Oophorectomy, Hysterectomy, and Risk of Alzheimer's Disease: A Nationwide Case-Control Study

Article type: Research Article

Authors: Imtiaz, Bushra^{a; *} | Tuppurainen, Marjo^{b; c} | Tiihonen, Miia^d | Kivipelto, Miia^{e; f} | Soininen, Hilkka^{a; g} | Hartikainen, Sirpa^{h; i} | Tolppanen, Anna-Maija^a

Affiliations: [a] Institute of Clinical Medicine – Neurology, University of Eastern Finland, Kuopio, Finland | [b] Bone and Cartilage Research Unit, Clinical Research Center, University of Eastern Finland, Kuopio, Finland | [c] Department of Obstetrics and Gynecology, Kuopio University Hospital, Kuopio, Finland | [d] Department of Pharmacy, Social Pharmacy, University of Eastern Finland, Kuopio, Finland | [e] Department of Neurology, University of Eastern Finland, Kuopio, Finland | [f] Aging Research Center (ARC), Karolinska Institute and Stockholm University, Stockholm, Sweden | [g] Department of Neurology, Kuopio University Hospital, Kuopio, Finland | [h] Kuopio Research Center of Geriatric Care, University of Eastern Finland, Kuopio, Finland | [i] School of Pharmacy, Social Pharmacy, University of Eastern Finland, Kuopio, Finland

Correspondence: [*] Correspondence to: Bushra Imtiaz, Department of Neurology, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland. Tel.: +358 4433 06675; E-mail: bushra.imtiaz@uef.fi.

Abstract: Background:Association between oophorectomy and/or hysterectomy and dementia in context of hormone therapy (HT) use is ambiguous. Objective:To assess whether oophorectomy, hysterectomy, and hysterectomy with bilateral oophorectomy are related to risk of Alzheimer’s disease (AD), whether the possible indication for surgery plays a role, and if the associations are modified by HT. Methods:Our nationwide register based case–control (1 : 1) study included all women with clinically-verified AD diagnoses, residing in Finland on December 31, 2005 (n of cases = 19,043, n of controls = 19,043). AD cases, diagnosed according to NINCS-ADRDA and the DSM-IV criteria, were identified from Special Reimbursement Register. Information on HT use was collected from national prescription register, and data on surgery and uterine/ovarian/cervical cancer were obtained from the hospital discharge register. Most of the women (91.8%) were over 51 years of age when the surgery was performed. Results:Oophorectomy, hysterectomy, and hysterectomy with bilateral oophorectomy were associated with lower risk of AD (OR/95% CI: 0.85/0.75–0.97, 0.89/0.81–0.97 and 0.85/0.75–0.98, respectively) among women without the history of uterine/ovarian/cervical cancer, although the absolute risk difference was small. The association was not evident in women with uterine/ovarian/cervical cancer history (3.00/0.20–44.87 for all surgeries). The associations were not modified by HT use, which was independently associated with AD risk, with longer use showing protective association. Conclusion:Our findings indicate that oophorectomy with or without hysterectomy after commencement of natural menopause is not an important determinant of AD risk in older age and support the critical window hypothesis for HT use.

Keywords: Alzheimer's disease, cognition, dementia, estrogen, hormone therapy, hysterectomy, menopause, oophorectomy, radical hysterectomy

DOI: 10.3233/JAD-140336

Journal: Journal of Alzheimer's Disease, vol. 42, no. 2, pp. 575-581, 2014