HRT May Prevent Accelerated Biological Aging for Alzheimer’s Gene Carriers

  • A little more than a decade ago, most physicians considered hormone replacement therapy an important part of treating postmenopausal women because of its ability to help control hot flashes, maintain bone health and lower the risk of colorectal cancer. Their enthusiasm for this treatment came to a halt in July of 2002, when the same physicians took their patients off HRT nearly across the board.


    An article in the New York Times explains what happened.  “A rigorous study found that the [HRT] drugs, a combination of estrogen and progestin, caused small increases in breast cancer, heart attacks, strokes and blood clots.”

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    Doctor’s attitudes have mellowed somewhat since that breaking news blew a hole in conventional thought. Now, hormone replacement therapy has been approved by the FDA to treat hot flashes and vaginal dryness related to menopause, but they recommend that it be used for the shortest amount of time possible, preferably no more than two years.


    HRT to prevent accelerated aging in ApoE4 Alzheimer gene carriers?

    A new wrinkle has just appeared on the HRT front. A recent study found that healthy menopausal women carrying a well-known genetic risk factor for Alzheimer's disease, known as ApoE4, showed measurable signs of accelerated biological aging. The encouraging part of the otherwise distressing study is that in ApoE4 carriers who started hormone therapy at menopause and remained on that therapy, this acceleration was absent. The study found that hormone replacement therapy for non-carriers of ApoE4 had no protective effect on their biological aging.


    First author of the study, Emily Jacobs, PhD, is a postdoctoral fellow at Harvard Medical School. In an interview with Science Daily, Jacobs said, "We know from numerous studies that ApoE4 is a major genetic risk factor for cognitive decline, Alzheimer's disease and early mortality. We wanted to see whether an accelerated rate of biological aging explained this risk."


    For this study, researchers used telomere shortening as an index of biological aging. A telomere is a region of repetitive nucleotide sequences at each end of a chromatid which protects the end of the chromosome from deterioration, or from fusion with neighboring chromosomes. Telomeres give researchers a glimpse of how we are aging biologically.


    The researcher drew blood samples from nearly 70 healthy women, most of them between the ages of 45 and 65, who had been on hormone therapy since menopause. These women were randomly divided into two groups, one of which remained on hormones, while the other group discontinued therapy. Through periodic blood tests, researchers calculated the change in telomere length that had taken place over the two-year period.


    According to Jacobs, telomere length is relatively easy to measure in blood cells, and it's an emerging marker of biological aging that predicts the incidence of age-related diseases and mortality.


    Among the many other assessments the researchers made on these women was their ApoE status. They found that ApoE4 carriers' telomeres were six times as likely as those of non-carriers to undergo significant shortening within the two-year study window. On average, the telomeres of ApoE4 carriers had shortened by an amount equivalent to what might be expected to take a decade, based on other studies of healthy women. However, hormone therapy effectively eliminated ApoE4's negative influence on telomere length over time. Carriers who remained on this regimen showed no evidence of telomere shortening.


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    Natalie Rasgon, MD, PhD, professor of psychiatry and behavioral sciences at the Stanford University School of Medicine and director of the Stanford Center for Neuroscience in Women's Health is a senior author for this study. She stated that, "Our take-home findings from this study were, first, that ApoE4 carriers are at greater risk of biological aging, which is associated with negative health outcomes and, second, if you were a postmenopausal ApoE4 carrier, being on estrogen therapy was a good thing for telomere length, an established measure of biological aging at the cellular level."


    Rasgon says that this information brings clinicians one step closer to being able to identify which women will benefit the most from estrogen replacement therapy.


    To me, the turmoil surrounding hormone replacement therapy is an excellent example of how often studies can contradict one another. I admire doctors who admit that modern medicine doesn’t have all of the answers, and that medical opinion can shift quickly as different study results emerge. If the ApoE4 study continues to stand up to scientific scrutiny, women who know that they are ApoE4 carriers should be given a choice about whether or not to use HRT based on their other risk factors. In situations like this, finding the right doctor is crucial.


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    Science Daily (2013, February 13) Accelerated Biological Aging, Seen in Women With Alzheimer's Risk Factor, Blocked by Hormone Therapy. Retrieved from


    Kolata, G. (2002, July 10) Hormone Replacement Study A Shock to the Medical System. New York Times. Retrieved from

    Hitti, M. (2009, February 4) Menopause Hormone Therapy: 'Safe' Time? New Studies Probe Timing of Hormone Replacement Therapy and Breast Cancer Risk. WebMD. Retrieved from


Published On: February 24, 2013