Clinical Trial May Shed Light on Herbs for Menopause

Ever since the Women’s Health Initiative (WHI) study found that some types of hormone replacement therapy (HRT) can lead to serious health complications, HRT use has been dropping. Although some women have returned to HRT, others have been trying botanical alternatives instead.

In October, a skeptical American College of Obstetricians and Gynecologists (ACOG; Washington, DC) task force issued a new set of HRT guidelines for women-guidelines that do not recommend botanicals. According to the ACOG, “Few nutritional supplements have been rigorously tested for safety and effectiveness.”

That situation is changing, however, as newer, better-designed clinical trials on herbs are in the works. In the past few years, the National Institutes of Health’s (Bethesda, MD) National Center for Complementary and Alternative Medicine (NCCAM) has greatly increased its financial support for research on botanical supplements. For instance, the University of Illinois at Chicago’s NCCAM-funded Center for Cognitive Medicine is now gearing up to study the effects of the herbs black cohosh (Cimicifuga racemosa) and red clover (Trifolium pratense) on menopausal symptoms.

Pauline Maki, PhD, associate professor at the Center for Cognitive Medicine, notes that although interest in herbs is high, scientific knowledge about their effects on menopause is still in its infancy.

“After the WHI, the use of HRT declined rapidly, and women looked to alternative botanical therapies as a ‘safer’ and ‘more natural’ option,” Maki says. “The problem was that there was very little evidence that botanicals had any efficacy and very little information on the possible side effects. There still is little information to help women make informed choices about these alternative therapies.”

Study: More Communication between Doctors and Herbal Consumers Needed

Researchers at Stanford University Medical Center (Palo Alto, CA) uncovered an interesting paradox during a recent survey of women aged 40–60: Many women want more information from their doctors about alternative therapies for menopause but few of these patients discuss their own use of these therapies with their physicians.

According to the Stanford researchers, who presented their findings at the 19th annual meeting of the North American Menopause Society (Mayfield Heights, OH) in Washington, DC, this October, about one-third of women who are either on hormone therapy or have used it in the past were frustrated that their doctors didn’t provide enough information about dietary supplements for menopause. However, 91% of premenopausal women and 80% of perimenopausal and postmenopausal women had not discussed the products with their physicians. Moreover, only 53% of perimenopausal and postmenopausal women who were taking herbal supplements had told their doctors. GlaxoSmithKline Consumer Healthcare (Research Triangle Park, NC), which markets the black cohosh (Cimicifuga racemosa) supplement RemiFemin, funded the survey.

To help shed some light on the subject, Maki and her colleagues will randomly assign up to 112 women to receive either black cohosh (standardized to contain 128 mg of triterpene glycosides), red clover (standardized to contain 120 mg of isoflavones), Prempro, or a placebo for 12 months. Before and after the treatment period, the volunteers will take written tests to assess their memory, attention, concentration, and mood. The study participants will also have the option of having brain scans, which will let the researchers study how the brain responds to the various treatments.

“The main goal of this study is to provide women who have had hot flushes with information about the impact of prescription hormone therapy, red clover, and black cohosh on psychological outcomes including mood, sleep, memory, and brain function,” Maki explains.

Maki’s team will use state-of-the-art neuroimaging equipment to gather important data about how each of the treatments affects cognitive functioning in the brain. “We will measure brain activity as women perform a memory task, both before and after treatment,” Maki says. “This will tell us what areas of the brain might change in relation to treatment.”

According to Maki, many of the early studies on black cohosh and red clover were not well controlled and were of limited size and duration. The design of the new study will enable Maki’s team to gauge the efficacy of the botanicals against HRT and a placebo.

“We recognize that women are using alternative botanical therapies despite a lack of convincing evidence of efficacy, so we want to help determine their safety and efficacy more precisely,” Maki says. “At least three randomized studies of isoflavones in young menopausal women showing cognitive benefits have been published, and one particularly well-conducted trial in older women showing no benefits was published recently in JAMA.”

“Unfortunately, there are no head-to-head comparisons of these compounds in a single study, so our study is a unique opportunity to compare the two most popular botanical supplements for women’s health and to examine their efficacy in relation to prescription hormone therapy,” Maki adds. “One quarter of the participants in our study will be randomized to placebo, so we’ll be able to see how large an effect these various treatments have in relation to what might happen if they received an inactive treatment.”

Although some of the early research is promising, Maki says more studies are necessary before manufacturers, practitioners, and consumers can be sure that herbal remedies for menopause are safe and effective.

“Much more research is needed,” Maki says, adding that more data about younger women would be helpful. “This study is the first head-to-head study of prescription hormone therapy and botanical therapies for menopausal symptoms. Although we plan to enroll 112 women, this study is still considered small in scale. If our study suggests efficacy, then we will plan a larger, Phase 3 study that will involve hundreds of women.”

Despite its small size, the study should provide important insights about the relative risks and benefits of various ways to treat menopausal symptoms. While research on herbal approaches to menopause may be in its infancy, baby steps now could lead to big strides later.

NEW PRODUCT LAUNCHES

American consumers value taste and convenience. Unfortunately, some important women’s products, like omega-3 and calcium formulas, can be difficult to swallow. Manufacturers have been working overtime to come up with new supplements that taste better and are easier to handle.

