Impact Of Androgen Deprivation Therapy Research Articles

Editorial Comment: Impact of Androgen Deprivation Therapy on Lumbar Spine Bone Health Using Quantitative Computed Tomography in a Propensity-Matched Cohort of Patients With Prostate Cancer

Editorial Comment: Impact of Androgen Deprivation Therapy on Lumbar Spine Bone Health Using Quantitative Computed Tomography in a Propensity-Matched Cohort of Patients With Prostate Cancer

Abstract 4766: Androgen deprivation in mice is linked with cognitive impairment

Abstract Androgens play a neuroprotective role in maintaining the normal physiological functions of the brain. It also plays a pivotal role in prostate cancer development and progression. Advance-stage prostate cancer treatment is primarily based on androgen deprivation therapy (ADT) that blocks the male hormone testosterone. Moreover, prostate cancer patients who undergo ADT develop cognition impairment such as loss of memory, learning, reasoning, and decision-making. Several studies have shown a positive association between ADT and the risk of cognitive impairment. Currently, there are no clinical markers to identify patients at-risk to ADT-mediated cognition. This demands a need for biomarkers that can help distinguish the vulnerability of patients toward cognitive impairment undergoing ADT. We utilized a in-vivo model to identify biomarkers and the impact of ADT in different regions of the brain. Sixteen-week-old BALB/c mice were gavage 50 mg/kg/day of enzalutamide (mimicking ADT) for 5 days per week (0.2 ml of vehicle consisting of 0.5% methylcellulose and 0.025% Tween 20) for a total of 8 weeks. Control animals received 0.2 ml vehicle per day for the same time period. Mice were observed for behavioral changes post-enzalutamide treatment and brain PET scans were generated. The experiment was terminated, the brain was excised for cortex, cerebellum, and hippocampus, and subjected to mass spectroscopic (MS) analysis. Differentially expressed proteins were identified and validated using qRT-PCR in the mice blood. Enzalutamide treatment for 8 weeks resulted in a modest weight gain and lack of attention and letharginess in these mice. Examination of PET scan and H&E sections of mice brain from control group by light microscopy showed a normal morphology of neurons in the cortex. Enzalutamide treatment showed lower neuron density and signs of neuron injury, as well as cytoplasmic swelling of the astrocytes. MS analysis identified a number of differentially expressed proteins that were validated in the blood. These include ABCB10, CAB, DAZAP1, DCU, DERL1, FBXO, MBNL, PUM2, SERL1, SLC8A3, SLC9A, TCF20, VIM, and ZYXIN. Among them, the expression of SLC8A3, PUM2, and SERL1, were significantly higher than others in the enzalutamide-treated group. Taken together, our findings suggest that enzalutamide treatment in mice leads to cognitive impairment like that observed in men on ADT protocol. Our study highlights that blood-based markers can be developed for ADT-mediated cognition which can lead to the identification of new strategies for prevention and early intervention to improve the quality-of-life of patients suffering with advance-stage prostate cancer. Citation Format: Shiv Shankar Verma, Diya Swain, Vaibhav Singh, Eswar Shankar, Zhenghong Lee, Sanjay Gupta. Androgen deprivation in mice is linked with cognitive impairment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4766.

(134) Early Impact of Androgen Deprivation Therapy on Endothelial Function and Metabolic Parameters in Prostate Cancer Patients: A Prospective Study

