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Risk of dementia and Parkinson's disease in patients treated with androgen deprivation therapy using gonadotropin-releasing hormone agonist for prostate cancer: A nationwide population-based cohort study.

ABSTRACT: Recent studies reported conflicting results on the association of androgen deprivation therapy (ADT) with dementia and Parkinson's disease in patients with prostate cancer (Pca). Therefore, this study aimed to investigate whether use of gonadotropin-releasing hormone agonist (GnRHa) increases the risk of both diseases. A nationwide population cohort study was conducted involving newly diagnosed patients with Pca %who started ADT with GnRHa (GnRHa users, n = 3,201) and control (nonusers, n = 4,123) between January 1, 2012, and December 31, 2016, using data from the National Health Insurance Service. To validate the result, a hospital cohort of patients with Pca consisting of GnRHa users (n = 205) and nonusers (n = 479) in a tertiary referral center from January 1, 2006 to December 31, 2016, were also analyzed. Traditional and propensity score-matched Cox proportional hazards models were used to estimate the effects of ADT on the risk of dementia and Parkinson's disease. In univariable analysis, risk of dementia was associated with GnRHa use in both nationwide and hospital validation cohort (hazard ratio [HR], 1.696; 95% CI, 1.425-2.019, and HR, 1.352; 95% CI, 1.089-1.987, respectively). In a nationwide cohort, ADT was not associated with dementia in both traditional and propensity score-matched multivariable analysis, whereas in a hospital validation cohort, ADT was associated with dementia only in unmatched analysis (HR, 1.203; 95% CI, 1.021-1.859) but not in propensity score-matched analysis. ADT was not associated with Parkinson's disease in either nationwide and validation cohorts. This population-based study suggests that the association between GnRHa use as ADT and increased risk of dementia or Parkinson's disease is not clear, which was also verified in a hospital validation cohort.

SUBMITTER: Shim M

PROVIDER: S-EPMC7773184 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Risk of dementia and Parkinson's disease in patients treated with androgen deprivation therapy using gonadotropin-releasing hormone agonist for prostate cancer: A nationwide population-based cohort study.

Shim Myungsun M Bang Woo Jin WJ Oh Cheol Young CY Lee Yong Seong YS Jeon Seong Soo SS Ahn Hanjong H Ju Young-Su YS Cho Jin Seon JS

PloS one 20201230 12

Recent studies reported conflicting results on the association of androgen deprivation therapy (ADT) with dementia and Parkinson's disease in patients with prostate cancer (Pca). Therefore, this study aimed to investigate whether use of gonadotropin-releasing hormone agonist (GnRHa) increases the risk of both diseases. A nationwide population cohort study was conducted involving newly diagnosed patients with Pca %who started ADT with GnRHa (GnRHa users, n = 3,201) and control (nonusers, n = 4,12 ...[more]

PMID: 33378392

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Project description:BackgroundThe main objective of the present work was to compare the effects of the gonadotropin-releasing hormone agonist (GnRH-a) and GnRH antagonist (GnRH-ant) on the gene expression profiles of oocytes obtained from Iranian infertile couples undergoing in vitro fertilization (IVF).MethodsFifty infertile couples who underwent IVF between June 2012 and November 2013 at the Infertility Center of Tehran Women General Hospital, Tehran University of Medical Sciences, were included in this study. We included women that had undergone IVF treatment because of male factor, tubal factor, or unexplained infertility. The women randomly underwent controlled ovarian stimulation (COS) with either the GnRH-a (n = 26) or the GnRH-ant (n = 24). We obtained 50 germinal vesicle (GV) oocytes donated by women in each group. After the sampling, pool of 50 GV oocytes for each group was separately analyzed by quantitative polymerase chain reaction (qPCR).ResultThe expression levels of Adenosine triphosphatase 6 (ATPase 6), Bone morphogenetic protein 15 (BMP15), and Neuronal apoptosis inhibitory protein (NAIP) genes were significantly upregulated in the GnRH-ant group compared to the GnRH-a group, with the fold change of 3.990 (SD ± 1.325), 6.274 (SD ± 1.542), and 2.156 (SD ± 1.443), respectively, (P < 0.001). Growth differentiation factor 9 (GDF9) mRNA did not have any expression in the GnRH-a group; however, GDF9 mRNA was expressed in the GnRH-ant group. Finally, it was found that the genes involved in the DNA repairing and cell cycle checkpoint did not have any expression in either group.ConclusionThe present study showed, for the first time, the expression levels of genes involved in the cytoplasmic maturity (BMP15, GDF9), adenosine triphosphate production (ATPase 6), and antiapoptotic process (NAIP), in human GV oocytes were significantly higher in the GnRH-anta group than in the GnRH-a group in COS. Higher expression level of these genes when GnRH-ant protocol is applied, this protocol seems to be a more appropriate choice for women with poly cystic ovarian syndrome, because it can probably improve the expression of the aforementioned genes.Trial registrationCurrent Controlled Trials: IRCT 2014031112307 N3.

Project description:To assess whether add-back therapy with norethindrone acetate or norethindrone acetate plus conjugated equine estrogens is superior to maintain bone health in adolescents and young women using gonadotropin-releasing hormone agonists for endometriosis. Gonadotropin-releasing hormone agonists are associated with deleterious effects on bone. Hormonal add-back may mitigate these effects.Adolescents and young women (n=51) received a random, double-blind assignment to add-back with norethindrone acetate (5 mg/day) plus conjugated equine estrogens (0.625 mg/day) or norethindrone acetate plus placebo for 12 months. Body composition, bone mineral content, and bone mineral density (BMD) were obtained by dual-energy X-ray absorptiometry every 6 months. Quality-of-life measures were collected every 3 months. Intention-to-treat comparison of outcomes was conducted by repeated-measures analysis of variance.Thirty-four adolescents and young women completed the trial; dropouts did not differ from those who completed the trial. Bone mineral density was normal at baseline. At 12 months, total body bone mineral content and BMD had increased in the norethindrone acetate plus conjugated equine estrogens group (bone mineral content +37 g, P<.001 and BMD +0.012 g/cm, P=.05), but not in those receiving norethindrone acetate plus placebo (bone mineral content P=.19 and BMD P=.95). Lean mass increased only in those receiving conjugated equine estrogens (+1.4 kg, P=.001). Improvements in physical functioning domains of quality-of-life assessments were greater with norethindrone acetate plus conjugated equine estrogens (P=.005). No differences were seen at the hip or lumbar spine by dual-energy X-ray absorptiometry. No significant adverse events occurred.Hormonal add-back successfully preserved bone health and improved quality of life for adolescents and young women with endometriosis during 12 months of gonadotropin-releasing hormone agonist therapy. Combination norethindrone acetate plus conjugated equine estrogens add-back appears to be more effective for increasing total body bone mineral content, areal BMD, and lean mass than norethindrone acetate monotherapy.ClinicalTrials.gov; www.clinicaltrials.gov, NCT00474851.I.

Dataset Information

Risk of dementia and Parkinson's disease in patients treated with androgen deprivation therapy using gonadotropin-releasing hormone agonist for prostate cancer: A nationwide population-based cohort study.

Publications

Risk of dementia and Parkinson's disease in patients treated with androgen deprivation therapy using gonadotropin-releasing hormone agonist for prostate cancer: A nationwide population-based cohort study.

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