Effect of estradiol on cognition in men undergoing androgen deprivation therapy: A randomized placebo-controlled trial.


Journal

Clinical endocrinology
ISSN: 1365-2265
Titre abrégé: Clin Endocrinol (Oxf)
Pays: England
ID NLM: 0346653

Informations de publication

Date de publication:
11 2022
Historique:
revised: 23 01 2022
received: 28 11 2021
accepted: 06 02 2022
pubmed: 13 2 2022
medline: 6 10 2022
entrez: 12 2 2022
Statut: ppublish

Résumé

Roles for estradiol in modulating cognition in men remain uncertain. We assessed the isolated effects of estradiol on cognition in men in the absence of testosterone. Randomized trial of transdermal estradiol 0.9 mg daily, or matched placebo, for 6 months, hypothesizing that estradiol would improve verbal learning, verbal memory, and spatial problem solving over time. Men receiving androgen deprivation therapy (ADT) for prostate cancer. Cognition was assessed by a tablet-based cognitive battery (Cogstate) at baseline, Month 1, Month 3, and Month 6. Anxiety and depression symptoms were assessed using the Hospital Anxiety and Depression Scale. Seventy-eight participants were randomized. Baseline mean scores were 21.0 (standard deviation [SD] 4.1) for the International Shopping List test (ISL), assessing verbal learning and memory (higher scores better), and 60.4 (SD 19.5) for the Groton Maze Learning test (GML), assessing spatial problem solving (lower scores better). There was no significant difference in performance over time for the estradiol group versus the placebo group for the ISL, mean adjusted difference (MAD) 0.7 (95% confidence interval [CI] -1.2 to 2.5), p = .36, or the GML, MAD -3.2 (95% CI -12.0 to 5.6), p = 0.53. There was no significant difference between groups over time in performance in any other cognitive domain, or on depression or anxiety scores. We found no major effects of estradiol on cognition in men with castrate testosterone concentrations. Although the cognitive effects of ADT are debated, this study suggests that any such effects are unlikely to be prevented by the administration of estradiol.

Identifiants

pubmed: 35150156
doi: 10.1111/cen.14689
doi:

Substances chimiques

Androgen Antagonists 0
Androgens 0
Testosterone 3XMK78S47O
Estradiol 4TI98Z838E

Types de publication

Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

622-633

Informations de copyright

© 2022 John Wiley & Sons Ltd.

