Quality of life and psychological symptoms in Greek postmenopausal ...

Gynecological Endocrinology, December 2006; 22(12): 660–668

MENOPAUSE

Quality of life and psychological symptoms in Greek postmenopausal women: Association with hormone therapy

KALLIOPI L. KOUNDI1, GEORGE E. CHRISTODOULAKOS2, IRENE V. LAMBRINOUDAKI2, IOANNIS M. ZERVAS1, ARETI SPYROPOULOU1, PANAGIOTA FEXI1, PAVLOS N. SAKKAS1, CONSTANTINOS R. SOLDATOS1, & GEORGE C. CREATSAS2 1

Athens University Medical School, Women’s Mental Health Clinic, Department of Psychiatry, Eginition Hospital, Athens, Greece, and 2Athens University Medical School, Menopause Clinic, 2nd Department of Obstetrics and Gynecology, Areteio Hospital, Athens, Greece (Received 20 July 2006; revised 8 September 2006; accepted 12 September 2006)

Abstract Quality of life (QoL) in menopause is influenced by many parameters, including vasomotor symptoms, psychological status and culture. The aim of the present study was to examine the association of hormone therapy (HT) with QoL and psychological symptoms in Greek postmenopausal women. The study assessed 216 postmenopausal women (mean age 54.5 years) attending a university menopause clinic in Greece. Fifty-three were users of HT and 163 were not. QoL was evaluated by the Utian Quality of Life Scale (UQOL) and psychological symptoms were assessed by the Symptom Checklist-90-R (SCL-90-R). Women on HT were younger and more educated than women not using HT. Adjusting the analysis for the women’s characteristics, HT users had better total UQOL scores than non-users (p 5 0.05). Marital status and education had independent effects on QoL, with married and more educated women scoring higher (p 5 0.05). Assessment of psychological symptomatology, after adjustment for sociodemographic variables across the different dimensions, revealed that HT users had better SCL-90-R scores than non-users for obsessionality, interpersonal sensitivity and for the general index (p 5 0.05). Concluding, even though the impact of sociodemographic and lifestyle variables must be factored into the assessment of QoL, HT use is independently related to an improvement in the total score and in most domains of QoL, and has a significant positive effect on many aspects of psychological well-being in Greek postmenopausal women.

Keywords: Quality of life, psychological symptoms, menopause, hormone therapy

Introduction Quality of life (QoL) is increasingly being recognized as an important parameter evaluating the impact of menopause. QoL assessment has become an essential component of clinical practice, so that clinicians can obtain a comprehensive picture of a woman’s subjective perception of menopause. The assessment of QoL is one of the most important considerations in therapeutic decisions of peri- and postmenopausal women [1]. Although there is a clear causative association of menopause with vasomotor symptomatology [2], there is inadequate data up to now to conclude that the menopausal transition is associated with either positive or negative effects on QoL [3].

This period is also characterized by physiological and psychosocial changes in a woman’s life. These psychosocial elements, as well as past psychiatric disorders, are often found in the background of menopausal mood disorders [4,5]. Furthermore, ethnic, cultural and religious factors very often influence the way a woman views menopause and the symptoms associated with the menopausal transition [6]. It is well known that the brain is a major estrogen target. Estrogen withdrawal produces changes in serotoninergic, noradrenergic and opioidergic tones, which contribute to the modifications in mood, behavior and pain perception [7]. Hormone therapy (HT) has been shown to have a direct effect on neural activity and on the modulation of opioidergic,

Correspondence: I. V. Lambrinoudaki, 27 Themistokleous Street, Dionysos, GR-14578 Athens, Greece. Tel: 30 210 6410944. Fax: 30 210 6410325. E-mail: [email protected] ISSN 0951-3590 print/ISSN 1473-0766 online ª 2006 Informa UK Ltd. DOI: 10.1080/09513590601010557

