Human Reproduction Vol.16, No.11 pp.

24182421, 2001

Prevalence and risk factors of adenomyosis at hysterectomy

T.Bergholt1,3, L.Eriksen1, N.Berendt2, M.Jacobsen2 and J.B.Hertz1
1Department

of Obstetrics and Gynaecology and 2Department of Pathology, Gentofte University Hospital, Niels Andersens Vej 65,
2900 Hellerup, Denmark
3To

whom correspondence should be addressed. E-mail: tbe@dadlnet.dk

BACKGROUND: The present study was performed to evaluate the prevalence and possible associated risk factors
for adenomyosis. METHODS: Medical records were retrieved and histo-pathological material re-examined for 549
consecutive women undergoing hysterectomy in a two-year period from 19901991. RESULTS: The prevalence of
adenomyosis in the study varied from 10.018.2%, depending on different diagnostic criteria. The presence of
endometrial hyperplasia at the time of hysterectomy was the only variable significantly associated with adenomyosis
(OR 3.0; 95% CI: 1.28.3). No statistically significant association was found between adenomyosis and previous
caesarean section, endometrial curettage or evacuation of the uterus. Furthermore, we did not see any significant
association between adenomyosis and pain-related symptoms, indication for hysterectomy, age, parity or number
of myometrial samples. CONCLUSIONS: Our study stresses the need for precise diagnostic criteria for adenomyosis,
and furthermore indicates that endometrial hyperplasia and adenomyosis may have a common aetiology.
Key words: adenomyosis/prevalence/risk factors

Introduction
Adenomyosis uteri is a pathological entity characterized by
the presence of endometrial glands and stroma embedded
within the myometrium without apparent contact with the
endo-myometrial junction. As the diagnosis of adenomyosis
is based on histological examination, the condition is best
described in women at the time of hysterectomy. Adenomyosis
is often seen in peri-menopausal women, and is suggested to
be related to bleeding disorders, dysmenorrhoea and parity.
The prevalence has been reported to range from 8.861.5% in
women at the time of hysterectomy (Hunter et al., 1947; Israel
and Wountersz, 1959; Molitor, 1971; Bird et al., 1972; Olawabi
and Strickler, 1977; Lee et al., 1984; Shaikh and Khan, 1990;
Seidman and Kjerulff, 1996), and some authors have described
this entity as elusive (Bird et al., 1972). As the results are
conflicting, several potential forms of bias may have influenced
the opposing findings of these studies. Various reports have
outlined the appearance of symptomatic endometrial tissue in
the abdominal wall following amniocentesis and pelvic surgery,
especially following caesarean section (Koger et al., 1993;
Hughes et al., 1997; Liang et al., 1998). This phenomenon has
been explained by implantation during surgery, followed by
the embedding and survival of the ectopic endometrium. For
this reason, a history of transuterine and transcervical surgery,
and other potential variables, were introduced into the present
study in order to determine whether they could be risk factors
for adenomyosis.
Materials and methods
In the period from January 1990 through to December 1991, 549
consecutive patients underwent hysterectomy at the Department

2418

of Obstetrics and Gynaecology, Gentofte University Hospital. The

hospital is a tertiary teaching hospital, serving a population of
~200 000 in Copenhagen County. The medical records were reviewed
by the authors, and age, parity, history of previous caesarean section,
curettage or evacuation of the uterus, pre-operative dyspareunia,
dysmenorrhoea or chronic pelvic pain, indications for hysterectomy,
and post-operative findings, including the presence of peritoneal
endometriosis, were obtained, together with the original pathological
reports. Caesarean section, uterine evacuation and transcervical
curettage were recorded in this study only if performed more than 6
months previous to hysterectomy. This was done in order to avoid
temporarily embedded endometrial tissue inside the myometrium
being diagnosed as adenomyosis.
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 endomyometrium 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
European Society of Human Reproduction and Embryology

Prevalence and risk of adenomyosis

Table I. Diagnostic criteria and prevalence of adenomyosis in 549 women

undergoing hysterectomy in Gentofte University Hospital, 19901991

Table III. Pelvic pain symptoms and the corresponding crude/adjusted odds
ratios for the prevalence of adenomyosis at hysterectomy

Distance between endometrial glands

and the endo-myometrial junction

Myometrial
hyperplasia

Prevalence of
adenomyosis (%)

Symptoms

1 mm

18.2
14.3
15.8
12.5
11.5
10.0

Dyspareunia
no
yes
Dysmenorrhoea
no
yes
Chronic pelvic pain
no
yes

3 mm
5 mm

Table II. Previous uterine surgery, parity, age and number of endomyometrial samples and crude/adjusted odds ratios for the prevalence of
adenomyosis at hysterectomy
Previous uterine surgery

Caesarean section
no
yes
Endometrial curretage
no
yes
Evacuation
no
yes
Parity
0
1
1
Age
45
4554
54
Number of endo-myometrial
4
46
6

Number of
patients

ORc

Number of
patients

ORc

ORadj (95% CI)

500
49

1.0
0.8

1.0
0.8 (0.32.4)

454
95

1.0
1.3

1.0
1.6 (0.83.3)

489
60

1.0
0.9

1.0
0.9 (0.42.2)

ORc crude odds ratio; ORadj odds ratio adjusted for age, parity,
endometrial status, number of histological samples from the endomyometrium, and all variables in the table; CI confidence interval.

