Strategies to improve menopausal quality of life: A systematic review
Mahboubeh Taebi1, Somayeh Abdolahian2, Gity Ozgoli3, Abas Ebadi4, Nourossadat Kariman3
1 Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran; Department of Midwifery and Reproductive Health, Isfahan University of Medical Sciences, Isfahan, Iran
2 Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3 Midwifery and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
4 Behavioral Sciences Research Center, School of Nursing, Baqiyatallah University of Medical Sciences, Tehran, Iran
|Date of Submission||04-Oct-2017|
|Date of Acceptance||06-Jan-2018|
|Date of Web Publication||06-Jul-2018|
Dr. Nourossadat Kariman
Midwifery and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran
Source of Support: None, Conflict of Interest: None
Background: Menopause and its complications could disturb the sense of well-being and health and affect the quality of life. The present study was performed to review the conducted interventional study related to the quality of life in menopausal women in Iran.
Methods: In the present systematic review, to achieve the intended studies, Iranian Registry for Clinical Trials and Magiran, SID, Google Scholar, Scopus, PubMed, Proquest, ScienceDirect, and Web of Science databases were searched using: menopause” and “quality of life” keywords without any time limitations. Based on Jadad criteria, studies with a score of 3 or more were enrolled in the study.
Results: From all the achieved studies at primary search, 12 were selected and enrolled in the study. Reviewing the results of the studies showed that participating physical exercise, using products containing phytoestrogens and isoflavones and participating in educational and counseling sessions have an effective role in the improvement of quality of life in menopausal women.
Conclusions: Evidence indicated that from the existing strategies to improve the menopausal quality of life, using complementary medicine is an efficient method and could be more effective when consumed along with performing physical exercises and participating in educational programs.
Keywords: Iran, menopause, quality of life, review
|How to cite this article:|
Taebi M, Abdolahian S, Ozgoli G, Ebadi A, Kariman N. Strategies to improve menopausal quality of life: A systematic review. J Edu Health Promot 2018;7:93
|How to cite this URL:|
Taebi M, Abdolahian S, Ozgoli G, Ebadi A, Kariman N. Strategies to improve menopausal quality of life: A systematic review. J Edu Health Promot [serial online] 2018 [cited 2018 Jul 21];7:93. Available from: http://www.jehp.net/text.asp?2018/7/1/93/236077
| Introduction|| |
Menopause is a unique event in women's life which occurs around the age of 50 and is a stage that all women would experience., The age of menopause has not changed during the past centuries; however, life expectancy has risen among women in the world and women spend about one-third of their lives during menopause period. During this period, following the lowered activity of the ovaries and changes in hormone levels symptoms such as headache, sleep disorder, mood swings, vasomotor symptoms such as hot flushes and night sweats and anxiety might occur.,, Duration, intensity, and impact of these symptoms differ from a person to another and in different societies. Some women might experience more severe symptoms that could deeply impact their personal and social performance and quality of life and make them encounter multiple serious issues in life., Therefore, the symptoms of menopause have a close relation with the quality of life during the menopause period and physiologically and psychologically, could affect their quality of life.,
One of the goals of health for all is to improve the quality of life. “Quality of life” is people's perception of their position in the social and cultural life, with regard to their goals and standards., Various studies have reported the negative effect of menopause on the quality of life.,, Although hormone therapy is the standard treatment for the early symptoms of menopause, due to its side effects such as the risk for embolism and breast cancer, using these combinations routinely is not considered appropriate. Using nonmedicinal methods for preventing the symptoms of menopause and improving the quality of life has been emphasized. Some studies have evaluated the effect of different educational and counseling methods,,, participating in physical activities,,,, using medical plants containing phytoestrogens and isoflavones and using food supplements such as soy, licorice, red clover, and fish oil  to improve and enhance the quality of life in menopausal women; but no review has been conducted on these studies in Iran so far. Hence, the present study was conducted to systematically review the conducted studies for introducing strategies to improve the quality of life in menopausal women.