Hormone therapy and quality of life adrenergic and serotoninergic tones in the central nervous system [7,8]. On the other hand, the alleviating effect of HT on hot flushes is well documented [9]. However, the impact of HT on QoL merits special attention. Although most authors suggest that HT improves QoL [10–12], other studies do not support this view [13,14]. The effect of HT on psychological symptoms associated with menopause is even more perplexing. Many investigators have shown that HT, beyond the mere control of symptoms, can restore the perception of health and general well-being of postmenopausal women [8,15–20]. In contrast, other studies suggest that there are no significant benefits of HT with respect to psychological symptoms [21–23]. The heterogeneity of study samples with respect to race, age and the presence of coexisting diseases, the history of premorbid personality and psychiatric disorders, as well as differences in the diagnostic tool employed to assess QoL and psychological symptomatology, are possible reasons for the discrepant results [24]. The present study is the first to assess QoL and psychological symptomatology in association with the use of HT in Greek postmenopausal women. Greek women have special cultural and religious characteristics [25], which may interfere with the way they perceive symptoms and cope with stress. Studies performed in Greek immigrants in the UK [26] and Australia [27] suggest that there might be a ‘genuine North–South difference in the expression of psychological distress’ [26]. More specifically, a study conducted in Greek menopausal women living in Melbourne indicated that there is a complex association between experiences of the menopause and family relationships, beliefs and theories of the body, religion and traditional approaches to healing and medicine [6]. Given the lack of data on the effect of HT on general aspects of health in Greek postmenopausal women, and due to the increasing importance of QoL as a determinant of the indications for postmenopausal HT, we undertook the present study in order to assess the association of HT use with QoL, mood and psychological symptoms in Greek postmenopausal women attending the menopause clinic of our department.

Methods Subjects Subjects were recruited from the menopause clinic of the 2nd Department of Obstetrics and Gynecology, University of Athens, Aretaieio Hospital. Participants were at least 1 year postmenopausal. Both non-users and current users of HT (conjugated equine estrogens 0.625 mg as estrogen therapy or combined with medroxyprogesterone acetate 5 mg as estrogen/

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progestin therapy (EPT), or 17b-estradiol 2 mg plus norethisterone acetate 1 mg as EPT, or tibolone 2.5 mg) were included in the study. Women who were past users of HT were not included in the study unless they had been off therapy for at least 6 months. Two hundred and fifty postmenopausal women who fulfilled the above criteria were invited to participate in the study. Thirty-four refused to participate (13.6%). Two hundred and sixteen postmenopausal women with a mean age of 54.5 + 5.5 years (+standard deviation, SD) were finally included in the study. All subjects signed informed consent and Institutional Review Board approval was obtained by the Ethics Committee of Aretaieio Hospital. Measures For each woman a detailed record was compiled which included age, years since menopause, occupation, educational attainment, marital status and number of children, as well as a detailed medical history including a list of medications. The questionnaire was anonymous and was handed to the women during their routine visit to the center. Climacteric symptoms were evaluated by the Greene’s scale. This scale provides total scores and sub-scores for psychological, physical and vasomotor symptoms [28]. QoL was evaluated by the Utian Quality of Life Scale (UQOL) [29]. This instrument contains 23 questions relating to four distinct but interrelated QoL domains: occupational, health, sexual and emotional. Questions were included in their respective domains based on factor structure analysis. Women rated their level of agreement concerning each statement on the questionnaire with regard to their experiences during the month preceding each visit. In addition, an overall UQOL total score was derived by summation of the separate domain scores. Higher scores mean better QoL. The UQOL was translated from English to Greek by two independent professional translators, native Greek language speakers and bilingual in the source language. The two versions were reviewed with the translators and the project manager and an agreement was reached for a pre-final Greek version of the questionnaire. A backward translation (from Greek to English) was performed by a professional translator, English native speaker and bilingual in the target language. Prior to the present work, a pilot study was conducted in a subgroup of women (n ¼ 24) as the final step of cognitive debriefing. Psychological symptoms were assessed by the Symptom Checklist-90-R (SCL-90-R) scale [30]. The SCL-90-R is a self-reporting symptom scale including 90 items, covering nine symptom dimensions and a global index. The respondent was asked

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to rate the occurrence of the symptoms during the previous week. The dimensions are somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation and psychoticism. High scores indicate high intensity of symptoms. Statistical analysis Variables were first tested for normality. Normal variables are expressed as mean + SD, while variables with skewed distribution are expressed as median (interquartile range). If the normality assumption was satisfied, Student’s t test was used for the comparison of means between two groups. Pearson correlations coefficients were used to explore the association of two continuous variables. The w2 test was used to explore the association of two categorical variables. The association between therapy and UQOL or SCL-90-R was modeled using multiple linear regression analyses. All models were adjusted for age, education level, employment status, family status, number of children, years since menopause and somatic illness. Regression coefficients and standard errors were computed from the results of the linear regression analyses. All reported p values are twotailed. To give an indication of clinical significance for a statistically significant variable, we also report in the text the effect size of such a variable on a dimension’s score, which is the regression coefficient as a percentage of the score’s SD in the cohort of women studied. Statistical significance was set at p 5 0.05 and analyses were conducted using STATA statistical software, version 6.0 (Stata Corp., College Station, TX, USA).

