Side Effects Of Androgen Deprivation Therapy Research Articles

Effects of Androgen Deprivation on Cerebral Morphometry in Prostate Cancer Patients – An Exploratory Study

BackgroundAndrogen deprivation therapy (ADT) is a common treatment for non-metastatic, low-risk prostate cancer, but a potential side effect of ADT is impaired brain functioning. Previous work with functional magnetic resonance imaging (MRI) demonstrated altered prefrontal cortical activations in cognitive control, with undetectable changes in behavioral performance. Given the utility of brain imaging in identifying the potentially deleterious effects of ADT on brain functions, the current study examined the effects of ADT on cerebral structures using high resolution MRI and voxel-based morphometry (VBM).MethodsHigh resolution T1 weighted image of the whole brain were acquired at baseline and six months after ADT for 12 prostate cancer patients and 12 demographically matched non-exposed control participants imaged at the same time points. Brain images were segmented into gray matter, white matter and cerebral ventricles using the VBM toolbox as implemented in Statistical Parametric Mapping 8.ResultsCompared to baseline scan, prostate cancer patients undergoing ADT showed decreased gray matter volume in frontopolar cortex, dorsolateral prefrontal cortex and primary motor cortex, whereas the non-exposed control participants did not show such changes. In addition, the decrease in gray matter volume of the primary motor cortex showed a significant correlation with longer reaction time to target detection in a working memory task.ConclusionsADT can affect cerebral gray matter volumes in prostate cancer patients. If replicated, these results may facilitate future studies of cognitive function and quality of life in men receiving ADT, and can also help clinicians weigh the benefits and risks of hormonal therapy in the treatment of prostate cancer.

Predictors of biochemical failure in patients undergoing prostate whole-gland salvage cryotherapy: a novel risk stratification model

Predictors of biochemical failure in patients undergoing prostate whole-gland salvage cryotherapy: a novel risk stratification model

High-risk prostate cancer

High-risk prostate cancer (PCa) harbours a risk of local, regional and systemic relapse requiring the combination of a loco-regional treatment such as external beam radiotherapy for controlling the pelvic-confined disease, combined with an androgen deprivation therapy (ADT) to potentiate irradiation and to destroy the infraclinical androgen-dependent disease outside the irradiated volume. Many phase III randomized trials issued from the Radiation Therapy Oncology Group (USA) and from the EORTC Radiation Oncology Group have paved the way for establishing the indications of this combined approach. For locally advanced PCa, the combination needs a long-term ADT (≥2 years) with luteinizing hormone-releasing hormone agonists. For high-risk localized PCa, the combination requires a 6-month complete androgen blockade. Image-guided intensity-modulated radiotherapy has replaced conventional irradiation and allows a dose escalation, improving the local control without increasing the toxicity. A multidisciplinary approach will enable physicians to tailor the treatment policy and a close cooperation with general practitioners and specialists will be set up to prevent as much as possible the side-effects of ADT.

Capsule Commentary on Shahinian et al.: Patterns of Bone Mineral Density Testing in Men Receiving Androgen Deprivation for Prostate Cancer

This analysis of SEER-Medicare data by Shahinian and Kuo compared bone mineral density (BMD) testing in prostate cancer survivors on androgen deprivation therapy (ADT) to prostate cancer survivors who were not receiving ADT.1 BMD testing in the men on ADT increased from less than 1% in 1996 to 11.5% in 2008. While BMD testing increased in the prostate cancer survivors not on ADT, it occurred at a much lower rate, increasing from less than 1% to 4.4%. This increase in BMD testing is not surprising and is clinically appropriate given that ADT use is associated with an increased risk of osteoporosis and fractures. The authors also show that patients who were cared for by a urologist alone were significantly less likely to undergo BMD testing than those cared for by both a urologist and a primary care physician (PCP). Given what we know about the bony side effects of ADT, why isn’t BMD testing more common? I believe that the answer lies not in the specialty of the treating physician but in the clinical uncertainty of what to do with the results of BMD testing when ordered. Obviously, if the test finds that the patient is osteoporotic, some type of treatment should be initiated, but should this be an oral alendronate, intravenous zoledronic acid or subcutaneous denosumab, all of which have been shown to be effective in preventing further bone loss?2–4 Furthermore, if BMD testing shows osteopenia or is normal, should one of these agents be used for prevention? The National Comprehensive Cancer Network (NCCN) guidelines on the treatment of prostate cancer suggest initiating treatment in patients at certain increased levels of fracture risk, based upon the FRAX nomogram from the World Health Organization.5 The guidelines, however, do not provide guidance on the frequency of BMD testing and are based primarily on expert opinion. Acknowledging these limitations, these guidelines still provide useful information for clinicians, and, as such, urologists and PCPs need to be more aware of bone health in prostate cancer survivors on ADT and perform BMD testing more often.

