Cleveland, Ohio - A scientific advisory panel to the North American Menopause Society has issued a new position statement on the use of hormone replacement therapy (HRT), which softens its previous stance on the issue [1].

"For women with severe menopausal symptoms, within a few years of their last period, hormone therapy shouldn't be as scary as it has been made out to be, " director of the North American Menopause Society and panel chair Dr Wulf Utian (Case Western Reserve University, Cleveland, OH) told heartwire.

For older women, the decision is more difficult, he says. Although there are fewer women of this age who will require HRT, some have menopausal symptoms for many years or have suffered symptoms after stopping HRT in the past few years, and this group wants to know whether they can restart therapy. But older women are at higher absolute risk of cancer and heart disease, so "it has to be a personal decision, our panel is stating that very clearly. An older woman must consider all the risks and benefits."

Initially, woman should start on the lowest dose of therapy possible and increase the dose only if relief of symptoms is not obtained, he says. The panel decided not to make recommendations on the duration of HRT; rather, it should be used "for a time consistent with the patient's needs and goals and based on her risk profile," he says.

Utian explained that the North American Menopause Society was the first professional body to respond with a formalized statement following the termination of the estrogen/progesterone arm of the Women's Health Initiative (WHI) study in 2002 and that it also issued updated guidelines in 2003 and 2004. "But a lot of stuff has happened in the past two years," he notes.

Based on the scientific evidence to date, Utian says, "There is no indication for HRT for the sole purpose of preventing cardiovascular disease, either for primary or for secondary prevention."

However, the evidence for an increase in early MI "is weak for women close to the menopause, and the fear of a heart attack has been overestimated," he notes.

The same applies to breast cancer and venous thromboembolism, the risks of which are "rare" as defined by WHO standards (<10 cases per 10 000 per year), he notes. The risk of stroke, however, does seem to be "slightly higher, especially for older women," he added.

And he notes that there are benefits of HRT. "It is the only drug to have shown a reduction in fractures in women who have not yet developed osteoporosis," he says, noting that the data on this came from the WHI study. Also, in that trial, the estrogen/progesterone HRT product showed a significant reduction in colon cancer, although the estrogen-only arm showed a null effect.

"Now doctors can give their patients numbers to indicate risks and benefits, they can advise them to start on the lowest dose of HRT available, and tell them to try to reduce their exposure to progesterone."

He explained that the question of whether progesterone in combined products—used to protect against endometrial cancer in women who still have a uterus—is responsible for the adverse breast cancer and cardiovascular outcomes in the WHI and HERS studies remains contentious.

"We think this is the case, but the data are not strong enough," he said. Hence the panel failed to reach a consensus on this issue, and it is one of more than 30 recommended areas of future research.

The panel was also unable to decide on whether an older woman who had started HRT simultaneously with menopause but then stopped because of the adverse publicity would have the same risk as a woman at the age of menopause onset, because she had been protected by the hormones she had taken, or a similar risk to her peers who had never taken HRT.

One issue raised in the new position statement is the suggestion from the WHI study that HRT might reduce the risk of new-onset diabetes mellitus. Women in the estrogen/progesterone arm had a 21% risk reduction in incident-treated diabetes mellitus, or 15 fewer cases per 10 000 women per year of therapy, and in the estrogen-only arm, there was a 12% reduction, or 14 fewer cases per 10 000 women per year.

The mechanism for this benefit is thought to be via lesser centripetal weight gain and/or reduced insulin resistance in women receiving HRT, but the panel concluded there is "insufficient evidence to recommend combined HRT for a sole indication of the prevention of diabetes mellitus in perimenopausal women." However, they note: "This is a promising area for future research."

The panel also cited several other recommendations for future research, including:

• Timing of initiation of HRT relative to menopause with regard to cardiovascular, cognitive, and other health outcomes.
• Cause of the increase in stroke with HRT and of increased CHD and breast cancer with combined products to better understand the pathophysiology of these events.
• Effects of HRT on risk of Alzheimer's' disease and other forms of dementia and on neuropsychiatric disorders.
• Determination of how women at risk of deep vein thrombosis and VTE can best be identified.