Abstract Introduction Androgen deprivation therapy (ADT) is considered one of the mainstays in the treatment of prostate cancer. ADT slows cancer progression, alleviates cancer-related symptoms, and is associated with survival gains. Despite these proven benefits, this treatment is related to several side effects, such as increased cardiovascular risk, changes in body composition and various metabolic changes. Although the well-established association between circulating testosterone level and endothelial integrity, the direct effects of ADT on endothelial function remain controversial. Objective This study aimed to investigate the impact of ADT on endothelial function, through the analysis of vascular parameters of the brachial artery and measurement of serum inflammatory markers. It was also our aim to evaluate the early impact of ADT on body composition and metabolic parameters. Methods We prospectively evaluated men with moderate to high-risk prostate cancer treated with ADT from January to December 2022 at our institution. Smokers and those who quit smoking less than five years ago, decompensated diabetics (glycated hemoglobin > 9%) and those who had already had a cardiovascular event were excluded. High-resolution B-mode ultrasound was used to assess vascular diameter and endothelium-dependent flow-mediated vasodilation (FMD) of the brachial artery. Our metabolic and inflammatory profile included measurement of serum total cholesterol and fractions, triglycerides, fasting glucose, glycated hemoglobin, basal insulin, C-reactive protein and assessment of body fat distribution through bioelectrical impedance. Subjects were evaluated at baseline and 3 months after starting ADT with goserelin acetate 10.80 mg. Results A total of 32 men were included. The mean age was 69 years and the prevalence of diabetes was 31.25%. FMD demonstrated a worsening trend after ADT, which did not reach statistical significance after 3 months (mean 3.39 ± 6.83 vs 1.16 ± 7.65; p = 0.14) (figure 1). Baseline brachial artery diameter also showed a tendency to worsen with ADT compared to baseline (0.44 ± 0.06 vs 0.42 ± 0.06; p = 0.06). With regard to the metabolic profile, ADT significantly increased insulin resistance: fasting glucose (mean 104.10 ± 18.96 vs 110.60 ± 25.29; p = 0.01), fasting insulin levels (mean 13.05 ± 8.76 vs 16.82 ± 11.36; p = 0.003), glycated hemoglobin (mean 5.89% ± 0.46 vs 6.15% ± 0.67; p = 0.008) and homeostatic model assessment insulin resistance (mean 3.47 ± 2.55 vs 5.05 ± 4.50; p = 0.005) increased significantly after 3 months. Triglycerides concentrations (mean 142.30 ± 69.66 vs 165.50 ± 93.04; p = 0.03) were higher after 3 months of ADT. Abdominal circumference (mean 98.66 ± 10.16 vs 99.76 ± 9.39; p = 0.02) and body mass index (mean 27.46 ± 4.06 vs 27.76 ± 3.89; p = 0.02) also increased after ADT. Conclusions Although not statistically significant, the present study demonstrated a trend towards a decrease in brachial artery FMD. We also observed an important and surprisingly early worsening of the metabolic profile with ADT, especially increased insulin resistance and dyslipidemia, which represent well-established risk factors for cardiovascular events. Disclosure No.

Examining the impact of androgen deprivation therapy, masculine self-esteem, and psychological flexibility on distress and quality of life in men with prostate cancer.

Studies suggest that androgen deprivation therapy (ADT) exacerbates psychological and quality of life (QoL) issues associated with prostate cancer (PCa). However, quantitative research examining underlying psychosocial mechanisms for this is limited. We examined the association of PCa symptoms with distress and QoL in ADT-treated and ADT-naïve patients, and the influence of masculine self-esteem and psychological flexibility (PF) on these relationships. Secondary analysis of a quantitative, cross-sectional survey of 286 PCa patients. Independent samples t-tests, moderation, and conditional process analysis were used to assess relationships between predictor, mediator, moderator, and outcome variables. ADT was associated with greater PCa symptomology, lower masculine self-esteem, and lower QoL. Moderation analysis showed that ADT potentiated adverse impacts of PCa symptomology on distress and QoL. High PF attenuated these relationships, though less so for ADT-treated participants. Conditional process analysis showed that masculine self-esteem mediated the predictive effect of symptoms on distress across treatments. However, ADT did not moderate this indirect effect, nor was moderation conditional on PF. PF appears to: (1) attenuate psychological distress in ADT patients; and (2) improve distress, QoL, and masculine self-esteem in ADT-naïve patients. Interventions targeting PF may thus be a viable adjunct to established approaches. However, their effects may be comparatively limited in ADT patients, who may benefit from more intensive and tailored treatment.

Impact of androgen deprivation therapy on cognitive function in men with prostate cancer.

