INTRODUCTION
Depression and depressive symptoms are frequently seen in menopause and in transition period to menopause. Menopausal changes in transition leads to critical influence on the woman’s biological, social and psychological status (1-3). Many reports emphasize sudden hot flashes and sweating due to dramatic decrease in estrogen, sleep disturbances as a result of hormonal changes may induce depression, panic and generalized anxiety disorders. Changes in the perception of body image and alterations in sexual life which is a major source of satisfaction may play a role in the development of depression (4).
Many women experience mood disorders associated with low estrogen levels during the menstruation, postpartum and menopause periods. Even though studies strongly emphasize the risk of depression in perimenopausal period, serum hormone levels was not found to be directly correlated with the severity of the mood disorder symptoms (5). Endogenous and exogenous estrogen fluctuations are reported to be related with cognitive functions, memory, sleep, stress response and mood control (1,2,6,7), but a distinct effect of hormone levels on depression is still not clear (8).
In this study, we aimed to investigate the effect of hormonal fluctuations and physical changes on symptoms of depression and anxiety in patients with hormonally confirmed menopause.
MATERIALS AND METHODS
Participants
This study was conducted in Bakirkoy Dr. Sadi Konuk Education and Research Hospital, Department of Obstetrics and Gynecology, Menopause outpatient Clinic between January and August 2009. A total of 171 female volunteers in spontaneous menopause who had amenorrhea in previous 12 consecutive months and whose hormonal levels indicate menopause included in the study. Local ethics committee approval and informed consent from all patients were taken. Patients with surgical menopause are regarded as a different category and excluded from the study. Before proceeding with the registration process, subjects were informed about the study and their personal information (name, age, date of admittance) were recorded. During the interview, patients were informed about the routine menopausal laboratory tests FSH and E2 (AIA-1800ST, Tosoh) and TSH measurements.
Scales
1. Socio-demographic data form: A questionnaire regarding the patients’ medical history of chronic diseases, any hormone replacement therapy and its route if it has done, premenstrual syndrome disorders, existence of previously diagnosed psychiatric disorders in patients or in their first degree relatives. The marital status, profession, education, economical level, siblings, living alone or in a family were recorded. Also vaginal atrophy diagnosis was sought by questioning vaginal burning, stinging, dryness and dyspareunia.
2. Hamilton Depression Rating Scale (HAM-D): This is a scale developed to rate the level of depression in patients with depression (9). Seventeen-item version was used in this study. The reliability and validation studies of Turkish version were done by Akdemir et al. (10). Scores between “0-7” indicate no depression, while “8-15” as mild depression, “16-28” as moderate depression and 29 or more indicate severe depression.
3. Hamilton Anxiety Rating Scale (HAM-A): A scale containing 14 questions was developed by Hamilton (11) scores the mental and physical symptoms. It predicts the level of anxiety, symptom distribution and measures the severity. Turkish validity and reliability studies were done by Yazici et al. (12). The scores obtained from the scale were classified as: “0-5” points no anxiety, “6-14” points minor anxiety, “15” points and above as major anxiety.
The local ethical committee of Bakirkoy Dr. Sadi Konuk Research and Training Hospital approved the study (03 June 2008/34).
Statistical Analysis
The findings of the study were assessed for statistical analysis, NCSS (Number Cruncher Statistical System) 2007 and PASS 2008 Statistical Software (Utah, USA) were used. Evaluations of the data were done by descriptive statistical methods (mean, standard deviation, frequency) and chi-square test was used for qualitative data. The significance level of p was accepted as over 0.05.
RESULTS
Analysis of the demographic characteristics revealed that the majority of patients were: between 45-55 years old (n=140, 81.9%), married (n=148, 86.5%), graduated from primary school (n=138, 80.7%) and housewives (n=116, 67.8%) (Table 1).
Of all patients 119 (69.6%) had history of premenstrual syndrome. 26 (15.2%) of the patients perceived the menopause as aging, 8 (4.7%) of them as end of femininity and sexuality, 17 (9.9%) of them as maturation, 91 (53.2%) of them as a normal stage of human life and 29 (17%) of them had no knowledge or idea about it. 94 (55%) of women had symptoms of vaginal atrophy and 36 (21.1%) had urinary incontinence.
