Background:

Oophorectomy prior to natural menopause places women at increased risk of dementia and/or Alzheimer's disease (AD). Recent findings from our Toronto group reveal a negative association between oophorectomy prior to natural menopause and verbal memory in middle-aged women. We have also found a positive association between estrogen levels and verbal recall. Taken together, these findings support previous work suggesting that oophorectomy, leading to reduced levels of estrogens, is detrimental to verbal memory. Estrogen withdrawal has also been correlated with reduced hippocampal volume and reduced hippocampal resting functional connectivity (FC), both early AD biomarkers. Thus, we wondered whether hippocampal volume and resting functional connectivity would be reduced in women with oophorectomy prior to natural menopause.

Methods:

In order to determine this, we recruited healthy, Swedish women (30 and 55 years) with the breast cancer mutation gene (BRCA1/2) who had a bilateral salpingo-oophorectomy (BSO) prior to natural menopause. Most women were between 1–7 years post-BSO and at least 6 months post-cancer treatment or had not had cancer. Using magnetic resonance imaging (3T scanner, Phillips) we measured functional resting state over 10 minutes and volume with a T1 structural scan. We collected urine in order to determine estrogen and progesterone levels.

Results:

We hypothesize that women with BSO will have structural and functional hippocampal changes compared to age matched controls. We predict that women with BSO will have smaller hippocampal volumes and reduced hippocampal FC. We further predict that lower levels of estrogens will correlate with these brain changes. Neuroimaging and endocrine analyses are ongoing.

Conclusions:

AD affects women in greater numbers and one possibility is that oophorectomy prior to natural menopause contributes to these numbers. Determining whether or not these women show the earliest biomarkers for AD will increase our understanding of estrogen withdrawal's effects on brain health as well as its importance for healthy brain aging. Importantly, results of this study will inform us on the early brain changes in a population at greater risk of AD.