Impact of androgen deprivation therapy on cognitive function in men with prostate cancer.

Antihormonal-Treatment Status Affects 68Ga-PSMA-HBED-CC PET Biodistribution in Patients with Prostate Cancer.

Androgen deprivation therapy (ADT) is known to influence the prostate-specific membrane antigen (PSMA) expression of prostate cancer, potentially complicating the interpretation of PSMA ligand PET findings and affecting PSMA radioligand therapy. However, the impact of ADT on PSMA ligand biodistribution in nontumorous organs is not well understood. Methods: Men (n = 112) with histologically proven prostate cancer who underwent 68Ga-PSMA-HBED-CC (68Ga-PSMA-11) PET/CT between November 2015 and July 2021 at the Medical University Vienna with known ADT status were retrospectively recruited. Fifty-six patients were on gonadotropin-releasing hormone-interfering ADT at the time of imaging (ADT group), whereas 56 patients with no history of ADT served as a control group. Physiologically PSMA-expressing organs (salivary glands, kidneys, liver, and spleen) were delineated, and their uptake was compared according to their data distributions. Multivariate regression analysis assessed the relationship between renal, hepatic, splenic, and salivary gland uptake and the explanatory variables metabolic tumor volume, glomerular filtration rate, and ADT status. Results: ADT was associated with lower levels of PSMA uptake in the kidneys (SUVmean: Δ[ADT - control] = -7.89; 95% CI, -10.73 to -5.04; P < 0.001), liver (SUVpeak: Δ[ADT - control] = -2.3; 95% CI, -5.72 to -0.93; P = 0.003), spleen (SUVpeak: Δ[ADT - control] = -1.27; 95% CI, -3.61 to -0.16; P = 0.033), and salivary glands (SUVmean: Δ[ADT - control] = -1.04; 95% CI, -2.48 to -0.13; P = 0.027). In a multivariate analysis, ADT was found to be associated with lower renal (SUVmean: β = -7.95; 95% CI, -11.06 to -4.84; P < 0.0001), hepatic (SUVpeak: β = -7.85; 95% CI, -11.78 to -3.91; P < 0.0001), splenic (SUVpeak: β = -5.83; 95% CI, -9.95 to -1.7; P = 0.006), and salivary gland (SUVmean: β = -1.47; 95% CI, -2.76 to -0.17; P = 0.027) uptake. A higher glomerular filtration rate was associated with a higher renal SUVmean (β = 0.16; 95% CI, 0.05 to 0.26; P = 0.0034). Conclusion: These findings suggest that ADT systemically modulates PSMA expression, which may have implications for treatment-optimizing and side-effect-minimizing strategies for PSMA radioligand therapies, particularly those using more potent 225Ac-labeled PSMA conjugates.

Cardiovascular Impact of Androgen Deprivation Therapy: from Basic Biology to Clinical Practice.

There have been increasing reports of cardiovascular complications of androgen deprivation therapy (ADT) leading to worse outcomes among patients with prostate cancer. While this may result from the direct effects of androgen suppression in the cardiovascular systems, there are ADT-type-specific distinct cardiovascular complications suggestive of mechanisms beyond androgen-mediated. Thus, it is critical to understand the biological and clinical impact of ADT on the cardiovascular system. Gonadotropin-releasing hormone (GnRH) agonists cause increased cardiovascular events compared to GnRH antagonists. Androgen receptor antagonists are linked to an increased risk of long QT syndrome, torsades de pointes, and sudden cardiac death. Androgen synthesis inhibitors are associated with increased rates of hypertension, atrial tachyarrhythmia, and, in rare incidences, heart failure. ADT increases the risk of cardiovascular disease. The risk among ADT drugs differs and must be evaluated to develop a medically optimal plan for prostate cancer patients.

Resistance Exercise Counteracts the Impact of Androgen Deprivation Therapy on Muscle Characteristics in Cancer Patients.

