http://informahealthcare.com/gye ISSN: 0951-3590 (print), 1473-0766 (electronic) Gynecol Endocrinol, 2014; 30(12): 918–924 ! 2014 Informa UK Ltd. DOI: 10.3109/09513590.2014.971236

METABOLIC SYNDROME

Evaluation of the presence and severity of menopausal symptoms among postmenopausal women screened for the metabolic syndrome Peter Chedraui1, Faustino R. Pe´rez-Lo´pez2, Luis Hidalgo1,3, Diego Villacreses1, Andrea Domı´nguez1, Gustavo S. Escobar1, Andrea R. Genazzani4, and Tommaso Simoncini4; Research Group for the Omega Women’s Health Project Gynecol Endocrinol Downloaded from informahealthcare.com by Michigan University on 12/25/14 For personal use only.

1

Institute of Biomedicine, Research Area for Women’s Health, Facultad de Ciencias Me´dicas, Universidad Cato´lica de Santiago de Guayaquil, Guayaquil, Ecuador, 2Department of Obstetrics and Gynecology, Facultad de Medicina, Universidad de Zaragoza, Lozano Blesa University Hospital, Zaragoza, Spain, 3Enrique C. Sotomayor Obstetrics and Gynecology Hospital, Guayaquil, Ecuador, and 4Division of Obstetrics and Gynecology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy Abstract

Keywords

Background: The prevalence of the metabolic syndrome (METS) increases after the menopause. Reports indicate that the METS and its components, especially obesity, enhance the intensity of menopausal symptoms. Objective: Assess the frequency and severity of menopausal symptoms in postmenopausal women. Factors related to the symptom severity were also analyzed including depressive and metabolic status. Methods: A total of 204 natural postmenopausal women (40–65 years) participating in a METS screening program were asked to fill out the Menopause Rating Scale (MRS), the Hospital Anxiety and Depression Scale (HADS), and a general socio-demographic questionnaire containing personal and partner data. Criteria of the American Heart Association were used to define the METS. Results: Median age of the whole sample was 56 years. A 52.9% presented the METS, with 37.3% presenting hyperglycemia, 51.5% hypertension, 58.3% abdominal obesity, 45.6% high triglyceride and 56.4% low HDL-C levels. Total and subscale MRS scores did not differ in accordance to the presence or not of the METS. The three top prevalent menopausal symptoms were muscle and joint problems (87.2%), physical and mental exhaustion (72%) and depressive mood (64.7%). A 19.6% of women presented total MRS scores above 16 defined as severe. Multivariate linear regression analysis determined that anxiety (higher HADS anxiety subscale scores) was significantly and positively correlated with all components of the MRS (Total and subscale scores). Higher total MRS scores correlated positively with abdominal perimeter and higher parity. Somatic scores correlated inversely with female education and positively with psychotropic drug use; and psychological MRS scores positively correlated depressed mood (higher HADS depressive subscale scores) and abdominal perimeter. Conclusion: In this postmenopausal sample, severity of menopausal symptoms correlated to abdominal obesity, mood and other personal aspects.

Hospital anxiety and depression scale, menopausal symptoms, menopause rating scale, metabolic syndrome, postmenopause

Introduction The prevalence and severity of menopausal symptoms may vary in relation to hormonal status, co-morbidity (disease and treatment), family and male characteristics and other socio-demographic factors. Aging and the menopausal transition relate to metabolic changes (glucose and lipid levels), obesity and hypertension [1]. Reports indicate that excessive body weight observed during female mid-life increases the frequency of vasomotor symptoms and urinary, sleep and muscle/joint problems [2–5]. Obesity is a pivotal component of the metabolic syndrome (METS) considered

Address for correspondence: Peter Chedraui, Institute of Biomedicine, Research Area for Women’s Health, Facultad de Ciencias Me´dicas, Universidad Cato´lica de Santiago de Guayaquil, PO BOX 09-01-4671, Guayaquil, Ecuador. Tel/Fax: + (5934) 220-6958. E-mail: [email protected]

History Received 5 July 2014 Accepted 27 September 2014 Published online 14 October 2014

a cluster of variables closely related to inflammation, insulin resistance, prothrombosis and atherogenesis, all which increase cardiovascular disease, cancer and other conditions [6]. It is a chronic condition related to lifestyle habits that affects a quarter of women and males worldwide. A 25–69% of mid-aged women present the METS. These rates vary depending on the studied country, cultural and diet factors, physical activity, and the used diagnostic methodology. Evidence shows that the METS and its dominant component (obesity) increase the prevalence and severity of menopausal symptoms [7]. In fact, recent studies have related vasomotor symptoms to increased cardiovascular risk [8]. Hence, there seems to be a link between the METS, obesity, vasomotor symptoms and cardiovascular risk. A possible explanation could be that the metabolic and inflammatory pathways exerted by the menopausal transition could relate to increased symptoms and additionally to vascular dysfunction and increased metabolic and cardiovascular risk [9,10].