Results The sample consisted of 216 women with a mean (+SD) age of 54.5 + 5.5 years. Fifty-three of them were users of HT and 163 were not. Sample characteristics are presented in Table I. HT users were younger (mean 52.6 years) and more educated (mean 13.2 years) than non-users (mean 55.1 years, p ¼ 0.005 and mean 11.9 years, p ¼ 0.046, respectively). The mean score for vasomotor symptoms was 1.2 in HT users, compared with 2.1 in non-users (p ¼ 0.003). Mean scores on the dimensions of UQOL according to therapy are presented in Table II. All dimensions except health were significantly better in HT users compared with non-users. The multiple regression analysis of UQOL dimensions as dependent variables and HT use and sociodemographic characteristics as independent variables is reported in Table III. When comparing the two groups after adjustment for sociodemographic variables and across the different dimensions, the scores of HT users were approximately 1 unit larger scores than those of non-users, the difference being statistically significant in the emotional dimension and the total score (effect size: 1.41/ 4.2, 34% and 4.07/11.8, 34% respectively, p 5 0.05). Increased scores on the occupational dimension were associated with more years of education (560.18 ¼ 0.9 score increase for 5 additional years of education; effect size 0.9/5.0 ¼ 18%); with employment status (effect size 1.71/5.0 ¼ 34% between employed and housewife; and effect size 2.92/5.0 ¼ 58% between employed and retired); and with marital status (effect size 3.37/5.0 ¼ 67% between married and single). On the health dimension, increased scores were associated with more years of education (560.22 ¼ 1.1 score increase for 5 additional years

Table I. Sample characteristics according to HT use. Total (n ¼ 216) Age (years), mean+SD Education (years), mean+SD

54.5+5.5 12.3+3.8

Employment status, n (%) Employed Housewife Unemployed Retired

98 67 7 44

HT users (n ¼ 53)

(45.4) (31.0) (3.2) (20.4)

52.6 (4.9) 13.2 (3.7) 29 18 1 5

(54.7) (34.0) (1.9) (9.4)

Family status, n (%) Married Single Separated/divorced/widowed

160 (74.1) 13 (6.0) 43 (19.9)

38 (71.7) 5 (9.4) 10 (18.9)

No. of children, median (IQR) Years since menopause, median (IQR)

2 (1–2) 6.8 (2–10)

2 (1–2) 6 (3–8)

Somatic illness, n (%) No Yes

148 (68.5) 68 (31.5)

38 (71.7) 15 (28.3)

Vasomotor symptoms

1.9+2.0

HT, hormone therapy; SD, standard deviation; IQR, interquartile range.

1.2+1.8

HT non-users (n ¼ 163) 55.1 (5.6) 11.9 (3.9) 69 49 6 39

p Value 0.005 0.046

(42.3) (30.1) (3.7) (23.9)

0.108

122 (74.9) 8 (4.9) 33 (20.2)

0.484

2 (1–2) 5 (2–11)

0.246 0.952

109 (66.9) 54 (33.1)

0.513

2.1+2.1

0.003

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Hormone therapy and quality of life of education; effect size 1.1/4.7 ¼ 23%); with housework employment (effect size 1.63/4.7 ¼ 35% between housewife and employed); with marital status (effect size 3.22/4.7 ¼ 69% between married and single); with number of children (effect size 0.78/ 4.7 ¼ 17%); and with being free of somatic illness (effect size 1.95/4.7 ¼ 41%). Table II. Mean UQOL scores according to HT use.