Quality of life in patients receiving herbal therapy for biochemically recurrent prostate cancer.

e16073 Background: Men who experience biochemical recurrence after curative therapy for prostate cancer are often treated with androgen deprivation therapy (ADT), though there is no proven survival benefit in this setting. Side effects of ADT negatively impact quality of life (QOL). There is interest in alternative therapies to control PSA without ADT side effects. In conjunction with clinical testing of prostate health cocktail (PHC), a combination herbal therapy for men with biochemically recurrent prostate cancer, we surveyed QOL in trial subjects who were still receiving PHC (n=11), or had moved on to ADT (n=12) or observation (n=16). Methods: Subjects were surveyed using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) instrument, in which respondents report their level of physical and psychological functioning during the past 7 days. The survey was completed in person, by phone, by mail or via online submission. Results: Of the 40 men (93% of total trial subjects) who responded to the survey, the median age was 66 (range 54-84) and PSA was 2.8 (range 1.1-84). 23% had received radiation as primary treatment, 25% radical prostatectomy, and 52% had received both. One patient was receiving radiation at the time of survey and was excluded. In the Physical Well-Being domain, which assesses energy, feeling ill, nausea, pain and trouble meeting needs, there was a significantly lower score among men receiving ADT (median 25; 95% CI 23.5-26.2) compared to those taking PHC (26.5; CI 24.2-27.8) or being observed (28; 26.4-28) (p =0.006). There was no significant difference among the groups in the other domains, though within the Prostate Cancer-Specific Concerns domain significantly more men indicated they were "not at all" able to have/maintain erections in the ADT group (11/12) compared to PHC (6/11) and observation (5/15) (p=0.009). Conclusions: Decisions about treatment for rising PSA levels after curative-intent therapy must be informed by therapeutic value as well as consideration for QOL. We found that men being treated with ADT have a significantly lower physical function score, and the relatively high QOL for patients on a clinical trial of an herbal supplement was similar to that of patients being observed. Clinical trial information: NCT00669656.

Osteoporosis Management Program Decreases Incidence of Hip Fracture in Patients With Prostate Cancer Receiving Androgen Deprivation Therapy

To evaluate the incidence of hip fracture in men with prostate cancer receiving androgen deprivation therapy (ADT). One of the detrimental side effects of ADT for prostate cancer is osteoporosis. Through an osteoporosis prevention program implemented in our healthcare system, the patients at risk undergo dual x-ray absorptiometry scans and receive treatment if the T-score indicates bone loss. We evaluated the incidence of hip fracture in men with prostate cancer who were receiving ADT through a retrospective, cohort study conducted within a managed care organization. The participants were all men newly diagnosed with prostate cancer from January 2003 to December 2007 receiving leuprolide injections. Patients who had had a dual x-ray absorptiometry scan beginning 3 months before the index date through the end of study were included in the intervention group; all others were included in the comparison group. The main outcome of interest was a hip fracture occurring after the index date, excluding cancer pathologic fractures, traumatic fractures, and fractures associated with epilepsy. A total of 1071 patients were in the intervention group, and 411 were in the comparison group. In the intervention group, 18 hip fractures occurred compared with 17 in the comparison group. The incidence rate of hip fractures per 1000 person-years was 5.1 (95% confidence interval 3.0-8.0) in the intervention group and 18.1 (95% confidence interval 10.5-29.0) in the comparison group. The incidence rate of hip fracture in this population was reduced >70% with enrollment in an osteoporosis management system, avoiding this morbid complication of ADT.

Mortality following hip fractures in men with prostate cancer.

