Hot flashes and Japanese herbal medicine: the lowdown on TU-025

Posted by Liz on Aug 1, 2011 in hot flash, Kampo/traditional Japanese medicine | 1 comment

Women who choose to go the alternative route for menopausal hot flashes have few evidenced-based options. Although acupuncture and standardized black cohosh have been shown to be effective in ameliorating hot flashes, others, including red clover and even soy, have been less successful. Consequently, herbal practitioners often turn to Traditional Chinese medicine (TCM) herbal formulations or the lesser known (in the U.S.) Japanese multiherb medicinal formulations known as Kampo. Interestingly, the term Kampo refers to ‘the way of China” and the practice which is several thousand years old is based on TCM.

Kampo is prescribed by over 90% of Japanese gynecologists and is regulated by the Japanese Ministry of Health to insure manufacturing standards and product stability.  One of the most popular Kampo agents for perimenopausal hot flash management is an 1,800 year old formulaton known as “keishibukuryogan” or in the US, as TU-025. Comprised of a combination of cinnamon bark, peony root, peach kernal and mountain bark, it active ingredient remains unknown. Japanese data from both the government and the manufacturer demonstrate a very low incidence of side effects and no estrogenic activity, which means that theoretically, it could be safely used by women who have had breast or gynecologic cancers. Nevertheless, its utility in American women has not been known, at least until now.

In a study published in the August issue of Menopause, 178 postmenopausal women were randomly assigned placebo, 7.5 g/daily TU-025 or 12.5 g/daily TU-025 for 12 weeks. All participants reported 28 or more hot flashes a week, had been in menopause for at least a year, had stopped using hormones for at least 8 weeks if they were already using them, smoked less than 10 cigarettes a day and most were slightly overweight or obese (based on body mass index). None were using antidepressants (which studies have shown may help alleviate hot flashes), nor did they have a history of breast or uterine cancer. While the 7.5 gram daily is the dose taken most often by Japanese women, the researchers upped the dose to 12.5 gm daily to account for a larger sized American woman.

In this trial, declines in hot flash scores (which measured both the frequency and severity of hot flashes) were significant but not statistically distinct between groups:

• Scores in women taking placebo decreased by 34%
• Scores in women taking the low dose TU-25 decreased by 40%
• Scores in women taking the high dose TU-25 decreased by 38%

The incidence of other factors related to hot flashes and menopause, including depression and sexual dysfunction also declined significantly across groups but were not measurably different between them. Sleep remained unaffected. At least 20% of women taking TU-025 regardless of dose, also experienced diarrhea.

The researchers say that unlike the Japanese experience, this particular study did not demonstrate any measurable clinical benefit in women taking TU-025, either for hot flashes, other symptoms or sleep. Moreover, the herbal formulation did not appear to be well tolerated in a fifth of women, who experienced diarrhea. Additionally, they state that although every woman in the study took a placebo for one week before taking the real medication or continuing on placebo, a strategy that is often utilized in clinical trials to minimize a placebo response, significant numbers of women taking placebo experienced meaningful declines in hot flash severity and frequency. Although the 34% decline is consistent with that reported in other trials, the effect is typically expected to go away before 12 weeks of therapy. Consequently, a placebo effect of this magnitude suggests that the formulation may not work as well in American women as it does in their Japanese peers. However, several women enrolled in the study also noted afterwards that they “enrolled to prove that herbal medicines work,” which the researchers say suggests the presence of a significant “meaning response,” i.e. the meaning that the brain assigns to placebo which causes some sort of physiological reaction.

So, is Kampo ineffective? There are few key factors require consideration:

• Traditional Kampo practitioners do not normally consider a woman’s menstrual status when selecting a formulation and in this study, participants had to have been in menopause for at least a year. What’s more, women who were confirmed with clinical depression were excluded from the study. Both of these factors introduce what researchers call “enrollment bias,” meaning that it is possible that other populations could have ultimately changed the results.
• Like TCM, Kampo uses evaluations of individual constitutional state, and TU-025 has traditionally been considered to be most effective in women who have stagnated chi, or energy flow, that is best characterized by subjective “coldness” and “metaphoric blood stagnation.”
• Finally, the researchers point out that there is no standard method for determining the proper dose of TU-025 in non-Japanese women and no guidance for amount and frequency. Consequently, it is possible that even the higher dose used in some women in this study wasn’t high enough or that the twice-daily frequency wasn’t enough.

Importantly, like ACUFLASH, the researchers write that trials of traditional Asian medicines need to account not only for these types of concerns but also for the nuances that distinguish Western and Kampo diagnoses.

Is TU-025 ineffective for American women with hot flashes? Under current study designs, it truly is. However, by incorporating other principals into standardized scientific trials, we may ultimately determine that like other alternatives, Kampo has a role in Western medicine. Stay tuned!

Want to read more on the same study? Reuters Health has a great writeup.