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  • Print publication year: 2008
  • Online publication date: August 2009

9 - Effect of hormones and hormonal treatment on cognition

Summary

Introduction

This chapter will address the possible influences of hormonal therapy on cognitive functioning. Hormonal therapy is an important treatment option for, among others, breast and prostate cancer. While there is increasing evidence that chemotherapy induces cognitive dysfunction in a subgroup of patients (Tannock et al., 2004), the effects of hormonal therapy on cognitive functioning have not been investigated thoroughly. Actually, it is conceivable that hormonal therapy also influences cognitive performance. After all, hormonal therapies interfere with serum levels of reproductive hormones (particularly estrogens and androgens) or with hormonal actions. There are indications that reproductive hormones are important in cognitive functioning (Bender et al., 2001). The mechanisms of action of reproductive hormones on brain structures are not entirely understood. One of the possibilities is that these hormones act through estrogen and androgen receptors that are present in those brain structures important for cognitive function, for example the hippocampi and the cerebral cortex (Norbury et al., 2003). Furthermore, it has been suggested that reproductive hormones have a beneficial effect on neurotransmitters that are involved in cognitive processes (Cholerton et al., 2002; Norbury et al., 2003).

Hormonal therapy is increasingly used for breast and prostate cancer, often for long periods and by elderly patients. Because intact cognitive functioning is essential for independent living and activities of daily life, elucidation of the possible effects of the various hormonal agents and treatment regimens is becoming increasingly important.

REFERENCES
Almeida, OP, Waterreus, A, Spry, Net al. (2004). One year follow-up study of the association between chemical castration, sex hormones, beta-amyloid, memory and depression in men. Psychoneuroendocrinology 29: 1071–1081.
Azad, N, Pitale, S, Barnes, WEet al. (2003). Testosterone treatment enhances regional brain perfusion in hypogonadal men. J Clin Endocrinol Metab 88: 3064–3068.
Barrett-Connor, E, Kritz-Silverstein, D (1993). Estrogen replacement therapy and cognitive function in older women. J Am Med Assoc 269: 2637–2641.
Beer, TM, Bland, LB, Bussiere, JRet al. (2006). Testosterone loss and estradiol administration modify memory in men. J Urol 175: 130–135.
Bender, CM, Paraska, KK, Sereika, SMet al. (2001). Cognitive function and reproductive hormones in adjuvant therapy for breast cancer: a critical review. J Pain Symptom Manag 21: 407–424.
Benson, JR (2002). Re: The effects of tamoxifen and estrogen on brain metabolism in elderly women. J Natl Cancer Inst 94: 1336–1337.
Bowen, RL, Martins, RN, Gregory, CWet al. (2005). Dementia and testosterone levels in men. J Am Med Assoc 293: 551.
Chen, D, Wu, CF, Shi, Bet al. (2002a). Tamoxifen and toremifene cause impairment of learning and memory function in mice. Pharmacol Biochem Behav 71: 269–276.
Chen, D, Wu, CF, Shi, Bet al. (2002b). Tamoxifen and toremifene impair retrieval, but not acquisition, of spatial information processing in mice. Pharmacol Biochem Behav 72: 417–421.
Cherrier, MM, Asthana, S, Plymate, Set al. (2001). Testosterone supplementation improves spatial and verbal memory in healthy older men. Neurology 57: 80–88.
Cherrier, MM, Rose, AL, Higano, C (2003). The effects of combined androgen blockade on cognitive function during the first cycle of intermittent androgen suppression in patients with prostate cancer. J Urol 170: 1808– 1811.
Cholerton, B, Gleason, CE, Baker, LDet al. (2002). Estrogen and Alzheimer's disease: the story so far. Drugs Aging 19: 405–427.
Cook, IA, Morgan, ML, Dunkin, JJet al. (2002). Estrogen replacement therapy is associated with less progression of subclinical structural brain disease in normal elderly women: a pilot study. Int J Geriatr Psychiatry 17: 610– 618.
Drake, EB, Henderson, VW, Stanczyk, FZet al. (2000). Associations between circulating sex steroid hormones and cognition in normal elderly women. Neurology 54: 599–603.
Eberling, JL, Reed, BR, Coleman, JEet al. (2000). Effect of estrogen on cerebral glucose metabolism in postmenopausal women. Neurology 55: 875–877.