Androgen deprivation therapy (ADT) forms the cornerstone in prostate cancer (PCa) treatment. However, ADT also lowers skeletal muscle mass. To identify the impact of ADT with and without resistance exercise training on muscle fiber characteristics in PCa patients. Twenty-one PCa patients (72 ± 6 years) starting ADT were included. Tissue samples from the vastus lateralis muscle were assessed at baseline and after 20 weeks of usual care (n = 11) or resistance exercise training (n = 10). Type I and II muscle fiber distribution, fiber size, and myonuclear and capillary contents were determined by immunohistochemistry. Significant decreases in type I (from 7401 ± 1183 to 6489 ± 1293 μm2, P < .05) and type II (from 6225 ± 1503 to 5014 ± 714 μm2, P < .05) muscle fiber size were observed in the usual care group. In addition, type I and type II individual capillary-to-fiber ratio (C/Fi) declined (-12% ± 12% and -20% ± 21%, respectively, P < .05). In contrast, significant increases in type I (from 6700 ± 1464 to 7772 ± 1319 μm2, P < .05) and type II (from 5248 ± 892 to 6302 ± 1385 μm2, P < .05) muscle fiber size were observed in the training group, accompanied by an increase in type I and type II muscle fiber myonuclear contents (+24% ± 33% and +21% ± 23%, respectively, P < .05) and type I C/Fi (+18% ± 14%, P < .05). The onset of ADT is followed by a decline in both type I and type II muscle fiber size and capillarization in PCa patients. Resistance exercise training offsets the negative impact of ADT and increases type I and II muscle fiber size and type I muscle fiber capillarization in these patients.

MO-0954 Impact of androgen deprivation therapy on Imaging treatment response following prostate radiotherapy

MO-0954 Impact of androgen deprivation therapy on Imaging treatment response following prostate radiotherapy

IL-1β Is an Androgen-Responsive Target in Macrophages for Immunotherapy of Prostate Cancer.

Great attention is paid to the role of androgen receptor (AR) as a central transcriptional factor in driving the growth of prostate cancer (PCa) epithelial cells. However, the understanding of the role of androgen in PCa-infiltrated immune cells and the impact of androgen deprivation therapy (ADT), the first-line treatment for advanced PCa, on the PCa immune microenvironment remains limited. On the other hand, immune checkpoint blockade has revolutionized the treatment of certain cancer types, but fails to achieve any benefit in advanced PCa, due to an immune suppressive environment. In this study, it is reported that AR signaling pathway is evidently activated in tumor-associated macrophages (TAMs) of PCa both in mice and humans. AR acts as a transcriptional repressor for IL1B in TAMs. ADT releases the restraint of AR on IL1B and therefore leads to an excessive expression and secretion of IL-1β in TAMs. IL-1β induces myeloid-derived suppressor cells (MDSCs) accumulation that inhibits the activation of cytotoxic T cells, leading to the immune suppressive microenvironment. Critically, anti-IL-1β antibody coupled with ADT and the immune checkpoint inhibitor anti-PD-1 antibody exerts a stronger anticancer effect on PCa following castration. Together, IL-1β is an important androgen-responsive immunotherapeutic target for advanced PCa.

Abstract 10351: Racial Differences in Chronic Stress or Allostatic Load Variation Due to Androgen Deprivation Therapy in Prostate Cancer

