Comparing Two Treatment Methods of Vitamin E Suppository and Conjugated Estrogen Vaginal Cream on the Quality of Life in Menopausal Women with Vaginal Atrophy

Introduction

Menopause is defined as the permanent cessation of menstruation for 12 consecutive months (1, 2). During this period, women experience long-lasting endocrinal, somatic and psychological changes (2).

Despite the increased life expectancy, age of menopause onset or menstruation cessation has not changed and women spend about 30 years or more (over a third) of their lives in menopausal or pre-menopausal period (3).

Vaginal atrophy, secondary to estrogen deficiency, is a common disease during the post-menopausal period (4). Symptoms of vaginal atrophy include vaginal itching, burning, tightness, dryness and bleeding after intercourse; in advanced cases, scarring and intrauterine adhesions may be seen (1, 5, 6).  Approximately 75% of women suffer from this condition in the menopausal period (7). As Palacios has stated, prevalence of symptoms due to vaginal atrophy is 15% during the pre-menopausal period and 40-57% in the post-menopausal period (8).

Symptoms of genitourinary atrophy can affect women’s comfort and quality of life (5, 9). In a study that examined the effects of menopause on vagina and vulva, negative effects on sexual life, confidence, marital relationship and social life were 40%, 17%, 13% and 7%, respectively (10).

As many subjects stated (32%), vaginal discomfort was related to women’s negative attitude towards aging; also, 14% of the subjects associated vaginal discomfort with low quality of life (10).

In menopausal women, quality of life incorporates menopausal signs such as hot flashes, night sweats and vaginal mucosa dryness. Surely, these symptoms affect women's quality of life. In addition, other aspects of quality of life such as health status, life satisfaction and psychological function are of great importance (3).

Nowadays, evaluation of quality of life is a controversial issue in clinical research and includes people’s feelings about their physical, emotional and social functioning. World Health Organization (WHO) defines quality of life as a person's perception of his/her life in the culture and value system in which he/she lives and in relation to his/her goals, standards, expectations and priorities (11).

Although no hormones have been associated with increased quality of life, hormonal therapy for symptomatic menopausal women can improve their quality of life (12). In vaginal atrophy treatment, hormonal and non-hormonal methods including topical and systemic estrogens are used (13). Estrogen increases the content of skin collagens, maintains skin thickness and increases mucopolysaccharides and hyaluronic acids to improve skin moisture and genitourinary symptoms (14).

Huber et al. (2002) aimed to evaluate the effects of tibolone and hormone replacement therapy on the bleeding rate, quality of life and tolerance of menopausal women. Both treatment methods improved women’s quality of life, health status, climacteric signs and urinary symptoms (15).

Hormone replacement therapy may improve women's quality of life and lead to decreased symptoms and signs, caused by menopause (16).  However, due to several reasons, especially women’s fear of the effects of estrogen, only 20-25% of women with symptoms of vaginal atrophy use this treatment modality (17, 18). Therefore, considering the inefficiency of hormonal therapy (as the confirmed treatment for vaginal atrophy) for some people and the associated side-effects, use of medications with fewer side-effects and therapeutic effects on vaginal atrophy is necessary.

Use of non-hormonal methods as first-line therapy for vaginal atrophy has been recommended by some researchers (6, 19). Use of vitamins, as a non-hormonal method, is relatively harmless and highly acceptable (14, 20, 21). In fact, some vitamins such as vitamin A, D and E have been used for the treatment of menopausal disorders and vaginal atrophy (14, 20).

Vitamin E, as an antioxidant, is used to limit oxidative damages and inflammatory diseases (22). This vitamin increases immune responses and improves disease resistance (23). Most effects of vitamin E are due to its antioxidant properties, which improve the function of respiratory system, blood circulation, reproduction, nervous system, and immune system (24). These vitamins keep arteries flexible and elastic, allowing blood to flow freely (25). They also inhibit prostaglandin production and show analgesic effects through stimulating the secretion of morphine-like substances in the nervous system (24).

According to Lark, vitamin E can be an alternative to estrogen (26). In some studies, use of vitamin E oil before intercourse has been reported to be useful (19). Capuron and colleagues (2009) conducted a study entitled, “Vitamin E status and quality of life in elderly people: influence of inflammatory processes". Results of this study showed that people with higher plasma vitamin E concentration (alpha-tocopherol) obtained higher scores in questionnaires related to health status and physical/mental aspects of quality of life (27).

Almost all women experience menopause. Thus, maintaining women’s physical and mental health during this period and eradicating problems such as vaginal atrophy due to menopause will improve their quality of life. Given the limited number of studies on non-hormonal treatment of vaginal atrophy and its effect on the quality of life of menopausal women in Iran, this study was performed to compare the efficacy of vitamin E vaginal suppository and conjugated estrogen vaginal cream on the quality of life of menopausal women with vaginal atrophy, referring to the gynecology clinic of Mashhad Ghaem Hospital in 2013.

Materials and Methods

This interventional, clinical trial was performed on 52 menopausal women (40-65 years old), referring to the gynecology clinic of Ghaem Hospital and healthcare centers No. 1 and 3 in Mashhad. The sample size was calculated as 30 patients per group, according to the formula for comparing the means of two independent populations (confidence interval=95%, power= 80%).