| Methods|| |
This systematic review was conducted on all the clinical trials related to the quality of life in menopausal women that were conducted in Iran until July 2017. The presentation methods, including determination of the studied problem, data gathering, data analysis, and data interpretation, were performed based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses. No time limitation was set for article search. To achieve the intended studies, published articles in national and international databases; Iranian Registry of Clinical Trials, Magiran, SID, Google Scholar, Scopus, PubMed, Proquest, Science Direct, and Web of Science databases were searched. To maximize comprehensiveness in searching “menopause” and “quality of life” words were searched in the abstracts, titles and keywords. To search English sources, by searching “Iran” in the affiliation or organizational affiliation were used in Advance Search option of the PubMed, Proquest, Scopus, and Science Direct database. Hence, all of the Iranian articles related to menopause were found. The inclusion criteria for articles were being an interventional study on menopausal women, being conducted in Iran and evaluating the quality of life in menopausal women.
To increase the validity and reliability of the study, two researchers searched the articles simultaneously and evaluated the quality of the articles based on the Jadad criteria, separately. Jadad scale is one of the most valid international scales for the evaluation of the article's quality. Articles with a score of 3 or higher were enrolled in the study. Jadad scale or the Oxford quality scoring system contains three main phrases for controlling bias in clinical trials that would evaluate randomization, blinding, sample loss report, and withdrawal from the study. The totals core of the scale based on these phrases is five. A Jadad score of <3 indicates poor quality of the articles and a score of 3 or more indicates desirable quality of the article. Based on this scale, eventually, 12 articles were enrolled in the study [Figure 1].
|Figure 1: The flowchart for selecting and enrolling the articles in the study|
Click here to view
| Results|| |
In this systematic review, from 31 related articles to the subject, 12 interventional studies about the quality of life in menopausal women with a sample size of 925 were enrolled for evaluation. Effective interventions on the quality of life in menopausal women in Iran could be categorized into three domains of physical activity, complementary medicine, and education [Table 1].
Quality of life, as a scientific concept, is a sense welfare which is caused by satisfaction or dissatisfaction in life. Improvement of quality of life is one of the most important goals of medical interventions  and since women would experience lower quality of life after menopause, applying interventions based on empowerment patterns could improve their quality of life in this period. Various studies using educational theories and models have been evaluated.,,
Physical activity and quality of life
Exercising and regular physical activity is effective in reducing vasomotor symptoms and improvement of hot flushing, sleep disorders,, and psychological problems ,, of menopausal women. The mechanism of the effect of exercising on hot flushes is through increasing the level of beta-endorphins in hypothalamus. In addition, by decreasing the level of a-serum lipoproteins and body mass index and fat percentage, it could be effective in improvement of cardiovascular diseases; so in general, physical activity could improve the quality of life in menopausal women by decreasing the symptoms of menopause.,
According to the results of the conducted studies, aerobic and walking exercises are effective in improvement of vasomotor, mental, social, physical,,, and sexual  symptoms and in general the quality of life in premenopausal and menopausal women ,,, and could be considered as an effective method for improvement of menopause symptoms in premenopausal and menopausal women. However, some studies did not find any significant relation between physical activity and the sexual domain of quality of life.,
Complementary medicine and quality of life
Using nonhormonal methods for decreasing the symptoms of menopause and improvement of quality of life in menopausal women is known as complementary medicine. In other words, complementary medicine for treating the symptoms of menopause includes a wide range of herbal medicine containing phytoestrogen, isoflavon products, and food supplements such as soy., Some of the introduced phytoestrogens for improvement of the symptoms and quality of life during menopause are using soy milk  and red clover. Only a study showed that using licorice has been effective on the improvement of quality of life in menopausal women and reported a significant relation between consumption of licorice and vasomotor, mental, social, and physical domains of quality of life and its total score. Besides containing phytoestrogen, licorice could decrease depression and stress in menopausal women by increasing the level of dopamine and norepinephrine. Furthermore, such as other phytoestrogens, licorice has anti-oxidants and antibacterial properties. Some studies have shown the effectiveness of licorice in decreasing the number and intensity of hot flushes.,
Royal jelly is another used drug in the complementary medicine which is traditionally used for improvement of many complications and problems of menopause due to its potential estrogenic properties and simulation of estrogen receptors., Royal jelly is a complex matter and a product of honey bee that contains protein, sugars, fats, amino acids, vitamins, and minerals and also gamma globulin and elements needed for maintaining good health with various biological activities in body cells and tissues., Furthermore, as a part of a beneficial diet, royal jelly contains many known useful minerals. It also affects the process of collagenization and the activity of skin fibroblasts. Some studies have been conducted on the anti-oxidant properties of royal jelly., Using vaginal royal jelly could be effective in improvement of vaginal dryness although it has a weaker performance in comparison with conjugated estrogen, it is an effective in improvement of quality of life and its domains in menopausal women. Another introduced supplement which is effective on quality of life is fish oil which could improve the quality of life in menopausal women due to its eicosapentaenoic acid and docosahexaenoic acid.,
