Actaea racemosa (Black Cohosh)
 

Drewe, J., C. Zimmermann and C. Zahner. 2013. The effect of a Cimicifuga racemosa extracts Ze 450 in the treatment of climacteric complaints - an observational study. Phytomedicine. pii: S0944-7113, 13: 84-86.

Abstract:

BACKGROUND: Root extracts of Cimicifuga racemosa (L.) Nutt. have been successfully used in the treatment of climacteric complaints.

METHOD: In this observational study, Cimicifuga racemosa (CR) extract Ze 450 was studied in 442 unselected ambulatory female outpatients with menopausal complaints under daily practice conditions. Physicians were suggested to treat patients for the first 3 months with 13mg/d CR (high dose, HD) and to continue over additional 6 months either with this treatment or to switch to 6.5mg/d CR (low dose, LD). The choice of treatment and its dose, however, was fully at the discretion of the physician.

RESULTS: After 3-months treatment with HD, symptom severity (Kupperman Menopause Index, KMI) decreased significantly (p<0.001) from baseline values. Continuation of treatment with HD or LD decreased total KMI and its sub-item scores further (HD, LD: p<0.001). However, more patients (84.9%) responded to HD than to LD (78.4%) and showed an improvement of symptoms (p=0.011).

CONCLUSION: This observational study demonstrated that treatment with CR in unselected patients with climacteric complaints under the conditions of daily practice resulted in a significant improvement of menopausal symptoms assessed by the total KMI score and its sub-item scores with an effect size similar to that in a previous randomized, controlled clinical trial.

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Kamel, H. H. 2013. Role of phyto-oestrogens in ovulation induction in women with polycystic ovarian syndrome. Eur J Obstet Gynecol Reprod Biol. 2115, 13: 7-9.

Abstract:

OBJECTIVE: To study the role of a phyto-oestrogen, Cimicifuga racimosa extract (Klimadynon(®), Bionorica, Neumarkt i.d.OBf., Germany), in ovulation induction in women with polycystic ovarian syndrome (PCOS).

STUDY DESIGN: Prospective randomized controlled trial in Minia University Hospital, Minia, Egypt. One hundred women with PCOS were allocated into one of two groups: one group (n=50) received clomiphene citrate 100mg daily for 5 days, and the other group (n=50) received C. racimosa 20mg daily for 10 days. Both groups received medication starting from the second day of the cycle for three consecutive cycles, during which changes in follicle-stimulating hormone (FSH), luteinizing hormone (LH), FSH/LH ratio, progesterone, endometrial thickness and pregnancy rate were measured.

RESULTS: The groups were similar in terms of age, clinical presentation and hormonal levels before treatment. Following treatment, significant favourable changes in LH level and FSH/LH ratio (p=0.007 and 0.06, respectively) were seen in the Klimadynon group. In this group the progesterone level was higher from the first treatment cycle, indicating better ovulation (p=0.0001), and endometrial thickness was greater (p=0.0004). The pregnancy rate was higher in the Klimadynon group but the difference between the groups was not significant (p=0.1).

CONCLUSION: Phyto-oestrogen can be used as an alternative to clomiphene citrate for ovulation induction in women with polycystic ovarian syndrome.

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Schellenberg, R., R. Saller, L. Hess, J. Melzer, C. Zimmermann, J. Drewe and C. Zahner. 2013. Dose-Dependent Effects of the Cimicifuga racemosa Extract Ze 450 in the Treatment of Climacteric Complaints: A Randomized, Placebo-Controlled Study. Evid Based Complement Alternat Med. 2012: 260301.