Références

Kaufman JM, Lapauw B, Mahmoud A, T'Sjoen G, Huhtaniemi IT. Aging and the male reproductive system. Endocr Rev. 2019;40(4):906-972. doi:10.1210/er.2018-00178
Cooke PS, Nanjappa MK, Ko C, Prins GS, Hess RA. Estrogens in male physiology. Physiol Rev. 2017;97(3):995-1043. doi:10.1152/physrev.00018.2016
Takahashi K, Hosoya T, Onoe K, et al. Association between aromatase in human brains and personality traits. Sci Rep-UK. 2018;8(1):16841. doi:10.1038/s41598-018-35065-4
Joue G, Chakroun K, Bayer J, et al. Sex differences and exogenous estrogen influence learning and brain responses to prediction errors. Cereb Cortex. 2021. doi:10.1093/cercor/bhab334
Reimers L, Kappo E, Stadler L, Yaqubi M, Diekhof EK. Endogenous testosterone correlates with parochial altruism in relation to costly punishment in different social settings. PeerJ. 2019;7:e7537. doi:10.7717/peerj.7537
Diekhof EK, Kraft S. The association between endogenous testosterone level and behavioral flexibility in young men: evidence from stimulus-outcome reversal learning. Horm Behav. 2017;89:193-200. doi:10.1016/j.yhbeh.2017.02.006
Wibowo E. Cognitive impacts of estrogen treatment in androgen-deprived males: what needs to be resolved. Curr Neuropharmacol. 2017;15(999):1-1. doi:10.2174/1570159x15666170313122555
Resnick SM, Matsumoto AM, Stephens-Shields AJ, et al. Testosterone treatment and cognitive function in older men with low testosterone and age-associated memory impairment. JAMA. 2017;317(7):717-727. doi:10.1001/jama.2016.21044
Huang G, Wharton W, Bhasin S, et al. Effects of long-term testosterone administration on cognition in older men with low or low-to-normal testosterone concentrations: a prespecified secondary analysis of data from the randomised, double-blind, placebo-controlled TEAAM trial. Lancet Diabetes Endocrinol. 2016;4(8):657-665. doi:10.1016/s2213-8587(16)30102-4
Young LA, Neiss MB, Samuels MH, Roselli CE, Janowsky JS. Cognition is not modified by large but temporary changes in sex hormones in men. J Clin Endocrinol Metab. 2010;95(1):280-288. doi:10.1210/jc.2009-1346
Nelson CJ, Lee JS, Gamboa MC, Roth AJ. Cognitive effects of hormone therapy in men with prostate cancer: a review. Cancer. 2008;113(5):1097-1106. doi:10.1002/cncr.23658
Jamadar RJ, Winters MJ, Maki PM. Cognitive changes associated with ADT: a review of the literature. Asian J Androl. 2012;14(2):232-238. doi:10.1038/aja.2011.107
Kluger J, Roy A, Chao HH. Androgen deprivation therapy and cognitive function in prostate cancer. Curr Oncol Rep. 2020;22(3):24. doi:10.1007/s11912-020-0884-1
McGinty HL, Phillips KM, Jim HS, et al. Cognitive functioning in men receiving androgen deprivation therapy for prostate cancer: a systematic review and meta-analysis. Supp Care Cancer. 2014;22(8):2271-2280. doi:10.1007/s00520-014-2285-1
Sun M, Cole AP, Hanna N, et al. Cognitive impairment in men with prostate cancer treated with androgen deprivation therapy: a systematic review and meta-analysis. J Urol. 2018;199(6):1417-1425. doi:10.1016/j.juro.2017.11.136
Beer TM, Bland LB, Bussiere JR, et al. Testosterone loss and estradiol administration modify memory in men. J Urol. 2006;175(1):130-135. doi:10.1016/s0022-5347(05)00049-2
Taxel P, Stevens MC, Trahiotis M, Zimmerman J, Kaplan RF. The effect of short-term estradiol therapy on cognitive function in older men receiving hormonal suppression therapy for prostate cancer. J Am Geriatr Soc. 2004;52(2):269-273.
Sherwin BB, Tulandi T. “Add-back” estrogen reverses cognitive deficits induced by a gonadotropin-releasing hormone agonist in women with leiomyomata uteri. J Clin Endocrinol Metabolism. 1996;81(7):2545-2549. doi:10.1210/jcem.81.7.8675575
Luine V, Rodriguez M. Effects of estradiol on radial arm maze performance of young and aged rats. Behav Neural Biol. 1994;62(3):230-236. doi:10.1016/s0163-1047(05)80021-4
Russell N, Hoermann R, Cheung AS, Zajac JD, Handelsman DJ, Grossmann M. Effects of estradiol on fat in men undergoing androgen deprivation therapy: a randomized trial. Eur J Endocrinol. 2021;186:9-23. doi:10.1530/eje-21-0663
Russell N, Hoermann R, Cheung AS, et al. Short-term effects of transdermal estradiol in men undergoing androgen deprivation therapy for prostate cancer: a randomized placebo-controlled trial. Eur J Endocrinol. 2018;178(5):565-576. doi:10.1530/eje-17-1072
NIH National Cancer Institute. Common Terminology Criteria for Adverse Events version 4.03. Published April 29, 2010. Accessed July 4, 2017. https://nciterms.nci.nih.gov/ncitbrowser/pages/advanced_search.jsf?dictionary=CTCAE%26version=4.03
Falleti MG, Maruff P, Collie A, Darby DG. Practice effects associated with the repeated assessment of cognitive function using the CogState Battery at 10-minute, one week and one month test-retest intervals. J Clin Exp Neuropsyc. 2006;28(7):1095-1112. doi:10.1080/13803390500205718
Lim YY, Jaeger J, Harrington K, et al. Three-month stability of the cogstate brief battery in healthy older adults, mild cognitive impairment, and Alzheimer's disease: results from the Australian Imaging, Biomarkers, and Lifestyle-Rate of Change Substudy (AIBL-ROCS). Arch Clin Neuropsych. 2013;28(4):320-330. doi:10.1093/arclin/act021
