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WORCESTER, Mass., July 12-Women who take hormones to relieve the hot flashes associated with menopause are likely to have symptoms return if they stop hormone therapy, researchers reported today.

For some women this may come as a nasty surprise that should be taken into account when counseling women about menopausal hormone therapy, said investigators in the July 13 issue of Journal of the American Medical Association.

Nevertheless, hot flashes and other menopausal symptoms such as sleeplessness, irritability, night sweats and mood swings respond to lifestyle changes such as exercise, increased fluid intake, and cutting back on caffeine, according to Judith K. Ockene, Ph.D., M.Ed., of the University of Massachusetts Medical School and colleagues from the Women's Health Initiative (WHI).

Use of herbal or natural hormone products was not, however, particularly helpful, they found.

The investigators reported on a cross-sectional survey of 8,405 women at 40 clinical centers that participated in the WHI. The surveys were mailed eight to 12 months after the study was stopped in 2002. The analysis includes responses from 4,085 women from the Prempro (conjugated equine estrogen plus progestin) arm and 4,320 women who were randomized to placebo.

As might be expected women who entered the study with symptoms were more likely to have a return of symptoms when the study medication was stopped, said the researchers. They reported that 55.5% of women who had vasomotor symptoms at baseline had a return of hot flashes and night sweats after stopping Prempro.

Interestingly, this symptom rebound also occurred in 21.3% of women with baseline vasomotor symptoms who were randomized to placebo.

The flipside of this is the finding that women who didn't report vasomotor symptoms at baseline were unlikely to develop symptoms when they stopped the study drug. This was especially encouraging news for women who were routinely assigned to hormone replacement in order to prevent the development of symptoms.

Overall, 21.2% of women randomized to Prempro and 4.8% of women in the placebo arm reported moderate to severe vasomotor symptoms after the study pill was stopped (P<0.001).

Compared with women randomized to placebo, women in the Prempro arm were almost six times more likely to report vasomotor symptoms after stopping the study drug and were more than twice as likely to report pain or stiffness after they stopped taking Prempro.

More women taking Prempro were also likely to report multiple symptoms (59.7%) after stopping the drug than women assigned to placebo (36.7%).

The higher prevalence of pain or stiffness among women who stopped Prempro "suggests an additional benefit of [Prempro]," the authors reported. "The high rate of this withdrawal symptom rivals the report of vasomotor symptoms and has not been well documented in the past."

Moreover, symptoms returned even though women were treated for an average of 5.7 years, which is longer than the brief hormone treatment currently recommended for menopausal symptoms.

Tens of thousands of women swore off hormone replacement three years ago when National Institutes of Health announced that the WHI found that healthy women taking Prempro had significantly increased the risk of heart attack, stroke, deep vein thrombosis, and breast cancer -- which was a stunningly negative finding for a study that investigated hormone treatment for primary prevention of cardiovascular disease.

The fallout from the WHI has continued unabated for the past three years as study after study reported yet another potential hazard of menopausal hormone therapy, while women continue to clamor for relief from symptoms.

All of the studies agree that hormone replacement, in various combinations of estrogen or estrogen plus progestin, is the most effective treatment for symptoms. Estrogen is also effective for preventing bone mineral loss.

In the latest cross-sectional study the WHI researchers reported the first systematic collection of data on life after hormone replacement.

More than 10% of women taking Prempro reported pain or stiffness, fatigue, vasomotor symptoms, difficulty sleeping, and bloating or gas after the medication was stopped. By contrast, 10% of the women in the placebo arm reported pain and stiffness and fatigue.

Lifestyle changes that proved effective at reducing symptoms included increased fluid intake, exercise, use of fans or air conditioners, self-help techniques, use of layered or cotton clothing, increased social life, and reduced caffeine.

Effective medical approaches included use of vaginal lubricants, and use of other medications including antidepressants and sleeping medications. And, not surprisingly, a return to prescription hormones was also highly effective at relieving symptoms.

In an editorial that accompanied the study, Diana B. Petitti, M.D. of Kaiser Permanente of Southern California, wrote that the " 'placebo withdrawal effect' -- combined with the data suggesting that simple lifestyle changes relieve some symptoms in at least some women -- raises questions about the physiological basis of some of the symptoms that have always been associated with an estrogen deficient state."

Dr. Petitti wrote that the findings the paper from Dr. Ockene's group suggested that hormones appear to have been falsely accused in the case of many so-called menopausal symptoms. The evidence, she said, points to a causal relationship between vasomotor symptoms and vaginal dryness -- and no more.

Finally, she said the high rate of rebound symptoms suggest that tampering off hormones appears to be a better clinical strategy than abruptly stopping the drugs.

Related articles:

• Hormone Therapy Causes or Worsens Urinary Incontinence in Postmenopausal Women

• Oral Estrogen Found to Increase Risk for Gallbladder Disease Among Healthy Postmenopausal Women