Introduction: The cumulative burden of chronic stress and life events can be measured by Allostatic load (AL), whose high values are related to poorer health outcomes and increased risk of cardiovascular disease (CVD). The primary objective of this study is to analyze the impact of androgen deprivation therapy (ADT) on AL variation in patients upon diagnosis of prostate cancer (PC). Hypothesis: ADT may increase AL variation in prostate cancer patients. Methods: Data were obtained from a Cleveland area integrated health care systems informatics platform. The initial cohort included males ≥18 years diagnosed with PC between 2005 and 2022. AL was calculated using multiple markers representing the cardiovascular, metabolic, and immune systems ( Table 1 ) before diagnosis and monthly during the first year. ADT use was captured based on prescribed medications. A linear-mixed-effects model, adjusted for patient demographics, CVD risk factors, and cancer characteristics, and treatment, was used to study AL monthly variation. The analysis was stratified by Non-Hispanic White (NHW) and Non-Hispanic Black (NHB) race. Results: We analyzed a total of 7,168 PC adenocarcinoma patients (31.7% NHB vs 68.3% NHW), of which 20.9% received ADT. NHBs had higher AL pre-PC diagnosis than NHWs (p=0.001). AL monthly variation was 0.15 (±0.02) higher in all PC patients on ADT (p&lt;0.001) and these results persisted stratifying by race (0.10 ± 0.04 for NHBs, p=0.01 and 0.16 ± 0.03 for NHW, p&lt;0.001). There was no racial difference between AL increase in those receiving only ADT (0.09 +/- 0.04; p = 0.06). The details of individual AL variable measures pre-PC diagnosis and the mixed-effects model are presented in Table 1. Conclusion: Pre-PC-diagnosis chronic stress/AL is higher among NHBs vs. NHWs with the addition of ADT increasing AL in both races after PC diagnosis. This study is hypothesis-generating, offering data that help explain, in part, the racial differences in ADT-mediated CVD.

Impact of androgen deprivation therapy on the bone and metabolic changes in men treated for localized prostate cancer

Impact of androgen deprivation therapy on the bone and metabolic changes in men treated for localized prostate cancer

Effect of hormonal therapy on 18F-fluciclovine PET/CT in the detection of prostate cancer recurrence, localization of metastatic disease, and correlation with prostate-specific antigen.

18F-Fluciclovine, is a positron emission tomography (PET) radiotracer approved for the localization of sites of prostate cancer recurrence in men with a rising prostate-specific antigen (PSA) after definitive treatment. To explore the impact of androgen deprivation therapy (ADT) on the performance of 18F-fluciclovine, we conducted a retrospective analysis to compare the 18F-fluciclovine PET/CT positivity rate in patients receiving ADT at the time of the scan with the rate achieved in patients not receiving ADT. A retrospective review of data from patients who underwent18F-fluciclovine PET/CT for biochemical recurrence of prostate cancer between December 2016 to March 2020 was performed.The cohort was divided into an ADT group (patient reportedly on ADT) anda non-ADT group (not currently receiving ADT). Patients with unknown ADT status or undetectable/unknown PSA were excluded. For each group, the number of positive18F-fluciclovine PET/CT scans (positivity rate) was evaluated for thewhole body, prostate/bed, and extraprostatic regions and rates were correlated with PSA. The Fisher's Exact test was applied to establish the significancebetween the ADT and non-ADT positivity groups. Mantel-Haenszel trend test was performed to assess linearity between the positivity rate and PSA level. In 320 patients, the status of ADT was known. At the time of the18F-fluciclovine scan,68/320 (21%) patients were on ADT, while 252/320 (79%) were not. The median Gleason score was 8 (range of 6-10) in the ADT group vs. 7 (range of 6-10) in the non-ADT group (P < 0.001). Overall, positivity rates demonstrated no statistical significance between the ADT and non-ADT groups; Positivity rates (ADT vs. non-ADT) were 82% (56/68) vs. 82% (206/252) for the whole body, 57% (39/68) vs. 60% (152/252) for prostate/bed, and 60% (41/68) vs. 53% (133/252) for extraprostatic regions (P > 0.05). A positive linear correlation was noted between PSA and each group's positivity rate (P < 0.01). However, no significant difference was observed between ADT and non-ADT groups at different PSA levels (P > 0.05). Detection of prostate cancer recurrence with 18F-fluciclovine PET/CT is not significantly influenced by ADT, suggesting that localization of disease in patients with detectable PSA who are receiving ADT is feasible with 18F-fluciclovine.