DOI: 10.3109/09513590.2014.971236

The relative contribution of the METS to the prevalence and severity of menopausal symptoms remains to be elucidated. Hence, the aim of the present study was to evaluate menopausal symptoms (frequency and severity) in postmenopausal women screened for the METS and its components. In addition, factors related to the severity of menopausal symptoms were analyzed including depressive and metabolic status.

Methods

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Study design and participants

Menopausal symptoms and the metabolic syndrome

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A waist circumference cut off value of 88 cm has recently been reported as optimal for defining the METS in postmenopausal Latin American women [13]. Women taking oral hypoglycemic or antihypertensive medication prescribed by a physician were considered, respectively, as diabetic or hypertense independent of the serum or blood pressure findings. Weight and height were recorded for each participant and body mass index (BMI) calculated as weight (in kg) divided by the square of height (in m). Obesity was defined as a BMI 30 kg/m2 [14]. Waist circumference (cm) was measured in supine position as previously described [15]. Subjects were defined as sedentary if carrying out less than 15 min of physical activity twice per week [16].

From December 2011 to June 2012, a METS screening program (cross-sectional design) was carried out at the Institute of Biomedicine of the Medical Faculty of the Universidad Cato´lica de Santiago de Guayaquil, Guayaquil, Ecuador. For this natural postmenopausal (40–65 years) non-hormone therapy using women were recruited through newspaper advertising and requested to fill out the Menopause Rating Scale (MRS), the Hospital Anxiety and Depression Scale (HADS) and a general questionnaire containing female and partner socio-demographic data. Women taking phytoestrogens or drugs intended to decrease lipid levels were excluded from the study. The research protocol of the study was reviewed and approved by the Scientific Committee of the Institute. Eligible women were asked to attend the Institute and be informed about the study, its purposes and provide written consent of participation. Those consenting and fulfilling the inclusion criteria were asked to return after an 8 h overnight fast, moment in which socio-demographic data, waist circumference, weight, height and blood pressure measurements were recorded. In addition, a 10–15 ml peripheral venous blood sample was obtained. Women were counseled and managed according to the results and additionally participated in educational group sessions aimed to discuss topics related to the menopause, the METS, its risk determinants and cardiovascular risk implications.

The Menopause Rating Scale (MRS) [17] is a questionnaire that assesses the presence and intensity of 11 menopausal symptoms. These are grouped into three subscales: the somatic subscale: assessing hot flushes/sweating, heart discomfort, sleeping problems, and muscle and joint discomfort (items 1–3 and 4 respectively); the psychological subscale: assessing depressive mood, irritability, anxiety, and physical and mental exhaustion (items 4–7 respectively); and the urogenital subscale: assessing sexual problems, bladder problems and vaginal dryness (items 8– 10, respectively). Each of the 11 items can be rated by the participant from 0 (not present) to 4 (1 ¼ mild, 2 ¼ moderate, 3 ¼ severe and 4 ¼ very severe). The scores obtained for each individual item are summed to provide the corresponding total subscale score. The sum of subscales scores provide the total MRS score. Higher scores are indicative of more severe symptoms. Indeed values above 8 (somatic), 6 (psychological), 3 (urogenital) and 16 (total MRS) were defined as severe [18]. This questionnaire has been validated in Spanish [19,20].

General questionnaire

The Hospital Anxiety and Depression Scale

An itemized questionnaire was constructed to assess and record all general data. This tool was validated in 50 women before being implemented and included the following female data: age (years), educational level (years), marital status, parity, years since menopause onset, self-perceived health status, sexually active (yes/no) and current partner status (yes/no). Lifestyle and other personal factors included in this section were sedentarism and tobacco, alcohol, coffee or psychotropic drug consumption. According to the time since menopause onset, women were further categorized as early (1–4 years) or late postmenopausal (5 years). Women provided the information related to their partner including: age (years), educational level (years), perceived health status (yes/no), faithfulness (yes/no), alcohol abuse (yes/ no), and the presence of sexual dysfunction (erectile dysfunction and/or premature ejaculation). Definitions for alcoholism, erectile dysfunction, and premature ejaculation have previously been described [11]. Health status (female/male) was defined according to criteria of the National Center for Health Statistics [12], as that enabling the performance of daily routine activities.