Table 2 shows the mean values of the patients’ hormonal levels. There was no statistically significant difference in the incidence of depression between two groups with high and low levels of FSH formed by cut-off point of 40 mIU/ml (p> 0.05). The measurement of E2 inversely correlated with severity of depression (p<0.01). Mild depression rates were higher in patients with E2 level below 50 mIU/ml, while moderate depression rates were higher in patients with E2 level higher than 50 mIU/mL (p<0.001) (Table 3).
The difference of depression incidences in patients with and without the presence of vaginal atrophy were statistically significant (p<0.05). The group with vaginal atrophy had higher rate of mild depression, while patients with no vaginal atrophy had low rate of depression (Table 3).
The incidence of anxiety according to the levels of FSH vs E2 were significantly different (p<0.01). In patients with FSH level <40 mIU/ml the incidence of minor anxiety was higher, while FSH levels above this value was related with higher incidence of major anxiety. In patients with E2 level below 50 mIU/ml, major anxiety was prominent while higher levels were related with less severe anxiety (p<0.05) (Table 4). Presence or absence of vaginal atrophy didn’t statistically differ by both incidence and severity of anxiety (p>0.05).
DISCUSSION
In this study, the relationship between hormonal status with depression and anxiety were investigated in menopausal women. The higher severity of depression was related with E2 levels lower than 40mIU/ml, while anxiety scores were higher in patients with lower levels of FSH and E2 significantly. Additionally, vaginal atrophy in women was related with higher rates of depression and anxiety.
The clinical studies reveal higher prevalence of depression in menopausal women compared with general population, since studies are generally done in cases admitted to hospitals by various complaints (2,13-16). Menopause may differ according to culture, individual differences, presence of an anxiety disorder or depression history and level of literacy about menopause. Depression and anxiety symptoms seen in this stage of women may be a result of biological, social and psychological factors (1-3). Some studies report that the changes in the level of estrogen during transition to menopause and while menopause would increase susceptibility to psychiatric disorders such as depression and anxiety (1,2,6,7). Nevertheless, the effect of hormone levels on depression and anxiety is still not clear entirely (8).
In our study, low level of E2 was found to be significantly related to high rates of depression and anxiety. Freeman et al. (16) reported any increase in depressive symptoms parallel to hormonal changes in women at menopausal transition. Some studies reported an association between menopause and depression (6,17-19), some had different conclusions (20-22). Hallstrom et al. (20) couldn’t find an association between depression and menopause. In a study with follow-up of 2,565 women between the ages of 45 to 55 for five years, reported that the depression did not increase with menopause but the presence of previous history of depression was the indicator of developing depression in menopause (21).
There are some limitations that may be considered when analysing the data of this study. First, comorbidities as diabetes, hypertension and medications may interfere with psychological well-being of patients. Another limitation of the study is the attitude of spouse that may aggravate or deactivate the psychological reaction of patient to her menopausal transition. We didn’t homogenize the patients according to these parameters.
CONCLUSION
According to the results of our study, serum levels of FSH and E2 in menopausal patients had a significant relationship between anxiety and depression. Various differences are present between the clinical studies and population-based studies, that parameters may change with environmental and social factors.
The lack of standardized scales accepted by all investigators and difficulty of creating homogeneous patient groups interfere with the results of studies on this subject. In this study, even though the menopause wasn’t accepted as the major cause of depression symptoms alone, it may be concluded that the gynecologists, family physicians and psychiatrists have to collaborate against the psychosomatic and psychosocial factors as a whole in evaluating patients with multidisciplinary approaches in premenopausal, perimenopausal and postmenopausal stages. Large scale studies taking the geographical region and culture comorbidities into account, and using standard criteria for depression are mandatory.
REFERENCES
1. Stoppe G. Critical apprasisal of effects of estrogen replacement therapy on symptoms of depressed mood. Arch Women Ment Health 2002; 5:39-47.
