Testosterone may not help memory after menopause

Researchers have wondered whether replacing the small amount of testosterone women stop producing after having hysterectomies could improve the memory loss many postmenopausal women experience. But testosterone treatment may not improve women’s memory skills after such surgeries, according to a new study, suggesting that it may not help other women after menopause either.

Women who took estrogen and testosterone after having surgery to remove their ovaries and uteruses did worse on one memory test, and no differently on others, than women who took estrogen alone.

Millions of postmenopausal women in the U.S. are prescribed hormone therapy - generally estrogen and a progesterone-like hormone - every year. The risks and benefits of hormone therapy remain controversial since the Women’s Health Initiative study was called off in 2002 when women on hormones were discovered to have an increased risk of ovarian and breast cancer and strokes, as well as heart disease.

The effect of hormone therapy on memory loss is still up for debate, especially for testosterone. In the current study, Dr. Marika Möller, a neuropsychologist at Kullbergska Hospital in Katrineholm, Sweden, and her colleagues treated 44 women who had hysterectomies for non-cancerous conditions. Half of those women took estrogen and testosterone and the other half took estrogen and an inactive placebo. After five and a half months, the women switched treatments.

At the beginning of the study, published in the journal Menopause, the authors put the women through a slew of memory tests to measure verbal, spatial and working memory and had them fill out a questionnaire about their memory problems. The tests and questionnaire were repeated after each round of treatment.

For most tests, women that had been taking estrogen and testosterone and women taking only estrogen performed about the same, with a general trend toward fewer everyday memory problems but mixed results on other memory tests. On one test, in which women had to recall a logical story, women on the testosterone plus estrogen treatment performed significantly worse than women just on estrogen.

Both groups improved over their baseline scores, however - suggesting that estrogen had a positive effect on this type of memory, but that testosterone cancelled out some of its benefits.

Testosterone capsules can be bought for about $2-3 a day, but are not FDA-approved for women. Side effects in women have been shown to include acne and excess facial hair, but the authors of the current study did not mention side effects.

Researchers, however, have thought that women might benefit from testosterone after surgical menopause because they lose their natural source of androgens. Androgens, a group of hormones that includes testosterone, have been shown to play a role in metabolism and libido, and possibly in learning and memory.

“After natural menopause the ovaries no longer make progesterone and they no longer make estradiol, but they continue to make androgens,” Dr. Victor Henderson, an epidemiologist and neurologist at Stanford University School of Medicine who was not involved with the study, told Reuters Health. “With natural menopause there’s really not much of a change in circulating testosterone. With surgical menopause you lose that source of androgens.”

There’s also a difference in the way estrogen and progesterone change in women’s bodies after natural or surgical menopause. While hormone levels slowly decline in natural menopause, they drop abruptly after surgical menopause. For this reason, Henderson said, there needs to be more research on treatment of this population

The study’s lead author, Möller, agrees, saying she doesn’t want researchers to give up on testosterone just yet. “I think it’s too early to say that it’s not safe,” she told Reuters Health. “It’s just one study.”

Scientists are still figuring out what kinds of women might benefit most from hormone therapy, especially at what age it is most effective, she said.

Dr. Barbara Sherwin, who studies behavioral neuroscience at McGill University in Montreal and was not involved in the study, said there’s no question that estrogen can enhance some types of memory in postmenopausal women. But, she said, whether it protects against memory loss in old age or Alzheimer’s is not as clear. Her research has also shown some positive benefits of testosterone in postmenopausal women - on their sense of well being and energy levels, as well as on their thinking and memory.

Because of the way men’s and women’s brains are hard-wired, she said, the brains of women taking testosterone should be expected to perform more like men’s brains than they would normally. This might be why women on testosterone in this study weren’t as good at a type of verbal learning - an area in which women typically outperform men.

But, she said, most of this is theoretical. “In the real world,” she told Reuters Health, “I honestly don’t think that (testosterone) would impair or increase someone’s function in a dramatic way at all.”

Memory function is just one thing to consider in weighing the risks and benefits of hormone therapy, Henderson said, and the picture is still complicated. “Like a lot of other brain functions,” he said, “there’s no simple answer here.”

Menopause: The Journal of the North American Menopause Society, online June 15, 2010.

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