Cynthia Holmes, an elderly African-American woman, began with the statement that she was not sure if she was coming to the right place. Her sister thought she was getting depressed and her friends told her she was not as mentally sharp as she used to be, but Cynthia herself felt that her problems were too minor to merit seeing a doctor. The ravages of osteoarthritis had reduced her height from six feet to five feet nine inches, and she shuffled into my office looking as if a strong wind was behind her back, bending her over. Her face was heavily lined with wrinkles, and she displayed a listless, apathetic look. I guessed that she was around eighty years old, but in fact she was only sixty-four. She said she was forgetting names more often, found it difficult to keep track of her checks and monthly bills, and tended to forget the sequence of cards during games that she occasionally played with friends. She also reported low energy and fatigue, and a loss of interest in crocheting and other hobbies that she used to enjoy. She had retired at the age of sixty from a clerical job, and since that time she had developed a somewhat negative, pessimistic outlook on life. She did not have any difficulty in sleeping, there was no change in her appetite, and her interest in sex was lower than what it used to be, a change that she attributed to the loss of her husband from a stroke eight years earlier.
She did not feel that she had significant memory loss or depression because, as she put it, "You know, I think it's normal to lose your memory a little, to feel a bit low about getting old. My body doesn't function the way it should. Many in my family have died, and some of my friends have passed away too. At my age, I don't see how things are going to get better for me."
She had come to our Memory Disorders Center at the insistence of her sister Myra, who had become worried about the changes that she had observed. When Myra walked into the office a few minutes later, the contrast between the two women was so striking that I momentarily wondered if the two were even related. Myra was well built, bouncy on her feet, and had a jovial, lively manner that lit up her face and was quite endearing.
"Your older sister was just telling me that she is no longer as interested in her hobbies," I said.
Myra looked at her sister Cynthia, turned toward me with a puzzled expression, and then suddenly laughed. ''You kiddin' me? She's not older. Cynthia, my little sister? She's six years younger than I am!"
I simply couldn't believe it. I had guessed that Myra was fifty, not seventy years old. And with my earlier impression of Cynthia being eighty rather than sixty-four, the contrast between the two sisters was even more striking to me. So I asked Myra about her own health habits. She went through the usual litany: a sound diet, regular exercise, no smoking, low alcohol intake, and a mellow, low-stress approach to life. Finally, she revealed that she was taking Premarin, a standard estrogen-replacement therapy for postmenopausal women.
I turned to ask her sister Cynthia if she had thought of taking estrogen herself.
"My aunt died of breast cancer, so I won't take the risk," she replied.
Myra explained that she had no problems on estrogen and that she had regular, frequent checkups with her gynecologist, including regular mammograms and pelvic exams. But Cynthia remained adamant that because there was a risk of cancer, she would not take estrogen.
Keeping this information in the front of my mind, I completed the diagnostic workup for Cynthia's memory loss, and possible depression. There were no abnormalities on neurological examination or any laboratory test, including MRI scan of the brain. Her neuropsychological testing showed only minimal deficits, which may have been due to mild depression. A twelve-week treatment course with the antidepressant medication paroxetine led to only slight improvement in her symptoms. Other antidepressant medications met the same fate. She refused to consider psychotherapy. She also did not want to try any memory-enhancing exercises or related techniques, so I asked her to start taking vitamin E 800 IUs daily. Adding the cholinesterase inhibitor donepezil (Aricept) had no significant impact on her memory. Cynthia's general health habits (sound diet, regular walks, no alcohol) were very good, so there wasn't much room for improvement there.
Over the next two years, Cynthia did not change very much. Occasional memory lapses persisted, but without any worsening over time. Her neuropsychological testing showed no significant changes during this period. My attempts to get her to reconsider estrogen therapy, or at least to discuss it with her gynecologist, were met with stony reffisal. Her older sister Myra, who accompanied Cynthia for some of her clinic visits, continued on her youthful, estrogen-filled way without any major health problems.
The main female sex hormone, estrogen, is produced by the ovaries. As Cynthia and Myra illustrate, its actions extend far beyond reproduction and sexual behavior. For Myra, estrogen prevented not only memory decline but also the ravages of the aging process itself.
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