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What is the effect of menopause on cognition in women with Down syndrome?

May 2019 | Brian Chicoine, MD - Medical Director, Adult Down Syndrome Center

What is the effect of menopause on cognition in women with Down syndrome?

Menopause, defined as the cessation of menses (periods) for 12 months, occurs at a slightly younger age in women with Down syndrome than in women without Down syndrome. The median age of menopause in women with Down syndrome is reported to be 48 years of age (Seltzer et al., 2001). The median age of menopause among white women from industrialized countries ranges between 50 and 52 years of age with slight evidence of increasing age at menopause over time historically. These onsets seem to vary by race and ethnicity and are affected by demographic and lifestyle factors (Gold, 2011).

Some women without Down syndrome report some confusion and memory impairment as they become menopausal. We suspect that this is true for some women with Down syndrome, too. How much of the change is caused by menopause and how much is caused by other factors (such as Alzheimer’s disease) is difficult to delineate, especially at the early stages. Progressive decline is more likely to be Alzheimer’s disease. Interestingly, Coppus et al. (2010) reported a significant correlation between age at menopause and diagnosis of dementia in women with Down syndrome. In their study, early age at menopause was associated with a 1.8-fold increased risk of dementia.

Several years ago, there was a great deal of interest about whether estrogen or hormone replacement therapy (ERT/HRT) could prevent confusion or even Alzheimer’s disease in women (with or without Down syndrome). Studies of the effect of ERT/HRT on preventing confusion and/or Alzheimer’s disease in women without Down syndrome have been inconclusive and contradictory. Some studies show a decrease in dementia, some show no effect, and some show an increase in dementia. We are not aware of any studies that have been done specifically in women with Down syndrome on the use of ERT/HRT to prevent Alzheimer’s disease. However, in a 2018 paper, Schupf et al. noted that women with Down syndrome have a short interval between menopause and the onset of cognitive decline. They write that this “suggests an opportunity to evaluate the efficacy of ERT/HRT for delaying or preventing dementia in this high-risk population, although questions concerning the optimal formulation and timing of the hormone therapy are not yet resolved.” Thus, more study is needed.

In conclusion:

  • We suspect at least some mild confusion and memory impairment may be associated with menopause in women with Down syndrome.

  • Earlier menopause is associated with increased risk of dementia in women with Down syndrome.

  • We are not aware of a study that demonstrates that taking ERT/HRT treats memory impairment or prevents Alzheimer’s disease in women with Down syndrome.



Coppus, A.M., Evenhuis, H.M., Verberne, G.J., Visser, F.E., Eikelenboom, P., van Gool, W.A., Janssens, A.C., & van Duijn, C.M. (2010). Early age at menopause is associated with increased risk of dementia and mortality in women with Down syndrome. Journal of Alzheimer’s Disease, 19(2), 545-50.

Gold, E.B. (2011). The timing of the age at which natural menopause occurs. Obstetrics and Gynecology Clinics of North America, 38(3), 425-440.

Schupf, N., Lee, J.H., Pang, D., Zigman, W.B., Tycko, B., Krinsky-McHale, S., & Silverman, W. (2018). Epidemiology of estrogen and dementia in women with Down syndrome. Free Radical Biology & Medicine, 114, 62-68.

Seltzer, G.B., Schupf, N., & Wu, H.S. (2001). A prospective study of menopause in women with Down’s syndrome. Journal of Intellectual Disability Research, 45(Pt 1), 1-7.

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