Impact of Androgen Deprivation Therapy on Cardiovascular Outcomes in Prostate Cancer

Purpose: Substantial evidence indicates that men with prostate cancer are at an increased risk for cardiovascular disease, and medical and surgical androgen deprivation therapy is associated with further increased cardiovascular risk. There are conflicting reports of differences in cardiovascular safety between gonadotropin-releasing hormone (GnRH) agonists and antagonists. The purpose of this narrative review is to compare data on the cardiovascular risks and safety outcomes associated with different hormonal treatment options in prostate cancer patients and to provide guidance on how to manage the increased risk associated with the condition. Methods: A PubMed search was conducted for papers published in the last 15 years using the following MeSH terms: “prostate neoplasms,” “gonadotropin-releasing hormone,” “androgen agonist,” “androgen antagonists,” “cardiovascular disease,” “epidemiology.” Results: Evidence regarding the risk of cardiovascular events during treatment with GnRH agonists and antagonists is conflicting. Some retrospective studies have shown that agonists are associated with a greater risk of cardiovascular disease and cardiovascular mortality and morbidity, and a similar risk with agonists and combined androgen blockade. Some studies have reported that antagonists are associated with a decreased risk of cardiovascular mortality and morbidity compared with agonists. With respect to coronary heart disease, ischemic heart disease, myocardial infarction, stroke, or sudden cardiac death, current evidence has failed to demonstrate a significant difference between antagonists and agonists. Cardiovascular risks in patients should be mitigated by regular monitoring of blood pressure, blood glucose, and lipids, as well as counseling patients to abstain from alcohol and improve their diet and exercise. Statins, metformin, and aspirin should also be considered. Conclusions: The evidence for the increased cardiovascular risk of GnRH agonists over antagonists for androgen deprivation therapy is unclear. Differences in methodology, population sizes, risk stratification, and outcomes between studies make direct comparisons problematic. The single prospective, randomized prostate cancer trial with a primary cardiovascular end point in men with pre-existing cardiovascular disease comparing GnRH agonist to antagonist was stopped early due to an interim futility analysis. The results are inconclusive.

Testosterone and Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disease that causes dementia in half of the cases. Asthma is usually found in people over 65 years of age. The etiopathogenesis of the disease is multifactorial and includes genetic factors, nutritional disorders, mitochondrial dysfunction, oxidative stress, and aging. Sex hormones have an important influence on the development of AD, as evidenced by a higher incidence in women than in men. Considering the significant influence of T on the maintenance of normal brain function, the present study is aimed at evaluating the impact of androgen deprivation therapy (ADT), as well as testosterone therapy, on the risk of AD development and progression. Although there is some clinical inconsistency between studies, androgens have a significant effect on brain function and are beneficial for AD patients. Low levels of circulating androgens should be considered as a significant risk factor for the development of AD and memory loss. With a reduced level of T in the plasma of men, its administration improves cognitive performance and memory, treatment should be started at an early stage of the disease. In men and women with AD, androgens improve mental state and slow the progression of the disease, providing a protective effect. In the future, it is necessary to conduct studies on a large population, taking into account personality factors and a more specific approach to assessing cognitive functions and the causal relationship of T administration in AD.

Cardiovascular Effects of Androgen Deprivation Therapy in Prostate Cancer Patients: A Systematic Review

The purpose of this study was to investigate the relationship between androgen deprivation therapy (ADT) and cardiovascular events in men with prostate cancer. Cardiovascular disease (CVD) is a primary cause of noncancer mortality in men with prostate cancer. Surveillance, Epidemiology, and End Results (SEER) Medicare-linked data revealed that CVD was responsible for about a quarter of deaths among men with prostate cancer, with a focus on the role of ADT as a contributing cause.We performed a literature search in November 2021 utilizing search engines such as PubMed, Scopus, Science Direct, and Google Scholar. Original publications with data published between 2006 and 2020 were used in the investigation of men with prostate cancer undergoing ADT treatment with a CVD outcome. Two reviewers independently examined the content of the studies and extracted data from the final papers after they had been validated for quality using quality assessment tools. A total of 14 observational studies and two randomized controlled trials are included in this systematic review. Sample sizes in the examined publications varied from 79 to 201,797 individuals. ADT was the intervention in all of the investigations. Seven of the included studies did not identify the type of ADT utilized; instead, they compared the outcomes of individuals who got ADT against those who did not. The specific type of ADT used is mentioned in the remaining nine studies included in the systematic review. Patients who got ADT, such as gonadotropin-releasing hormone (GnRH) agonists, combination androgen blockade, surgical castration, and oral anti-androgen, are compared to those who did not receive ADT to discover who had a better prognosis.In conclusion, even though ADT has several negative metabolic side effects that increase the risk of cardiovascular toxicity, published research utilizing a variety of designs has demonstrated inconsistency in the impact of ADT on cardiovascular outcomes. While the risk of CVD should be considered when prescribing ADT, the findings suggest that it should not be considered a contraindication if the expected benefit is substantial.

