Washington, DC -- The American College of Obstetricians and Gynecologists (ACOG) today announced the most comprehensive, evidence-based clinical recommendations to date on hormone therapy (HT). ACOG's Hormone Therapy report, written by a task force of 21 national experts, "is an exhaustive, one-stop guide for doctors and their menopausal patients reviewing the risks, benefits, and continuing questions about hormone therapy," says ACOG President Vivian M. Dickerson, MD.

In addition to reaffirming most of the recommendations it issued after the landmark 2002 Women's Health Initiative study -- e.g., that combined HT (estrogen plus progestin) is effective treatment for menopausal symptoms but should not be taken to prevent certain diseases -- ACOG tempers some of its earlier advice regarding the length of time and reasons women might take hormone therapy. ACOG's encyclopedic report also "catalogues what medical science knows so far about the effect of reproductive hormones on everything from sex life to mental health, cancer to weight gain," adds Isaac Schiff, MD, chair of the ACOG Task Force on Hormone Therapy.

Among the findings released today in a special supplement to the October issue of ACOG's Obstetrics & Gynecology journal:

• Jury Still Out on Sex Drive - There have been too few studies to prove that taking estrogen or the male hormone testosterone -- either orally or topically -- can improve a woman's sexual libido (sex drive). However, there is ample evidence that estrogen given topically or orally can improve the quality of a woman's sex life, by relieving vaginal dryness and related symptoms that make sexual intercourse uncomfortable for many menopausal women.
• SSRIs Relieve Hot Flashes; Herbal Remedies Do Not - The category of anti-depressants known as selective serotonin reuptake inhibitors (SSRIs) can be effective alternatives to HT for the relief of menopausal vasomotor symptoms like hot flashes. As for herbal remedies, the Task Force concludes: "Treatment with wild yam extract, black cohosh, or dietary phytoestrogen supplements derived from the isoflavone red clover has no significant effects on vasomotor symptoms."
• Estrogen May have Anti-Depressive Effects - Estrogen appears to have mood- elevating effects in some perimenopausal women, who may be more vulnerable to depression than pre- or post-menopausal women. Due to its risks, estrogen should not be a first-choice treatment for depression, but it may be appropriate therapy under certain circumstances.

Beyond the WHI

ACOG experts say the report puts the 2002 Women's Health Initiative (WHI) study in the context of the wide range of research studies that came before and after it. "The WHI was a huge milestone in our understanding of the risks and benefits of hormone therapy," says Dr. Dickerson. "Though significant, it's only an early step in the continuing quest to understand how women's hormones affect their health."

Over two years ago, WHI study authors announced not only that the risks of combined HT outweighed its benefits when used to prevent certain diseases, but that it could actually increase the risk of certain conditions it was previously believed to prevent, such as a heart attack. Dr. Schiff believes that ACOG's Task Force, which was created prior to the 2002 WHI announcement by past ACOG president Charles B. Hammond, MD, has had the benefit of reviewing multiple studies over several years and can now look at the big picture.

"When the WHI came out, the pendulum of popular opinion on hormones swung wildly, from a mistaken belief that estrogen was the panacea for a variety of ills, to the frightened belief that it was now anathema even for conditions like hot flashes," says Dr. Schiff.

"Approximately 65% of women on HT stopped therapy after the WHI," notes Dr. Schiff. "Two years later, reports suggest that about 1 in 4 women who stopped HT went back on it because it still offers the best relief for menopausal symptoms. So we're moving back to an appropriate balance -- accepting that HT has risks, but recognizing that it can be appropriate for conditions like hot flashes so long as women are informed about the risks and weigh their decision with their doctor."

Adds Deborah M. Smith, MD, an advisor to ACOG's Managing Menopause consumer magazine, "From the WHI we also learned more about what we don't know. For example, the average age of women in the WHI study was 63. ACOG would like to see more research that answers key questions. Are the effects of hormones different for the more typical menopausal patient at the average age of 51, or for younger women who have undergone surgical or premature menopause? Are hormones more dangerous or beneficial at one time of life than another and, if so, why?"

