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Effect of black cohosh (Cimicifuga racemosa) on perfusion and liver function in postmenopausal women.

Effect of black cohosh (Cimicifuga racemosa) on perfusion and liver function in postmenopausal women.

Due to the increase in life expectancy, women spend more than a third of their lives in postmenopausal women. Symptoms associated with menopause are known throughout the world [1]. Hormone replacement therapy (HRT) is an established form of treatment for these symptoms. However, both patients and medical practitioners changed their views on HRT significantly after the publication of the results of two studies focused on the risks of HRT. – A pioneering randomized controlled trial of women’s health in 2002 and an observational study involving 1 million women in 2003 [1,2].

HRT has also been associated with an increased risk of breast cancer [3]. And the desire of scientists to actively use alternative treatment was quite natural. – safe, effective and non-hormonal.

Black cohosh (Cimicifuga racemosa) – one of the most commonly used herbal remedies for correcting menopausal symptoms, with a proven very good safety profile over the years [4,5]. At the same time, the safety of C. racemosa has recently been questioned after the report of isolated, but serious cases of hepatotoxicity [6–eight]. In 2006, hepatotoxic reactions were reported in 42 women using C. racemosa. Nevertheless, experts from the European Medicines Agency stated that all similar cases and pharmacovigilance reports described in the literature were «poorly documented» [nine].

We believe that it is obvious that there is a need for clinical studies on C. racemosa-induced hepatotoxicity, since only a few clinical observations have appeared in recent reports. All this prompted us to conduct our own prospective clinical study in order to get a real picture of how safe the use of C. racemosa is for women’s health. 100 healthy women in menopause were recruited into the study following ethics approval – female patients in the gynecological clinic of the Assiut University Hospital for Women’s Health in Egypt.

The final analysis included 87 women who completed all 12–monthly observation period. Their ages ranged from 45 to 54 years (average age – 50.21±2.18 years). Inclusion criteria: age over 40 years with the expiration of 1 year after the last menstruation, the presence of symptoms associated with menopause, the absence of gynecological diseases, the natural nature of menopause, not using HRT during > 6 months before the start of the study, obtaining written consent to participate in the study after a detailed acquaintance with the study design, as well as the possibility of regular visits to the doctor during the observation period. Crete­Exceptions: vaginal bleeding, active or chronic liver disease and / or liver dysfunction, history of thromboembolism, breast or uterine tumors, endometrial thickness greater than 5 mm with transvaginal ultrasound, and the use of alternative, complementary or herbal remedies to relieve symptoms menopause within 3 months prior to study initiation.

Menopause was confirmed by high FSH levels in all study participants. All women underwent a complete clinical examination, ultrasound of the abdominal cavity and small pelvis, were tested for hepatitis B and C. Before taking a daily dose of 40 mg of dry extract of C. racemosa (Klimadinon; Biono­Rika AG, Neumarkt, Ger­mania) and 12 months after the start of treatment, the patient completed a questionnaire on the subjective assessment of menopausal symptoms (in particular, hot flashes). Total hepatic blood flow was also assessed using color Doppler scanning. In addition, the prothrombin time and the concentration of serum albumin, bilirubin, in–glutamyl­trance­ferase (GGT), alkaline phosphatase, alani­us­but­trance­ferase (ALT) and aspartate aminotransferase (AST).

Ultrasound equipment used for Doppler examination – Siemens Sonoline Sienna Ultrasound Imaging (Siemens, Munich, Germany). This system operates in several modes: in two-dimensional real-time mode, V– and M–modes, spectral and color Doppler modes and in standby mode. Dopple­moat­The study was carried out in accordance with the standard settings [10]. Issle­The dosing was carried out by the same specialist after an overnight fast of the patient and rest for 15 minutes in the supine position while holding the breath in the middle of the expiration. Obsle­The assessment included assessment of the portal vein and major hepatic arteries.

Calculation of blood flow requires measuring the diameter of the portal vein (in cm) and the maximum flow rate (in cm / s): portal blood flow = 22 / 7x (d2) / 4xVmax / 2×60 (mm / min) [11]. Likewise, hepatic artery blood flow was measured in the main hepatic artery. Total hepatic blood flow was calculated as the average of three measurements of the sum of flows in the common hepatic artery and portal vein (total hepatic blood flow = hepatic arterial blood flow + portal vein blood flow).

About­throm­bin time was estimated using the DiaPlastin kit [12] (DiaMed AG, Morat, Switzerland). Serum albumin, total and direct bilirubin, ALT, AST, alkaline phosphatase, alkaline phosphatase (ALP), UUN levels were measured using a colorimetric test on an automated clinical chemistry analyzer (BM / Hitachi 911; Beringer, Mannheim, Germany). Microsoft Access (Microsoft Corporation, Redmond, WA) was used to collect data that included the demographic and clinical characteristics of patients before and after treatment. Dan­were described statistically as the mean ± standard deviation (SD) for continuous values ​​and as frequencies and percentages for categorical values.

