Hormone replacement therapy and hippocampal volume

Historically, women´s health has been neglected in medical research. Much has improved in the past three decades (e.g., The Women´s Health Initiative Study) although we still can do better. One area of research that is bound to be female-oriented is research on hormone replacement therapy (HRT).

Estrogen products were approved for short-term treatment in the early forties to counteract symptoms of menopause. HRT later became to be seen as a possible preventative therapy for various afflictions of aging, including osteoporosis, heart disease and Alzheimer´s disease. It was, in fact, seen as a potential fountain of youth. These expectations were not born out. HRT is no longer recommended for the prevention of dementia and has been linked to an increased risk of cancer. But the effects of estrogen on the brain are still being investigated.

In our previous posts (e.g., here and here) the hippocampus, which is important for normal memory,  has frequently been the topic of interest because “One of the most frequently employed, and validated, measure of “brain health” in older adults is hippocampal volume” (Wnuk and colleagues, p. 187). The hippocampus has a high-density of estrogen receptors and therefore the relationship between hippocampal volume and HRT has been actively investigated.

Estrogen, memory and hippocampal volume

Early studies showed that HRT improved verbal memory in post-menopausal women. Several studies supported these results by showing that women who had received HRT had larger hippocampi (plural of hippocampus) than women who had never taken hormones. It has also been shown that hippocampal volume starts to decline earlier in males than in women, possibly because estrogen offers some protection in menstruating women. Other studies have, on the other hand, found that HRT is associated with smaller hippocampi and increased dementia rate. Finally, other studies have found no difference in hippocampal size between groups of women receiving HRT and those not receiving HRT.

What explains these different results? Well, not all the studies are conducted in the same manner. Although the different researchers are apparently studying the same thing, comparing studies is complicated. The age bracket of the participants in various studies is not the same and they have taken hormones for various periods of time, starting at different ages. For example, in one study the women had received HRT from 6 months to 26 years! In other studies the duration of treatment has been a lot less. This is very important because it has been suggested that temporary HRT might be protective and good for the brain, whereas treatment for a long time might have the opposite effect. It has also been proposed that initiating HRT during the onset of menopause is helpful whereas starting therapy later might be harmful. There may be a window of opportunity where hormonal treatment is effective. But the window closes after a certain number of years and administering hormones to women who already have Alzheimer´s disease is of no use.

Lifestyle choices for a healthy brain

There is no magic potion, dietary supplement or a drug, which will prevent dementia or maintain your hippocampi in tip-top shape. You cannot do anything about your genetic makeup either. However, what you can do is to make sensible lifestyle choices to decrease the likelihood of disease: healthy diet, exercise, lots of sleep, little stress and an active mind. Hormone replacement therapy and dietary supplements will not override an unhealthy lifestyle.

Based on:

Henderson, V. W. (2010). Actions of estrogens in the aging brain: Dementia and cognitive aging. Biochimica et Biophysica Acta, 1800, 1077-1083.

Lord, C., Buss, C., Lupien, S. J. & Pruessner, J. C. (2008). Hippocampal volumes are larger in postmenopausal women using estrogen therapy compared to past users, never users and men: A possible window of opportunity effect. Neurobiology of Aging, 29, 95-101.

Sally A. Shumaker, et al. (2003), Estrogen Plus Progestin and the Incidence of Dementia and Mild Cognitive Impairment in Postmenopausal Women: The Women’s Health Initiative Memory Study: A Randomized Controlled Trial. JAMA, 289(20). 2717-2719.

Schneider, L. S. (2004). Estrogen and Dementia Insights From the Women’s Health Initiative Memory Study. JAMA, 291(24), 3005-3007.

Wnuk, A., Korol, D. L. & Erickson, K. I. (2012). Estrogens, hormone therapy, and hippocampal volume in postmenopausal women. Maturitas, 73, 186-190.

A book of interest: The Estrogen Elixir: A History of Hormone Replacement Therapy in America by Elizabeth S. Watkins: http://www.amazon.com/The-Estrogen-Elixir-History-Replacement/dp/0801894867/ref=sr_1_1?ie=UTF8&qid=1353883928&sr=8-1&keywords=The+Estrogen+Elixir%3A+A+History+of+Hormone+Replacement+Therapy+in+America

A report from the Institute of Medicine in the US (2010): http://www.iom.edu/~/media/Files/Report%20Files/2010/Womens-Health-Research-Progress-Pitfalls-and Promise/Womens%20Health%20Research%202010%20Report%20Brief.pdf

Illustration credit: http://www.flickr.com/photos/netdoktorde/4403006675/


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