Educational programs and quality of life
Studies have shown that menopausal women usually suffer from lack of information. Education, especially during menopause, would increase awareness, and awareness has a positive effect on their healthcare and improvement of health behaviors. Besides increasing the awareness, participating in educational classes could improve women's attitude too. In addition, these would feel more empowered and valuable; therefore, their perception of the severity of the menopause's symptoms would be decreased and their quality of life would be improved., Education could be used for increasing the level of information and skill about menopause in menopausal women. The educations in the forms of self-care packages could be provided through speech and educational films, supportive groups  and education through group discussions along with education for strengthening the muscles, relaxation techniques, and coping with problems of menopause. Results indicated the effectiveness of the educations on menopausal women.
| Discussion|| |
The present study was conducted to evaluate the efficiency of the strategies to improve the quality of life in menopausal period. Jadad scale was used to evaluate the articles and studies that gained a score of 3 or more based on this scale had desirable quality and were enrolled in the study for evaluation. Quality of life in the selected studies was evaluated using quality of life questionnaires including the World Health Organization questionnaire and menopause-specific quality of life (MENQOL). This questionnaire was designed by Hilditch et al. in the Toronto University of Canada to assess the quality of life in menopausal women; it has 23 items with a scoring range of 0–6 based on the Likert scale and contains four domains of vasomotor (3 questions), psychosocial (7 questions), physical (16 questions), and sexual (3 questions). The gained score ranges from 0 to 174 and higher scores indicate more severe symptoms of menopause and lower quality of life. Since this questionnaire assesses the four domains of vasomotor, psychosocial, physical, and sexual, which are the main common symptoms of menopause during this period, it is considered a valid scale for evaluating the quality of life in menopausal women and has been used in various studies.
Before menopause, most women have a negative attitude toward menopause and results of the study showed that the more negative women's attitude toward menopause, the more severe their perception of the experienced symptoms. Hence, educating women in different fields including introduction to menopause and its problems, its coping strategies, diet, and body relaxation techniques  could have an important role in accepting menopause and improving women's quality of life during this period. Conducting weekly educational classes for menopausal women not only would help in changing their attitude toward menopause, but it could also be effective in decreasing the severity of the perceived symptoms and improving the quality of life. About education it should be noted that; in some studies, improvement of women's quality of life was occurred after 12 weeks of education (compared to 8 weeks)., Hence, to assure effectiveness and durability of the education, repeating the sessions during a longer period of time would be more effective.
On the other hand having regular physical activity and performing aerobic exercises are effective in improvement of the quality of life and its domains. However, two studies showed that performing physical activities is not effective on the sexual domain of quality life., Since sexual disorders in menopausal women are multifactorial, it could be caused due to mental disorders such as depression or anxiety, disrupted interpersonal relationships, fatigue, stress, drug consumption, history of physical or sexual abuse, and physical disorders that would lead to painful sexual performance such as endometriosis or atrophic vaginitis. Furthermore, considering that the level of testosterone would naturally decrease in menopausal women, it might cause decreased levels of excitation and sexual respond  and decreased sexual desire. Therefore, using phytoestrogen products along with performing aerobic exercises is recommended. Consumption of red clover by menopausal women could increase the level of luteinizing hormone, decrease the level of sex-hormone-binding globulin, increase the level of testosterone and also increase the level of blood estradiol; although it has no effect on the thickness of endometrium, it could decrease the severity of hot flushes  and improve the symptoms of vaginal dryness and the dyspareunia caused by it. However, the onset of effectiveness of licorice is faster than other herbal medicines, especially soy and red clover; on the other hand, licorice is native to Iran, and it is cheaper  which makes it more accessible. Along with these products, due to its pseudo-estrogenic effects, simultaneous topical use of royal jelly could be effective in decreasing sexual complications and improvement of quality of life in menopausal women.
| Conclusions|| |
Results of reviewing the studies showed that using phytoestrogen and isoflavone products along with performing physical exercises and participating in educational and counseling classes have an effective role in the improvement of the quality of life in menopausal women; it is recommended that aerobic exercises and educational classes would be continued.
