Long-term risk of depressive and anxiety symptoms after early bilateral oophorectomy

Division of Epidemiology, Department of Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Menopause (Impact Factor: 3.36). 11/2008; 15(6):1050-1059. DOI: 10.1097/gme.0b013e318174f155


Objective: We studied the long-term risk of depressive and anxiety symptoms in women who underwent bilateral oophorectomy before menopause.
Design: We conducted a cohort study among all women residing in Olmsted County, MN, who underwent bilateral oophorectomy before the onset of menopause for a noncancer indication from 1950 through 1987. Each member of the bilateral oophorectomy cohort was matched by age with a referent woman from the same population who had not undergone an oophorectomy. In total, we studied 666 women with bilateral oophorectomy and 673 referent women. Women were followed for a median of 24 years, and depressive and anxiety symptoms were assessed using a structured questionnaire via a direct or proxy telephone interview performed from 2001 through 2006.
Results: Women who underwent bilateral oophorectomy before the onset of menopause had an increased risk of depressive symptoms diagnosed by a physician (hazard ratio = 1.54, 95% CI: 1.04-2.26, adjusted for age, education, and type of interview) and of anxiety symptoms (adjusted hazard ratio = 2.29, 95% CI: 1.33-3.95) compared with referent women. The findings remained consistent after excluding depressive or anxiety symptoms that first occurred within 10 years after oophorectomy. The associations were greater with younger age at oophorectomy but did not vary across indications for the oophorectomy. In addition, treatment with estrogen to age 50 years in women who underwent bilateral oophorectomy at younger ages did not modify the risk.
Conclusions: Bilateral oophorectomy performed before the onset of menopause is associated with an increased long-term risk of depressive and anxiety symptoms.

