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The average age of natural menopause is about 51 years. In the absence of hormone therapy, systemic exposures to ovarian hormones are greatly reduced after menopause, with consequences that vary by organ or tissue. Health-related effects are likely to be more pronounced after premature menopause, defined by menopause at age 40 years or younger.


Potential effects of premature menopause might include an elevated risk of developing dementia later in life and greater age-related cognitive decline in the absence of dementia. Few studies, however, have considered these outcomes after premature menopause or have assessed long-term cognitive outcomes after surgical menopause (bilateral oophorectomy) separately from natural menopause. The latter is potentially important because surgical menopause is distinguished not only by younger age – by definition, surgical menopause is induced before the age at which natural menopause would have occurred – but also by abrupt transition and by lower levels of testosterone (derived in part after natural menopause from the ovarian stroma), in addition to low levels of estradiol, estrone, and progesterone [1].


These issues were examined by Ryan and colleagues in the population-based Three-City Study, based in the French cities of Montpellier, Bordeaux, and Dijon [2]. Women ([i]n[/i] = 4868) were aged 65 years and older at the time of recruitment (mean age 75 years), and investigators examined cognitive outcomes in relation to age at menopause and to type of menopause (natural or surgical). Ten percent of women reported surgical menopause, and 7.6% reported a premature menopause. Well-defined procedures were in place to diagnose dementia and to detect cognitive decline. About 10.5% of 3739 women followed longitudinally developed dementia. Alzheimer’s disease was not assessed separately from all-cause dementia, and analyses were not adjusted for multiple comparisons.


  • Victor W. Henderson
    Departments of Health Research & Policy (Epidemiology) and of Neurology & Neurological Sciences, Stanford University, USA


  1. Henderson VW, Sherwin BB. Surgical versus natural menopause: cognitive issues. Menopause 2007;14:572-9
  2. Ryan J, Scali J, Carriere I, et al. Impact of a premature menopause on cognitive function in later life. BJOG 2014 May 7. Epub ahead of print
  3. Rocca WA, Bower JH, Ahlskog JE, Grossardt BR, de Andrade M, Melton LJ, 3rd. Increased risk of cognitive impairment or dementia in women who underwent oophorectomy before menopause. Neurology 2007;69:1074-83
  4. Phung TK, Waltoft BL, Laursen TM, et al. Hysterectomy, oophorectomy and risk of dementia: a nationwide historical cohort study. Dement Geriatr Cogn Disord 2010;30:43-50
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