PRACA ORYGINALNA / ORIGINAL ARTICLE

Wpływ pluskwicy groniastej (Cimicifuga racemosa) na parametry hemodynamiczne i jakość życia u kobiet w okresie okołomenopauzalnym z nadciśnieniem tętniczym

Natalia V. Gorach

Higher State Educational Establishment of Ukraine O.O. Bogomolets National Medical University, Kyiv, Ukraine

 

ABSTRACT

Introduction: Increased blood pressure is major risk factors for morbidity and mortality from coronary heart disease, stroke and heart failure. Special studies have shown that women in perimenopause are a category of high risk of cardiovascular diseases and complications developing.

The aim of research was to study the effects of cimicifuga racemosa on the hemodynamics parameters and quality of life in perimenopausal women with arterial hypertension.

Materials and methods: The research involved 78 symptomatic perimenopausal women with arterial hypertension (AH) and menopausal syndrome (MS) and 30 hypertensive women with AH without MS manifestations as a control group. After prescription to all patients standard antihypertensive therapy, all women with AH and MS were randomized into 2 groups — the research group (40 patients) and the comparison group (38 patients). Cimicifuga racemosa extract BNO 1055 added to standard treatment of the research group, patients of comparison group and group of hypertensive women without MS continued receiving standard antihypertensive therapy. Before randomization and 8 weeks after prescribing therapy, ambulatory blood pressure monitoring (ABPM) and quality of life (QoL) evaluation were made.

Results: After treatment, according to ABPM measurements there was a significant decrease of day and night systolic and diastolic blood pressure, more pronounced in the research group who received cimicifuga racemosa. Data of systolic blood pressure variability per day and night in research group were significantly reduced to normal values, in comparison group was just systolic blood pressure variability decrease. After 8 weeks treatment QoL improved in the all study groups, but the most pronounced effect was observed in a group of patients who received of cimicifuga racemosa with a standard antihypertensive treatment.

Conclusions: The data have shown positive effects of cimicifuga racemosa on the hemodynamics parameters and quality of life in perimenopausal women with arterial hypertension.

Wiad Lek 2018, 71, 5, -1014

 

INTRODUCTION

Arterial hypertension (AH) is one of the most significant problems of modern cardiology. Increased blood pressure is major risk factors for morbidity and mortality from coronary heart disease, stroke and heart failure [1]. Special studies have shown that women in perimenopause are a category of high risk of cardiovascular diseases and complications developing [2,3].

On the background of progressing estrogen deficiency in perimenopausal women manifest vasomotor, physical and emotional disorders – parts of the menopausal or climacteric syndrome (MS), which significantly impair quality of life [4, 5]. Quality of life (QoL) assessment in patients with chronic diseases that require long-term treatment has a great scientific and practical importance [6].

According to recent trials and guidelines, attention has been paid to the hormone replacement therapy (HRT) for the treatment of menopausal disorders, including those in women with CVD. However, according to clinical observations, the use of HRT in women with CVD is limited, because indications are not defined well. In the presence of absolute or relative contraindications, or unwillingness of women to take HRT, alternative medicines for MS disorders correction are prescribed [7, 8].

Among methods of menopausal disorders correction particular attention is attracted to selective estrogen receptor modulators (SЕRМ), especially plant origin (phyto-SЕRМ). The studies carried out with the cimicifuga racemosa have been shown, that mechanism of its action is similar to the effect of low doses of conjugated estrogens and has proven efficacy on menopausal symptoms, minimizes risk of developing treatment complications. [9-12].

THE AIM

The aim of our research was to study the effects of cimicifuga racemosa (black cohosh, CR BNO 1055, Klimadynon) on the hemodynamics parameters and quality of life in perimenopausal women with arterial hypertension.

MATERIALS AND METHODS

The research involved 78 symptomatic perimenopausal women with arterial hypertension (AH) and menopausal syndrome (MS) and 30 hypertensive women with a stable course of AH without manifestations of the MS as a control group. Groups of the research consisted of patients, who received antihypertensive therapy irregularly or did not receive treatment at all. Before participation in our research every patient signed the informed consent according to the requirements of the Declaration of Helsinki 1975. The day before randomization and 8 weeks after prescribing differentiation therapy in patient groups, ambulatory blood pressure monitoring (ABPM) and quality of life (QoL) evaluation were made.

