Estrogen Alternatives Available for Hot Flashes : Remedies such as progestins often are proposed, but few have been evaluated in controlled studies.


SAN FRANCISCO — In the wake of the Women's Health Initiative, “It's easier to get OxyContin out of a doctor's office than Prempro,” Melissa A. McNeil, M.D., joked at the annual meeting of the American College of Physicians.

The question then is how is a physician to manage the vasomotor symptoms of menopause?asked Dr. McNeil, who is women's health program director at the University of Pittsburgh. Although many remedies have advocates, few have been evaluated in controlled studies. She offered several evidence-based suggestions:

Time. Tincture of time works for many women. Although 75% of menopausal women do experience hot flashes, for 30%–50% of them, the symptoms improve within months, and hot flashes resolve completely for most women within 4–5 years.

“That can be a very long 4 or 5 years,” Dr. McNeil acknowledged. In addition, “A substantial minority will continue to have hot flashes for years beyond menopause.”

The fact that women's hot flashes frequently resolve spontaneously leads to a large placebo effect—in the neighborhood of 25%—in various studies of drugs and supplements.

Progestins. There's good evidence from randomized, controlled trials for the efficacy of a number of progestins. Medroxyprogesterone and megestrol (Megace) both were reported to result in a 74% reduction in hot flashes. Depo-Provera was reported in one study to result in a 90% reduction in hot flashes. Uterine bleeding is a frequent side effect of progestin therapy, limiting its use in women who have uterine cysts. Furthermore, there are no long-term safety data available.

The most significant bar to progestin therapy, however, comes from Women's Health Initiative results, which suggest that progesterone supplementation may confer an increased risk of certain cancers or adverse cardiovascular events, compared with estrogen alone.

Clonidine and methyldopa. Studies of antihypertensive agents such as clonidine and methyldopa suggest a relatively small effect on hot flashes. Use of clonidine, in particular, is limited by side effects, including dry mouth, constipation, and drowsiness. Still, these drugs may be useful in women who need blood pressure treatment in addition to relief from their hot flashes.

Nonhormonal therapies. Antidepressants, which are the most promising nonhormonal therapies for hot flashes, have become the mainstay of treatment. Venlafaxine, fluoxetine, and paroxetine all appear to result in 50%–65% reductions in hot flashes in controlled trials, although some of those trials studied breast cancer survivors, who may not be exactly representative of the entire population of menopausal women.

One advantage of antidepressants is that their effect on hot flashes seems to begin relatively quickly. Some patients have reported results in about 1–2 weeks, compared with about a month for their effects on depression. This allows for relatively rapid dose titration.

Gabapentin. This drug appears to have a modest effect on hot flashes, with a reduction of about 50% in one small trial. About half of the women who participated in that trial said they experienced at least one adverse event, including dizziness, somnolence, palpitations, or peripheral edema.

Nutritional supplements. Although these supplements have received a lot of coverage in the lay press, scientific evidence of their efficacy in treating hot flashes generally is lacking. Soy phytoestrogens engendered a great deal of enthusiasm a few years ago, and several small studies seemed to indicate effectiveness. But more recently, a larger controlled trial found they had no effect on hot flashes.

Mixed evidence of effectiveness has been found for vitamin E and black cohosh, but most studies have been small and unblinded. Evening primrose oil, ginseng, and wild yam cream all have been shown to be ineffective.

In selecting a treatment for a patient's hot flashes, Dr. McNeil said that she always looks for a twofer. “If I'm treating depression, I'll go for an antidepressant,” she said. “If they have chronic pain, I think about gabapentin. And if they have hypertension I might use clonidine. If they're straight out of the starting block, I'd think about venlafaxine as my starting point.”

Dr. McNeil said she has no conflicts of interest with regard to her presentation at the meeting.

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