Total

HT users

HT non-users

p Value

24.0 + 5.0 23.7 + 4.7 20.3 + 4.2 8.4 + 3.0 76.5 + 11.8

25.4 + 5.3 24.7 + 4.9 21.6 + 4.0 9.3 + 2.9 81.0 + 12.0

23.5 + 4.9 23.4 + 4.6 20.0 + 4.2 8.2 + 3.0 75.2 + 11.3

0.017 0.092 0.018 0.019 0.002

Dimension Occupational Health Emotional Sexual Total score

UQOL, Utian Quality of Life Scale; HT, hormone therapy; data are presented as mean + standard deviation.

Apart from HT use, increased scores on the emotional dimension were associated only with being free of somatic illness (effect size 1.11/4.2 ¼ 26%). Increased scores on the sexual dimension were associated with marital status (effect size 1.33/ 3 ¼ 44% between married and separated, divorced or widowed); and with being free of somatic illness (effect size 1.18/3.0 ¼ 39%). The total score of UQOL, apart from being associated with HT use, was also associated with more years of education (effect size of 560.54/ 11.8 ¼ 23% for 5 additional years of education); with marital status (effect size 9.41/11.8 ¼ 80% between married and single); with number of children (effect size 1.94/11.8 ¼ 16%); and with being free of somatic illness (effect size 3.09/11.8 ¼ 26%). Results relative to the SCL-90-R scales according to therapy are shown in Table IV. Significant differences for the mean scores between the two

Table III. Multiple linear regression models on dimensions of the UQOL. Occupational

Health

Emotional

Therapy HT non-user (reference) HT user

1.18 + 0.81

1.13 + 0.78

0.70 + 0.50

4.07 + 1.88*

Education (years) Age (years)

0.18 + 0.09* 0.04 + 0.08

0.22 + 0.09* 0.09 + 0.08

0.09 + 0.08 70.04 + 0.07

0.03 + 0.06 70.04 + 0.05

0.54 + 0.22* 0.03 + 0.19

Employment status Employed (reference) Housewife Unemployed Retired

71.71 + 0.86* 70.34 + 2.32 72.92 + 0.99**

1.63 + 0.83* 2.84 + 2.21 1.04 + 0.94

0.68 + 0.74 0.43 + 1.98 0.41 + 0.84

70.06 + 0.53 1.35 + 1.41 70.90 + 0.60

0.56 + 2.01 4.48 + 5.34 72.29 + 2.27

Family status Married (reference) Single Separated/divorced/widowed

73.37 + 1.69* 70.60 + 0.92

73.22 + 1.61* 70.32 + 0.88

71.77 + 1.44 0.04 + 0.78

71.64 + 1.03 71.33 + 0.56*

79.41 + 3.89* 72.13 + 2.12

No. of children

70.39 + 0.42

70.78 + 0.40*

70.57 + 0.35

70.39 + 0.25

71.94 + 0.96*

71.18 + 0.45**

73.09 + 1.55*

70.01 + 0.05

70.09 + 0.18

1.41 + 0.66*

Somatic illness No (reference) Yes

70.12 + 0.74

71.95 + 0.71*

71.11 + 0.56*

Years since menopause

70.12 + 0.08

70.03 + 0.07

0.03 + 0.07

Sexual

Total score

UQOL, Utian Quality of Life Scale; HT, hormone therapy; data are regression coefficients + standard error; *p 5 0.05, **p 5 0.01.

Table IV. Mean SCL-90-R scores for psychological symptoms according to HT use. Dimension Somatization Obsessionality Interpersonal sensitivity Depression Anxiety Anger/aggressiveness Phobic anxiety Paranoid ideation Psychotism Total score

Total

HT users

HT non-users

p Value

0.79 + 0.63 1.10 + 0.63 0.76 + 0.50 0.95 + 0.63 0.70 + 0.54 0.67 + 0.62 0.25 + 0.37 0.87 + 0.60 0.30 + 0.29 0.70 + 0.38

0.65 + 0.65 0.95 + 0.54 0.80 + 0.37 0.82 + 0.57 0.65 + 0.47 0.55 + 0.51 0.33 + 0.46 0.82 + 0.52 0.25 + 0.24 0.61 + 0.32

0.83 + 0.63 1.15 + 0.64 0.65 + 0.54 0.99 + 0.65 0.71 + 0.56 0.72 + 0.65 0.22 + 0.34 0.88 + 0.53 0.32 + 0.31 0.73 + 0.39

0.076 0.042 0.064 0.094 0.556 0.082 0.072 0.513 0.154 0.040

SCL-90-R, Symptom Checklist-90-R; HT, hormone therapy; data are presented as mean + standard deviation.

