Concluding remarks

The Women's Health Initiative Memory Study (WHIMS), an ancillary study of the Women's Health Initiative, comprised two large parallel randomized placebo-controlled clinical trials, one of women with a uterus and one of women who had undergone hysterectomy. The largest study of its kind, the WHIMS had been set up to further investigate the promising protective effects of estrogen treatment on the aging brain. The primary outcomes were specified as all-cause dementia or Alzheimer's disease, but other cognitive outcomes were explored as well. The WHIMS reported a completely unexpected increased risk of dementia with combined conjugated equine estrogens (CEE) and medroxy-progesterone acetate (MPA) treatment in women of 65 years of age and older and a trend for increased risk with CEE alone. The number of incident cases was too small to consider Alzheimer's disease as a separate outcome. Secondary ancillary analyses also showed negative effects on verbal memory functions after an average of three years of treatment. This was particularly surprising, as verbal memory functions were thought to be more likely to benefit from estrogens treatment and are usually the earliest affected cognitive functions in dementia due to Alzheimer's disease. Many researchers argued that there may have been subgroups for whom hormone treatment (HT) would have been successful. Perhaps women from the WHIMS might not have been representative because they were too often obese or had too many other risk factors for dementia. In Chapter 2 authors presented novel statistical techniques to analyze data using artificial neural networks to identify treatment responders.