EstroG-100^® clinical studies

Lee KH, Lee DJ, Kim SM, Je SH, Kim EK, Han HS, Han IK. Evaluation of Effectiveness and Safety of Natural Plants Extract (Estromon^®) on Perimenopausal Women for 1 Year. J. of Korea Society of Menopause. Vol. 11 No.1 March 2005, p1–11.

Due to the reports from the WHI study on the increased risk of hormone therapy for the occurrence of breast cancer, heart disease, stroke and thrombosis and the FDA warning against the long-term use of oestrogen replacement therapy and the lack of approval for phytoestrogens in Korea, the aim of this study at that time in 2003 was to investigate an extract from three natural plants in a clinical study for its efficacy and safety in women with menopausal symptoms.

Prospective randomised, double-blind, placebo-controlled clinical study in women over 45 years of age with menopausal symptoms who received two capsules twice daily of verum (Estromon^®=EstroG100^®) or placebo (corn starch) for 48 weeks.

• Primary endpoint: Change in menopausal symptoms after three months of capsule use.
• Secondary endpoint: Change in individual variables after 12 months of capsule use.

The women’s age, pregnancy and menopause data as well as height, weight, waist circumference, body mass index, blood pressure, pulse, compliance with study material and additional comedications were documented at defined points after one, three, six, nine and twelve months, nine and twelve months at a hospital visit, with oestrogen, FSH, hGH, cholesterol, LDL, HDL, AP, osteocalcin, triglycerides, bone density and general haematological parameters determined, and interviews were conducted on improvement in menopausal symptoms within three months.

48 women over 45 years of age with menopausal symptoms were enrolled in the study between 2003 and 2004. Of these, 24 women received Estromon® and 24 women received corn starch as a placebo for 48 weeks. 42 patients could be included in the complete final evaluation. Of the drop-outs, five left the study for their own reasons and one because she had skin symptoms. 19 patients were evaluated from the study group and 23 women from the placebo group. The mean age was 54 years with a range of 46–66. At the baseline examination at the start of the study, there were no significant differences in biophysical profiles except for a higher mean bone density in the verum group.

Three months after the start of the study, 14 of 24 women in the verum group but only five of 23 women in the placebo group showed improvements in their climacteric symptoms (significant with an odds ratio of 5.04). Among the women who already had symptoms at the baseline assessment, the difference was not significant (4/7 vs. 5/6).

Femoral neck bone density at 12 months was significantly higher in the verum group (p0.05), while it decreased significantly in the placebo group (p0.05). Serum osteocalcin at 12 months was significantly lower in the verum group (p-values not clear in the table) and significantly higher in the placebo group (p0.05). Serum alkaline phosphatase was significantly lower in the verum group (p0.05). Serum hGH increased significantly in both the verum and placebo groups after 12 months, increasing by 268% in the former and 42% in the latter (p0.05). Serum triglycerides decreased in both groups, not significantly in the placebo group and significantly in the verum group after 12 months (p0.05).

Serum cholesterol showed no differences in either group after 12 months, nor did blood pressure, oestrogen, weight, BMI, FSH, LDL, HDL or spinal bone density.

Estromon^® is composed of Phlomis umbrosa, which contains saponin including triterpene glycosides, and Cynanchum wilfordii contains saponin including wilforside and cyanuricuoside, which leads the authors to believe that the saponin activates the steroidal oestrogen receptor and thereby improves menopausal symptoms. Furthermore, Estromon^® contains Angelica gigas, and its decursin acts as a coumarin derivative and thus as a phytoestrogen.

The authors conclude that Estromon^® can be used to relieve climacteric symptoms such as hot flushes, joint pain and sweating without the usual side effects such as weight gain or increase in BMI or serum triglycerides.

Chang A, Kwak BY, Yi K, Kim JS. The effect of herbal extract (EstroG-100^®) on pre-, peri- and post-menopausal women: a randomized double-blind, placebo-controlled study. Phytother Res. 2012 Apr;26(4):510–6.

Since the WHI study data showed a 26% increase in risk of breast cancer, 29% increase in risk of heart disease and 41% increase in risk of stroke with hormone replacement therapy, and there is a lack of scientific evidence on the efficacy of herbal supplements, EstroG-100^® should be investigated for its efficacy on menopausal symptoms in a clinical study in non-Asian American women.

Prospective, randomised, double-blind, placebo-controlled clinical study of the safety and efficacy of EstroG-100^® in women with moderate to severe menopausal symptoms (Kupperman index score > 20). All study participants received either the verum preparation or a placebo, given as a tablet twice a day for 12 weeks.

The primary endpoint was an improvement in quality of life on the Kupperman index (menopausal index) as well as individual symptoms (vasomotor symptoms, numbness and tingling, sleep disturbances, nervousness, depressed mood, dizziness, fatigue, joint pain, headache, palpitations and tingling) and vaginal dryness.

Height, weight, BMI, smoking and alcohol consumption, blood pressure, pulse, body temperature, serum markers AP, osteocalcin, triglycerides, LDL, HDL, cholesterol, blood count, AST; ALT, creatinine, total protein, albumin, fasting glucose, oestradiol (E2) and FSH were also assessed.