Eberling, JL, Wu, C, Tong-Turnbeaugh, Ret al. (2004). Estrogen- and tamoxifen-associated effects on brain structure and function. Neuroimage 21: 364–371.
Ernst, T, Chang, L, Cooray, Det al. (2002). The effects of tamoxifen and estrogen on brain metabolism in elderly women. J Natl Cancer Inst 94: 592–597.
Espeland, MA, Rapp, , Shumaker, SAet al. (2004). Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study. J Am Med Assoc 291: 2959–2968.
Fonda, SJ, Bertrand, R, O'Donnell, Aet al. (2005). Age, hormones, and cognitive functioning among middle-aged and elderly men: cross-sectional evidence from the Massachusetts Male Aging Study. J Gerontol A Biol Sci Med Sci 60: 385–390.
Ganz, PA, Castellon, SA, Silverman, DH (2002). Estrogen, tamoxifen, and the brain. J Natl Cancer Inst 94: 547–549.
Gleason, CE, Cholerton, B, Carlsson, CMet al. (2005). Neuroprotective effects of female sex steroids in humans: current controversies and future directions. Cell Mol Life Sci 62: 299–312.
Goss, PE, Strasser, K (2001). Aromatase inhibitors in the treatment and prevention of breast cancer. J Clin Oncol 19: 881–894.
Green, HJ, Pakenham, KI, Gardiner, RA (2000). Effects of luteinizing hormone releasing hormone analogs on cognition in women and men: a review. Psychol Health Med 5: 407–418.
Green, HJ, Pakenham, KI, Headley, BCet al. (2002). Altered cognitive function in men treated for prostate cancer with luteinizing hormone-releasing hormone analogues and cyproterone acetate: a randomized controlled trial. BJU Int 90: 427–432.
Hampson, E (1990). Variations in sex-related cognitive abilities across the menstrual cycle. Brain Cogn 14: 26–43.
Haren, MT, Wittert, GA, Chapman, IMet al. (2005). Effect of oral testosterone undecanoate on visuospatial cognition, mood and quality of life in elderly men with low-normal gonadal status. Maturitas 50: 124–133.
Hausmann, M, Slabbekoorn, D, Goozen, SHet al. (2000). Sex hormones affect spatial abilities during the menstrual cycle. Behav Neurosci 114: 1245–1250.
Hellerstedt, BA, Pienta, KJ (2002). The current state of hormonal therapy for prostate cancer. CA Cancer J Clin 52: 154–179.
Henderson, VW, Guthrie, JR, Dudley, ECet al. (2003). Estrogen exposures and memory at midlife: a population-based study of women. Neurology 60: 1369–1371.
Herr, HW, O'Sullivan, M (2000). Quality of life of asymptomatic men with nonmetastatic prostate cancer on androgen deprivation therapy. J Urol 163: 1743–1746.
Hogervorst, E, Williams, J, Budge, Met al. (2001). Serum total testosterone is lower in men with Alzheimer's disease. Neuroendocrinol Lett 22: 163–168.
Hogervorst, E, Jager, C, Budge, Met al. (2004). Serum levels of estradiol and testosterone and performance in different cognitive domains in healthy elderly men and women. Psychoneuroendocrinology 29: 405–421.
Janowsky, JS, Chavez, B, Orwoll, E (2000). Sex steroids modify working memory. J Cogn Neurosci 12: 407–414.
Jenkins, VA, Bloomfield, DJ, Shilling, VMet al. (2005). Does neoadjuvant hormone therapy for early prostate cancer affect cognition? Results from a pilot study. BJU Int 96: 48–53.
Juul, A, Skakkebaek, NE (2002). Androgens and the ageing male. Hum Reprod Update 8: 423–433.
Kenny, AM, Bellantonio, S, Gruman, CAet al. (2002). Effects of transdermal testosterone on cognitive function and health perception in older men with low bioavailable testosterone levels. J Gerontol A Biol Sci Med Sci 57: M321–M325.
Luoto, R, Manolio, T, Meilahn, Eet al. (2000). Estrogen replacement therapy and MRI-demonstrated cerebral infarcts, white matter changes, and brain atrophy in older women: the Cardiovascular Health Study. J Am Geriatr Soc 48: 467–472.
