndrome in Men Treated for Metastatic Prostate Cancer

Androgen deprivation therapy (ADT) has become the cornerstone of treatment for men with metastatic prostate cancer. However, treatments are associated with a number of adverse effects that collectively are referred to as andropause syndrome, or the male menopause. This study explored the experience and impact of andropause symptoms, particularly hot flashes, among men undergoing ADT for metastatic prostate cancer. Twenty-one men receiving ADT for metastatic prostate cancer underwent a qualitative interview focusing on the adverse effects of ADT and the impact of these symptoms on daily living and coping strategies. The most frequently mentioned adverse effects were hot flashes and night sweats, gynecomastia, cognitive decline, and changes in sexual function. Hot flashes did impact on everyday functioning, and night sweats regularly disturbed sleep patterns and led to participants feeling tired and irritable. Participants reported a lack of control over their hot flashes and night sweats. There was reluctance among our sample to disclose the type of symptoms experienced to others. The occurrence of andropause symptoms, including hot flashes and night sweats, was common among this sample. Participants reported a range of cognitive and behavioral responses to these symptoms. There was some reluctance about discussing a prostate cancer diagnosis or the occurrence of symptoms with others. The findings have implications for a range of individual and couple interventions to manage the impact of this constellation of symptoms.

Adding short-term androgen-deprivation therapy to radiotherapy improved survival in localized prostate cancer

ACP Journal Club15 November 2011Adding short-term androgen-deprivation therapy to radiotherapy improved survival in localized prostate cancerSteven E. Canfield, MDSteven E. Canfield, MDUniversity of Texas Medical School at Houston, Houston, Texas, USA (S.E.C.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-155-10-201111150-02007 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationJones CU, Hunt D, McGowan DG, et al. Radiotherapy and short-term androgen deprivation for localized prostate cancer. N Engl J Med. 2011;365:107-18. https://pubmed.ncbi.nlm.nih.gov/21751904Clinical Impact RatingsGIM/FP/GP: References1 Bannuru RR, Dvorak T, Obadan N, et al. Comparative evaluation of radiation treatments for clinically localized prostate cancer: an updated systematic review. Ann Intern Med. 2011;155:171-8. [PMID: 21646550] Google Scholar2 Taylor LG, Canfield SE, Du XL. Review of major adverse effects of androgen-deprivation therapy in men with prostate cancer. Cancer. 2009;115:2388-99. [PMID: 19399748] Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Texas Medical School at Houston, Houston, Texas, USA (S.E.C.)This article was published at Annals.org on 1 November 2011. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byGenomic analysis of DNA repair genes and androgen signaling in prostate cancer 15 November 2011Volume 155, Issue 10Page: JC5-7KeywordsAdenocarcinomaAndrogensCancer treatmentHormonal therapyLymph nodesProstate cancerSurvival analysis ePublished: 15 November 2011 Issue Published: 15 November 2011 Copyright & PermissionsCopyright © 2011 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...

The role of exercise in managing the adverse effects of androgen deprivation therapy in men with prostate cancer

Background: Androgen deprivation therapy (ADT) is used in the treatment of prostate cancer; however, the side effects of this therapy can be detrimental to a man’s physical and mental health. There has been a growing interest in exercise as a management strategy for many of these problems.Objectives: The aim of this paper is to critically review the ways that resistance and aerobic exercise can ameliorate the adverse effects of ADT in men with prostate cancer. We also provide guidelines for exercise prescription and suggestions to improve adherence.Methods: Studies investigating the effectiveness of exercise for men receiving ADT were reviewed. The online MEDLINE database was searched systematically using appropriate keywords. Citation tracking from these retrieved papers was also used.Major findings: Moderate to high intensity exercise has been shown to reduce the negative impact of many of the side effects of ADT such as muscle loss, decreased strength, fatigue, decreased functional performance, and impaired quality of life.Conclusion: Exercise should be viewed as a primary way to combat the detrimental effects of ADT. Men starting or already undergoing this treatment should be given guidelines for resistance and aerobic exercises.

Localized Prostate Cancer—What the Medical Oncologist Needs to Know

Prostate cancer is the most commonly diagnosed cancer among men and the second leading cause of cancer-related deaths among men in the US. In the post-prostate specific antigen (PSA) era, about 85% of all prostate cancers diagnosed are clinically localized prostate cancers. Most cancers are diagnosed in asymptomatic men, and T1c (stage I) is the most commonly diagnosed stage of prostate cancer. Consequently, medical oncologists are increasingly being asked to participate in multidisciplinary prostate cancer clinics and provide recommendations on localized prostate cancer, particularly related to active surveillance as well as neoadjuvant and adjuvant therapies such as androgen deprivation therapy (ADT) and chemotherapy. This article reviews the potential role of the medical oncologist as a team member in the management of localized prostate cancer. The role of active surveillance as well as neo-adjuvant and adjuvant therapies such as ADT and chemotherapy is discussed in detail. The long-term adverse effects of ADT and potential supportive measures are also reviewed.