The Hospital Anxiety and Depression Scale (HADS) was developed to identify cases of anxiety and depression in nonpsychiatric settings [21]. The tool includes 14 items, seven for anxiety (odd numbered items scored 3 to 0) and seven for depression (even numbered items scored from 0 to 3). Ratings for each item are summed to provide the corresponding total anxiety and depression subscale score. Subjects achieving a score of 8 or more on each subscale were defined as having anxiety and depressed mood. Subscale scores were used as independent variables for the multiple linear regression analysis.

Diagnostic criteria for the metabolic syndrome

Statistical analysis

Diagnostic criteria recommended by the American Heart Association [6] was used to define the METS. This was the case if three or more of five criteria were encountered: abdominal obesity (waist circumference 488 cm), increased serum triglycerides (TG) (150 mg/dL), decreased high density lipoprotein cholesterol (HDL-C) (550 mg/dL), high fasting glucose (100 mg/dL) and increased blood pressure (130/85 mmHg) [6].

Statistical analysis was performed using the SPSS version 20.0 (IBM, Armonk, NY). Data are presented as means (± standard deviations), medians (interquartile ranges [IQR]), percentiles (p25–p75), percentages, beta coefficients and 95% confidence intervals. The Kolmogorov–Smirnov test was used to determine the normality of data distribution and the Bartlett test to evaluate the homogeneity of the measured variance. According to this,

Validated instruments The Menopause Rating Scale

Serum biochemical assays Blood samples withdrawn from each participant were centrifuged at 5  C for 10 min at 3000 rpm. Obtained serum was stored at 70  C until analysis. TG, HDL-C and glucose levels were assayed using the enzymatic colorimetric method with a Hitachi 717 automatic photometric analyzer (Roche Diagnostics GmbH, Mannheim, Germany).

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Table 1. Basal characteristics of studied women and their partners, and total MRS scores according to these features.

n ¼ 204

Female data Age (years) 40–49 50–59 60–65

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Educational level (years) 0 to 6 7 to 12 13

56 19 126 59

[7; 53–60] (9.3) (61.8) (28.9)

10 73 68 63

[9; 6–15] (35.8) (33.3) (30.9)

Married Yes No

93 (45.6) 111 (54.4)

Parity 0 1–5 45

3 17 160 27

Time since menopause onset (years) 1–4 5

7.5 [10; 3–13] 74 (36.3) 130 (63.7)

Tobacco consumption Yes No

[2; 2–4] (8.3) (78.4) (13.2)

4 (2.0) 200 (98.0)

Depressed mood (HADS  8; depression subscale) Yes 32 (15.7) No 172 (84.3)

Total MRS scores 12 [10; 8–18] 11 [8; 7–15] 9 [8; 6–14] p ¼ 0.15* 11 [8; 8–16] 11.5 [9; 7–16] 8 [8; 4–12] p ¼ 0.006 11 [9; 7–16] 10 [8; 7–15] p ¼ 0.45 5 [5; 3–8] 11 [8; 7–15] 13 [9; 8–17] p ¼ 0.001 12 [8; 8–16] 9 [9; 6–15] p ¼ 0.08 13 [4; 9–13] 10.5 [8; 7–15] p ¼ 0.23 15.5 [9; 10–19] 9.5 [8; 6–14] p ¼ 0.0002

Anxiety (HADS 8; anxiety subscale) Yes No

61 (29.9) 143 (70.1)

16 [8; 11–19] 8 [7; 5–12] p ¼ 0.0001

Psychotropic use Yes No

17 (8.3) 187 (91.7)

14 [12; 8–20] 10 [9; 6–15] p ¼ 0.04

Self-perceived health status Yes No

160 (78.4) 44 (21.6)

10 [9; 6–15] 11 [9; 8–17] p ¼ 0.12

Sedentarism Yes No

69 (33.8) 135 (66.2)

9 [9; 9–14] 11 [9; 7–16] p ¼ 0.20

Currently has partner Yes No

127 (62.3) 77 (37.7)