The criteria for inclusion of women into the research were: perimenopausal period; AH without associated clinical conditions and willingness to cooperate. Exclusion criteria were: presence of coronary heart disease, myocardial infarction or stroke, organic valve diseases, severe heart rhythm and conduction disturbances, heart failure, peptic ulcer, chronic respiratory diseases, chronic kidney disease, symptomatic arterial hypertension, cancer. All patients were examined by a gynecologist, had an intact uterus and ovaries.

The protocol of the study included anamnesis collection, objective investigation, obligatory laboratory and instrumental studies due to the recommendations of the European Society of Cardiology [13]. The degree of MS manifestations was evaluated by counting the Kupperman modified menopausal index (MMI) [14]. In order to evaluate the treatment efficacy, ambulatory monitoring of blood pressure was performed using the devises “ABPM-02” and “ABPM-04” (Meditech, Hungary) in the automatic mode according to the generally accepted method [15,16]. Evaluation of QoL indices was conducted using the World Health Organization questionnaire WHO-100 [17, 18]. Assessment of the overall QoL and the six major domains of QoL: physical and psychological domain, level of independence, social relationships, environment and spiritual was determined.

After a preliminary examination by simple randomization method, patients with AH and MS were randomized into 2 groups – the research group (40 patients) and the comparison group (38 patients). Standard antihypertensive therapy (ACE inhibitors, diuretics, long-acting calcium antagonists, β-blockers) were prescribed to all patients, according to the recommendations of the European Society of Cardiology [13]. The study groups were related to the age and duration of AH, there were no significant differences in the severity and duration of MS manifestations in the research and the comparison group.

Cimicifuga racemosa extract (black cohosh, CR BNO 1055, Klimadynon) in a dose of 20 mg per os (30 drops or 1 tablet) 2 times a day added to standard treatment of the research group perimenopausal women. Patients of the comparison group and group of hypertensive women without MS manifestations continued receiving of standard antihypertensive therapy.

Statistical data were analyzed using SPSS version 16 with Student-t test parametric criterion, non-parametric Mann-Whitney test, the parametric and nonparametric coefficients of the correlation according to the generally accepted recommendations. Data of statistical analysis was presented as M+σ, where M was the mean value, σ – standard deviation. The level of p<0,05 was considered statistically significant.

RESULTS

After 8 weeks of treatment in all study groups, number and severity of complaints were decreased. However, the positive dynamics of MS complaints was more pronounced in patients of research group, who received Cimicifuga racemosa with standard antihypertensive therapy. According to MMI, it was found that the parameters of neurovegetative and psychoemotional manifestations in the research group were significantly lower than in comparison group (neurovegetative manifestations in research group decreased from 27,8 ± 4,3 to 11,7 ± 2,2 points (p <0.001) and psychoemotional from 10,6 ± 2,4 to 5,9 ± 1,7 points (p <0.05), in comparison group neurovegetative manifestations decreased from 26,8 ± 4,3 to 22,1 ± 2,7 points (p> 0.1), psychoemotional – from 10,3 ± 2,3 to 8,1 ± 1,7 points (p> 0.1)), which indicated a greater effectiveness of complex treatment.

Analysis of ABPM indicators showed in the patients of all study groups before treatment, the 24-hours, day and night indicators of SBP and DBP exceeded the established norm values (table I). The variability of SBP and DBP per day in groups of perimenopausal women with MS were also higher than normal, indicating excessive blood pressure fluctuations. An analysis of the daily profile of BP in patients of all treatment groups has demonstrated the advantage of the non-dipper type over the “dipper”.

Under the treatment influence, ABPM indicators in all groups had a unidirectional tendency: treatment resulted in lowering SBP and DBP in the daytime and at night. In general, patients of research group who received standard antihypertensive treatment with cimicifuga racemosa found a more pronounced decrease in the SBP and DBP for day and night compared with patients in the comparison group receiving standard antihypertensive therapy.

Indicators of SBP and DBP variability for the 24 hours, day and night in patients of research group after 8 weeks of treatment significantly reduced to the recommended normal values; patients of comparison group under the influence of standard antihypertensive therapy observed a significant decrease only the SBP variability, but these parameters still remained above the recommended normal values, significant decrease of the DBP variability did not occur. Comparison of variability parameters among patients of research and comparison groups showed that parameters of SBP variability for 24-h, day and night in the research group were significantly lower than those of comparison group of women.