In addition, MENQOL with four domains of vasomotor, psychosocial, physical, and sexual, which are truly related to the common effective symptoms on quality of life during menopause, is considered a valid questionnaire for assessing the quality of life in menopausal women and is an appropriate scale for studies on the quality of life in menopausal women. Since the purpose of systematic review studies is to regularly and systematically reviewing the studies, qualitatively gathering the results of the studies, combining the results of different studies and providing a general interpretation of the results, presenting a general conclusion from the results of the reviewed studies about effective strategies for improving the quality of life in menopausal women is one of the strengths of the present study. Although in this study, the researchers tried to gather all of the Iranian studies, inaccessibility to some of the studies, and unpublished results of other studies were the limitations of the present study.
The authors would like to thank all the researchers that their results were used for the present study, and also the deputy of research and technology of the Shahid Beheshti University of medical Sciences for providing library and electronic resources.
Financial support and sponsorship
This study was financially supported by Shahid Beheshti Medical Science University.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Ghazanfarpour M, Kaviani M, Abdolahian S, Bonakchi H, Najmabadi Khadijeh M, Naghavi M, et al.
The relationship between women's attitude towards menopause and menopausal symptoms among postmenopausal women. Gynecol Endocrinol 2015;31:860-5.
Abedzadeh M, Taebi M, Saberi F, Sadat Z. Quality of life and related factors in menopausal women in Kashan city. Iran South Med J 2009;12:81-8.
Abedzadeh Kalarhoudi M, Taebi M, Sadat Z, Saberi F. Assessment of quality of life in menopausal periods: A population study in Kashan, Iran. Iran Red Crescent Med J 2011;13:811-7.
Mirghafourvand M, Mohammad-Alizadeh-Charandabi S, Nedjat S, Mehrnaz A. Effects of aerobic exercise on quality of life in premenopausal and postmenopausal women: A randomized controlled trial. Iran J Obstet Gynecol Infertil 2014;17:19-26.
Ghazanfarpour M, Sadeghi R, Latifnejad Roudsari R, Mirzaii Najmabadi K, Mousavi Bazaz M, Abdolahian S, et al.
Effects of red clover on hot flash and circulating hormone concentrations in menopausal women: A systematic review and meta-analysis. Avicenna J Phytomed 2015;5:498-511.
Asgari P, Zand S, Narenji F, Bahramnezhad F, Mahmoudi M. The effect of Glycyrriza glabra
on quality of life in postmenopausal women. Complement Med J Fac Nurs Midwifery 2015;2:1146-54.
Yazdkhasti M, Keshavarz M, Merghati Khoei E, Hosseini AF. The effect of structured educational program by support group on menopause women's quality of life. Iran J Med Educ 2012;11:986-94.
Chen Y, Lin SQ, Wei Y, Gao HL, Wu ZL. Menopause-specific quality of life satisfaction in community-dwelling menopausal women in China. Gynecol Endocrinol 2007;23:166-72.
Kulasingam S, Moineddin R, Lewis JE, Tierney MC. The validity of the menopause specific quality of life questionnaire in older women. Maturitas 2008;60:239-43.
Forouhari S, Khajehei M, Moattari M, Mohit M, Rad MS, Ghaem H, et al.
The effect of education and awareness on the quality-of-life in postmenopausal women. Indian J Community Med 2010;35:109-14.
] [Full text]
Nikpour S, Haghani H. The effect of exercise on quality of life in postmenopausal women referred to the bone densitometry centers of Iran University of Medical Sciences. J Midlife Health 2014;5:176-9.
Chiu YW, Moore RW, Hsu CE, Huang CT, Liu HW, Chuang HY, et al.
Factors influencing women's quality of life in the later half of life. Climacteric 2008;11:201-11.