Until­The subjects were analyzed using the Social Science Statistical Package (version 13: SPSS Inc. Chicago, IL). Comparison of quantitative variables was performed using t–Stu test­Dent, Wilcoxon, and Pearson correlation analysis to examine individual correlations between pre- and post-treatment measurements. To compare categorical data, the x2 test was performed.

Differences were considered statistically significant at p < 0.05. There were no statistically significant changes in weight or systolic and diastolic blood pressure after 12 months of using Klimadinon. However, there was a significant reduction in the prevalence, daily frequency and severity of hot flashes at 12 months (Table 1). The essence­no venous changes according to the results of the Doppler study of the blood flow of the hepatic artery, portal vein, or general blood flow of the liver after 12 months of using Klimadinon were not revealed (Table 1), as well as­chennye indicators of liver function (table.

1). Every year in the world, millions of women enter the menopausal period. World Health Organization­in­Protection indicates that by 2030, approximately 1.2 billion women will be over 50, nearly 3 times the number of women in this age group in 1990 [13].

Many women refrain from using HRT to treat menopausal symptoms and turn to herbal remedies. Unfortunately, in most parts of the world, herbal medicines are not well regulated by federal agencies, such as the FDA in the United States. This leads to significant fluctuations in the composition, standardization, dosage and quality of available drugs [13]. Studies have shown that more than 3/4 of women in the peri– and postmenopausal women in the richest countries are taking or have taken herbal medicines in the past. More than 2/3 of women describe them as healthy, natural, safer and more in line with their values, beliefs and lifestyle [13].

C. racemosa – Black cohosh is a racemose herb, typical for North America, from the buttercup family, containing triterpene glycosides, flavonoids, aromatic acids and other constituents [5]. Many studies have shown the efficacy of C. racemosa in the control of vasomotor symptoms with a reduction in hot flashes [5,14]. Black cohosh has been reported to have a favorable safety profile with a shelf life of up to 6 months. The most common side effects are minor stomach complaints, which usually disappear after some time.–that time. High doses, however, can cause headache, vomiting and dizziness [14].

There are no documented cases of drug interactions with black cohosh racemes [15]



. Recently, there have been several alarming reports of cases of liver failure in women using black cohosh [16–eighteen]. As mentioned above, in 2006 the European Medicines Agency reported hepatotoxic reactions in 42 women treated with C. racemosa, but only in 4–x cases, the connection with the drug intake was significant, in 2–x – possible in 2–x – probable [9]. Amery­can­nazi­about­The National Institutes of Health recently stated that the potential biological mechanism that could explain the hepatotoxic effects of black cohosh is not known, and that millions of women using black cohosh have minimal side effects. Nevertheless, it was proposed to monitor liver function when studying black cohosh [19].

In the present study, C. racemosa was effective in relieving vasomotor symptoms, particularly hot flashes, resulting in significant reductions in prevalence, daily frequency and severity after 12 months of treatment (p<0.001). These positive results are consistent with the findings of many other studies [5,14]. With regard to hepatotoxic reactions, potential drug mechanisms have been tested.–mediated hepatotoxicity. First – vascular mechanism, through a possible change in blood flow to the liver, which was assessed using color Doppler ultrasonography.

Second mechanism – direct toxic effect on liver cells was assessed according to the selected indicators of liver function. Given the dual blood supply to the liver, blood flow was measured in both the portal vein and the common hepatic artery. This is, to our knowledge, the first report on the effect of C. racemosa on hepatic perfusion. There were no significant changes in the blood flow of the hepatic artery according to the results of Doppler examination, portal vein and total blood flow after 12 months of using C. racemosa. In addition, there were no significant changes in any indicator of liver function after 1 year of application of C. racemosa, and the level of all markers remained within the normal range of values.

These results are consistent with data from two recently completed studies [9,20]. However, our data are inconsistent with the results of a recent animal study in which C. racemosa exerted a hepatotoxic effect in vivo and in vitro, which manifested itself in apoptotic cell death in rats [21]. Based on the results of this study and the available current literature, we believe that the use of a daily dose of 40 mg dry extract of C. racemosa for 12 months in healthy postmenopausal women with no history of liver disease and normal liver function is safe. We also suggest monitoring liver function while treating women with impaired liver function.

It is hoped that this study will be a valuable contribution to the evidence base for the safety of C. racemosa (black cohosh) in relation to the liver. Nevertheless, large randomized controlled trials are required to confirm the validity of this statement..

The abstract was prepared by E.A. Klimova based on the article by A. Nasr, H. Nafeh «Influence of black cohosh (Cimicifuga racemosa) use by postmenopausal women on total hepatic perfusion and liver functions, Fertility and Sterility, Vol. 92, No.

5, November 2009.

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