Maki, PM (2004). Hormone therapy and risk for dementia: where do we go from here?Gynecol Endocrinol 19: 354–359.
Maki, PM, Resnick, SM (2000). Longitudinal effects of estrogen replacement therapy on PET cerebral blood flow and cognition. Neurobiol Aging 21: 373–383.
Maki, PM, Rich, JB, Rosenbaum, RS (2002). Implicit memory varies across the menstrual cycle: estrogen effects in young women. Neuropsychologia 40: 518–529.
Meyer, PM, Powell, LH, Wilson, RSet al. (2003). A population-based longitudinal study of cognitive functioning in the menopausal transition. Neurology 61: 801–806.
Miller, WR (1996). Estrogens and Endocrine Therapy for Breast Cancer. Estrogen and Breast Cancer. Heidelberg: Springer Verlag.
Moffat, SD, Zonderman, AB, Metter, EJet al. (2004). Free testosterone and risk for Alzheimer disease in older men. Neurology 62: 188–193.
Muller, M, Aleman, A, Grobbee, et al. (2005). Endogenous sex hormone levels and cognitive function in aging men: is there an optimal level?Neurology 64: 866–871.
Newton, C, Slota, D, Yuzpe, AAet al. (1996). Memory complaints associated with the use of gonadotropin-releasing hormone agonists: a preliminary study. Fertil Steril 65: 1253–1255.
Nickelsen, T, Lufkin, EG, Riggs, BLet al. (1999). Raloxifene hydrochloride, a selective estrogen receptor modulator: safety assessment of effects on cognitive function and mood in postmenopausal women. Psychoneuroendocrinology 24: 115–128.
Norbury, R, Cutter, WJ, Compton, Jet al. (2003). The neuroprotective effects of estrogen on the aging brain. Exp Gerontol 38: 109–117.
Nystedt, M, Berglund, G, Bolund, Cet al. (2000). Randomized trial of adjuvant tamoxifen and/or goserelin in premenopausal breast cancer – self-rated physiological effects and symptoms. Acta Oncol 39: 959–968.
O'Connor, DB, Archer, J, Hair, WMet al. (2001). Activational effects of testosterone on cognitive function in men. Neuropsychologia 39: 1385–1394.
Osborne, CK, Zhao, H, Fuqua, SA (2000). Selective estrogen receptor modulators: structure, function, and clinical use. J Clin Oncol 18: 3172–3186.
Owens, JF, Matthews, KA, Everson, SA (2002). Cognitive function effects of suppressing ovarian hormones in young women. Menopause 9: 227–235.
Paganini-Hill, A, Clark, LJ (2000). Preliminary assessment of cognitive function in breast cancer patients treated with tamoxifen. Breast Cancer Res Treat 64: 165–176.
Phillips, SM, Sherwin, BB (1992). Effects of estrogen on memory function in surgically menopausal women. Psychoneuroendocrinology 17: 485–495.
Rapp, , Espeland, MA, Shumaker, SAet al. (2003). Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial. J Am Med Assoc 289: 2663–2672.
Resnick, SM, Maki, PM, Golski, Set al. (1998). Effects of estrogen replacement therapy on PET cerebral blood flow and neuropsychological performance. Horm Behav 34: 171–182.
Rosario, ER, Chang, L, Stanczyk, FZet al. (2004). Age-related testosterone depletion and the development of Alzheimer disease. J Am Med Assoc 292: 1431–1432.
Salminen, E, Portin, R, Korpela, Jet al. (2003). Androgen deprivation and cognition in prostate cancer. Br J Cancer 89: 971–976.
Salminen, EK, Portin, RI, Koskinen, Aet al. (2004). Associations between serum testosterone fall and cognitive function in prostate cancer patients. Clin Cancer Res 10: 7575–7582.
Salminen, EK, Portin, RI, Koskinen, AIet al. (2005). Estradiol and cognition during androgen deprivation in men with prostate carcinoma. Cancer 103: 1381–1387.
Sanders, G, Sjodin, M, Chastelaine, M (2002). On the elusive nature of sex differences in cognition: hormonal influences contributing to within-sex variation. Arch Sex Behav 31: 145–152.
Schagen, SB (2002). Cognitive function following chemotherapy: a study in breast cancer patients. Ph.D Thesis. University of Amsterdam.