49 Background: Rapid loss of bone-mineral density is a known side-effect of androgen deprivation therapy (ADT) for prostate cancer (PCa). Hip fractures are also independently associated with risk of mortality. To our knowledge few population-based observational studies have yet investigated the risk of dying following fractures among men with PCa. We aimed to assess skeletal-related events and mortality in more detail by specifically studying the link between hip fractures in PCa men and risk of death. Methods: PCBaSe Sweden 2.0 is based on the National Prostate Cancer Register and contains age and county matched men free of PCa. We selected all men (n=14,205) who had been hospitalized with a hip fracture, as registered in the National Patient Register, between 2006 and 2010. A total of 2300 were diagnosed with PCa before the hip fracture and 66% of them were treated with ADT. The main outcome was death as registered in the National Cause of Death Register. The risk of death was estimated using multivariate Cox Proportional Hazards regression analyses and standardized mortality ratios (SMRs) taking into account PCa risk category, history of fractures, civil status, Charlson Comorbidity Index, and treatment with bisphosphonates. Results: In the analysis for risk of death >90 days after a hip fracture, there was an increased risk of death among PCa men on ADT, especially those aged <84 years (e.g., HR at 3-6 months after hip fracture: 2.47 (95%CI: 1.85-3.30) compared to men free of PCa with a hip fracture). The SMRs showed that PCa men on ADT who got a hip fracture were seven times more likely to die than expected in the reference population of all men with PCa, whereas PCa men who were not on ADT and had a hip fracture were 13 times more likely to die than expected in this reference population. However, the absolute risk difference between men with and without a hip fracture was 30 per 1,000 person-years when evaluating the effect of a hip fracturing among men on ADT, whereas a hip fracture would cause an additional 20 per 1,000 person-years to die among PCa men without ADT as well as among men free of PCa. Conclusions: Our SMRs and absolute risk calculations show that hip fractures are more dangerous in PCa men treated with ADT than in PCa men without ADT or in men free of PCa.

Androgen deprivation therapy: evidence‐based management of side effects

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The benefits of androgen deprivation therapy (ADT) are well recognized and a multitude of studies have documented the benefits of ADT in conjunction with other therapies. Given the widespread use of ADT due to its important clinical implications, it is imperative that clinicians understand the side effects to limit treatment-related morbidity. There are numerous well recognized adverse effects of ADT, including vasomotor flushing, loss of libido and impotence, fatigue, gynaecomastia, anaemia, osteoporosis and metabolic complications, as well as effects on cardiovascular health and bone density. Present study focuses on the most recent evidence-based treatment options for various side effects of ADT. To familiarize clinicians with the various side effects of androgen deprivation therapy (ADT). The present study focuses on the most recent evidence-based treatment strategies for the common side effects of ADT. A PubMed database search was conducted from 2000 to 2012. All prospective clinical studies were selected, including randomized and non-randomized clinical trials, as well as meta-analysis studies concerning preventive and therapeutic interventions for various side effects of ADT. 'The Oxford 2011 Levels of Evidence' classification system for treatment benefits was used to categorize selected studies. Gabapentin shows moderate efficacy for the long-term treatment of hot flashes in a dose-dependent manner. A combined resistance/aerobic exercise programme leads to significant improvement in fatigue, sexual function and cognitive function. A home-based/group exercise programme also improves fatigue and unfavourable metabolic changes. Denosumab increases lumbar spine, hip and radius bone mass density, and also reduces the risk of vertebral fractures in men receiving ADT for non-metastatic prostate cancer. Metformin coupled with lifestyle intervention is a safe, well-tolerated intervention for adverse metabolic changes. Toremifene improves the lipid profile. Intermittent ADT improves early side effects, such as hot flashes, sexual activity, fatigue, and quality of life, although its effect on long-term side effects remains inconclusive. Despite significant improvement in management strategies for the side effects of ADT, the best way of preventing side effects is to use ADT only when it is absolutely indicated.