Fredrickson J, Maruff P, Woodward M, et al. Evaluation of the usability of a brief Computerized Cognitive Screening Test in older people for epidemiological studies. Neuroepidemiology. 2010;34(2):65-75. doi:10.1159/000264823
Koyama AK, Hagan KA, Okereke OI, Weisskopf MG, Rosner B, Grodstein F. Evaluation of a self-administered computerized cognitive battery in an older population. Neuroepidemiology. 2015;45(4):264-272. doi:10.1159/000439592
Zigmond AS, Snaith RP. The Hospital Anxiety and Depression Scale. Acta Psychiat Scand. 1983;67(6):361-370. doi:10.1111/j.1600-0447.1983.tb09716.x
Herrmann C. International experiences with the Hospital Anxiety and Depression Scale: a review of validation data and clinical results. J Psychosom Res. 1997;42(1):17-41.
Nead KT, Sinha S, Yang DD, Nguyen PL. Association of androgen deprivation therapy and depression in the treatment of prostate cancer: a systematic review and meta-analysis. Urol Oncol. 2017;35(11):664.e1-664.e9. doi:10.1016/j.urolonc.2017.07.016
Harwood DT, Handelsman DJ. Development and validation of a sensitive liquid chromatography-tandem mass spectrometry assay to simultaneously measure androgens and estrogens in serum without derivatization. Clin Chim Acta. 2009;409(1-2):78-84. doi:10.1016/j.cca.2009.09.003
Bates D, Mächler M, Bolker B, Walker S. Fitting linear mixed-effects models using lme4. J Stat Softw. 2015;67(1):1-48. doi:10.18637/jss.v067.i01
Handelsman DJ, Ly LP. An accurate substitution method to minimize left censoring bias in serum steroid measurements. Endocrinology. 2019;160(10):2395-2400. doi:10.1210/en.2019-00340
R Core TeamR: A language and environment for statistical computing. R Foundation for Statistical Computing; 2021. https://www.R-project.org
Fox J, Weisberg S. Visualizing fit and lack of fit in complex regression models with predictor effect plots and partial residuals. J Stat Softw. 2018;87(9):1-27. doi:10.18637/jss.v087.i09
Cogstate pediatric and adult normative data. Cogstate Ltd.; 2018.
Racine AM, Clark LR, Berman SE, et al. Associations between performance on an abbreviated cogstate battery, other measures of cognitive function, and biomarkers in people at risk for Alzheimer's Disease. J Alzheimer's Dis. 2016;54:1-14. doi:10.3233/jad-160528
Matousek RH, Sherwin BB. A randomized controlled trial of add-back estrogen or placebo on cognition in men with prostate cancer receiving an antiandrogen and a gonadotropin-releasing hormone analog. Psychoneuroendocrinology. 2010;35(2):215-225. doi:10.1016/j.psyneuen.2009.06.012
Miles C, Green R, Hines M. Estrogen treatment effects on cognition, memory and mood in male-to-female transsexuals. Horm Behav. 2006;50(5):708-717. doi:10.1016/j.yhbeh.2006.06.008
Guerrieri GM, Wakim PG, Keenan PA, et al. Sex differences in visuospatial abilities persist during induced hypogonadism. Neuropsychologia. 2016;81:219-229. doi:10.1016/j.neuropsychologia.2015.12.021
Emmelot-Vonk MH, Verhaar HJ, Nakhai Pour HR, et al. Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men: a randomized controlled trial. JAMA. 2008;299(1):39-52.
Sahab-Negah S, Hajali V, Moradi HR, Gorji A. The impact of estradiol on neurogenesis and cognitive functions in Alzheimer's disease. Cell Mol Neurobiol. 2020;40(3):283-299. doi:10.1007/s10571-019-00733-0
Khosrow-Khavar F, Rej S, Yin H, Aprikian A, Azoulay L. Androgen deprivation therapy and the risk of dementia in patients with prostate cancer. J Clin Oncol. 2017;35(2):201-207. doi:10.1200/jco.2016.69.6203
Handelsman DJ, Yeap B, Flicker L, Martin S, Wittert GA, Ly LP. Age-specific population centiles for androgen status in men. Eur J Endocrinol. 2015;173(6):809-817. doi:10.1530/eje-15-0380
Russell N, Cheung A, Grossmann M. Estradiol for the mitigation of adverse effects of androgen deprivation therapy. Endocr Relat Cancer. 2017;24(8):R297-R313. doi:10.1530/erc-17-0153
Bhasin S, Travison TG, O'brien L, et al. Contributors to the substantial variation in on-treatment testosterone levels in men receiving transdermal testosterone gels in randomized trials. Andrology-us. 2018;6(1):151-157. doi:10.1111/andr.12428

Auteurs

Nicholas Russell (N)

Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Australia.
Department of Endocrinology, Austin Health, Heidelberg, Australia.

James Allebone (J)

Department of Psychiatry, Austin Health, The University of Melbourne, Heidelberg, Australia.

Orwa Dandash (O)

Department of Psychiatry, Austin Health, The University of Melbourne, Heidelberg, Australia.

Rudolf Hoermann (R)

Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Australia.

Ada S Cheung (AS)

Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Australia.
Department of Endocrinology, Austin Health, Heidelberg, Australia.

Jeffrey D Zajac (JD)

Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Australia.
Department of Endocrinology, Austin Health, Heidelberg, Australia.

David J Handelsman (DJ)

Department of Andrology, ANZAC Research Institute, Concord Hospital, University of Sydney, Sydney, New South Wales, Australia.

Richard A Kanaan (RA)

Department of Psychiatry, Austin Health, The University of Melbourne, Heidelberg, Australia.

Mathis Grossmann (M)

Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Australia.
Department of Endocrinology, Austin Health, Heidelberg, Australia.

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