Abstract: Extracts from Cimicifuga racemosa (CR, synonym Actaea racemosa) have shown efficacy in trials in women with menopausal symptoms. Yet, dose dependency remains unclear. Therefore, 180 female outpatients with climacteric complaints were treated for 12 weeks in a randomized, double-blind, placebo-controlled, 3-armed trial (CR extract Ze 450 in 6.5 mg or 13.0 mg, or placebo). Primary outcome was the difference in menopausal symptoms (vasomotor, psychological, and somatic), assessed by the Kupperman Menopausal Index between baseline and week 12. Secondary efficacy variables were patients' self-assessments of general quality of life (QoL), responder rates, and safety. Compared to placebo, patients receiving Ze 450 showed a significant reduction in the severity of menopausal symptoms in a dose-dependent manner from baseline to endpoint (mean absolute differences 17.0 (95% CI 14.65-19.35) score points, P < 0.0001 for 13.0 mg; mean absolute differences 8.47 (95% CI 5.55-11.39) score points, P = 0.0003 for 6.5 mg). QoL and responder rates corresponded with the main endpoint. Changes in menopausal symptoms and QoL were inversely correlated. Reported adverse events and clinical laboratory testing did not raise safety concerns. The CR extract Ze 450 is an effective and well-tolerated nonhormonal alternative to hormone treatment for symptom relief in menopausal women.

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H. H. Kamel. 2013. Role of phyto-oestrogens in ovulation induction in women with polycystic ovarian syndrome. Eur J Obstet Gynecol Reprod Biol. 168, 1: 60-63. 

Abstract:

OBJECTIVE: To study the role of a phyto-oestrogen, Cimicifuga racimosa extract (Klimadynon(®), Bionorica, Neumarkt i.d.OBf., Germany), in ovulation induction in women with polycystic ovarian syndrome (PCOS).

STUDY DESIGN: Prospective randomized controlled trial in Minia University Hospital, Minia, Egypt. One hundred women with PCOS were allocated into one of two groups: one group (n=50) received clomiphene citrate 100mg daily for 5 days, and the other group (n=50) received C. racimosa 20mg daily for 10 days. Both groups received medication starting from the second day of the cycle for three consecutive cycles, during which changes in follicle-stimulating hormone (FSH), luteinizing hormone (LH), FSH/LH ratio, progesterone, endometrial thickness and pregnancy rate were measured.

RESULTS: The groups were similar in terms of age, clinical presentation and hormonal levels before treatment. Following treatment, significant favourable changes in LH level and FSH/LH ratio (p=0.007 and 0.06, respectively) were seen in the Klimadynon group. In this group the progesterone level was higher from the first treatment cycle, indicating better ovulation (p=0.0001), and endometrial thickness was greater (p=0.0004). The pregnancy rate was higher in the Klimadynon group but the difference between the groups was not significant (p=0.1).

CONCLUSION: Phyto-oestrogen can be used as an alternative to clomiphene citrate for ovulation induction in women with polycystic ovarian syndrome.

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Colau, J. C., S. Vincent, P. Marijnen and F. A. Allaert. 2012. Efficacy of a Non-Hormonal Treatment, BRN-01, on Menopausal Hot Flashes: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial. Drugs R D. 12(3): 107-19

Abstract:

Background: Homeopathic medicines have a place among the non-hormonal therapies for the treatment of hot flashes during the menopause. Objective: The objective of this study was to evaluate the efficacy of the non-hormonal treatment BRN-01 in reducing hot flashes in menopausal women. Study Design: This was a multicenter, randomized, double-blind, placebo-controlled study carried out between June 2010 and July 2011. Setting: The study was conducted in 35 active centers in France (gynecologists in private practice). Patients: One hundred and eight menopausal women, ≥50 years of age, were enrolled in the study. The eligibility criteria included menopause for <24 months and ≥5 hot flashes per day with a significant negative effect on the women's professional and/or personal life. Intervention: Treatment was either BRN-01 tablets, a registered homeopathic medicine containing Actaea racemosa (4 centesimal dilutions [4CH]), Arnica montana (4CH), Glonoinum (4CH), Lachesis mutus (5CH), and Sanguinaria canadensis (4CH), or identical placebo tablets, prepared by Laboratoires Boiron according to European Pharmacopoeia standards. Oral treatment (2 to 4 tablets per day) was started on day 3 after study enrollment and was continued for 12 weeks. Main Outcome Measure: The main outcome measure was the hot flash score (HFS) compared before, during, and after treatment. Secondary outcome criteria were the quality of life (QoL) [measured using the Hot Flash Related Daily Interference Scale (HFRDIS)], severity of symptoms (measured using the Menopause Rating Scale), evolution of the mean dosage, and compliance. All adverse events (AEs) were recorded. Results: One hundred and one women were included in the final analysis (intent-to-treat population: BRN-01, n = 50; placebo, n = 51). The global HFS over the 12 weeks, assessed as the area under the curve (AUC) adjusted for baseline values, was significantly lower in the BRN-01 group than in the placebo group (mean ± SD 88.2 ± 6.5 versus 107.2 ± 6.4; p = 0.0411). BRN-01 was well tolerated; the frequency of AEs was similar in the two treatment groups, and no serious AEs were attributable to BRN-01. Conclusion: BRN-01 seemed to have a significant effect on the HFS, compared with placebo. According to the results of this clinical trial, BRN-01 may be considered a new therapeutic option with a safe profile for hot flashes in menopausal women who do not want or are not able to take hormone replacement therapy or other recognized treatments for this indication.