Osteoporosis knowledge, health beliefs, and healthy bone behaviours in patients on androgen‐deprivation therapy (ADT) for prostate cancer

To describe in patients with prostate cancer, receiving androgen-deprivation therapy (ADT): (i) knowledge, self-efficacy (SE), and health beliefs about osteoporosis (OP); (ii) current engagement in healthy bone behaviours (HBBs). To explore the relationships between knowledge, SE, and health beliefs, and engagement in HBBs. 175 patients receiving ADT by injection completed questionnaires assessing current HBBs, OP knowledge, SE, and health beliefs (motivation, perceived susceptibility, and seriousness). Descriptive statistics and independent samples t-tests were used to assess relationships between knowledge, SE, health beliefs, and engagement in HBBs. Only 38% of patients had undergone a dual X-ray absorptiometry scan in the past 2 years. OP knowledge was low (mean [sd, range] 9.6 [4.4, 0-19]) and perceived SE moderate (84.7 [24.5, 0-120]). Health motivation was fairly high (23.6 [3.1, 6-30]), but perceived susceptibility (16.8 [4.3]) and seriousness (16.8 [4.2]) of OP were low. Few patients met the recommendations for vitamin D intake (42%) and exercise (31%), and 15% were at risk of over-supplementation of calcium. Patients taking calcium supplements (P = 0.04), and meeting guidelines for vitamin D (P = 0.008) and for exercise (P = 0.002) had significantly greater knowledge than those who did not. Patients who were engaging in less than four of five HBBs had lower knowledge (P < 0.001) and health motivation (P = 0.01) than those who were engaging in four or all five HBBs. Most patients who are receiving ADT are not receiving appropriate screening, lack basic information about bone health, and are not engaging in the appropriate HBBs. These findings support the application of the Health Belief Model in this population: interventions that teach patients about the implications of bone loss, encourage proper uptake of HBBs, and promote feelings of SE could increase engagement in HBBs to prevent and manage bone loss.

Androgen Deprivation Therapy and Cardiovascular Risk

Androgen deprivation therapy (ADT) is an established therapy for metastatic prostate cancer (PC) and some cases of locally advanced and/or localized PC (1). However, concerns have been raised about the cardiovascular side effects of ADT and their impact on the survival of elderly patients with PC (1). Several studies have demonstrated an increased incidence of coronary heart disease, heart failure and acute myocardial infarction in patients on ADT. For instance, in a study on 1015 patients that received ADT (mean duration: 4.1 months), the use of ADT statistically significantly increased the risk of death from cardiovascular causes (HR = 2.6, P = 0.002) (2). In another study on 22816 patients with PC, multivariate analysis revealed that ADT significantly increased cardiovascular morbidity (3). Regardless of the studies that indicate the correlation of ADT with increased cardiovascular risk, surprisingly little is known on the potential mechanisms. ADT increases insulin concentration despite unchanged plasma glucose, which is suggestive of insulin resistance (4). Peripheral resistance to insulin can induce or precipitate type 2 diabetes mellitus (DM) and metabolic syndrome (4). Furthermore, ADT changes the body mass composition as it leads to muscular atrophy and an increase in subcutaneous fat, a situation characterized as “sarcopenic obesity” (5). A study in patients on ADT (mean duration: 3 months) has shown a 4.3% increase in fat mass and a 1.4% decrease in lean body mass (6). Moreover, studies have demonstrated that ADT is associated with dyslipidemias, lower levels of high density lipoprotein and higher levels of triglycerides, total cholesterol and low density lipoprotein concentrations (7). Furthermore, Chen et al. (8) revealed that long-term ADT (mean duration: 2.5 years) significantly decreased the levels of apolipoproteins I and II. Lastly, Nishiyama et al. (9) demonstrated that after 6 months of ADT, body weight, levels of fasting blood sugar, serum total cholesterol, blood urea nitrogen, compensated calcium, inorganic phosphorus, bone-specific alkaline phosphatase, and compensated urinary deoxypyridinoline increased significantly Arterial stiffness increase is another potential mechanism explaining the increased cardiovascular risk in patients on ADT. In a relevant study, arterial stiffness was assessed with pulse-wave analysis (10). After 3 months of ADT, the augmentation index increased from 24% to 29% (P = 0.003), while the timing of wave reflection was reduced from 137 to 129 msec (P = 0.003). Fat mass increased from 20.2 to 21.9 kg (P = 0.008), whereas lean body mass decreased from 63.2 to 61.5 kg (P = 0.016). In a subgroup of patients whose treatment was discontinued after 3 months, the augmentation index decreased from 31% at month to 29% at month 6, in contrast to patients receiving continuous ADT, where the augmentation index remained elevated at month 6 (P = 0.043). These results have been confirmed by other relevant studies (11). In the following diagram (Figure 1) we propose potential mechanisms contributing to the increased cardiovascular risk in patients on ADT. Relevant studies are ongoing and their results are warranted. Figure 1 Mechanisms of Increased Cardiovascular Risk During ADT

