Testosterones Offer Hope for Patients

Women are living longer than in the past, but at a cost.

Women are experiencing greater loss of years of healthy life, with dementia now the fourth most important cause of disability-adjusted years of life lost among women in Western countries.

It is expected to be the leading cause of disability by the year 2016, according to a speaker at the annual conference of the Australian Menopause Society.

Dr. Susan Davis, from Monash University's department of medicine in Victoria, told the conference that women have a greater rate of Alzheimer's disease and cognitive decline than men.

True gender gap

One theory points to the fact that there are more older women than older men.

But this is not the case, she said, as there appears to be a true gender discrepancy, such that women are more vulnerable to developing Alzheimer's than men.

"In vitro and in vivo research findings provide biological plausibility that the hypo-estrogenic state adversely affects neurological tissues.

"The widespread distribution of intracellular estrogen receptors alpha and beta throughout many regions of the brain has been confirmed using increasingly precise and sensitive localization techniques.

"And in vitro studies have shown that estrogen directly influences neuronal growth and neurochemical systems that change with age-related cognitive decline."

Although hormone therapy has gone out of favour since the Women's Health Initiative study, more recent data, including from Dr. Davis's research, suggest that one factor may be changes in hormones through midlife that put women at greater risk.

Intervene early

"There is still a hypothesis that soon after the menopausal transition, the drop in estrogen has a critical effect, and if you intervene then, you reduce the risk of cognitive decline later.

"However, if you intervene later with estrogen, it will be a bad thing."

Dr. Davis is also studying the effect of androgens on Alzheimer's disease.

A recent study looked at men with Alzheimer's and testosterone levels in the brain, she said.

Men who die of Alzheimer's have much lower testosterone levels in their brain than do men who die of other causes.

"There is a continuum: Men with no Alzheimer's have much higher testosterone levels in their brain than men with non-cognitive decline, and the lowest is in men with Alzheimer's. So there is a gradient.

"We did a small study of 60 women recently where we showed that testosterone replacement was associated with beneficial effects on cognition in women."

She plans to repeat this work in a much larger, placebo-controlled trial.

"Clinically, many of my patients stay on testosterone because they say they think better. This could have massive implications for the treatment of women, because Alzheimer's is going to be the leading cause of disability in aged women in the future, with a huge cost burden to the community."

Testosterone benefits

In another study, Dr. Davis and colleagues are examining the effects of giving testosterone to women, since testosterone is the building block for estrogen.

Of 60 women who were already on hormone replacement therapy, half were given an aromatase inhibitor drug, which totally blocks the conversion of testosterone to estrogen, and half were given a placebo.

"We were interested to see whether that blocking also resulted in blocking the effects of testosterone but, in fact, it did not."

Women had significant improvements in certain domains of cognition and this was unaffected by the blocking of testosterone conversion to estrogen, she said.

"So these effects are clearly testosterone effects.

"We also looked at sexual function and found it improved in all women very significantly, but there was no effect if we blocked testosterone conversion to estrogen."

More information