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Molla, M. D., J. J. Hidalgo-Mora and M. G. Soteras. 2011. Phytotherapy as alternative to hormone replacement therapy. Front Biosci (Schol Ed). 1, 3: 191-204.

Abstract: Phytoestrogens are a group of non-steroidal compounds of plant origin that present structural and functional similarities with estradiol. Isoflavones are their most widely known category. There are different mechanisms of action of isoflavones accepted, although they may be considered as selective modulators of estrogen receptors. On the other hand, Cimicifuga Racemosa is a perennial plant used traditionally for problems related to menstruation. Its action mechanisms have not been totally identified. There is a growing interest in the usefulness of phytotherapy in the treatment of symptoms and menopause-related diseases. Isoflavones and Cimicifuga racemosa moderately improve vasomotor symptoms in menopausal women, particularly in those who have a greater number of hot flushes. Furthermore, trials performed with soy isoflavones have observed a reduction of the loss of bone mineral density in postmenopausal women and a slight decrease in LDL cholesterol. In short, phytotherapy will constitute a therapeutic option that can offer assistance to women who want to improve their quality of life through relief of vasomotor symptoms or benefit from other effects for their health.

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Rostock, M., J. Fischer, A. Mumm, U. Stammwitz, R. Saller and H. H. Bartsch. 2011. Black cohosh (Cimicifuga racemosa) in tamoxifen-treated breast cancer patients with climacteric complaints - a prospective observational study. Gynecol Endocrinol. [Epub ahead of print].

Abstract:

Objective. The antihormonal therapy of breast cancer patients with the antiestrogen tamoxifen often induces or aggravates menopausal complaints. As estrogen substitution is contraindicated, herbal alternatives, e.g. extracts of black cohosh are often used. Design. A prospective observational study was carried out in 50 breast cancer patients with tamoxifen treatment. All patients had had surgery, most of them had undergone radiation therapy (87%) and approximately 50% had received chemotherapy. Every patient was treated with an isopropanolic extract of black cohosh (1-4 tablets, 2.5 mg) for 6 months. Patients recorded their complaints before therapy and after 1, 3, and 6 months of therapy using the menopause rating scale (MRS II). Results. The reduction of the total MRS II score under black cohosh treatment from 17.6 to 13.6 was statistically significant. Hot flashes, sweating, sleep problems, and anxiety improved, whereas urogenital and musculoskeletal complaints did not change. In all, 22 patients reported adverse events, none of which were linked with the study medication; 90% reported the tolerability of the black cohosh extract as very good or good. Conclusions. Black cohosh extract seems to be a reasonable treatment approach in tamoxifen treated breast cancer patients with predominantly psychovegetative symptoms.

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Mazaro-Costa, R., M. L. Andersen, H. Hachul and S. Tufik. 2010.

Medicinal plants as alternative treatments for female sexual dysfunction: utopian vision or possible treatment in climacteric women?. J Sex Med. 7, 1: 3695-3714.