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    • "Bilateral oophorectomy (46 year) (3.9 mg / week; td; 3 month) Anxiolytic [34] Hysterectomy and bilateral oophorectomy (3.9 mg / week; td; 6 mouth) Anxiolytic [41] Tibolone Hysterectomy and bilateral oophorectomy (47 year) (2.5 mg/day; v. o.; 6 month) Anxiolytic Increased risk of stroke in women over 60 years (Cummings et al., 2008). Nausea, headache, breast tenderness, weight gain, bloating (Gupta et al., 2013 "
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    ABSTRACT: Generalized anxiety disorder is one of the most common psychiatric disorders, affecting a high percentage of human beings around the world. This emotional disorder possesses marked gender differences and occurs more often in women than in men, in a proportion of 2:1. Accompanying the reproductive cycle of women are significant fluctuations in plasma and brain steroid hormone concentrations, including oestradiol, progesterone, and allopregnanolone, among others. These hormonal changes are related to some illnesses and with the development of anxiety and mood swings occurring in the premenstrual and postpartum period, and particularly during the menopause. Menopause is a clinical term used to indicate the cessation of the woman's reproductive ability that occurs naturally, but also may be surgically induced by bilateral oophorectomy, with or without the removal of the Fallopian tubes and uterus. Natural menopause includes specific periods related to the physiological and hormonal changes produced by ovarian failure, it is usually a natural stage that occurs to women in midlife, during their late 40s or early 50s, indicating the end of the reproductive period in the woman. During the menopause transition years, women experience changes in the production of ovarian hormones, which are associated with significant changes in the physiological, emotional, and affective processes. Unfortunately, surgical menopause occurs at an early age, and produces similar physiological and psychiatric disorders, but they are more severe in this instance. In both cases, typical symptoms associated with menopause critically deteriorate the mental health of the women. In this way, the therapeutic management of clinical symptoms of menopause include replacement hormone therapy, the use of anxiolytic and antidepressant drugs, and other natural alternatives based on the use of chemical compounds obtained from plants such as soya. However, a general effective treatment for menopause symptoms does not yet exist. For this reason, experimental studies have proposed ovariectomy in rats as a potential tool to study the effects of a long-term absence of ovarian hormones associated with surgical menopause, which also allowed the study of substances with potential therapeutic application to ameliorate typical symptoms associated with surgical menopause. The aim of this chapter is to review the participation of ovarian hormones in the regulation of emotional and affective disorders in women with natural or surgical menopause; particularly their anatomical pathways, neurotransmission systems, and the resulting behavioural patterns. Finally, preclinical and clinical research suggested that long-term absence of ovarian hormones associated with natural or surgical menopause is the principal cause of physiological and psychiatric disorder in the women; therefore, oestrogenic compounds seem to play a important role in the maintenance of the brain structures that regulate anxiety, mood, memory, and cognitive functions in menopausal women.
    A fresh look anxiety disorders., First edited by Durbano F, 09/2015: chapter Anxiety in natural and surgical menopause – Physiologic and therapeutic bases.: pages 173-198; InTech., ISBN: 978-953-51-4277-5
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    • "Rocca et al. [16] [17] 1,252 women with unilateral and 1,075 women with bilateral ophorectomy, and 2,368 referent women. "
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    ABSTRACT: Over the past two decades, there has been a significant amount of research investigating the risks and benefits of hormone replacement therapy (HRT) with regards to neurodegenerative disease. Here, we review basic science studies, randomized clinical trials, and epidemiological studies, and discuss the putative neuroprotective effects of HRT in the context of Alzheimer's disease, Parkinson's disease, frontotemporal dementia, and HIV-associated neurocognitive disorder. Findings to date suggest a reduced risk of Alzheimer's disease and improved cognitive functioning of postmenopausal women who use 17β-estradiol. With regards to Parkinson's disease, there is consistent evidence from basic science studies for a neuroprotective effect of 17β-estradiol; however, results of clinical and epidemiological studies are inconclusive at this time, and there is a paucity of research examining the association between HRT and Parkinson's-related neurocognitive impairment. Even less understood are the effects of HRT on risk for frontotemporal dementia and HIV-associated neurocognitive disorder. Limits to the existing research are discussed, along with proposed future directions for the investigation of HRT and neurodegenerative diseases.
    International Journal of Alzheimer's Disease 04/2012; 2012(2):258454. DOI:10.1155/2012/258454
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    • "The risk of colorectal cancer also is decreased (van Wayenburg et al. 2000), and despite an increase in death from uterine and ovarian cancer with increasing age at menopause, the net effect of later menopause is an increased lifespan (Ossewaarde et al. 2005). As might be expected, early reproductive endocrine dyscrasia, occurring naturally or induced by unilateral or bilateral oophorectomy in premenopausal women, is associated with increased risk of developing dementia, cognitive decline, stroke, fatal and nonfatal coronary heart disease, Parkinsonism, osteoporosis , hip fracture, lung cancer, depression, and anxiety (Parker and Manson 2009; Parker et al. 2009; Rivera et al. 2009a, b; Rocca et al. 2006; Nappi et al. 1999; Rocca et al. 2007; Shuster et al. 2010; Gleason et al. 2005; Rocca et al. 2008a, b, c, 2009; Lisabeth et al. 2009; Baba et al. 2010; Koushik et al. 2009). Indeed, the increased prevalence of cognitive disease in women correlates with the abrupt earlier loss of gonadal function (Jorm et al. 1987; McGonigal et al. 1993; Brookmeyer et al. 1998; Gao et al. 1998; Andersen et al. 1999; Hy and Keller 2000). "
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    ABSTRACT: The reproductive-cell cycle theory of aging posits that reproductive hormone changes associated with menopause and andropause drive senescence via altered cell cycle signaling. Using data from the Wisconsin Longitudinal Study (n = 5,034), we analyzed the relationship between longevity and menopause, including other factors that impact "ovarian lifespan" such as births, oophorectomy, and hormone replacement therapy. We found that later onset of menopause was associated with lower mortality, with and without adjusting for additional factors (years of education, smoking status, body mass index, and marital status). Each year of delayed menopause resulted in a 2.9% reduction in mortality; after including a number of additional controls, the effect was attenuated modestly but remained statistically significant (2.6% reduction in mortality). We also found that no other reproductive parameters assessed added to the prediction of longevity, suggesting that reproductive factors shown to affect longevity elsewhere may be mediated by age of menopause. Thus, surgical and natural menopause at age 40, for example, resulted in identical survival probabilities. These results support the maintenance of the hypothalamic-pituitary-gonadal axis in homeostasis in prolonging human longevity, which provides a coherent framework for understanding the relationship between reproduction and longevity.
    Age 12/2011; 35(1). DOI:10.1007/s11357-011-9342-1 · 3.45 Impact Factor
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