It should be noted that in women of the research group under the influence of therapy with cimicifuga racemosa was determined a significant increase in the daily index of SBP – from 10,1± 1,7 mm Hg. to 12,8 ± 1,4 mm Hg (p <0,05), which indicates a more pronounced decrease in blood pressure at night and, probably, the restoration of the physiological circadian rhythm of BP. In women of the comparison group, receiving standard antihypertensive therapy, there was no significant daily index change.

The treatment led to positive dynamics of QoL domains in all groups of patients: there was a significant increase of the physical domain indexes (p<0,01 in research group, p<0,05 in comparison group), which was a consequence of improving the health condition, reducing fatigue, increasing vital activity (table II). But the physical domain in women of research group after 8 weeks of treatment was significantly higher than that of the comparison group (p <0.01). Also in the research group, under the influence of standard antihypertensive treatment with cimicifuga racemosa, there was an increase in the indicators of the psychological domain and the domain of independence (p<0,05); in the comparison group only a tendency of the increase of the indicated domains was observed; the indicators of the domains were significantly lower compared with the research group. In all groups of patients, after 8 weeks of treatment, a significant increase of overall QoL and and general health perceptions was recorded, which was evidence of the treatment efficiency (p <0.05).

DISCUSSION

Recent studies shows that the occurrence of long-lasting chronic diseases is associated with inequalities in QoL (physical and psychological domains) [22]. In other study, the participants with AH had significantly lower scores in the QoL overall and physical health, that is suggested that more attention should be paid to the quality of life management among hypertensive patients [9, 20].

Midlife women are a category of risk of adverse health outcomes because of menopause [23]. Duration of menopausal symptoms over the menopause transition may be different and sometimes can significantly decrease the QoL of midlife women, which requires a medicine correction [24].

Clinical studies confirm results, that Cimicifuga racemosa (Black cohosh) significantly reduce components of MS (vasomotor, psychiatric, physical, and sexual symptoms) and may therefore be an alternative to hormone replacement therapy in this item. [9,12].

Present study shows, that menopausal syndrome significantly worsens the course of arterial hypertension in women in the period of perimenopause. According to ABPM, women with AH with MS manifestations together with SBP and DBP increase showed an increment of systolic and diastolic blood pressure variability, which leads to increase of the cardiovascular complications risk. The disturbances of QoL in women with AH and MS in perimenopause are manifested by the inhibition of physical activity, mental functions, reduced workability, which result in a significant reduction of the overall QoL.

Standard antihypertensive therapy according to ABPM in perimenopausal women with AH and MS leads to a significant reduction in the level of SBP and DBP, partly influence on vegetative imbalance without normalization of the variability of systolic and diastolic blood pressure and does not significantly influence on the dynamics of neurovegetative and psychoemotional manifestations of MS according to the MMI assessment.

Appointment to perimenopausal women with AH and MS cimicifuga racemosa in addition to antihypertensive treatment leads to a significant decrease in neurovegetative and psychoemotional components of the MMI, contributes to a significant reduction in systolic and diastolic blood pressure per day, normalization of the of blood pressure variability parameters. On the background of 8 weeks treatment, as evidence of therapy effectiveness the quality of life of women is improving.

CONCLUSIONS

Thus, the use of cimicifuga racemosa in addition to antihypertensive treatment in perimenopausal women with AH and MS has a positive impact on systolic and diastolic blood pressure, normalization of the of blood pressure variability parameters, improve quality of life of this patients, which has been the basis for further study and widespread introduction into clinical practice.

References

1. “Center for Health Statistics Ministry of Health of Ukraine” «Zdorov’ja dlja vsіh» [Electronic resource]. – Access mode: http://medstat.gov.ua/ukr/statdov.html.

2. Soto-Rodríguez A, García-Soidán JL, de Toro-Santos M, et al. Clinical trial with educational intervention in perimenopausal women with cardiovascular risk factor. Gac Sanit. 2017 Jan – Feb;31(1):48-52.

3. Dosi R, Bhatt N, Shah P, et al. Cardiovascular disease and menopause. J Clin Diagn Res. 2014 Feb;8(2):62-4.

4. Harlow SD, Karvonen-Gutierrez C, Elliott MR et al. It is not just menopause: symptom clustering in the Study of Women’s Health Across the Nation. Womens Midlife Health. 2017;3. pii: 2. doi: 10.1186/s40695-017-0021-y.

5. Brooks HL, Pollow DP, Hoyer PB. The VCD mouse model of menopause and perimenopause for the study of sex differences in cardiovascular disease and the metabolic syndrome. Physiology (Bethesda). 2016 Jul;31(4):250-7.