The impact of androgen deprivation therapy on the lipid profile in patients with prostate carcinoma

BackgroundDyslipidemia is directly related to morbidity and mortality in elderly prostate carcinoma patients. The purpose of this study was to evaluate the effects of androgen deprivation therapy (ADT) on the lipid profile among Indian patients with locally advanced and metastatic prostate carcinoma.MethodsThe prospective database of prostate carcinoma patients, who received ADT and whose lipid profile data for the first two years of treatment with ADT was available, were divided into two groups for retrospective analysis: Group A patients are those who had undergone bilateral orchidectomy, while group B patients received luteinizing hormone-releasing hormone agonist (LHRHa). The data analyzed include baseline characteristics, prostate-specific antigen (PSA), and lipid profile.ResultsA total of 69 eligible patients were divided into two groups: group A—29 patients and group B—40 patients. Patients of both the groups reported a significant decrease in the mean serum PSA level from the commencement of ADT and remained close to nadir level till 24 months. In the group A patients, lipid profile parameters except high-density lipoprotein cholesterol showed statistically insignificant deterioration with maximum impact at 6 months. Among the group B patients, the total cholesterol (11.9%), triglycerides (22.2%), and low-density lipoprotein cholesterol (21.1%) increased significantly at 6 months and returned to the near baseline at 12 months and thereafter persisted at the similar level. The mean very low-density lipoprotein level (15.5%) also increased significantly at 6 months and then showed a gradual decline till 24 months of follow-up.ConclusionsLHRH agonist used as ADT for prostate carcinoma leads to a statistically significant but clinically insignificant temporary worsening in the lipid profile.

The Impact of Androgen Deprivation Therapy on COVID-19 Illness in Men With Prostate Cancer.

BackgroundTMPRSS2, a cell surface protease regulated by androgens and commonly upregulated in prostate cancer (PCa), is a necessary component for SARS-CoV-2 viral entry into respiratory epithelial cells. Previous reports suggested a lower risk of SARS-CoV-2 among PCa patients on androgen deprivation therapy (ADT). However, the impact of ADT on severe COVID-19 illness is poorly understood.MethodsWe performed a multicenter study across 7 US medical centers and evaluated patients with PCa and SARS-CoV-2 detected by polymerase-chain-reaction between March 1, 2020, and May 31, 2020. PCa patients were considered on ADT if they had received appropriate ADT treatment within 6 months of COVID-19 diagnosis. We used multivariable logistic and Cox proportional-hazard regression models for analysis. All statistical tests were 2-sided.ResultsWe identified 465 PCa patients (median age = 71 years) with a median follow-up of 60 days. Age, body mass index, cardiovascular comorbidity, and PCa clinical disease state adjusted overall survival (hazard ratio [HR] = 1.16, 95% confidence interval [CI] = 0.68 to 1.98, P = .59), hospitalization status (HR = 0.96, 95% CI = 0.52 to 1.77, P = .90), supplemental oxygenation (HR 1.14, 95% CI = 0.66 to 1.99, P = .64), and use of mechanical ventilation (HR = 0.81, 95% CI = 0.25 to 2.66, P = .73) were similar between ADT and non-ADT cohorts. Similarly, the addition of androgen receptor–directed therapy within 30 days of COVID-19 diagnosis to ADT vs ADT alone did not statistically significantly affect overall survival (androgen receptor–directed therapy: HR = 1.27, 95% CI = 0.69 to 2.32, P = .44).ConclusionsIn this retrospective cohort of PCa patients, the use of ADT was not demonstrated to influence severe COVID-19 outcomes, as defined by hospitalization, supplemental oxygen use, or death. Age 70 years and older was statistically significantly associated with a higher risk of developing severe COVID-19 disease.