ACOG's Hormone Therapy report includes 15 chapters examining available studies on hormone therapy and its relation to over 20 health conditions. These include sexual dysfunction, depression, cognition and dementia, coronary heart disease, breast and gynecologic cancers, osteoporosis, weight and insulin resistance, skin, stroke, gall bladder conditions, and genitourinary tract changes. The following are some report highlights:

Use of HT: Some Confirming, Some Loosening of Post-WHI Recommendations

In Hormone Therapy, ACOG reaffirms many of its earlier recommendations issued in the months immediately following the 2002 WHI announcement on combined HT, and the 2004 WHI announcement on estrogen-alone (ET) therapy. This includes advice that:

• Combined hormone therapy should not be used for prevention of diseases such as cardiovascular disease, due to the small but significant increased risk of conditions such as breast cancer, heart attack, stroke, and blood clots;
• Estrogen-alone therapy, used for women who have had a hysterectomy, should also not be used for prevention of diseases, due to increased risks of blood clots and stroke. Although ET carries fewer risks than combined HT, women with a uterus should not use estrogen alone due to their increased risk of uterine cancer;
• Hormone therapies are appropriate for the relief of vasomotor symptoms, so long as a woman has weighed the risks and benefits with her doctor; and
• Women on combined HT or ET should take the smallest effective dose for the shortest possible time and annually review the decision to take hormones.

The Task Force also softens some recommendations on the duration and need for hormone treatment, noting that although women should use HT for the shortest possible time, about 10% of menopausal women will continue to have vasomotor symptoms beyond the average four years it takes such symptoms to resolve. "It is inappropriate to withhold HT from persistently symptomatic women who prefer to continue HT or who do not derive relief from currently available alternatives," concludes the report.

"The report also says it is appropriate to treat women who feel better on hormone therapy or who feel it improves sexuality," says Dr. Schiff.

Although the report notes that hormone therapies should not be used solely for disease prevention, there are instances where disease prevention is appropriate as a secondary benefit for women who are already taking hormones for vasomotor symptoms. This includes its use to prevent osteoporosis, or to treat depression under certain limited circumstances for women with mild to moderate depression.

Alternatives to HT: What Does and Doesn't Work

Other Medications

The report affirms that to date estrogen is the most effective treatment for symptoms like hot flashes or night sweats, and that nasal sprays or transdermal (patch) hormone treatments provide comparable results to hormones taken orally. The report also catalogues the range and quality of research studies on alternative treatments for women who cannot or do not wish to take hormones.

"So far, research that includes randomized, double-blind studies shows that SSRI anti-depressants appear to be effective in reducing or relieving hot flashes," notes Dr. Schiff. "This is probably not surprising, given that certain types of serotonin receptors in the brain are believed to play a role in causing hot flashes."

Another agent that showed relief in a small, randomized, double-blind, placebo-controlled trial is an anticonvulsant medication known as gabapentin. "The reasons why it improves hot flashes are not yet understood," he adds.

Herbal Alternatives

"There has been a lack of published reports on most alternative medicine treatments," says Dr. Schiff. "The few studies done so far show disappointing results about the effectiveness of botanical treatments."

Studies on wild yam showed little difference in results between this method and placebo, and there was a high withdrawal rate of study participants due to unrelieved symptoms.

Soy contains isoflavones, one of the types of plant-based estrogens or phytoestrogens. The report notes, "A few very limited studies have suggested that soy helps with vasomotor symptoms in the short-term (less than 2 years), while other studies show little difference between soy beverages or extracts and placebo."

A study of two dietary phytoestrogen supplements derived from red clover showed no clinical effects on hot flashes or other symptoms.

Although black cohosh is a botanical treatment widely used in Europe for menopausal symptoms, "its benefits have been evaluated primarily in small short-term studies using since-invalidated measures," notes Dr. Schiff. The few randomized, controlled trials on black cohosh showed no significant reduction in hot flashes.