2. Genazzani AR, Spinetti A, Gallo R, Bernardi F. Menopause and the central nervous system: intervention options. Maturitas 1999; 31:103-110.
3. Yazici K, Pata O, Yazici A. The effect of hormon replacement therapy in menopause on symptoms of anxiety and depression. Turk Psikiyatri Derg 2003; 14:101-105.
4. Kaptanoğlu C. Psikiyatrik Açıdan Menopoz, Klinikte Menopoz: In Hassa H (editor). Türkiye nüfus ve sağlık araştırması. Ankara, 1994 (Article in Turkish).
5. Bezircioğlu İ, Gülseren L, Öniş A, Kındıroğlu N. Depression-anxiety and disability in the premenopausal and postmenopausal Period. Turk Psikiyatri Derg 2004; 15:199-207.
6. Hunter M, Battersby R, Whitehead M. Relationships between phsychological symptoms, somatic complaints and menopausal status. Maturitas 1986; 8:217-228.
7. Genazzani AR. Estrogen effect on neuroendocrine function: the new challenge of pulsed therapy. Climacteric 2002;5:50-56.
8. Llaneza P, García-Portilla MP, Llaneza-Suárez D, Armott B, Pérez-López FR. Depressive disorders and the menopause transition. Maturitas 2012; 71:120-130.
9. Williams BW. A structured interview guide for Hamilton Depression Rating Scale. Arch Gen Psychiatr 1978; 45:742-747.
10. Akdemir A, Orsel S, Dağ İ, Turkcapar H, İşcan N, Ozbay H. Hamilton Depresyon Derecelendirme Ölçeği’nin (HDDO) geçerliliği, güvenilirliği ve klinikte kullanımı. Psikiyatri Psikoloji Psikofarmakoloji Dergisi 1996; 4:251-259 (Article in Turkish).
11. Hamilton M. The assesment of anxiety states by rating. Br J Med Psychol 1959; 32:50-55.
12. Yazıcı MK, Demir B, Tanrıverdi N, Karaağaoğlu E, Yolaç P. Hamilton anxiety rating scale: interrater reliabilty and validity study. Turk Psikiyatri Derg 1998; 9:114-117.
13. Sherwin BB. Hormones, mood, and cognitive functioning in postmenopausal women. Obstet Gynecol 1996; 87:20-26.
14. Katz-Bearnot S. Menopause depression and loss of sexual desire: a psychodynamic contribution. J Am Acad Psychoanal Dyn Psychiatry 2010; 38:99-106.
15. Coryell W, Endicott J, Keller M. Major depression in a nonclinical sample: demographic and clinical risk factors for first onset. Arch Gen Psychiatry 1992; 49:117-125.
16. Freeman EW, Sammel MD, Rinaudo PJ, Sheng L. Premenstrual syndrom as a predictor of menopausal symptoms. Obstet Gynecol 2004; 103:960-966.
17. Weismann MM. The myth of involutional melancholia. JAMA 1979; 242:742-744.
18. Anderson E, Hamburger S, Liu JG, Rebar RW. Characteristics of menopausal women seeking assistance. Am J Obstet Gynecol 1987; 156:428-433.
19. Smith RNJ, Studd JWW. Estrogens And Depression In Women: In Lobo RA (editor). Treatment Of The Postmenopausal Woman: Basic And Clinical Aspects. New York: Raven Pres., 1994, 129-136.
20. Hallstrom T, Samuilsson S. Mental health in the climacteric: The longitudinal study of women in Gothenburg. Acta Obstetrics Gynecology Scand 1985; 130:13-18.
21. Avis NE, Brambilla D, McKinlay SM, Vass K. A longitudinal analysis of the association between menopause and depression. Results from the Massachusetts Women’s Health Study. Ann Epidemiol 1994; 4:214-220.
22. Harlow BL, Cohen LS, Otto MW, Spiegelman D, Cramer DW. Prevalence and predictors of depressive symptoms in older premenopausal women: The Harvard Study of moods and cycles. Arch Gen Psychiatry 1999; 56:418-424.