11 [9; 7–16] 10 [6; 7–13] p ¼ 0.31

Sexually active Yes No

100 (49.0) 104 (51.0)

10.5 [8; 7–15] 11 [9; 6–15] p ¼ 0.96

Diagnostic features of the METS Abdominal circumference (cm) Abdominal obesity (waist 488 cm) Yes No

91.0 [15; 84–99]

Glycemia (mg/dL) Hyperglicemia ( 100 mg/dL) Yes No

94.0 [22; 88–110]

119 (58.3) 85 (41.7)

76 (37.3) 128 (62.7)

11 [8; 7–15] 10 [9; 6–15] p ¼ 0.63

11 [10; 7–17] 10 [9; 6–15] p ¼ 0.21 (continued )

non-parametric continuous data were compared with the Mann– Whitney U test (two independent samples) or the Kruskal–Wallis test (various independent samples). Spearman Rho coefficients were calculated to determine correlations between MRS scores (Total and subscales) and various numeric variables (bivariate analysis). Cronbach’s alphas were computed for the MRS (total and subscales) to determine internal consistency. Multivariate linear regression analysis was performed to assess variables related to higher scores for the MRS and its subscales. A primary regression model was generated using a forward/ backward stepwise procedure and included all potential interaction variables. This model was constructed from independent variables achieving p ¼ 0.10 during bivariate analysis. Subsequently, a final reduced best fit model was generated without interaction variables. Total and subscale MRS scores were considered as dependent variables. Independent variables tested during bivariate analysis included among the most important: age, parity, educational level, marital status, time since the menopause, presence of the METS and its diagnostic features, self-perceived health status, sedentarism, habits (tobacco or coffee consumption), presence of anxiety or depressed mood, psychotropic drug use and partner variables. For all calculations a p value less than 0.05 was considered statistically significant. Sample size calculation We have previously reported that 41.5% of postmenopausal women present the METS [22]. Hence, a minimal sample size of 179 participants was calculated assuming that 35% of surveyed women would present the METS with a 7% desired precision and a 95% confidence level.

Results A total of 207 natural postmenopausal women were invited to participate in the study. Three did not meet inclusion criteria, hence statistical analysis was performed on 204 complete surveys. Baseline characteristics of surveyed women and their partners and total MRS scores according to these features are depicted on Table 1. Median age for the whole sample was 56 years. According to the HADS 15.7% of surveyed women presented depressed mood, and 29.9% anxiety. An 8.3% used psychotropic drugs, 62.3% currently had a partner, 58.3% were abdominally obese (38.2% according to BMI value) and 52.9% presented the METS. More than 40% of women had hypertension or dyslipidemia (low HDL-C or high TG levels). Regarding the partner, 31.5% abused alcohol, 34.6% displayed erectile dysfunction and 25.2% premature ejaculation. Total MRS scores were found to be significantly higher in relation to educational level, parity, depressed mood, anxiety and psychotropic drug (bivariate analysis). Prevalence and severity of menopausal symptoms according to the MRS (total and subscale scores included) are presented on Table 2. Mean scores (total and subscales) are also presented. The three most frequently presenting menopausal symptoms were muscle and joint problems (87.2%), physical and mental exhaustion (72%) and depressive mood (64.7%). The three most highly rated symptoms (severe-very severe) were anxiety, muscle and joint problems and vaginal dryness. According to the rated scores, these were considered as severe in 5.4% (somatic); 16.7% (psychological); 33.9% (urogenital); 19.6% (total MRS scores). Spearman coefficient correlations between MRS scores and various numeric variables are presented in Table 3. Mild to moderate significant correlations were found between total MRS scores and female educational level (inverse), parity, HADS depressive and anxiety scores, abdominal circumference and glucose levels. A similar trend was observed for each of the MRS

Menopausal symptoms and the metabolic syndrome

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Table 2. Prevalence and severity of menopausal symptoms according to the MRS (total subscale scores included) among studied women. Female data Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Hypertension ( 130/85 mmHg) Yes No

n ¼ 204 123.5 [26;114–140] 80.0 [12; 70–82] 105 (51.5) 99 (48.5)

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Triglycerides (mg/dL) 143.0 [96; 104–200] Hypertriglyceridemia ( 150 mg/dL) Yes 93 (45.6) No 111 (54.5) HDL-C (mg/dL) Low HDL-C (550 mg/dL) Yes No