Abstract:

INTRODUCTION: Female sexual dysfunction (FSD) is a complex and multifactorial condition. An increased incidence of FSD is especially associated with the decline of estrogen. Thus, menopause is a critical phase for FSD complaints. In this context, medicinal plants may be a therapeutic option.

AIM: To identify and describe the popular and clinical uses of medicinal plants for FSD treatment in climacteric women. We highlighted the majority of the plants commonly involved with the female reproductive system including: Angelica sinensis, Cimicifuga racemosa, Ferula hermonis, Ginkgo biloba, Humulus lupulus, Lepidium meyenii, Tribulus terrestris, Trifolium pratense, and Vitex agnus-castus.

METHODS: This study is a narrative review of studies of plants that are possible alternative treatments for FSD. The species described have clinical and popular uses in different cultures as well as medical indications for female reproductive disturbances, mainly in climacteric women. We have also analyzed the evidence level of clinical studies.

MAIN OUTCOME MEASURES: The main outcome assessed is the efficacy of plants in improving the symptoms of FSD.

RESULTS: There is little evidence from the literature to recommend the use of medicinal plants when treating FSD. The majority of studies with a strong level of evidence are associated with the treatment of the vasomotor symptoms of menopause. Ferula hermonis, Angelica sinensis, and Gingko biloba may be suggested for arousal disorder studies. Cimicifuga racemosa, Trifolium pratense, and Vitex agnus-castus may be recommended for several FSD. Humulus lupulus and Tribulus terrestris may help with desire disorder studies. Lepidium meyenii should be studied further.

CONCLUSIONS: Studies of these plants indicate that they may be useful as a possible alternative and/or complementary approach for studies aimed at the treatment of FSD. At this time, however, this review cannot recommend a plant that has a strong enough level of evidence for treatment of FSD. Thus, there is a need for clinical (double-blinded and randomized) studies to evaluate the efficacy and safety of several plants that can exert a positive effect on the management of FSD.

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Molla, M. D., J. J. Hidalgo-Mora and M. G. Soteras. 2010. Phytotherapy as alternative to hormone replacement therapy. Front Biosci (Schol Ed). 3: 191-204.

Abstract: Phytoestrogens are a group of non-steroidal compounds of plant origin that present structural and functional similarities with estradiol. Isoflavones are their most widely known category. There are different mechanisms of action of isoflavones accepted, although they may be considered as selective modulators of estrogen receptors. On the other hand, Cimicifuga racemosa is a perennial plant used traditionally for problems related to menstruation. Its action mechanisms have not been totally identified. There is a growing interest in the usefulness of phytotherapy in the treatment of symptoms and menopause-related diseases. Isoflavones and Cimicifuga Racemosa moderately improve vasomotor symptoms in menopausal women, particularly in those who have a greater number of hot flushes. Furthermore, trials performed with soy isoflavones have observed a reduction of the loss of bone mineral density in postmenopausal women and a slight decrease in LDL cholesterol. In short, phytotherapy will constitute a therapeutic option that can offer assistance to women who want to improve their quality of life through relief of vasomotor symptoms or benefit from other effects for their health.

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van Breemen, R. B., W. Liang, S. Banuvar, L. P. Shulman, Y. Pang, Y. Tao, D. Nikolic, K. M. Krock, D. S. Fabricant, S. N. Chen, S. Hedayat, J. L. Bolton, G. F. Pauli, C. E. Piersen, E. C. Krause, S. E. Geller and Farnsworth. 2010. Pharmacokinetics of 23-epi-26-deoxyactein in women after oral administration of a standardized extract of black cohosh. Clin Pharmacol Ther. 87, 2: 219-225.

