1 Department of Obstetrics and Gynaecology and 2Department of Pathology, Gentofte University Hospital, Niels Andersens Vej 65, 2 900 Hellerup, Denmark
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Abstract |
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Key words: adenomyosis/prevalence/risk factors
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Introduction |
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Materials and methods |
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All the histological specimens were re-examined by the same pathologists, with special emphasis on the appearance of adenomyosis, the distance between foci of adenomyosis and the endo-myometrial junction, and the presence of surrounding myometrial hyperplasia. Other histopathological variables were also noted, such as endometrial status and the number of histological samples from the endo-myometrium of each uterus.
A total of 538 women (98%) were scheduled for abdominal hysterectomy, and 11 (2%) for vaginal hysterectomy. The mean age was 54 years (range 2388). Indications were divided into four main categories, with 183 women having more than one indication. Bleeding disorders were found in 278 women (50.6%), malignant neoplasia in the genital tract in 185 (33.7%), pelvic pain in 146 (26.6%) and pelvic relaxation in 142 women (25.9%). The most frequent combination of diagnosis was bleeding disorder and pelvic pain, in 123 cases. Only 23 women underwent hysterectomy with pelvic pain as the only indication.
In the statistical analysis, the odds ratios (OR) and their corresponding 95% confidence interval (CI) were calculated using multiple logistic regression analysis in SAS for Windows, Release 6.12. If the value 1.0 was not covered by the CI, the test result was considered statistically significant (P < 0.05). The study was approved by the Local Ethical Committee of Copenhagen County.
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Results |
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Discussion |
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The present study has demonstrated that the prevalence of adenomyosis at hysterectomy varies from 10.018.2%, depending on different histological criteria with regard to the distance from the endo-myometrial junction to the foci of adenomyosis and the presence or absence of myometrial hyperplasia around the foci. Most previously published studies utilize one low-power field as the minimal distance in the diagnostic criteria. Great variation has been demonstrated in the area of microscopic fields using different microscopes, and the authors conclude that the exact measure of the area should be used (Ellis and Whitehead, 1981). This problem is also discussed by Ferenczy, suggesting a relative measure of 25% of the uterine wall as the ideal distance for the diagnosis of adenomyosis (Ferenczy, 1998
). Inaccurate measuring could explain some of the great variation in the prevalence of adenomyosis. A third factor could be the number of histological samples taken for investigation. A proportional correlation between the number of samples taken and the presence of adenomyosis in the same uterus has been shown (Bird et al., 1972
). In addition, it has been suggested that the pathologists' awareness of this condition could have an influence on the prevalence. In order to eliminate this possible information bias, we decided to re-examine all the histological specimens using strict objective criteria. We suggest the criteria for adenomyosis should be the presence of endometrial foci embedded in the myometrium at least 3 mm from the endo-myometrial junction surrounded by myometrial hyperplasia. This includes an absolute distance and consequently should be easy to reproduce, irrespective of the microscope used.
In recently published studies, parity, previous spontaneous abortions, dilatation and curettage for gynaecological indications, age between 40 and 59 years, and endometrial hyperplasia have been positively statistically associated with adenomyosis, whereas smoking was found to be negatively correlated (Shaikh and Khan., 1990; Vercellini et al., 1995
; Parazzini et al., 1997
). In the present study we have introduced all of these possible confounding variables into our multiple regression model, with the exception of data on smoking habits, which were not available. Data retrieved from the medical records were retrospective. As they were obtained and described before the time of histological examination of the uterus, they may have lacked precision, but could not introduce bias into the statistical analysis due to differential misclassification.
We did not find any statistical association between adenomyosis and previous transcervical or transmural surgery, and we have consequently been unable to verify the suggested hypothesis of surgically-induced endometrial implantation as a possible cause of adenomyosis. Neither did we find any significant relationship between adenomyosis and pain-related symptoms, indication for hysterectomy, age, parity or the number of endo-myometrial samples, although a slight tendency was seen in women with pre-operative dysmenorrhoea or aged 55 years or more. The only significant association in our data was the relationship between adenomyosis and endometrial hyperplasia. The result substantiates previously published findings of a relationship between high concentrations of oestrogen and adenomyosis (Parazzini et al., 1997), and the elevated oestrogen concentration in the menstrual blood of women with adenomyosis (Takahashi et al., 1989
). In addition, relatively high oestrogen biosynthesis due to aromatase activity in human adenomyotic tissue has been described, and it is suggested that this contributes to the growth of adenomyosis. This synthesis of oestrogens could be blocked by danazol (Urabe et al., 1989
; Yamamoto et al., 1993
). Furthermore, Tamoxifen has been described as inducing adenomyosis in post-menopausal women treated for breast cancer, because of its oestrogenagonistic effect (Cohen et al., 1997
). Taken together, these findings indicate that oestrogen plays an essential role in the aetiology of adenomyosis. However, whether adenomyosis is the cause or effect of a local increased oestrogen concentration in the uterine environment cannot be inferred using a prevalence study design. With the continuous advance in the fields of endovaginal ultrasound and magnetic resonance scanning (Mark et al., 1987
; Ascher et al., 1994
; Vercellini et al., 1998
), it may be possible in the future to perform non-invasive population-based prospective incidence studies of adenomyosis, thus throwing a clearer and more homogeneous light on the effect of oestrogen and other potential risk factors on this elusive condition.
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Notes |
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References |
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Submitted on April 4, 2001; accepted on July 25, 2001.