46.9 [21; 40–61]

Body mass index (BMI, kg/m2) Obesity (BMI 30.0) Yes No

28.2 [6.5; 25–31.5]

METS 3 or more positive items Yes No Partner Alcohol abuse Yes No

Total MRS scores

115 (56.4) 89 (43.6)

78 (38.2) 126 (61.8)

108 (52.9) 96 (47.1)

Subscale and symptoms 10 [9; 7–16] 11 [9; 6–15] p ¼ 0.67

11 [9; 7–16] 9 [9; 6–15] p ¼ 0.23

10 [8; 7–15] 11 [10; 6–16] p ¼ 0.44

10.5 [9; 7–16] 11 [9; 6–15] p ¼ 0.71

10.5 [8; 7–15] 11 [9; 6–15] p¼0.77

n ¼ 127 40 (31.5) 87 (68.5)

13 [11; 6–17] 10 [8; 7–15] p ¼ 0.23

Erectile dysfunction Yes No

44 (34.6) 83 (65.4)

13 [10; 7–17] 10 [9; 6–15] p ¼ 0.08

Premature ejaculation Yes No

32 (25.2) 95 (74.8)

12.5 [11; 7–18] 10 [10; 6–16] p ¼ 0.10

Data are presented as medians [interquartile ranges; p25–p75] or n (%). Variables not displayed were not significant; MRS, Menopause Rating Scale; METS, metabolic syndrome; HDL-C, high density lipoprotein cholesterol. *p values determined with the Mann–Whitney or the Kruskal–Wallis test according to case.

subscales scores. The MRS (total and subscales) displayed a good internal consistency as computed Cronbach’s alphas were determined to be high (ranging from 0.81 to 0.89). The final multivariate linear regression model for factors related to higher MRS scores (total and subscales) are presented in Table 4. Anxiety (higher HADS anxiety subscale scores) was determined to be a factor positively correlating with all components of the MRS. Higher total MRS scores correlated positively with abdominal perimeter and higher parity. Somatic scores correlated inversely with female education and positively with psychotropic drug use. Psychological MRS scores positively correlated with depressed mood (higher HADS depressive subscale scores) and abdominal perimeter. Discussion The present study determined that the intensity of menopausal symptoms, as assessed with the MRS, did not differ in relation to the presence or not of the METS. Despite this, obesity (a main component of the METS) was related to more intense menopausal

n (%) or mean ± SD

Somatic Hot flushes, sweating (item 1) 117 (57.3) Heart discomfort (item 2) 107 (52.4) Sleeping problems (item 3) 108 (52.9) Muscle and joint problems 178 (87.2) (item 11) Total somatic subscale 4.3 ± 2.4 Severe somatic symptoms (score 48) 11.0 (5.4) Psychological Depressive mood (item 4) 132 (64.7) Irritability (item 5) 137 (67.1) Anxiety (item 6) 107 (52.4) Physical and mental exhaustion 147 (72.0) (item 7) Total psychological subscale 4.0 ± 2.9 Severe psychological symptoms 34 (16.7) (scores 4 6) Urogenital Sexual problems (item 8) 92 (45.0) Bladder problems (item 9) 97 (47.5) Vaginal dryness (item 10) 107 (52.4) Total urogenital subscale 2.7 ± 2.5 Severe urogenital symptoms 69 (33.9) (scores 43) Total MRS score 11.0 ± 5.9 Severe menopausal symptoms 40 (19.6) (total MRS scores 4 16)

% presenting severe– very severe scores n (%)* 21 8 13 39

(10.3) (3.9) (6.4) (19.1)

20 16 44 15

(9.8) (7.8) (21.6) (7.3)

23 (11.3) 14 (6.9) 25 (12.2)

Data are presented as n (%) or mean ± standard deviations (SD). *Items rated as 3 or 4.