ORadj (95% CI)

517
32

1.0
1.0

1.0
1.0 (0.33.1)

361
188

1.0
1.1

1.0
1.2 (0.72.1)

413
136

1.0
1.3

1.0
1.2 (0.72.2)

99
116
334

1.0
1.1
1.0

1.0
1.2 (0.52.8)
1.0 (0.52.0)

140
203
206
samples
126
349
74

1.0
1.1
1.4

1.0
1.2 (0.62.4)
2.4 (1.05.8)

1.0
0.7
1.6

1.0
0.8 (0.41.5)
1.3 (0.32.4)

ORc crude odds ratio; ORadj odds ratio adjusted for endometrial status
and all variables in the table; CI confidence interval.

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.

Results
The prevalence of adenomyosis in our study is presented in
Table I according to (i) the various distances between the
endomyometrial junction and the endometrial glands and
stroma and (ii) the presence or absence of myometrial hyperplasia. As may be seen, the prevalence ranges from 10.0
18.2%. In the subsequent analysis, we decided on the following
criterion for adenomyosis: 3 mm distance from the foci of
the glands and stroma to the endo-myometrial junction and
surrounding myometrial hyperplasia, resulting in a prevalence
of 12.5%. Of these 68 cases, 45 were histologically classified
as diffuse, and the rest as focal.
A history of previous Caesarean section, endometrial
curettage or evacuation did not demonstrate any association
with adenomyosis in the present study population, as is
presented in Table II. Moreover, no association was established

Table IV. Indications and the corresponding crude/adjusted odds ratios for
the prevalence of adenomyosis at hysterectomy. Each patient may have
more than one indication
Indication

Number of
patients

Bleeding disorder
no
271
yes
278
Pelvic relaxation
no
407
yes
142
Pelvic pain
no
403
yes
146
Neoplasia of the genital tract
no
364
yes
185

ORc

ORadj (95% CI)

1.0
1.0

1.0
0.7 (0.31.5)

1.0
0.7

1.0
0.5 (0.21.2)

1.0
0.8

1.0
0.7 (0.31.3)

1.0
1.0

1.0
0.6 (0.21.4)

ORc crude odds ratio; ORadj odds ratio adjusted for age, parity,
endometrial status, number of histological samples from the endomyometrium, and all variables in the table; CI confidence interval.

between adenomyosis and parity or the number of histological

samples from the endo-myometrium. However, an age of
54 years had an adjusted OR 2.4 (95% CI: 1.05.8),
indicating a tendency towards an association with adenomyosis. Table III presents the association between painrelated symptoms and adenomyosis. No relationship was found
between dyspareunia, dysmenorrhea, chronic pelvic pain and
adenomyosis. With regard to the four categories of indications
used in this study, none demonstrated significant associations
with the presence of adenomyosis in the adjusted multivariate
analysis, as presented in Table IV. In the analysis of the
endometrial status demonstrated in Table V, only hyperplasia
(OR 3.0; 95% CI: 1.28.3) demonstrates a significant
positive association with adenomyosis.
Discussion
In the study of adenomyosis, the optimal study-population
would consist of women with a uterus in situ. As the diagnosis
of this condition at the present time is based on histological
examination of the entire uterus, present knowledge is mainly
2419

T.Bergholt et al.

Table V. Endometrial status and the corresponding crude/adjusted odds

ratios for the prevalence of adenomyosis at hysterectomy
Endometrial
status
Atrophia
no
yes
Cycling
no
yes
Hyperplasia
no
yes
Endometroid
carcinoma
no
yes
Peritoneal
endometriosis
no
yes

Number of
patients

ORc

ORadj (95% CI)

482
67

1.0
0.3

1.0
0.4 (0.12.0)

345
204

1.0
1.2

1.0
2.2 (0.85.8)

485
64

1.0
3.0

1.0
3.0 (1.28.3)

508
41

1.0
0.3

1.0
0.4 (0.12.0)

488
51

1.0
0.6

1.0
0.6 (0.21.9)

ORc crude odds ratio; ORadj odds ratio adjusted for age, parity,
endometrial status, number of histological samples from the endomyometrium, and all variables in the table; CI confidence interval.

based on women undergoing hysterectomy. As there is great

variation in the use and indication for hysterectomy on national
as well as international levels (Haas et al., 1993; Hall and
Cohen, 1994, Keskimaki et al., 1994; Ferenczy, 1998) populations of women undergoing hysterectomy in different regions
are heterogeneous, and consequently subject to demographic
variation. This fact is probably responsible for some of the
great variation seen in the prevalence of adenomyosis at
hysterectomy worldwide.
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 endo2420

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.