Cluster sampling was applied, i.e., two healthcare centers (healthcare centers No. 1 and 3) were randomly selected from 5 main healthcare centers of Mashhad; four clusters were selected from healthcare centers No. 1 and 3. By employing easy, accessible sampling, the researcher selected the sample size among women, who met the inclusion criteria and referred to these healthcare centers. Afterwards, the patients were randomly divided into vitamin E suppository and estrogen cream groups.

Inclusion criteria were as follows: 1) age range of 40-65 years; 2) experiencing menstruation cessation for at least 12 months or follicle-stimulating hormone (FSH) level > 40 international units; 3) no removal of bilateral ovaries (with or without uterus removal) over the past six weeks or more; 4) normal Pap smear over the past 3 years; 5) signs of vaginal atrophy (vaginal burning, itching, dryness and pain during intercourse) according to the patient's self-report and examination by the researcher; 6) Vaginal Maturation Value (VMV) ≤55; 7) PH>5; and 8) non-stressful events within the last 6 months (since such events can decrease one’s quality of life, subjects experiencing stressful events were excluded in order to determine the exclusive effect of vaginal atrophy on quality of life).

Exclusion criteria were as follows: 1) failing to answer all the questions in the questionnaire (considering the credit scoring system, in case of failure to completely answer the questionnaire, the scoring system was confounded and the questionnaire lost its scientific validity); 2) known or suspected endometrial or breast cancer; 3) genital tract abnormalities; 4) abnormal vaginal bleeding; 5) diabetes mellitus; 6) chronic renal diseases; 7) arthritis, cardiovascular diseases, or active liver/gallbladder diseases; 8) use of medications lowering blood pressure (due to the effects of these medications on reducing vaginal lubrication); 9) vaginal infection; 10) allergy to estrogen compounds or vitamin E; and 11) hormonal therapy 8 weeks before the study.

Data collection tools included a demographic questionnaire, forms of laboratory results (including data related to VMV and percentages of superficial, intermediate and basal cells), and Menopause-Specific Quality of Life (MENQOL) questionnaire.

MENQOL questionnaire, designed and standardized by Hyldich and colleagues (1996) at University of Toronto, Canada, is a valid tool for evaluation of quality of life. In addition, Falahzadeh et al. (2008) confirmed the reliability of this questionnaire by Cronbach's alpha in Iran (α=0.85) (28).

This tool consists of 29 questions regarding the symptoms and signs of menopause. It includes vasomotor (3 questions), psycho-social (7 questions), physical (16 questions), and sexual (3 questions) domains, measured using a Likert scale (score 1 indicating minimum severity and score 6 denoting maximum severity); the total score is calculated with respect to each question. Higher scores in each domain indicate lower quality of life and lower scores show higher quality of life.

Validity of laboratory result forms in this study was confirmed by content validity and reliability of the demographic questionnaire was evaluated, using internal reliability (r=0.7). The reliability of laboratory result forms was determined using equivalent method (r=0.8).

If a patient with symptoms of vaginal atrophy was referred to one of the studied clinics and met the inclusion criteria, she was included in the study. A vaginal discharge sample was obtained for determination of Vaginal Maturation Index (VMI) by shaving 1/3 of the upper wall of vagina inside the cervix using a plastic spatula. To ensure the absence of any problems, Pap smear test was performed for each patient by the researcher and the results were sent to the laboratory, along with vaginal wall samples.

Swab specimens of vaginal wall discharge were taken and evaluated by a pathologist in terms of quality and quantity after staining. Different cellular lines (surface, middle and basal cells) and their percentages were identified and VMV was determined:

VMV= (Percentage of middle cells × 0.5) + (percentage of superficial cells)

If Pap smear results were normal, PH was > 5 and VMV was ≤ 55, the person was included in the study.

Before performing the research, study objectives were explained to all subjects and written consents were obtained. Participants in the study were given 12 weeks of treatment regimen and randomly assigned to either vitamin E vaginal suppository (dosage of 100 IU) or conjugated estrogen vaginal cream (0.625 mg, manufactured by Aboureihan Company) (0.5 g is equivalent to 1.8 of the cream applicator) group.

The patients were advised to use the medications every night during the first two weeks and twice per week for the rest of the intervention (next 10 weeks). In case of any possible side-effects during the treatment, the intervention was interrupted and the MENQOL questionnaire was again completed by the subjects. Among 60 participants in this study, 8 patients (4 cases in vitamin E suppository group and 4 cases in estrogen cream group) were excluded due to improper use or sensitivity to medications.

Fisher’s exact test, repeated measures ANOVA, Mann-Whitney and t-test were performed, using SPSS version 11.5.

This study was approved by the ethics committee of Mashhad University of Medical Sciences. RCT code: IRCT2013060913611N1.

Results

The results of this study showed that in the vitamin E suppository group, the mean age of subjects was 52.11±4.70 years, duration of menstruation cessation was 54.46±52.21 months, mean parity was 5±2.78 children, and body mass index (BMI) was 27.25 ± 5.03 kg/m². In the estrogen cream group, the mean age of subjects was 52.88±6.30 years, duration of menstruation cessation was 62.76±59.23 months, mean parity was 5±2.48 children, and BMI was 28.62±4.46 kg/m²; the difference between the two groups was not statistically significant.