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groups of women were detected for obsessionality, while the dimensions somatization, interpersonal sensitivity, depression, anger/aggressiveness and phobic anxiety tended to have significant different scores between the two groups. Results of the multiple linear regression analyses with SCL-90-R scales as the dependent variables are reported in Tables V and VI. After entering the sociodemographic variables into the model, HT users had lower scores than non-users for

obsessionality (effect size 0.19/0.63 ¼ 30%), for interpersonal sensitivity (effect size 0.18/0.5 ¼ 36%) and for the general index (effect size 0.13/ 0.38 ¼ 34%). No other factors were associated with interpersonal sensitivity or with the general index. For somatization and depression, lower scores were associated only with being married versus single (respective effect sizes: 0.48/0.63 ¼ 76%, 0.54/ 0.63 ¼ 86%); whereas for anger/aggressiveness, lower scores were associated only with being

Table V. Multiple linear regression models on psychological symptom dimensions of the SCL-90-R. Somatization

Obsessionality

Therapy HT non- user (reference) HT user

70.16 + 0.11

70.19 + 0.09*


70.01 + 0.01 70.01 + 0.01

0.001 + 0.01 70.01 + 0.01


70.17 + 0.12 0.38 + 0.31 70.17 + 0.13

70.07 + 0.11 0.50 + 0.30 70.14 + 0.12

70.02 + 0.09 0.01 + 0.25 70.15 + 0.11


0.48 + 0.22 70.05 + 0.12

0.09 + 0.22 0.09 + 0.12

70.07 + 0.18 70.02 + 0.10

0.54 + 0.22* 0.01 + 0.12

0.58 + 0.17** 70.01 + 0.10

70.02 + 0.04

0.04 + 0.06

0.09 + 0.04*

0.06 + 0.06

0.08 + 0.05


0.06 + 0.10

0.07 + 0.10


0.01 + 0.01

0.02 + 0.008*

No. of children

Interpersonal sensitivity

Depression

Anxiety

70.18 + 0.09*

70.13 + 0.11

70.07 + 0.09

70.01 + 0.01 70.01 + 0.01

70.01 + 0.01 0.01 + 0.01

0.01 + 0.01 70.002 + 0.01

70.05 + 0.11 0.37 + 0.30 70.06 + 0.13

70.08 + 0.09 0.30 + 0.23 70.13 + 0.11

0.05 + 0.08

0.09 + 0.10

0.08 + 0.08

70.0006 + 0.01

0.53 + 0.62

70.003 + 0.01

SCL-90-R, Symptom Checklist-90-R; HT, hormone therapy; data are regression coefficients + standard error; *p 5 0.05, **p 5 0.01.

Table VI. Multiple linear regression models on psychological symptom dimensions of the SCL-90-R. Anger/aggressiveness

Phobic anxiety

Paranoid ideation

Psychotism

General index

Therapy HT non- user (reference) HT user

70.16 + 0.10

0.09 + 0.06

70.08 + 0.10

70.10 + 0.05


0.01 + 0.01 70.01 + 0.01

0.01 + 0.01 0.01 + 0.01

0.01 + 0.01 70.01 + 0.01

0.01 + 0.006* 70.002 + 0.01

70.004 + 0.01 0.001 + 0.01


0.05 + 0.11 0.29 + 0.29 70.11 + 0.13

70.01 + 0.07 70.27 + 0.18 70.19 + 0.08*

0.07 + 0.11 0.58 + 0.29* 70.04 + 0.13

0.01 + 0.05 0.21 + 0.14 70.09 + 0.06

70.06 + 0.07 0.19 + 0.16 70.12 + 0.08


0.02 + 0.21 70.22 + 0.11*

70.01 + 0.13 0.05 + 0.07

0.06 + 0.21 0.02 + 0.12

0.05 + 0.10 0.04 + 0.06

0.18 + 0.13 70.002 + 0.07

No. of children

70.05 + 0.05

0.01 + 0.03

0.003 + 0.05

70.01 + 0.03

0.03 + 0.03


70.03 + 0.10

0.04 + 0.06

70.10 + 0.10

0.01 + 0.05

0.04 + 0.06

0.01 + 0.01

70.003 + 0.01

0.0009 + 0.01

0.01 + 0.004

0.01 + 0.005


SCL-90-R, Symptom Checklist-90-R; HT, hormone therapy; data are regression coefficient + standard error; *p 5 0.05.