Schmidt, R, Fazekas, F, Reinhart, Bet al. (1996). Estrogen replacement therapy in older women: a neuropsychological and brain MRI study. J Am Geriatr Soc 44: 1307–1313.
Sharifi, N, Gulley, JL, Dahut, WL (2005). Androgen deprivation therapy for prostate cancer. J Am Med Assoc 294: 238–244.
Shaywitz, SE, Shaywitz, BA, Pugh, KRet al. (1999). Effect of estrogen on brain activation patterns in postmenopausal women during working memory tasks. J Am Med Assoc 281: 1197–1202.
Sherwin, BB (1988). Estrogen and/or androgen replacement therapy and cognitive functioning in surgically menopausal women. Psychoneuroendocrinology 13: 345–357.
Sherwin, BB (2000). Oestrogen and cognitive function throughout the female lifespan. Novartis Found Symp 230: 188–196.
Sherwin, BB (2003). Steroid hormones and cognitive functioning in aging men: a mini-review. J Mol Neurosci 20: 385–393.
Sherwin, BB (2005). Estrogen and memory in women: how can we reconcile the findings?Horm Behav 47: 371–375.
Sherwin, BB, Tulandi, T (1996). “Add-back” estrogen reverses cognitive deficits induced by a gonadotropin-releasing hormone agonist in women with leiomyomata uteri. J Clin Endocrinol Metab 81: 2545–2549.
Shilling, V, Jenkins, V, Fallowfield, Let al. (2003). The effects of hormone therapy on cognition in breast cancer. J Steroid Biochem Mol Biol 86: 405–412.
Shumaker, SA, Legault, C, Rapp, SRet al. (2003). Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial. J Am Med Assoc 289: 2651–2662.
Shumaker, SA, Legault, C, Kuller, Let al. (2004). Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study. J Am Med Assoc 291: 2947–2958.
Simpson, ER, Dowsett, M (2002). Aromatase and its inhibitors: significance for breast cancer therapy. Recent Prog Horm Res 57: 317–338.
Tannock, IF, Ahles, TA, Ganz, PAet al. (2004). Cognitive impairment associated with chemotherapy for cancer: report of a workshop. J Clin Oncol 22: 2233–2239.
Taxel, P, Stevens, MC, Trahiotis, Met al. (2004). The effect of short-term estradiol therapy on cognitive function in older men receiving hormonal suppression therapy for prostate cancer. J Am Geriatr Soc 52: 269– 273.
Tripathy, D, Benz, CC (2001). Hormones and cancer. In FS, Greenspan, DG, Gardner (eds.) Basic and Clinical Endocrinology. New York: Lange Medical Books.
Verghese, J, Kuslansky, G, Katz, MJet al. (2000). Cognitive performance in surgically menopausal women on estrogen. Neurology 55: 872–874.
Visvanathan, K, Davidson, NE (2003). Aromatase inhibitors as adjuvant therapy in breast cancer. Oncology (Huntingt) 17: 335–342, 347.
Wolf, OT, Kirschbaum, C (2002). Endogenous estradiol and testosterone levels are associated with cognitive performance in older women and men. Horm Behav 41: 259–266.
Wolf, OT, Neumann, O, Hellhammer, DHet al. (1997). Effects of a two-week physiological dehydroepiandrosterone substitution on cognitive performance and well-being in healthy elderly women and men. J Clin Endocrinol Metab 82: 2363–2367.
Yaffe, K, Sawaya, G, Lieberburg, Iet al. (1998). Estrogen therapy in postmenopausal women: effects on cognitive function and dementia. J Am Med Assoc 279: 688–695.
Yaffe, K, Krueger, K, Sarkar, Set al. (2001). Cognitive function in postmenopausal women treated with raloxifene. N Engl J Med 344: 1207–1213.
Yaffe, K, Lui, LY, Zmuda, Jet al. (2002). Sex hormones and cognitive function in older men. J Am Geriatr Soc 50: 707–712.
Yaffe, K, Krueger, K, Cummings, SRet al. (2005). Effect of raloxifene on prevention of dementia and cognitive impairment in older women: the Multiple Outcomes of Raloxifene Evaluation (MORE) randomized trial. Am J Psychiatry 162: 683–690.