The impact of androgen deprivation therapy on bone mineral density in men treated for paraphilic disorder: A retrospective cohort study.

Guidelines suggest treating men with paraphilic disorder with androgen-deprivation therapy (ADT). However, little evidence is available about the long-term impact on bone loss and how to manage this adverse event. The aim of this study is to assess the impact of ADT on bone mineral density (BMD) in men treated for paraphilic disorder with the androgen receptor blocker cyproterone acetate (CPA) and/or GnRH agonist triptoreline (GnRHa) and to evaluate the effect of treatment with bisphosphonates. Baseline and follow-up dual-energy X-ray absorptiometry scan (DXA-scan) data (lumbar and femoral T-scores) were retrospectively extracted from electronic medical files of paraphilic men who received CPA and/or GnRHa. A total of 53 patients with a mean age of 39.1 years (range 17.5-74.6) were included. Lumbar (-0.39 ± 0.17, Mean ± SEM, p=0.046), femoral neck (-0.34 ± 0.09, p=0.002) and total femur (-0.33 ± 0.12, p=0.014) T-scores decreased significantly in the CPA-only group (n=13) during a mean follow-up of 6.0 ± 5.3 years. In the GnRHa group (n=29), T-scores at all sites decreased significantly over 6.6 ± 4.4 years (lumbar: -0.55 ± 0.12, p<0.001, femoral neck: -0.53 ± 0.09, total femur: -0.44 ± 0.09, p<0.001). In the group, who received bisphosphonates (n=11), no significant T-score change was observed (lumbar: -0.25 ± 0.14, p=0.106, femoral neck -0.15 ± 0.17, p=0.402, total femur -0.25 ± 0.14, p=0.106) during 5.0 ± 2.8 years of follow-up. Following a mean duration of 6 years of ADT, we observed a significant decline in BMD of approximately half a standard deviation in T-score at lumbar and femoral site. Although the number of patients who received bisphosphonates was limited, this treatment seems to have a positive stabilizing effect on bone density.

The clinical impact of androgen deprivation therapy on SARS-CoV-2 infection rates and disease severity.

The protective effect of androgen deprivation therapy (ADT) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel hypothesis. ADT may protect patients with prostate cancer through the inhibition of androgen receptor-dependent transmembrane serine protease type 2. We analyzed the role of ADT on SARS-CoV-2 infection risk and disease severity. Between August 2020 and June 2021, patients with prostate cancer were included in our study. Patients were divided into two groups as men receiving ADT or not. Patients' characteristics such as prostate cancer grade and stage, comorbidities, SARS-CoV-2 infection status, and infection severity were assessed. SARS-CoV-2-infected close relatives and patients' compliance with the precautions against SARSCoV- 2 were also analyzed. A total of 365 patients, 138 (37.8%) with ADT and 227 (62.2%) without ADT, were included in our analysis. Patients with ADT were older (71.8 vs 66.9 years, P ¼ .001) and had a higher rate of chronic obstructive pulmonary disease (11.6% vs 5.7%, P ¼ .044). Patients receiving ADT were more often locally advanced and metastatic (80.4% vs 32.6%, P ¼ .001). SARS-CoV-2 infection rates were statistically similar between patients who received and did not receive ADT (9.4% vs 13.2%, P ¼ .275, respectively). There was no significant difference between two groups in terms of hospitalization rates (2.9% vs 0.9%, P ¼ .205). In multivariate analysis, the presence of SARS-CoV-2-infected close relatives and precautions score were only independent predictors for both risk of SARS-CoV-2 infection and infection severity. We could not find any effect of ADT on risk and severity of SARS-CoV-2 infection. SARSCoV- 2 infection and hospitalization rates were similar between patients with and without ADT.