6. Bener A, Falah A. A measurement-specific quality-of-life satisfaction during premenopause, perimenopause and postmenopause in Arabian Qatari women. J Midlife Health. 2014 Jul;5(3):126-34.

7. Lewis CE, Wellons MF. Menopausal hormone therapy for primary prevention of chronic disease. JAMA. 2017;318(22):2187-9.

8. Hickey M, Banks E. NICE guidelines on the menopause. BMJ; 2016: 352.

9. Leach MJ, Moore V. Black cohosh (Cimicifuga spp.) for menopausal symptoms. Cochrane Database Syst Rev. 2012 Sep 12;(9):CD007244. doi: 10.1002/14651858

10. Amsterdam JD, Yao Y, Mao JJ, et al. Randomized, double-blind, placebo-controlled trial of Cimicifuga racemosa (black cohosh) in women with anxiety disorder due to menopause. J Clin Psychopharmacol. 2009 Oct;29(5):478-83.

11. Wuttke W, Seidlová-Wuttke D, Gorkow C. The Cimicifuga preparation BNO 1055 vs. conjugated estrogens in a double-blind placebo-controlled study: effects on menopause symptoms and bone markers. Maturitas. 2003 Mar 14;44 Suppl 1:S67-77.

12. Wuttke W, Jarry H, Becker T, et al. Phytoestrogens: endocrine disrupters or replacement for hormone replacement therapy? Maturitas. 2008 Sep-Oct;61(1-2):159-70.

13. Parati G, Stergiou G, O’Brien E., et al. European society of hypertension practice guidelines for ambulatory blood pressure monitoring. J Hypertens. 2014 Jul;32(7):1359-66.

14. Tatarchuk T.F. Eddokrinnaia giniekologiia. Kijev: Med. unform. agenstvo, 2003:304

15. Grossman E. Ambulatory blood pressure monitoring in the diagnosis and management of hypertension. Diabetes Care. 2013 Aug; 36(Suppl 2): S307–11.

16. O’Brien E., Parati G., Stergiou G., et al. European society of hypertension position paper on ambulatory blood pressure monitoring. J Hypertens. 2013;31(9):1731-68.

17. Resources for new WHOQOL Centers. Translation Methodology. Preparation and administration of the Pilot WHOQOL. Scoring and Analysis. Geneva: WHO;1995:22.

18. Metodyka ocinky jakosti zhyttia Vsesvitnioi organizacii okhorony zdorovia: ukrainska versia: Rekomendacii po vykorystaniu. Za nauk. red. SV Pkhidenko. Dnipropetrovsk: Porogy;2001:58

19. Höfelmann DA, Gonzalez-Chica DA., Peres KG, et al. Chronic diseases and socioeconomic inequalities in quality of life among Brazilian adults: findings from a population-based study in Southern Brazil. Eur J Public Health. 2017 Dec 25. doi: 10.1093/eurpub/ckx224.

20. Cao W, Hou G, Guo C, et al. Health-promoting behaviors and quality of life in older adults with hypertension as compared to a community control group. J Hum Hypertens. 2018 May 23. doi: 10.1038/s41371-018-0073-y.

21. Soto Rodríguez A, García Soidán JL, Arias Gómez MJ, et al. Educational intervention on cardiovascular parameters in perimenopausal women with a cardiovascular risk factor. Randomised clinical trial. Med Clin (Barc). 2018 Mar 9;150(5):178-84.

22. Avis NE,  Crawford SL, Greendale G, et al. Duration of Menopausal Symptoms over the Menopause Transition. JAMA Intern Med 2015Apr 1; 175(4): 531-9.

23. Harlow SD, Karvonen-Gutierrez C, Elliott MR, et al. It is not just menopause: symptom clustering in the Study of Women’s Health Across the Nation. Womens Midlife Health. 2017;3. pii: 2. doi: 10.1186/s40695-017-0021-y. Epub 2017 Jul 27.

24. Mehrpooya M, Rabiee S, Larki-Harchegani A, et al. A comparative study on the effect of “black cohosh” and “evening primrose oil” on menopausal hot flashes. J Educ Health Promot. 2018 Mar 1;7:36.

Conflicts of interest:

The Author declare no conflict of interest.

