Assessment of therapeutic effects of TMN-1 and DHJST on menopausal symptoms and osteoarthritis

Context: There is a paucity of data supporting the efficacy of herbal medicines in treating both menopausal symptoms and osteoarthritis in knee.
Objective: One is to evaluate safety and efficacy of the finished Chinese herbal product TMN-1 in the treatment of menopausal symptoms in climacteric women. Second is to evaluate both the safety and efficacy of the finished Chinese herbal product, DU-HUO-JI-SHENG-TANG, in reducing the symptoms of degenerative osteoarthritis (OA) of the knee.
Design and Setting: Two prospective, observational follow-up studies were carried out. TMN-1 trial was conducted in 4 hospitals in Taiwan between July 2003 and December 2004. DHJST trial was conducted in two hospitals in Taipei between April and October 2005.
Participants:
TMN-1 trial : Initially 126 women were included who were between 45 and 55 years of age, were experiencing hot flashes, and were without hormone replacement therapy. Women were excluded if they had any signs of active cancer. Of the participants, 82% completed the study. The reasons for withdrawal included adverse effects (n = 7), failed to return (n = 7), lack of efficacy (n = 6), and from protocol deviation (n = 3).
DHJST trial : Initially 87 subjects sought for medical help were screened. 69 of them were diagnosed as a degenerative OA of the knee through roentgenography diagnosed by radiologists. After the collection of baseline data, 1 of them failed to return for lack of efficacy, while the rest completed the study.
Intervention:
TMN-1 trial : Every participant received TMN-1 treatment 4 gm, 3 times per day, for 12 weeks.
DHJST trial : Each of the sample participants received DU-HUO-JI-SHENG-TANG treatment at a rate of 2.5 gm, twice per day, for four weeks.
Main Outcome Measure:
TMN-1 trial : Primary measures were change in frequency of hot flashes and severity of menopausal symptoms measured by Kupperman Index (KI). Secondary outcomes included changes in quality of life and adverse events.
DHJST trial : Baseline scores were measured on the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC), followed by further measures at the end of weeks 1, 2 and 4. The World Health Organization Quality of Life (WHOQOL) assessment was undertaken as a secondary outcome, with pattern identification (bian zheng) questionnaires being adopted and adverse events also being measured. Multivariate regression models were constructed to explore the differences between the WOMAC and WHOQOL scores at weeks 2 and 4, self-compared with the baseline by various determinants, including age, gender, body mass index, severity at baseline, use of rescue medication, aversion to cold and flaccidity of the lower back and knees.
Results:
TMN-1 trial : Significant improvement in scores of hot flashes and KI at weeks 4 and 12 in the 50 peri- and 53 postmenopausal women who completed this study (p<0.001). Logistic regression analyses showed that perimenopausal women with hot flashes had sevenfold (95% confidence interval [CI], 1.8 to 28.0) odds of improvement in favor of treatment, whereas that of the postmenopausal group was 1.5 (95% CI, 0.5 to 4.2). Further analyses showed that TMN-1 produced superior benefit in women with moderate and severe menopausal symptoms (KI >=21), compared with those with mild symptoms. It also improved symptoms of insomnia, nervousness, melancholia, and palpitation in perimenopausal women. Five adverse drug reactions were detected: three single events of nausea, abdominal pain, and abdominal fullness, and 2 events of diarrhea.
DHJST trial : Amongst the 68 participants, there were statistically-significant reductions in WOMAC scores for pain, stiffness and physical functioning in the second and fourth weeks, with the effects first appearing during week 2. By week 4, the mean WOMAC scores had fallen from 22.2 to 16.1 for pain, from 28.1 to 18.5 for stiffness, and from 22.6 to 18.2 for physical functioning, whilst the global score for pain under the ‘visual analogue scale’ (VAS) was reduced from 38.7 to 27.8. The results indicate that the magnitudes of the reductions in the above symptoms were associated with the baseline severity of the symptoms. Contrary to the hypotheses proposed in an ancient text on traditional Chinese medicine, there were no significant effects on flaccidity of the lower back and knees, or aversion to cold. There was also no significant change in either the WHOQOL assessment or the pattern difference based upon traditional theory. There were only four adverse drug reactions judged to be potentially related to the treatment, involving single events of skin discoloration, flashes, diarrhea and tachycardia.
Conclusion:
TMN-1 trial : This study provides evidence that 12 weeks of TMN-1 therapy is a viable alternative treatment to consider in perimenopausal women with hot flashes, particularly in those with palpitation, emotional disturbance, and insomnia.
DHJST trial : For degenerative OA of knee, four-week therapy with the Chinese herbal products DU-HUO-JI-SHENG-TANG seemed to be ineffective in treating flaccidity or aversion to cold, but appeared both to reduce pain and stiffness, and to improve physical function.
In conclusion, observational studies have specific advantages in studying aspects of clinical safety. The use of such studies to prove efficacy is limited because bias in patient selection may occur. However, the results we found from this kind of studies can provide more precious information to verify whether it is a potential treatment or not to symptom relief during climacteric period or symptomatic knee in patients with OA. Nevertheless, the level of evidence on efficacy of both TMN-1 and DHJST can be significantly increased by well-designed double blind randomized studies.