References
Ascher, S.M., Arnold, L.L., Patt, R.H. et al. (1994) Adenomyosis: prospective
comparison of MR and transvaginal sonography. Radiology, 190, 803806.

Prevalence and risk of adenomyosis

Bird, C.C., McElin, T.W. and Manalo-Estrella, P. (1972) The elusive
adenomyosis of the uterus. Am. J. Obstet. Gynecol., 112, 583593.
Cohen, I., Beyth, Y., Shapira, J. et al. (1997) High frequency of adenomyosis
in postmenopausal breast cancer patients treated with tamoxifen. Gynecol.
Obstet. Invest., 44, 200205.
Ellis, P.S.J. and Whitehead, R. (1981) Mitosis counting a need for reappraisal.
Hum. Pathol., 12, 34.
Ferenczy, A. (1998) Pathophysiology of adenomyosis. Hum. Reprod. Update,
4, 312322.
Haas, S., Acker, D., Donahue, C. et al. (1993) Variation in hysterectomy rates
across small geographic areas of Massachusetts. Am. J. Obstet. Gynecol.,
169, 150154.
Hall, R.E. and Cohen, M.M. (1994) Variation in hysterectomy rates in Ontario:
does the indication matter. C.M.A.J., 151, 17131719.
Hughes, M.L., Bartholomew, D. and Palluzi, M. (1997) Abdominal wall
endometriosis after amniocentesis. A case report. J. Reprod. Med., 42,
597599.
Hunter, W.C., Smith, L.L. and Reiner, W.C. (1947) Uterine adenomyosis.
Incidence, symptoms and pathology in 1856 hysterectomies. Am. J. Obstet.
Gynecol., 53, 663668.
Israel, S.L. and Woutersz, T.B. (1959) Adenomyosis: a neglected diagnosis.
Obstet. Gynecol., 14, 168173.
Keskimaki, I., Aro, S. and Teperi, J. (1994) Regional variation in surgical
procedures in Finland. Scand. J. Soc. Med., 22, 132138.
Koger, K.E., Shatney, C.H., Hogde, K. et al. (1993) Surgical scar endometriosis.
Surg. Gynecol. Obstet., 177, 243246.
Lee, N.C., Dicker, R.C., Rubin, G.L. et al. (1984) Confirmation of the
preoperative diagnoses for hysterectomy. Am. J. Obstet. Gynecol., 150,
283287.

Liang, C.C., Liou, B., Tsai, C.C. et al. (1998) Scar endometriosis. Int. Surg.,
83, 6971.
Mark, A.S., Hricak, H., Heinrichs, L.W. et al. (1987) Adenomyosis and
leiomyoma: Differential diagnosis with MRI. Radiology, 163, 527529.
Molitor, J.J. (1971) Adenomyosis: a clinical and pathological appraisal. Am.
J. Obstet. Gynecol., 110, 275284.
Olawabi, T.O. and Strickler, R.C. (1977) Adenomyosis a neglected diagnosis.
Obstet. Gynecol., 50, 424427.
Parazzini, F., Vercellini, P., Panazza, L.C. et al. (1997) Risk factors for
adenomyosis. Hum. Reprod., 12, 12751279.
Seidman, J.D. and Kjerulff, K.H. (1996) Pathologic findings from the Maryland
Womens Health Study: practice patterns in the diagnosis of adenomyosis.
Int. J. Gynecol. Pathol., 15, 217221.
Shaikh, H. and Khan, K.S. (1990) Adenomyosis in pakistani women: four
year experience at the Aga Khan University Medical Centre, Karachi. J.
Clin. Pathol., 43, 817819.
Takahashi, K., Nagata, H. and Kitao, M. (1989) Clinical usefulness of
determination of estradiol level in the menstrual blood for patients with
endometriosis. Acta Obstet. Gynaecol. Jpn., 41, 18491850.
Urabe, M., Yamamoto, T., Kitawaki, J. et al. (1989) Estrogen biosynthesis in
human uterine adenomyosis. Acta Endocrinol. (Copenhagen), 121, 259264.
Vercellini, P., Parazzini, F., Oldani, S. et al. (1995) Adenomyosis at
hysterectomy:A study on frequency distribution and patient characteristics.
Hum. Reprod., 10, 11601162.
Vercellini, P., Cortesi, I., De Giorgi, O. et al. (1998) Transvaginal
ultrasonography versus uterine needle biopsy in the diagnosis of diffuse
adenomyosis. Hum. Reprod., 13, 28842887.
Yamamoto, T., Noguchi, T., Tamura, T. et al. (1993) Evidence for estrogen
synthesis in adenomyotic tissue. Am. J. Obstet. Gynecol., 169, 734738.
Received on April 4, 2001; accepted on July 25, 2001

2421