70.13 + 0.06*

Hormone therapy and quality of life separated/divorced/widowed versus married (effect size: 0.22/0.62 ¼ 35%). On the dimension of obsessionality, higher scores were associated with the duration of menopause (effect size 560.02/0.63 ¼ 16% for every 5-year increase in duration). On the dimension of anxiety, lower scores were associated with being married versus single (effect size 0.58/0.54 ¼ 107%) and higher scores with having more children (effect size 0.09/0.54 ¼ 17%). On the dimension of phobic anxiety, lower scores were associated only with being retired versus being employed and on the dimension of paranoid ideation higher scores were associated with being unemployed versus being employed (effect size: 0.19/0.37 ¼ 51% and 0.58/0.60 ¼ 97%, respectively). Lower scores of psychotism were statistically associated with fewer years of education (effect size 560.01/0.29 ¼ 17% for every 5 additional years of education). Discussion Greek postmenopausal women on HT attending our menopause clinic were younger and more educated than women not on HT. Furthermore, there was a trend for HT users to be more professionally active compared with non-users, among whom a greater percentage was retired. This finding is common among HT users in other European countries [8] and may suggest that the acceptance of HT on the long term may require a certain educational and cultural background. This is especially true for Greek women, among whom the fear of cancer imposed by public media and social surroundings prevails over the possible benefits of HT. Surprisingly, we did not find a difference with respect to somatic illness between HT users and non-users, contrary to previous reports [8]. This could be explained by the fact that our population was young and healthy, with only minor chronic conditions present, which do not pose a contraindication to the initiation of HT. QoL is the result of the fine tuning of various factors including physiological body functioning, family, friends, profession and cultural background. Any change in body physiology may be perceived differently by women of different socioeconomic background. In our study, marital status seemed to have a strong correlation with QoL. Single and childless women had lower QoL and higher anxiety scores than married parous women. This finding is in agreement with previous reports indicating that married women with children have a better state of overall health [4,8,31,32]. In a large prospective study on British women through midlife, Hardy and Kuh [33] found that the largest increases in psychological symptoms were seen among women who reported their family life getting worse during the last year. Very recently, Papadopoulos and

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colleagues published a study on the prevalence of depression in the older inhabitants (over 60 years of age) of a rural town in central Greece. In multivariate analysis, marital status was the only significant predictor of the presence of depression, with single subjects having significantly higher risk than married people [34]. Furthermore, in a cross-sectional health survey conducted in a Greek municipality, marital status significantly affected a person’s ability to function normally in his or her everyday life [35]. Beyond the practical issues raised by ‘living alone’, our findings, as well as that of previous reports, may reflect the ‘unacceptability’ of single status in midlife encountered in Greek culture. Single childless women may feel socially isolated and these feelings may render them more vulnerable to the hormonal changes associated with the menopause transition. Education had a positive independent effect on QoL of women in our study. Women with a higher educational status seemed to have better general health and a higher overall QoL, a finding corroborated by previous reports [8,36]. As the years of education increase, the chances of having a highly qualified and more rewarding job increase in parallel. Job satisfaction is critical in determining self-image and self-esteem. This, in turn, may modulate the way women react and handle somatic changes in midlife. Polit and LaRocco [37], studying the effect of demographic and personality variables on the nature and intensity of subjectively perceived menopausal symptoms in 135 peri- and postmenopausal women, found that women who reported a higher number of menopausal symptoms tended to be less educated, were less likely to be working, and viewed themselves generally in poorer health. During the past few years much attention has been drawn to the impact of HT on the breast and cardiovascular system, while the issue of QoL has been neglected. Indeed, QoL compromise is the main reason why women seek help and professional advice in menopause clinics [38]. We have found a positive association of HT with QoL in Greek postmenopausal women, independently of sociodemographic characteristics. Although there are no other reports concerning Greek women, our results are in agreement with numerous studies from other countries showing that HT improves women’s wellbeing [10,39–43]. Dennerstein and associates [2] indicated the need to control for sociodemographic variables, which have a profound influence on the association of HT and the dimensions of QoL. Older women with a long duration of menopause may in fact not profit from HT in terms of QoL, as was pointed out by the Women’s Health Initiative analysis [44]. On the other hand, when women are recruited from menopause clinics as was the case in our study and in the large survey of Genazzani and co-workers in Italian women [8], HT appears to have

