Consumers who hope the U.S. Food and Drug Administration will ensure the reliability of black cohosh are bound for disappointment. Herbs fall under the category of dietary supplements. Unlike drug manufacturers, producers of supplements are not required to provide the FDA with evidence of their products' safety or effectiveness. Instead, manufacturers of dietary supplements can make product claims based on their own review and interpretation of studies without FDA authorization. Government investigators act only if they receive complaints from doctors or patients. Even after receiving such complaints, the burden of proof is on the FDA to prove the product should be pulled.
And while they are required to accurately list ingredients in herbal preparations, few products are independently tested. This can make getting reliable laboratory samples a tricky business. Sauter's investigation, by using capsules prepared at the University and tested for consistency, already has a leg up on studies that rely on over-the-counter preparations. "If you start out with an unreliable preparation, your results, I would argue, are in question," he says.
The study's design is simple: For 12 weeks, twice each day, postmenopausal women ingest capsules containing 40 milligrams of black cohosh. Sauter's research assistants then collect blood and breast fluid from each of the subjects three times: first on day one, then at four weeks and finally at 12 weeks. If saponin levels increase after the women have taken the capsules, Sauter will conclude that black cohosh has reached the breast.
Determining whether the saponins stimulate, block or have no effect on estrogen production comes next. Sauter accomplishes this by measuring biomarker levels in the women's blood and breast fluid. These biomarkers include the estrogen estradiol and two hormones produced by the pituitary gland -- the follicle-stimulating hormone, and the luteinizing hormone which stimulates estrogen and progesterone production.
Sauter tests the biomarker levels once again at 24 weeks, the point at which the women have gone 12 weeks without taking black cohosh, to determine whether the levels return to baseline, the condition subjects presented at the beginning of the study. This step is important, Sauter says, because the persistence of any changes could indicate how frequently women might have to take black cohosh.
"If it has a persistent effect, you might not have to take the pill every day for the rest of your life," he says. "It might be a permanent effect, although it's more likely it would not be permanent."
Of course, whether black cohosh's effect is permanent matters only if it actually helps patients. To test this, Sauter is using a standard scale doctors call the Kupperman Menopause Index (KMI). The KMI seeks to assess menopausal symptoms by grading their severity as described by patients. "Severe" rates a 3, "moderate" 2, "mild" is 1 and no symptoms is zero. A patient's total score is computed as a weighted sum of all 10 symptom scores. A score of 15-19 indicates mild symptoms, 20-35 moderate and 35-48 severe, with a score of 20 or greater commonly the cutoff for enrollment into clinical trials.
In Sauter's study, the women score their symptoms each time they give blood and breast fluid samples. If their reports indicate they are feeling better -- and if their blood and breast fluid samples do not show black cohosh having the previously described estrogenic effect -- then Sauter says he'll consider the results favorable.
The next step, according to the success scenario, would be a placebo-controlled trial. "You don't do placebo-controlled trials in a preliminary study," he says. "You get the preliminary data, and if it's encouraging, if it's positive, you ask for bigger money, and then you do the placebo-controlled. That's our plan."
In the meantime, Sauter will continue to recruit women. He expects to take new participants for at least another year, and urges interested women to call him at (573) 882-1895. "We need to recruit at least 73 women," he says. "More is better."