CORRESPONDING AUTHOR

Natalia V. Gorach

Stetsenka str., 8, ap. 68, 04136, Kiev, Ukraine

tel: +380632412666

e-mail: natagorach@gmail.com

Received: 30.03.2018

Accepted: 25.06.2018

Table I. Analysis of ABPM indices in perimenopausal women groups before and after treatment

Variable

Research

group (n=40)

р

Comparison group (n=38)

р

Control group (n=30)

р

SBP 24-h, mmHg

Before

150,91±13,84

0,001

151,69±11,26

0,001

148,42±9,76

0,001

After

122,86±11,73*

127,42±9,87

121,94±8,39

SBP day, mmHg

Before

154,87±14,31

0,001

155,73±15,18

0,001

153,92±9,43

0,001

After

126,76±11,24*

131,42±10,69

126,14±9,97

SBP night, mmHg

Before

137,37±16,41

0,001

138,16±18,91

0,001

134,34±12,88

0,001

After

117,64±8,28#

123,78±8,53

119,87±7,42

DBP 24-h, mmHg

Before

89,46±9,97

0,001

90,82±11,36

0,05

87,17±8,49

0,001

After

78,27±8,64#

83,18±8,51

76,18±7,92

DBP day, mmHg

Before

95,18±8,93

0,001

93,46±9,33

0,001

90,64±7,83

0,001

After

79,76±7,49*

86,93±8,42

78,61±8,37

DBP night, mmHg

Before

79,33±9,68

0,001

78,63±10,28

0,087

77,83±10,49

0,001

After

74,82±9,28

76,94±8,36

72,97±8,16

SBP variability 24-h, mmHg

Before

18,74±2,92

0,011

18,36±3,17

0,053

14,24±2,38

0,087

After

13,87±2,43*

16,49±2,73

13,67±1,92

SBP variabilityday, mmHg

Before

20,67±3,23

0,001

19,94±2,92

0,051

15,43±2,18

0,052

After

13,38±2,46*

17,18±3,11

12,86±1,81

SBP variabilitynight, mmHg

Before

17,84±3,67

0,013

17,36±4,39

0,054

13,42±2,68

0,081

After

13,92±2,19#

15,64±2,47

11,93±1,81

DBP variability 24-h, mmHg

Before

14,28±2,49

0,052

14,42±2,27

0,068

12,64±2,16

0,076

After

11,73±1,67

12,83±1,96

11,47±1,58

DBP variabilityday, mmHg

Before

15,62±2,38

0,014

15,37±2,16

0,073

13,63±1,76

0,082

After

11,86±2,19#

13,94±2,78

11,92±2,27

DBP variabilitynight, mmHg

Before

13,43±2,61

0,017

13,84±2,47

0,062

12,48±2,14

0,746

After

11,28±1,76#

12,69±1,82

11,07±1,63

Notes:

1. M – the sample mean, σ – standard quadratic deviation

2. * – p <0.01 comparing research and comparison groups indices after treatment

3. # – р<0,05 comparing research and comparison groups indices after treatment

Table II. Dynamics of quality of life indicators in perimenopausal women groups before and after treatment

Domains of quality of life

researchgroup (n=40)

р

comparisongroup (n=38)

р

controlgroup (n=30)

р

Physical

Before

11,24±2,05

0,018

11,78±1,93

0,053

14,27±2,01

0,124

After

15,49±1,91*

13,86±1,74

15,89±1,94

Psychological

Before

12,23±1,73

0,024

12,18±1,51

0,717

14,62±2,19

0,053

After

15,04±1,67*

13,26±1,78

16,28±1,98*

Level of Independence

Before

13,39±1,94

0,051

13,26±2,27

0,084

14,38±1,84

0,054

After

15,64±1,82#

13,97±2,02

15,67±1,54*

Social Relationships

Before

12,57±1,96

0,086

12,63±2,16

0,094

14,46±2,21

0,131

After

13,34±1,71

13,41±2,20

14,79±1,44

Environment

Before

12,39±1,62

0,065

12,28±1,52

0,128

13,23±2,11

0,129

After

13,02±1,43

12,74±1,21

13,99±1,87

Spirituality/ Religion/ Personal Belief

Before

13,32±1,64

0,136

13,51±1,47

0,143

14,38±2,08

0,118

After

13,96±1,26

13,77±1,39

15,24±1,93

Over all QoL and general health perceptions

Before

12,36±1,38

0,028

12,23±1,40

0,05

13,84±2,18

0,038

After

14,39±1,24*

14,01±1,38*

15,51±1,89*

Notes:

1. M – the sample mean, σ – standard quadratic deviation

2. * – p <0.01 comparing research and comparison groups indices after treatment

3. # – р<0,05 comparing research and comparison groups indices after treatment