Abstract: Dietary supplements containing black cohosh are alternatives to conventional hormone replacement therapy in menopause. This study investigates the maximum tolerated dose of a 75% ethanol extract of black cohosh and determines the pharmacokinetics of one of its most abundant triterpene glycosides, 23-epi-26-deoxyactein. Single doses of black cohosh extract containing 1.4, 2.8, or 5.6 mg of 23-epi-26-deoxyactein were administered to 15 healthy, menopausal women. Serial blood samples and 24-h urine samples were obtained; blood chemistry, hormonal levels, and 23-epi-26-deoxyactein levels were determined. No acute toxicity or estrogenic hormone effects were observed. Pharmacokinetic analyses of 23-epi-26-deoxyactein in sera indicated that the maximum concentration and area under the curve increased proportionately with dosage, and that the half-life was ~2 h for all dosages. Less than 0.01% of the 23-epi-26-deoxyactein was recovered in urine 24 h after administration. No phase I or phase II metabolites were observed either in clinical specimens or in vitro.

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Geller, S. E., L. P. Shulman, R. B. van Breemen, S. Banuvar, Y. Zhou, G. Epstein, S. Hedayat, D. Nikolic, E. C. Krause, C. E. Piersen, J. L. Bolton, G. F. Pauli and N. R. Farnsworth. Safety and efficacy of black cohosh and red clover for the management of vasomotor symptoms: a randomized controlled trial. Menopause. 16, 6: 1156-1166.

Abstract:

OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of black cohosh and red clover compared with placebo for the relief of menopausal vasomotor symptoms.

METHODS: This study was a randomized, four-arm, double-blind clinical trial of standardized black cohosh, red clover, placebo, and 0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate (CEE/MPA; n = 89). Primary outcome measures were reduction in vasomotor symptoms (hot flashes and night sweats) by black cohosh and red clover compared with placebo; secondary outcomes included safety evaluation, reduction of somatic symptoms, relief of sexual dysfunction, and overall improvement in quality of life.

RESULTS: Reductions in number of vasomotor symptoms after a 12-month intervention were as follows: black cohosh (34%), red clover (57%), placebo (63%), and CEE/MPA (94%), with only CEE/MPA differing significantly from placebo. Black cohosh and red clover did not significantly reduce the frequency of vasomotor symptoms as compared with placebo. Secondary measures indicated that both botanicals were safe as administered. In general, there were no improvements in other menopausal symptoms.

CONCLUSIONS: Compared with placebo, black cohosh and red clover did not reduce the number of vasomotor symptoms. Safety monitoring indicated that chemically and biologically standardized extracts of black cohosh and red clover were safe during daily administration for 12 months.

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Amsterdam, J. D., Y. Yao, J. J. Mao, I. Soeller, K. Rockwell and J. Shults. 2009. Randomized, double-blind, placebo-controlled trial of Cimicifuga racemosa (black cohosh) in women with anxiety disorder due to menopause. J Clin Psychopharmacol. 29, 5: 478-483.

Abstract:

OBJECTIVE: We conducted a randomized, double-blind, placebo-controlled, parallel group trial of the efficacy and tolerability of Cimicifuga racemosa (black cohosh) extract for the treatment of anxiety disorder due to menopause. We hypothesized that black cohosh would be superior to placebo in reducing anxiety symptoms of menopause, with a comparable tolerability profile to placebo.

MATERIALS AND METHODS: Subjects were randomized to therapy with either pharmaceutical-grade black cohosh extract (n = 15) or placebo (n = 13) for up to 12 weeks. The primary outcome measure was changed over time in total Hamilton Anxiety Rating Scale (HAM-A) scores. Secondary outcomes included a change in scores on the Beck Anxiety Inventory, Green Climacteric Scale (GCS), and Psychological General Well-Being Index (PGWBI) and the proportion of patients with a change of 50% or higher in baseline HAM-A scores.

RESULTS: There was neither a significant group difference in change over time in total HAM-A scores (P = 0.294) nor a group difference in the proportion of subjects with a reduction of 50% or higher in baseline HAM-A scores at study end point (P = 0.79). There was a significantly greater reduction in the total GCS scores during placebo (vs black cohosh; P = 0.035) but no group difference in change over time in the GCS subscale scores or in the PGWBI (P = 0.140). One subject (3.6%) taking black cohosh discontinued treatment because of adverse events.

CONCLUSIONS: We found no statistically significant anxiolytic effect of black cohosh (vs placebo). However, small sample size, choice of black cohosh preparation, and dosage used may have been limiting factors producing negative results.