Chen Y, Lin SQ, Wei Y, Gao HL, Wang SH, Wu ZL, et al.
Impact of menopause on quality of life in community-based women in China. Menopause 2008;15:144-9.
Williams RE, Levine KB, Kalilani L, Lewis J, Clark RV. Menopause-specific questionnaire assessment in US population-based study shows negative impact on health-related quality of life. Maturitas 2009;62:153-9.
Bahri N, Yoshany N, Morowatisharifabad MA, Noghabi AD, Sajjadi M. The effects of menopausal health training for spouses on women's quality of life during menopause transitional period. Menopause 2016;23:183-8.
Yazdkhasti M, Keshavarz M, Khoei EM, Hosseini A, Esmaeilzadeh S, Pebdani MA, et al.
The effect of support group method on quality of life in post-menopausal women. Iran J Public Health 2012;41:78-84.
Asghari M, Mirghafourvand M, Mohammad-Alizadeh-Charandabi S, Malakouti J, Nedjat S. Effect of aerobic exercise and nutrition educationon quality of life and early menopause symptoms: A randomized controlled trial. Women Health 2017;57:173-88.
Alizadeh-Charandabi SM, Mirghafourvand M, Malakouti J, Asghari M, Nedjat S. Effect of nutrition education alone or combined with aerobic exercise on quality of life in perimenopausal and postmenopausal women: A randomized controlled trial. J Mazandaran Univ Med Sci 2014;24:63-74.
Nourozi M, Haghollahi F, Ramezanzadeh F, Hanachi P. Effect of soy milk consumption on quality of life in Iranian postmenopausal women. J Family Reprod Health 2015;9:93-100.
Ehsanpour S, Salehi K, Zolfaghari B, Bakhtiari S. The effects of red clover on quality of life in post-menopausal women. Iran J Nurs Midwifery Res 2012;17:34-40.
Moghadam R, Rostamkhani F, Raufi Kolachaye S. Effect of fish oil supplement on quality of life among middle age. Complement Med J 2014;4:891-903.
Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al.
Assessing the quality of reports of randomized clinical trials: Is blinding necessary? Control Clin Trials 1996;17:1-2.
Wang G, Mao B, Xiong ZY, Fan T, Chen XD, Wang L, et al.
The quality of reporting of randomized controlled trials of traditional Chinese medicine: A survey of 13 randomly selected journals from Mainland China. Clin Ther 2007;29:1456-67.
Seyyedi F, Kopaei MR, Miraj S. Comparison between vaginal royal jelly and vaginal estrogen effects on quality of life and vaginal atrophy in postmenopausal women: A clinical trial study. Electron Physician 2016;8:3184-92.
Karimy M, Aminshokravi F, Zareban E, Koohpayezadeh J, Baradaran H, Khoshdel A. The effect of education based on individual empowerment model on the quality of life in the menopause women in Zarandieh. Sci Mag Yafte 2014;16:80-90.
Abedzadeh M, Taebi M, Saberi F, Sadat Z. Comparison of quality of life in both menopausal and non-menopausal women. Paesh 2012;11:697-70.
Salahi S, Javanbakhtian R, Hasheminia A, Habibzadeh H. The effect of family-centered empowerment model on quality of life of hemodialysis patients. J Nurs Midwifery Urmia Univ Med Sci 2012;10:1.
Rasouli D, Mohammadpour Y, Safaie Z, Jafarizadeh H. The effect of two methods of self-empowerment training program on quality of life of diabetic patients attending the diabetes clinic in Urmia University of Medical Sciences, 2013. J Nurs Midwifery Urmia Univ Med Sci 2016;14:389-96.
Moriyama CK, Oneda B, Bernardo FR, Cardoso CG Jr., Forjaz CL, Abrahao SB, et al.
Arandomized, placebo-controlled trial of the effects of physical exercises and estrogen therapy on health-related quality of life in postmenopausal women. Menopause 2008;15:613-8.
Mansikkamäki K, Raitanen J, Malila N, Sarkeala T, Männistö S, Fredman J, et al.
Physical activity and menopause-related quality of life – A population-based cross-sectional study. Maturitas 2015;80:69-74.
