Sauter, with funding from the NIH, is working to come up with answers. First, he hopes to determine whether black cohosh reduces the symptoms of menopause by stimulating estrogen receptors, proteins that help regulate the production of estrogen in the breast. It's important to rule out this particular mechanism of action, he says, because estrogenic stimulation has been shown to increase a woman's risk of breast cancer.
Based on what he's seen so far, Sauter is betting that black cohosh has no estrogenic effect. If true, that finding would open the door to more promising research questions. "If we find no estrogen effect on the breast, which is a real possibility, then I would propose it's working essentially in the brain," he says.
And if it's working on the brain, he adds, the next step would be finding out if it works through estrogen or, more likely, through some other mechanism. Either finding has the potential to confirm that black cohosh is a safe and effective route to symptom relief.
Sauter began his study by creating a standard preparation of black cohosh -- a process complicated by the fact that he was dealing with an herb rather than a pharmaceutical. Working with a typical pharmaceutical, he explains, is easy. "You say, 'We're going to give you this many milligrams of aspirin, which is acetylsalicylic acid.' It's one chemical. You measure the concentration, and you're done. It either has it, or it doesn't. A plant's got thousands of chemicals, and it's physically impossible to standardize to all chemicals. So you pick one or two or three that you think may be at least some of the active ingredients.
"We're choosing to standardize the dose based on the total black cohosh concentration in milligrams and, separately, to standardize it to one of the saponins, which we think may be part of the active ingredient mix in black cohosh."
Saponin is a glycoside, or plant-sugar derivative, that is characterized by its distinctive foaming quality. (The name derives from the plant Saponaria, which was historically used as a soap.) Saponines have been shown in previous studies to bind to estrogen receptors: That makes them of interest to Sauter. Binding, however, does not necessarily indicate stimulation. Once bound to a receptor, chemicals such as saponins may stimulate, block or have no effect on the receptor cell's production.
The saponin Sauter is using is called 27-deoxyactein, the same one companies marketing black cohosh often use to standardize their products. Unfortunately, Sauter says, there is reason to question just how "standard" those commercial preparations really are. Sauter's research team tested a number of over-the-counter capsules and found chemical concentrations that did not match the ones advertised on the preparations' labels. Even so, Sauter is careful not to condemn all commercial preparations of black cohosh.
"It's not fair to state, in my opinion, that every over-the-counter preparation that contains black cohosh is inconsistent," he says. "All we can say is that in the ones we tested, we were not able to measure the saponin that the package claimed to contain, and therefore it raises the question of the reliability of the concentration of that saponin, or any other ingredient, claimed to be present in the preparation."