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a favorable effect on QoL independently of background factors. The association of HT with psychological symptoms is more controversial. Experimental studies in rats have demonstrated that estrogen administration decreases a-adrenergic activity and increases dopaminergic and serotoninergic neural tones. Furthermore, estrogens may have a psychoactive effect by modulating the opiate pathways [45]. On clinical grounds, however, studies on the effect of estrogens on mood are more divergent. Our study found an independent negative association of HT use with the presence of psychological symptoms. Our findings are in accordance with previous reports which indicate that postmenopausal women without clinical depression may benefit from HT with regard to psychological symptomatology [24,45–47]. Furthermore, even women with diagnosed depression may actually benefit from HT, in terms of clinical severity of the depressive episode and the response to primary antidepressive treatment [48,49]. On the other hand, other authors maintain that HT does not have an independent effect on mood in either healthy [13,43] or depressed postmenopausal women [50]. The main reasons for this discrepancy may be the methodological differences among all these studies. Furthermore, race is a critical factor influencing the expression of mood disturbances. As shown elegantly in the study of Olson and colleagues [24], white women differ from black women both in terms of baseline psychological symptoms and in the particular aspects of symptomatology that HT improves. More specifically, black women scored higher in baseline depression and hostility than white women. According to the authors, while HT use was associated with fewer depressive symptoms in white women, this was not the case in black women, in whom the effect of HT was confined only to lowering the aggression score. Chinese peri- and postmenopausal women, on the other hand, exhibit very low scores of depressive symptoms, possibly due to high dietary intakes of phytoestrogens and their cultural attitude toward the menopause [13]. Chinese women, therefore, are unlikely to benefit from HT with regard to mood disturbances and QoL [13]. Beyond race, culture very strongly influences the way mood disorders are expressed. Marmanidis and collaborators conducted a cross-cultural study on the symptomatology of individuals with a depressive disorder, evaluating Greek and Australian patients in their native environment. Although the individuals in their study were identical in terms of depressive clinical severity, regarding somatic complaints Greeks scored significantly higher on dizziness, paresthesias and masticatory spasms, indicating anxiety-induced hyperventilation, compared with the Australian patients who scored significantly higher in sleep disturbances [27]. Furthermore, in

their comparative survey on Greek and British community-dwelling individuals, Mavreas and Bebbington [26] reported that Greek subjects demonstrated higher rates of psychological disturbances, mainly accounted for by higher rates of generalized anxiety. Large surveys evaluating mental health in the Greek population are unfortunately lacking. From the existing limited evidence, however, it may be concluded that the prevalence of psychological symptomatology after midlife, indicative of a possible mental disorder, is comparable to that in other countries [34,51,52]. One could therefore hypothesize that the favorable association of HT use with overall psychological symptomatology detected in our study could reflect the palliative effect of HT on background mood disorders encountered in Greek postmenopausal women. The limitations of our study should be shortly summarized. Being cross-sectional in design, our study can only be indicative and cannot confirm causality or the direction of a relationship. Furthermore, due to the fact that our sample was drawn from our menopause clinic, our results cannot be extrapolated to all postmenopausal women in the community, although our clinic is a referral center for central and south Greece and our sample thus encompasses women from both rural and urban territories and from a variable socioeconomic background. In conclusion, clinicians must be aware of the multiple and divergent factors that may affect women’s physical and psychological well-being and constitute the dimensions of QoL. In our study HT use was associated with better QoL as well as with a positive effect on mood in Greek postmenopausal women. The evaluation of QoL is of paramount importance in the assessment of therapeutic strategies. Psychological well-being and QoL rather than the mere control of vasomotor symptoms should be regarded as a therapeutic target of HT in postmenopausal women. Acknowledgements The authors thank the Associate Professor Constantine Frangakis and Hara Tzavara for their valuable help with data analysis.

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