Mirmohammadali M, Zendehdel-Rakhshandeh T, Sadeghniiat-Haghighi K, Faghihzadeh S, Taheri M. Evaluation of valerians' effect on sleep quantity and quality of menopausal women: Cross-over clinical trial. J Kermanshah Univ Med Sci 2014;17:687-97.
Vallance JK, Murray TC, Johnson ST, Elavsky S. Quality of life and psychosocial health in postmenopausal women achieving public health guidelines for physical activity. Menopause 2010;17:64-71.
Elavsky S, McAuley E. Physical activity and mental health outcomes during menopause: A randomized controlled trial. Ann Behav Med 2007;33:132-42.
Moore TR, Franks RB, Fox C. Review of efficacy of complementary and alternative medicine treatments for menopausal symptoms. J Midwifery Womens Health 2017;62:286-97.
Woyka J. Consensus statement for non-hormonal-based treatments for menopausal symptoms. Post Reprod Health 2017;23:71-5.
Dhingra D, Sharma A. Antidepressant-like activity of Glycyrrhiza glabra
L. in mouse models of immobility tests. Prog Neuropsychopharmacol Biol Psychiatry 2006;30:449-54.
Nahidi F, Kariman N, Simbar M, Mojab F. The study on the effects of Pimpinella anisum
on relief and recurrence of menopausal hot flashes. Iran J Pharm Res 2012;11:1079-85.
Ghazanfarpour M, Sadeghi R, Abdolahian S, Latifnejad Roudsari R. The efficacy of Iranian herbal medicines in alleviating hot flashes: A systematic review. Int J Reprod Biomed (Yazd) 2016;14:155-66.
Mishima S, Suzuki KM, Isohama Y, Kuratsu N, Araki Y, Inoue M, et al.
Royal jelly has estrogenic effects in vitro
and in vivo
. J Ethnopharmacol 2005;101:215-20.
Narita Y, Nomura J, Ohta S, Inoh Y, Suzuki KM, Araki Y, et al.
Royal jelly stimulates bone formation: Physiologic and nutrigenomic studies with mice and cell lines. Biosci Biotechnol Biochem 2006;70:2508-14.
Park HM, Cho MH, Cho Y, Kim SY. Royal jelly increases collagen production in rat skin after ovariectomy. J Med Food 2012;15:568-75.
Ishii R, Horie M, Murayama M, Maitani T. Analysis of tetracyclines in honey and royal jelly by LC/MS/MS. Shokuhin Eiseigaku Zasshi 2006;47:277-83.
Koya-Miyata S, Okamoto I, Ushio S, Iwaki K, Ikeda M, Kurimoto M, et al.
Identification of a collagen production-promoting factor from an extract of royal jelly and its possible mechanism. Biosci Biotechnol Biochem 2004;68:767-73.
Viuda-Martos M, Ruiz-Navajas Y, Fernández-López J, Pérez-Alvarez JA. Functional properties of honey, propolis, and royal jelly. J Food Sci 2008;73:R117-24.
Bogdanov S. Royal jelly, bee brood: Composition, health, medicine: A review. Lipids 2011;3:8-19.
Rondanelli M, Giacosa A, Opizzi A, Pelucchi C, La Vecchia C, Montorfano G, et al.
Effect of omega-3 fatty acids supplementation on depressive symptoms and on health-related quality of life in the treatment of elderly women with depression: A double-blind, placebo-controlled, randomized clinical trial. J Am Coll Nutr 2010;29:55-64.
Golyan Tehrani S, Ghobadzadeh M, Arastou M. Promoting health status of menopausal women by educating self care strategies. Hayat 2007;13:67-75.
Hilditch JR, Lewis J, Peter A, van Maris B, Ross A, Franssen E, et al.
Amenopause-specific quality of life questionnaire: Development and psychometric properties. Maturitas 1996;24:161-75.
Ayers B, Forshaw M, Hunter MS. The impact of attitudes towards the menopause on women's symptom experience: A systematic review. Maturitas 2010;65:28-36.
Cumming GP, Herald J, Moncur R, Currie H, Lee AJ. Women's attitudes to hormone replacement therapy, alternative therapy and sexual health: A web-based survey. Menopause Int 2007;13:79-83.