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Shahin, A. Y., A. M. Ismail and O. M. Shaaban OM. 2009. Supplementation of clomiphene citrate cycles with Cimicifuga racemosa or ethinyl oestradiol--a randomized trial. Reprod Biomed Online. 19, 4: 501-507.

Abstract: The anti-oestrogenic activity of clomiphene citrate (CC) on the cervical mucous and endometrium may be the reason for the relatively low pregnancy rates in CC induction cycles. Various follicular-phase supplements have been tried to improve cycle outcome in these patients. This study compared follicular-phase supplementation with either phytoestrogen (PE) or ethinyl oestradiol (EE) in CC induction cycles for the treatment of unexplained infertility. A total of 134 patients were randomly allocated to each treatment group (67 each). The PE group needed significantly fewer days for adequate follicular maturation, had a thicker endometrium and higher oestradiol concentration at the time of human chorionic gonadotrophin injection (all P < 0.001). The PE group had higher luteal-phase serum progesterone compared with the EE group. No significant difference was found regarding clinical pregnancy rates (14.0% versus 21.1%, respectively). In conclusion, the cycle characteristics in unexplained infertility women treated with clomiphene citrate induction and timed intercourse improved after follicular-phase supplementation with PE compared with EE supplementation. Further studies are needed to confirm the mechanism beyond these effects.

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Farnsworth, N. R. and G. B. Mahady. 2009. Research highlights from the UIC/NIH Center for Botanical Dietary Supplements Research for Women's Health: Black cohosh from the field to the clinic. Pharm Biol 47, 8: 755-760.

Abstract: In 1999, the Department of Medicinal Chemistry and Pharmacognosy at the College of Pharmacy, University of Illinois (UIC) at Chicago was funded to establish a Botanical Dietary Supplements Research Center from the National Institutes of Health (NIH). The emphasis of the UIC/NIH Center for Botanical Dietary Supplements Research (CBDSR) is botanical dietary supplements (BDS) for women's health. Center's research has focused on BDS that may improve women's health and quality of life, specifically in the areas of menopause, premenstrual syndrome, and persistent urinary tract infections. Center investigators have overcome many challenges associated with botanical dietary supplements research, including acquiring and identifying plant species for investigation, isolating and identifying active constituents, elucidating the mechanisms of action of these botanicals, and conducting phase I and phase II clinical studies. Black cohosh [Actaea racemosa L. (Ranunculaceae)] has been used as a model to illustrate the steps involved in taking a botanical dietary supplement from the field, all the way to clinical trials. Bioassays are described that were necessary to elucidate the pertinent biological studies of plant extracts and their mechanisms of action. The Center has used an innovative multidisciplinary approach to this type of research, and thus has been very successful in fulfilling its specific aims.

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Farnsworth, N. R., E. C. Krause, J. L. Bolton, G. F. Pauli, R. B. van Breemen and J. G. Graham. 2008. The University of Illinois at Chicago/National Institutes of Health Center for Botanical Dietary Supplements Research for Women's Health: from plant to clinical use. Am J Clin Nutr. 87, 2: 504S-508S.

Abstract: The University of Illinois at Chicago/National Institutes of Health Center for Botanical Dietary Supplements Research began in 1999 with an emphasis on botanical dietary supplements for women's health. We have concentrated on plants that may improve women's health, especially to reduce hot flashes in menopausal women, alleviate the symptoms of premenstrual syndrome, and reduce persistent urinary tract infections. The primary focus of this article is to describe the operation of our center, from acquiring and identifying botanicals to isolating and identifying active constituents, to elucidating their mechanisms of action, and to conducting phase I and phase II clinical studies. Black cohosh (Actaea racemosa; syn Cimicifuga racemosa) has been used as a model to illustrate the steps involved in taking this plant from the field to clinical trials. Bioassays are described that were necessary to elucidate the pertinent biological studies of plant extracts and their mechanisms of action. We conclude that this type of research can only be successful with the use of a multidisciplinary approach.

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