The report also cautions that since soy and dietary isoflavones appear to affect estrogen receptors, they may not be safe for women with estrogen-dependent cancers such as breast cancer.

Sexual Function: Too Few Studies on Female Sexual Libido, but Several Options for Relieving Vaginal Discomfort

"After years of publicity about Viagra and other products to improve male sexual performance, we still know pitifully little about what hormones or other products might enhance female sexual functioning," notes Dr. Dickerson.

Sexual response and function in women are complex, adds Dr. Dickerson, and include biologic, physiologic, and social factors. A National Health and Social Life Survey of 1,749 women ages 18-59 years found that 43% of respondents reported sexual dysfunction.

Sexual Libido

"Despite some claims about the benefits of certain hormone creams for sexual libido, it's still too early to know whether reproductive hormones like testosterone or estrogen, applied either topically or orally, can improve women's sex drive," says Dr. Dickerson. "There just haven't been enough studies on these or other therapies," she notes.

The report observes that the use of oral estrogen to improve sexual desire is supported by only one short-term, randomized, placebo-controlled trial. The same is true for the use of testosterone added to estrogen therapy. The most noteworthy improvements to sexual function were seen in studies involving women who have had an oophorectomy (ovary removal, or surgical menopause). These women are much more likely than women who have had a hysterectomy to report adverse changes in their libido and orgasmic response. Significant improvements in sexual desire were seen in these women when transdermal testosterone was added to ET, but only at high doses (300 micrograms).

"It's still premature to say what does or doesn't work in improving women's sexual libido, but researchers are learning more all the time," says Dr. Dickerson. Just this month, for example, the US Food and Drug Administration granted priority review to an investigational female testosterone patch for the treatment of low sexual desire in women who have undergone oophorectomy.

Relief of Vaginal Pain

"What we do know," adds Dr. Dickerson, "is that there are ample studies showing that even very low doses of estrogen can relieve vaginal dryness, which has been associated not only with painful intercourse, but with a decrease in sexual desire. The good news," she says, "is that there are several methods for relieving vaginal dryness with estrogen, including pills, vaginal creams or rings."

Heart Health and Weight: Lifestyle and Other Factors, Not Estrogen, Make the Difference

"One of the most notable results of the WHI was its confirmation that higher-evidence studies give us more reliable results," says Dr. Smith. "Nowhere was that more apparent than in our understanding of estrogen and heart disease."

The WHI was the largest randomized, double-blind, placebo-controlled study on hormone therapy to date, meaning that neither the health providers nor the patients in the study knew whether the patients were taking hormones or placebo. Prior to that study, smaller observational studies suggested that HT protected against heart disease by elevating the levels of so-called good cholesterol (HDL) and reducing so-called bad cholesterol (LDL) that can be a factor in heart disease.

"Now we know that at least two things were going on," says Dr. Smith. "First, there was probably 'user bias' in those earlier studies, meaning that the women on HT were already healthier than the women not taking hormones. Second, medical experts may have overestimated the effect of cholesterol in heart health, and been unaware of other factors in heart disease that we still don't understand."

"Where does that leave us today?" questions Dr. Smith. "Since the average age of WHI participants was 63, ACOG believes that more research is needed to determine whether hormones taken in perimenopause or early in menopause have a different effect on heart health. But very importantly, we know that lifestyle factors -- such as eating a healthy diet, not smoking, and getting plenty of exercise -- are the biggest contributors to heart disease prevention."

"Finally," notes Dr. Smith, "the Task Force reminds us that it's not hormone therapy, but the normal process of aging that accounts for the average weight gain of women during middle age." She points to what the report calls the "single biggest modifier for weight gain: physical activity."

"No matter how many studies are conducted about weight, we can't avoid the inevitable," concludes Dr. Smith. "If we want to lose, we've got to move."

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