A Randomized Trial of Aerobic versus Resistance Exercise in Prostate Cancer Survivors

Androgen-deprivation therapy (ADT) for prostate cancer (PCa) has side effects that significantly impair health-related quality of life (HRQOL). Exercise ameliorates many side effects of ADT, but different modalities, particularly in the home-based setting, have not been well studied. In this study the authors randomly assigned 66 PCa survivors receiving ADT to 6 mo of home-based aerobic or resistance training. Psychosocial well-being and physical fitness were measured at baseline, 3 and 6 mo, and then 6 mo postintervention. Intention-to-treat analyses showed that fatigue and HRQOL were not significantly different between groups; however, in a per-protocol analysis the resistance-exercise training group demonstrated clinically significant improvements in HRQOL. Differential within-group effects on physical fitness were also observed at various time points. At all time points, the aerobic-training group engaged in significantly more physical activity than the resistance-training group, a finding that should be further examined given evidence-based guidelines for activity volume in cancer survivors.

Systemic bias in the medical literature on androgen deprivation therapy and its implication to clinical practice

LHRH agonists are used for androgen deprivation therapy (ADT) to treat prostate cancer, but have many side effects that reduce of the quality of life of prostate cancer patients and their partners. Patients are poorly informed about the side effects of these drugs and how to manage them. To test the hypothesis that there is bias in the peer-reviewed literature on ADT that correlates with an association between authors and the luteinising hormone-releasing hormone (LHRH) agonists pharmaceutical industry. We assessed 155 articles on ADT published in English-language peer-reviewed journals in terms of how comprehensive they were in acknowledging LHRH agonists' side effects. Although the literature regarding ADT is substantial, the vast majority of articles failed to acknowledge many of the more stressful side effects of ADT for patients and their partners. Articles most likely to acknowledge the psychosocial impact of ADT were significantly less likely to have had industrial support than those articles that did not mention those side effects. Alternative treatments to the LHRH agonists were rarely mentioned. Authors who indicated some association with a pharmaceutical company tended to minimise the side effects of LHRH agonists and not acknowledge alternatives to the LHRH agonists for ADT. Industrial support is associated with a proliferation of articles published in the peer-reviewed literature directed at practising physicians. Such flooding of the literature may, in part, limit physicians' knowledge of the side effects of these drugs and, in turn, account for the poor knowledge that patients on LHRH agonists have about the drugs they are taking and ways to manage their side effects.

The Importance of Supportive Care in Optimizing Treatment Outcomes of Patients with Advanced Prostate Cancer

Optimal oncologic care of older men with prostate cancer, including effective prevention and management of the disease and treatment side effects (so-called best supportive care measures) can prolong survival, improve quality of life, and reduce depressive symptoms. In addition, the proportion of treatment discontinuations can be reduced through early reporting and management of side effects. Pharmacologic care may be offered to manage the side effects of androgen-deprivation therapy and chemotherapy, which may include hot flashes, febrile neutropenia, fatigue, and diarrhea. Nonpharmacologic care (e.g., physical exercise, acupuncture, relaxation) has also been shown to benefit patients. At the Georges Pompidou European Hospital, the Program of Optimization of Chemotherapy Administration has demonstrated that improved outpatient follow-up by supportive care measures can reduce the occurrence of chemotherapy-related side effects, reduce cancellations and modifications of treatment, reduce chemotherapy wastage, and reduce the length of stay in the outpatient unit. The importance of supportive care measures to optimize management and outcomes of older men with advanced prostate cancer should not be overlooked.

Prostate cancer treatments and their side effects are associated with increased insomnia