symptoms, as expressed by higher total and psychological MRS subscale scores. In addition, women who displayed more anxiety concomitantly displayed more intense menopausal symptoms. Higher depressive HADS scores correlated with higher MRS psychological subscale scores. Individuals with the METS have significantly impaired health related quality of life as compared to subjects without the syndrome. Moreover, impairment of overall, physical and mental health increases with the number of METS components [23,24]. Reports indicate that socio-economical factors, education and gender (especially female) may influence the presence of the METS [25]. Female mid-life is frequently associated to menopausal symptoms of varying prevalence and severity, with many factors being involved [26]. Contrary to what we had hypothesized, despite the high prevalence of the METS, this was not related to more severe menopausal symptoms. Our results are opposed to those of Lee et al [7] reporting that Korean women with the METS displayed higher MRS total and somatic subscale scores and a higher rate of hot flashes and sweating than those without the syndrome. Furthermore, high TG levels and the number of METS items were associated with higher somatic symptom subscale values [7]. Although the latter study used similar METS diagnostic criteria, discrepancies of our results are most likely to be related to ethnical, lifestyle and other cultural and socio-economical factors. Hence, populations are not comparable. Despite the high prevalence of the METS and its components found among our studied women, other factors such as low education, high parity and psychotropic drug use (as opposed to the metabolic profile) correlated to more intense symptoms. This provides support to previous observations from Ecuador [22] and Latin American [27]. As opposed to the METS, the present study found that abdominal obesity (main component),

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Table 3. Spearman correlation coefficients between MRS scores (total and subscales) and various numeric variables (including Cronbach’s alphas).

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Female age (years) Educational level (years) Time since menopause onset (years) Parity HADS depressive total subscale score HADS anxiety total subscale score Abdominal circumference (cm) Glycemia (mg/dL) Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Triglycerides (mg/dL) HDL-C (mg/dL) Body mass index Number of METS items Partner age (years) Partner educational level (years)

Total MRS (0.82)

Somatic (0.85)

Psychological (0.81)

Urogenital (0.89)

0.08 0.25* 0.13 0.26* 0.38* 0.56* 0.56* 0.15* 0.07 0.08 0.11 0.08 0.02 0.05 0.02 0.18

0.19 0.25* 0.08 0.22* 0.35* 0.40* 0.13 0.07 0.09 0.08 0.10 0.09 0.07 0.02 0.06 0.18

0.13 0.24* 0.09 0.26* 0.47* 0.63* 0.04 0.10 0.02 0.04 0.04 0.08 0.02 0.02 0.05 0.16

0.08 0.08 0.14* 0.11 0.09 0.24* 0.08 0.14* 0.05 0.07 0.11 0.04 0.02 0.10 0.03 0.08

Values in parenthesis are Cronbach’s alpha. HDL-C, high density lipoprotein cholesterol. *p50.05. Table 4. Factors related to higher MRS scores (total and subscales) among women: multivariate linear regression analysis (n ¼ 204). Factors

Beta Coefficient

Standard Error

95% CI

0.78 0.06 0.30

0.08 0.02 0.13

0.63 to 0.94 0.01 to 0.11 0.03 to 0.57

0.20 0.08 1.22

0.04 0.03 0.55

0.13 to 0.28 0.13 to 0.02 0.12 to 2.31

0.38 0.13 0.03

0.04 0.05 0.01

0.14

0.04

t

p Value

a

Total MRS scores Anxiety (HADS anxiety subscale score) Abdominal perimeter (cm) Parity Somatic subscaleb Anxiety (HADS anxiety subscale score) Female education Psychotropic use Psychological subscalec Anxiety (HADS anxiety subscale score) Depressive mood (HADS depression subscale score) Abdominal perimeter (cm) Urogenital subscaled Anxiety (HADS anxiety subscale score)

9.85 2.31 2.21

0.0001 0.02 0.02

5.51 2.82 2.20

0.0001 0.005 0.03

0.28 to 0.46 0.02 to 0.24 0.01 to 0.05

8.44 2.37 2.31

0.0001 0.02 0.02

0.07 to 0.22

3.49

0.001

MRS, Menopause Rating Scale; CI, Confidence intervals. r ¼ 0.68; adjusted r2 ¼ 0.67, p50.0001. b 2 r ¼ 0.52; adjusted r2 ¼ 0.51, p50.0001. c 2 r ¼ 0.48; adjusted r2 ¼ 0.47, p50.0001. d 2 r ¼ 0.49; adjusted r2 ¼ 0.48, p50.0001. a 2

