Both low-dose regimens of the conjugated estrogen cream led to significant improvement in vaginal maturation index, vaginal pH, and most bothersome symptoms compared with placebo, Gloria Bachmann, M.D., of Robert Wood Johnson Medical School in New Brunswick, N.J., said at the North American Menopause Society meeting.

The improvement was statistically significant at 12 weeks and persisted during follow-up for a year.

In a subgroup of patients who had endometrial biopsies, no cases of endometrial hyperplasia or carcinoma occurred with either estrogen cream regimen.

"Low-dose [vaginal estrogen cream] represents an important therapy for treating atrophic vaginitis without endometrial safety concerns over a one-year study period," Dr. Bachmann and colleagues concluded.

As many as 40% of postmenopausal women are affected by atrophic vaginitis. Vaginal application of topical low-dose estrogens is thought to reduce systemic exposure to estrogen and limit its stimulatory effects on the endometrium, the investigators said.

Both daily and twice-weekly vaginal administration of low-dose vaginal estrogen cream have demonstrated efficacy for reducing symptoms of atrophic vaginitis. Dr. Bachmann reported findings from a randomized clinical trial comparing the two regimens.

Both active-therapy regimens led to significantly greater improvement in all outcome measures at 12 weeks compared with placebo.

A total of 155 patients treated with either regimen of vaginal estrogen cream had evaluable endometrial biopsies. In the patients assigned to daily therapy, six of 85 had evidence of proliferative endometrium. Among 72 assigned to twice-weekly treatment, six had proliferative endometrium.

In general, adverse events were similar in the active-treatment and placebo groups, Dr. Bachmann reported, and treatment-emergent adverse events were uncommon. Treatment-emergent vaginal bleeding occurred in no more than two patients in any randomized group during the double-blind and open-label phases of the study.

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Patients (about 40% women, mean age about 68) were randomly assigned to a 24-week, home-based exercise program or to an education and usual-care group.

At 18-month follow-up, the exercisers showed a statistically significant though modest difference of 0.69 points on cognitive tests compared with the usual-care control group.

Participants in the exercise group were asked to perform at least 150 minutes of moderate-intensity physical activity per week in three 50-minute sessions each week.

The most frequently recommended and used activity was walking. However, participants could choose light strength training or other aerobic exercise.

Participants also received regular mailed newsletters to reinforce the key messages of the program. The intervention did not include home-based equipment.

Individuals in the usual care group received educational material about memory loss, stress management, healthful diet, alcohol consumption, and smoking, but not about physical activity. Participants in the physical activity group were offered the same educational materials.

Those in the exercise group achieved 142 minutes more physical activity a week or 20 minutes a day more than those in the usual care group.

Cognitive function over 18 months was assessed with the Alzheimer Disease Assessment Scale -- Cognitive Substance Subscale (ADAS-COG), a measure that included 11 brief cognitive tests (possible range, 0 to 70).

In an intent-to-treat analysis, participants in the intervention group improved 0.26 points (95% confidence interval −0.89 to 0.54), whereas those in the usual-care group deteriorated 1.04 points (95% CI 0.32 to 1.82) on the ADAS-Cog measure.

At 18 months, participants in the intervention group improved 0.73 points (95% CI −1.27 to 0.03) on the ADAS-Cog, while those in the usual-care group improved only 0.04 points (95% CI −0.46 to 0.88) for a 0.69 difference.

Delayed word recall and Clinical Dementia Rating improved modestly as well, whereas total immediate word recall, digit symbol coding, verbal fluency, Beck depression score, and the Medical Outcomes summary did not change significantly.

Although the average improvement was small, it is potentially important given the relatively modest amounts of physical exercise undertaken by study participants, the investigators said.

The mechanisms by which physical activity improves cognition in these patients are not clear, the researchers said, but possible explanations include alteration in cerebral vascular function and brain perfusion or environmental enrichment associated with greater activity.

It is also possible that the benefits in this trial were attenuated by preexisting or ongoing deleterious effects of APOE ε 4, the researchers said.

Limitations of the study included the fact that the sample was relatively small and may not have represented the population at high risk for cognitive decline.

In addition, it was a single-site study, and the investigators had no access to brain imaging or biochemistry, making it impossible to study potential physiological mechanisms.

Finally, the researchers said, the study cannot be used to infer that physical activity reduces the risk of dementia among older adults, because it was not powered to investigate development of dementia.

But, the researchers said, physical activity has health benefits that are not confined to cognitive function alone as suggested by other findings for depression, quality of life, falls, cardiovascular function, and disability, the investigators said.

In an accompanying editorial, Eric B. Larson, M.D., of the Group Heath Center for Health Studies in Seattle, wrote that despite the statistically significant mean "improvement" in the exercise group of 0.74 versus 0.04 for the controls, neither patients, family members, nor clinicians could easily detect that level of difference.

On the other hand, Dr. Larson said, although it is easier to take a pill, patients and their families are likely to be gratified by the benefits of habitual exercise and often may be disappointed with the effects of cholinesterase inhibitors.

Neither exercise nor drugs are very potent and no evidence to date shows that either method can prevent conversion to Alzheimer disease, Dr. Larson said.

For an illness that starts so late in life, prevention means delaying onset, he said. If exercise is protective in delaying loss of cognition and if its effects can be sustained, presumably with minimum cost and adverse effects, then it is an attractive strategy in an increasingly aging society.

Future larger multi-site trials including persons older than 70 could test the effect of habitual exercise on cognitive decline and conversion to dementias. These studies could also evaluate which methods are most worthwhile in promoting behavior change, Dr. Larson concluded.

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