61 women were enrolled in the study between May 2009 and January 2010. The verum group showed a highly significant decrease in the Kupperman index because of treatment and also a highly significant greater decrease than the placebo group (from a mean of 29.5 to 13.6 at six and 11.3 at twelve weeks versus from 29.2 to 23.3 and 23.7 respectively, p<0.01). With regard to the individual symptoms, the verum group also showed a highly significant improvement in vasomotor complaints, as well as insomnia, nervousness, depressive mood, dizziness and fatigue, palpitations, tingling sensations after six and after twelve weeks, the symptoms of paraesthesia and joint pain after twelve weeks compared to the baseline (p<0.01) and versus the placebo group also at twelve weeks (p<0.05), and also on vaginal dryness versus the baseline at six and twelve weeks (p<0.01) and versus the placebo group (p<0.05), with the latter also showing a highly significant improvement in vaginal dryness at twelve weeks.

Safety: E2 and FSH levels did not change significantly during treatment, nor did weight and BMI in either group.

No side effects of the medication occurred in the verum group during the study.

Twelve weeks of treatment with EstroG-100^® showed a statistically significant improvement in various menopausal symptoms such as hot flushes, night sweats, numbness, sleep disturbances, nervousness, depressed mood, dizziness, fatigue, joint pain and vaginal dryness compared to the placebo group. No side effects were reported after taking EstroG-100^®, nor were changes in weight, BMI, serum E2 or FSH levels, or liver enzymes.

Short version: EstroG-100^® was shown to be an effective and safe dietary supplement in pre-, peri- and postmenopausal women with menopausal symptoms.

Lee DJ, Kim T, Seo SK. The Evaluation of the Efficacy and Safety of Herbal Extract (PAC EX01: EstroG 100^®) on Menopausal Symptoms: 12 weeks, Multi Centre, A randomized, Double Blind Placebo-Controlled Clinical Study.

After numerous promising in vitro and in vivo studies on the plant root extract EstroG-100^® (Cynanchum wilfordii, Phlomis umbrosa, and Angelica gigas) and initial clinical studies on the effect of EstroG-100^® on menopausal symptoms, the aim of this study was to investigate the effect of EstroG-100^® taken orally on menopausal symptoms in a larger number of women with such symptoms in a multi-centre setting.

Prospective, randomised, double-blind, multi-centre clinical study of the safety and efficacy of EstroG-100^® in women with moderate to severe menopausal symptoms (Kupperman menopausal index > 20). The primary endpoint was an improvement in quality of life on the Kupperman index (menopausal index), and the secondary endpoint was an improvement in the individual symptoms of the Kupperman index (vasomotor complaints, numbness, sleep disturbances, nervousness, depressive mood, dizziness, fatigue, joint pain, headaches, palpitations, tingling) and vaginal dryness.

Furthermore, height, weight, BMI, smoking and alcohol consumption, blood pressure, pulse, body temperature, serum markers AP, osteocalcin, triglycerides, LDL, HDL, cholesterol, blood count, AST; ALT, creatinine, total protein, albumin, fasting glucose, oestradiol (E2) and FSH were examined.

Study participants received either the verum drug or a placebo, each as two tablets per day for 12 weeks.

122 women with menopausal symptoms were screened between November 2013 and August 2014 and of these, 105 were included in the study. Nine women were excluded from the final analysis before reaching the endpoint. In total, 96 women with a mean age of 54 years were included in the analysis. The groups did not differ in their general baseline data. The women in the verum group had a slightly higher Kupperman index at the start of the study. After four weeks, there was a significantly greater decrease in the Kupperman index in the verum group than in the placebo group (from a mean of 35.1 to 23.2 vs. 33.1 to 24.7, p<0.05) and a highly significant stronger decrease after 12 weeks (14.8 vs. 20.1, p<0.01). With regard to the individual symptoms, the verum group showed a significantly greater improvement in vasomotor complaints, tingling and numbness and nervousness, depressive mood, dizziness, fatigue and joint pain, palpitations (heart palpitations), tingling sensations and also vaginal dryness after 12 weeks of treatment, as well as a barely non-significant improvement in sleep disorders (p=0.052).

Regarding safety: AP and triglyceride levels were significantly higher in both groups after treatment than at the baseline (p<0.01 and p<0.05, respectively), while creatinine levels were highly significantly lower (for the total and verum groups p<0.01, for the control group p<0.05), with all mean values remaining within the normal range. White blood cell counts were significantly increased in the verum group compared to the baseline and also compared to the placebo group (p<0.01), while also remaining within the normal range. Although there was no significant increase in fasting glucose in the verum group, it was significantly higher in the verum group than in the placebo group after treatment (p<0.05). Weight, BMI and blood pressures were not significantly changed after treatment, nor were they between the groups. E2 and FSH levels were also not significantly different.

No side effects of the medication occurred in the verum group during the study.

EstroG-100^®, administered over 12 weeks, significantly improved the quality of life and also the nine different individual symptoms of the Kupperman index in women with menopausal symptoms, without any side effects being reported or the laboratory values examined changing to pathological.

Short version: EstroG-100^® proved to be a safe and effective herbal preparation in the treatment of quality of life and individual symptoms in women with menopausal symptoms.