Between 25% and 40% of prostate cancer patients report insomnia symptoms. Although a possible role of androgen deprivation therapy (ADT) and radiation therapy (RTH) and some of their side effects have been postulated, this issue has rarely been investigated. This study aimed to (1) compare the evolution of insomnia symptoms and somatic symptoms, which may affect sleep quality (i.e., hot flashes, night sweats, and urinary symptoms), in patients receiving combined ADT and RTH with that in patients receiving RTH only and (2) assess the mediating role of somatic symptoms in the relationship of ADT and RTH with insomnia symptoms. Sixty men scheduled to receive RTH for prostate cancer, with (n = 28) or without (n = 32) ADT, were assessed prior to receiving any treatment (baseline) and at seven additional times over 16 months (1, 2, 4, 6, 8, 12, and 16 months) using the Insomnia Severity Index and the Physical Symptoms Questionnaire. A significant interaction effect was found indicating an increase in insomnia scores in ADT-RTH patients at 2, 4, and 6 months, as compared with baseline, and stable scores in RTH patients. A significant mediating role of hot flashes and night sweats was found in the relationship between ADT and insomnia symptoms. The relationship with RTH was also significantly mediated by these two symptoms albeit more strongly by excessive urinary frequency. Androgen deprivation therapy is associated with an increased risk for insomnia, and side effects of ADT and RTH appear to play a role in the development of insomnia in this population.

Efficacy of walking exercise in promoting cognitive-psychosocial functions in men with prostate cancer receiving androgen deprivation therapy

BackgroundProstate cancer is the most commonly diagnosed non-melanoma cancer among men. Androgen deprivation therapy (ADT) has been the core therapy for men with advanced prostate cancer. It is only in recent years that clinicians began to recognize the cognitive-psychosocial side effects from ADT, which significantly compromise the quality of life of prostate cancer survivors. The objectives of the study are to determine the efficacy of a simple and accessible home-based, walking exercise program in promoting cognitive and psychosocial functions of men with prostate cancer receiving ADT.MethodsA 6-month prospective, single-blinded, randomized controlled trial will be conducted to compare the Exercise Group with the Control Group. Twenty men with prostate cancer starting ADT will be recruited and randomly assigned to one of the two groups: the Exercise Group will receive instructions in setting up an individualized 6-month home-based, walking exercise program, while the Control Group will receive standard medical advice from the attending physician. The primary outcomes will be psychosocial and cognitive functions. Cognitive functions including memory, attention, working memory, and executive function will be assessed using a battery of neurocognitive tests at baseline and 6 months. Psychosocial functions including depression, anxiety and self-esteem will be assessed at baseline, 3 and 6 months using the Center for Epidemiological Studies Depression Scale, Spielberger State-Trait Anxiety Inventory, and Rosenberg Self-Esteem Scale.DiscussionThe significance of the cognitive-psychosocial side effects of ADT in men with prostate cancer has only been recently recognized, and the management remains unclear. This study addresses this issue by designing a simple and accessible home-based, exercise program that may potentially have significant impact on reducing the cognitive and psychosocial side effects of ADT, and ultimately improving the health-related quality of life in men with prostate cancer receiving ADT.Trial registrationNCT00856102

Improving the management of patients with prostate cancer receiving long‐term androgen deprivation therapy

In many patients with prostate cancer, androgen deprivation therapy (ADT) is administered over prolonged periods of time. The benefits of long-term ADT in patients with advanced disease are well established and, more recently, studies have shown that long-term adjuvant ADT used in combination with radiotherapy improves survival in patients with earlier stages of disease. Nevertheless, clinicians should remain aware of the potential long-term side effects of ADT and the strategies that can be used to manage or prevent long-term complications. One such strategy is intermittent androgen deprivation (IAD), in which patients receive cycles of ADT, the duration of which is usually determined by PSA levels. Accumulating data indicate that this approach improves the tolerability of ADT (particularly sexual dysfunction) and patients' quality of life, without compromising clinical outcomes (progression and survival). Indeed, the latest European Association of Urology guidelines state that IAD should no longer be considered investigational. Nevertheless, some questions remain unanswered, including: who are the most suitable patients for IAD and what are the optimal PSA levels for stopping and restarting treatment? Osteoporosis (and the resultant increased risk of fractures) is a well-recognized complication of long-term ADT. Bone mineral density should be measured before and during long-term ADT and patients advised to make appropriate lifestyle changes to help preserve bone health. Pharmacological intervention is also an option. Denosumab (an NF-κB ligand inhibitor) significantly reduces ADT-induced bone loss and the risk of fractures in patients with non-metastatic disease. In those whose disease has metastasized, zoledronate and denosumab are licensed to prevent skeletal-related events and a large randomized study has shown that denosumab is more effective than zoledronate in this setting.

Impact of androgen deprivation therapy (ADT) on bone mineral density (BMD) over 3 years in men with nonmetastatic prostate cancer.