correlated to more intense symptoms. This is in agreement with a previous Spanish study reporting that obesity was related to more intense menopausal symptoms as assessed with the Kupperman Index [2]. As assessed with the MRS the top three symptoms were muscle and joint problems, physical and mental exhaustion and depressive mood. A 19.6% of women presented total MRS scores defined as severe (Total MRS score 416). Interestingly, vasomotor symptoms were not the most prevalent symptoms. This is contrary to what others have reported [28,29], yet in accordance to what has been described for Latin America [30]. In accordance to our findings, a recent multinational Latin American study found that muscleskeletal pain was not only the most prevalent symptom yet the most highly rated [30]. Analysis of a large sample from the Study of Women’s Health Across the Nation found that prevalence of aches and pains was high (1 out of 6 women reported daily symptoms) and that early peri-, late peri- or postmenopausal women reported more aches and pains than premenopausal ones [31]. This points out to the fact that estrogens (or less age) might have some protective effect against aches and pains. The present study could not address the influence of menopausal status as only postmenopausal women were analyzed. In addition it is also

important to bear in mind that muscleskeletal symptoms are more prevalent in women than in men and can be related to other conditions unrelated to the menopause, including osteoarthritis, vitamin D deficit, fibromyalgia, sarcopenia, and rheumatoid arthritis [32–34]. Pain complaints correlate with high distress and avoidance behavior or ineffective coping mechanisms to avoid problems [35]. Muscle and skeletal pain may also be determined by systemic metabolic adjustments such as those related with adipokines and cytokines produced in subjects with obesity and/or the METS [36,37]. These unhealthy conditions and the hormonal changes observed during the menopausal transition, might contribute to a higher prevalence of muscle and joint pain. Although we did not find differences in somatic scores between women with and without METS, correlation between cytokines levels and the METS, obesity and depression deserve to be analyzed in the near future; moreover, metabolic imbalance may alter muscle and joint health and cartilage turnover. During the menopausal transition mood morbidity is highly frequent [38,39]. According to the HADS, the present study found that 15.7% and 29.9% of surveyed women displayed depressed mood and anxiety, respectively, and 8.3% were on psychotropic drug treatment. These issues were found to be independent factors

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DOI: 10.3109/09513590.2014.971236

related to higher MRS scores, and hence more severe menopausal symptomatology. This is in agreement with our previous reports [38,40] and highlights the fact that mood and menopausal symptoms (especially hot flushes) significantly correlate; in other words, women with more severe hot flushes have higher scores for depression and anxiety [39] and vice-versa depressed women are prone to have more intense hot flushes [38]. To date, the intrinsic involved mechanisms are still not clearly defined, but must be related to neuroendocrine peptide and adipose cytokine secretion at various levels. Our results point out to the fact that the relationship between the METS, obesity, mood and perhaps cardiovascular risk is complex. Indeed, longitudinal studies suggest that women with depression, tension, stress and anger display a higher risk of developing insulin resistance, METS and cardiovascular risk [41–44]; and vice-versa the METS is a predictive factor for future female anxiety and anger [42]. More longitudinal studies are warranted that include the aforementioned discussed variables. As for the limitations of the present study, one can mention: (a) its cross-sectional design. A longitudinal design that involve studying the effect of time and menopausal status is warranted; and (b) the local nature of the sample, which does not allow extrapolating results to the rest of the Ecuadorian or Latin American population. Despite these potential limitations, it is important to mention that METS data in relation to the menopause and related symptoms coming from Hispanic populations is scarce. Hence, this may be considered as a strength. Although the METS was excluded as a possible factor related to more severe menopausal symptoms, obesity its main risk factor was not. This points out to the fact that the METS should not be considered a category yet a complex accumulate of risk factors which should be analyzed individually, especially when it comes to analyzing cardiovascular or any other disease risk. In conclusion, in this postmenopausal sample, severity of menopausal symptoms was not related to the METS yet to obesity (an important component), mood and other female personal aspects.

Acknowledgements Authors would like to thank the women who participated in this initiative and also Isabel Vintimilla-Sigu¨enza, Lucı´a Romero-Huete, Winston Jaramillo, Flor Lo´pez, Rita Loja, Cecibel Ramı´rez, Isabel Naranjo, Marı´a F. Carpio and Christian Cando-Dumancela for their support.

Declaration of interest The authors declare no conflicts of interest. This research was supported by the Universidad Cato´lica de Santiago de Guayaquil, Ecuador, through grant No. SIU-3373-2011 (The Omega Women’s Health Project 2011) provided by the Sistema de Investigacio´n y Desarrollo.

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Evaluation of the presence and severity of menopausal symptoms among postmenopausal women screened for the metabolic syndrome.

The prevalence of the metabolic syndrome (METS) increases after the menopause. Reports indicate that the METS and its components, especially obesity, ...
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