In October, Mead Johnson Nutritionals (Evansville, IN) launched Expecta LIPIL, a docosahexaenoic acid (DHA) formula for pregnant and nursing women. Expecta uses softgel capsules and 200 mg of DHA supplied by Martek Biosciences Corp. (Columbia, MD). Martek’s DHA is derived from algae, rather than fish, so it is vegetarian and lacks the fishy taste and odor associated with some other omega-3 formulas.

According to a survey of more than 1000 women conducted by Impulse Research (Culver City, CA) for Mead Johnson Nutritionals, awareness of DHA is high but consumption is low. About two-thirds of the women surveyed said they were aware of the role DHA can play in infant development, but only 19% incorporated DHA-rich foods into their prenatal diet. Moreover, according to the survey, 61% of pregnant or breastfeeding women rarely or never ate DHA-rich fish during pregnancy.

“While women are pregnant or nursing, they are the sole source of nutrition for their baby,” says John Vanderhoof, MD, Mead Johnson Nutrition’s vice president of global medical affairs. “By supplementing with Expecta LIPIL in addition to their prenatal vitamin, women can help increase their DHA intake and help support their baby’s brain and eye development.”

Although Martek’s DHA is already an ingredient in several baby formula products, Expecta is one of the first algae-derived DHA supplements to be marketed to pregnant and nursing women. “Martek’s DHA will now be widely available to moms, their fetuses, and their babies with the Expecta LIPIL launch,” says Henry “Pete” Linsert Jr., Martek’s CEO and chairman. “I believe that optimizing DHA levels for mom and her baby during this critical time should result in significant benefits for their future health and well-being.”

CALCIUM PRODUCTS

According to U.S. Surgeon General Richard Carmona, MD, half of all Americans over age 50 could be at risk for fractures from osteoporosis and low bone mass by 2020. In an October 14 report, the surgeon general said 10 million Americans over age 50 currently have osteoporosis and another 34 million are at risk for developing it.

Carmona called on all citizens to take action to improve and maintain bone health by getting the recommended amounts of calcium and vitamin D (1000 mg of calcium and 200 IU of vitamin D for the average person), maintaining a healthy weight and being physically active, and minimizing the presence of hazards that may cause falls.

“Osteoporosis isn’t just your grandmother’s disease,” Carmona said. “We all need to take better care of our bones. The good news is that you are never too old or too young to improve your bone health. With healthy nutrition, physical activity every day, and regular medical checkups and screenings, Americans of all ages can have strong bones and live longer, healthier lives. Likewise, if it’s diagnosed in time, osteoporosis can be treated with new drugs that help prevent bone loss and rebuild bone before life-threatening fractures occur.”

One reason why the problem is growing is that it can be difficult for some people to get all of the calcium and vitamin D they need from dietary sources: one cup of vitamin D–fortified milk contains just 304 mg of calcium and 50 IU of vitamin D.

Although leafy green vegetables, soybeans, yogurt, and cheese are other good sources of calcium, supplements are also an option, Carmona said. However, supplements that deliver high amounts of calcium tend to be bulky.

To make it easier for women to get the calcium they need, Pharmavite (Northridge, CA) used proprietary, patent-pending technology to create its new Calcium Minis, which are up to 30% smaller than traditional calcium supplements. Katherine Mardesich, product manager for Pharmavite’s Nature Made line, notes that in a 2002 Gallup study, 50% of consumers who didn’t take vitamins or supplements said the reason was tablet size.

“The smaller tablet size of the Nature Made Calcium Minis will make it quick and easy for adults to obtain this important mineral and will help them receive the recommended daily dosage of calcium,” Mardesich says.

Mardesich adds that Pharmavite has also launched a consumer campaign, Stop Osteoporosis Now!, which will include educational materials, an on-line calculator that lets consumers determine their osteoporosis risk factors, and a consumer hotline to answer questions about calcium and bone loss.

“As the dietary supplement industry leader, we are well positioned to lead a consumer osteoporosis awareness campaign,” Mardesich says. “The Stop Osteoporosis Now! campaign and Nature Made’s extensive calcium product offering provides consumers the tools they need to take control of their bone health.”

HERBAL APPROACHES

Protykin, a root extract of the herb Japanese knotweed (Polygonum cuspidatum), may have both estrogenic and cardioprotective effects, according to Gary Troxel, executive vice president of InterHealth USA Inc. (Benicia, CA), which manufactures the extract.

“Protykin is a high-potency, 200:1 standardized extract that contains 50% phytoestrogens,” Troxel says. “As a phytoestrogen, Protykin helps maintain normal estrogen activity, but it also helps with other issues related to menopause by helping to reduce hot flashes, balance mood swings, and promote healthy bone density.”

Troxel notes that resveratrol, the principal phytoestrogen in Protykin, has been studied for its effects on estrogen metabolism. “Researchers at Northwestern University Medical School have shown that the principal ingredient in Protykin functions as a phytoestrogen,” Troxel says. “In their studies, this ingredient was found to bind to estrogen receptors in cells and resulted in estrogenlike effects, including increased expression of estrogen-related genes and the growth of estrogen-dependent cells.”

“In addition to its phytoestrogen benefits, Protykin is a powerful antioxidant and cardioprotectant,” Troxel says. In December 2003, InterHealth received a $140,000 research grant from the National Institutes of Health (Bethesda, MD) to study the potential cardiovascular benefits of Protykin, and is partnering with the University of Connecticut School of Medicine (Farmington, CT) to conduct the research. Results are expected in 2005.