193 Background: Decreased BMD is a common side effect of ADT, leading to increased fracture risk. Although loss of BMD appears to be greatest within the first 12 months of starting ADT, few data on BMD changes exist beyond 12 months, and other risk factors for bone loss in men on ADT are not well-characterized. Methods: Men age 50+ with non-metastatic prostate cancer and starting continuous ADT were enrolled in a prospective longitudinal study. BMD was determined by dual-energy x-ray absorptiometry at baseline and yearly for 3 years. A matched control group of men with prostate cancer but not on ADT was also enrolled. Medication use was recorded at each visit. Multivariable regression analyses were done to examine predictors of BMD loss. Results: 80 ADT users and 80 controls were enrolled (mean age 69.4 y); 49.7% had osteopenia and 4.6% had osteoporosis at baseline. ADT was associated with significant losses in lumbar spine BMD in year 1 compared to controls (p=0.004) and trends towards greater declines at femoral neck and total hip sites. Changes in year 2 and 3 were much smaller and not statistically different from controls (Table). Vitamin D use but not calcium use was associated with improved BMD at the lumbar spine in year 1 (+5.77%, p=0.006) with positive trends at other sites (+2.19% femoral neck, +1.76% total hip) primarily in year 1. Age was not associated with changes in BMD. Conclusions: Losses in BMD with ADT use are greatest at the lumbar spine and in the first year compared to years 2 and 3 and are independent of age. Vitamin D appears to be protective particularly in the first year of ADT use. [Table: see text]

Patients and partners lack knowledge of androgen deprivation therapy side effects

ObjectiveAndrogen deprivation therapy (ADT) is the primary treatment for advanced prostate cancer (CaP). There is growing evidence that ADT negatively affects men's psychosocial well-being (e.g., causing sexual dysfunction, bodily feminization) and physical health (e.g., increasing the risk of osteoporosis and metabolic syndrome). Although strategies for managing the majority of side effects exist, it is not clear that patients are benefiting from this knowledge. MethodsSeventy-nine newly prescribed ADT patients and 54 of their partners were given a checklist of various common and uncommon ADT side effects. They were asked to indicate the drug side effects that they had heard of or anticipated. ResultsBoth patients and their partners were poorly informed about the side effects of luteinizing hormone-releasing hormone (LHRH) agonists used for ADT. More than 70% did not know that anemia, memory problems, loss of body hair, and depression can occur following treatment. Over 50% were unaware of significant potential side effects such as reduced muscle mass, osteoporosis, increased fracture risk, weight gain, genital shrinkage, and gynecomastia. Concurrently, more than 20% mistakenly anticipated dizziness and itching. ConclusionThe lack of awareness of ADT side effects may partially explain why ADT currently results in significant decreases in the quality of life of patients and their partners. Patients uninformed about side effects do not engage in behaviors to prevent or reduce the risk of adverse effects. Improved efforts to educate patients about treatment side effects and coping strategies may result in improved psychosocial and physical health for CaP patients undergoing ADT.

The Interactions between Insulin and Androgens in Progression to Castrate-Resistant Prostate Cancer

An association between the metabolic syndrome and reduced testosterone levels has been identified, and a specific inverse relationship between insulin and testosterone levels suggests that an important metabolic crosstalk exists between these two hormonal axes; however, the mechanisms by which insulin and androgens may be reciprocally regulated are not well described. Androgen-dependant gene pathways regulate the growth and maintenance of both normal and malignant prostate tissue, and androgen-deprivation therapy (ADT) in patients exploits this dependence when used to treat recurrent and metastatic prostate cancer resulting in tumour regression. A major systemic side effect of ADT includes induction of key features of the metabolic syndrome and the consistent feature of hyperinsulinaemia. Recent studies have specifically identified a correlation between elevated insulin and high-grade PCa and more rapid progression to castrate resistant disease. This paper examines the relationship between insulin and androgens in the context of prostate cancer progression. Prostate cancer patients present a promising cohort for the exploration of insulin stabilising agents as adjunct treatments for hormone deprivation or enhancers of chemosensitivity for treatment of advanced prostate cancer.

Interstitial High-Dose-Rate Brachytherapy as Monotherapy for Early Stage Prostate Cancer: Median 8-Year Results in 317 Patients

Interstitial High-Dose-Rate Brachytherapy as Monotherapy for Early Stage Prostate Cancer: Median 8-Year Results in 317 Patients