European Journal of Obstetrics & Gynecology and Reproductive Biology 199 (2016) 137140

Contents lists available at ScienceDirect

European Journal of Obstetrics & Gynecology and

Reproductive Biology
journal homepage: www.elsevier.com/locate/ejogrb

Myoma-associated pain frequency and intensity: a retrospective

evaluation of 1548 myoma patients
Matthias David a,*, Clara Maria Pitz a, Adriana Mihaylova a, Friederike Siedentopf b
a
Department of Gynecology, Virchow Campus, Charite University Hospital, Berlin, Germany
b
Breast Center, Department of Gynecology and Obstetrics, Martin Luther Hospital, Berlin, Germany

A R T I C L E I N F O A B S T R A C T

Article history: Objective: To analyze the possible relation between symptoms (especially pain) reported by myoma
Received 2 November 2015 patients and objective features of their myomas as determined by ultrasound. Specically: (1) What is
Received in revised form 2 February 2016 the frequency and intensity of myoma-related pain? (2) Does the pain intensity depend on the number,
Accepted 11 February 2016
size, or location of the myomas? (3) Is there any correlation between premenstrual pain, menstrual pain,
and pain during sexual intercourse?
Keywords: Study design: A retrospective analysis of data from a patient questionnaire and ultrasound exams,
Myomas
collected from February 2009 until January 2013 at the myoma clinic of a university hospital in a large
Uterine broids
European city. The study analyzed data from 1548 myoma patients. Patients completed a 010 Likert
Pain
Patient survey scale questionnaire about their symptoms. The number, size, and location of myomas were determined
from ultrasound exams.
Results: The three most frequent symptoms reported were hypermenorrhea, dysmenorrhea, and
premenstrual pain. There was no statistically signicant relationship between premenstrual pain or pain
during sexual intercourse on the one hand and the number, size, or location of myomas on the other
hand. For women with severe dysmenorrhea (Likert-scale scores of 810), submucosal myomas were
signicantly more frequent than all other myoma locations (p = 0.01). Severe dysmenorrhea (Likert-scale
scores of 810) was reported by a signicantly (p < 0.001) greater portion of the women whose largest
myoma had a largest diameter of <5 cm than by the women whose largest myoma had a diameter
5 cm. The number of myomas did not have a signicant inuence on the dysmenorrhea intensity. The
three types of pain (premenstrual, menstrual, and/or during sexual intercourse) had moderate pairwise
correlations (r values from 0.304 to 0.542) that were all statistically highly signicant (p < 0.001).
Conclusion: Myoma-associated pain is, alongside hypermenorrhea, the most frequent problem reported
by the affected patients. Unlike premenstrual pain and pain during sexual intercourse, the intensity of
menstrual pain is clearly dependent on the location and size of the largest myoma. Further research is
needed to better understand the degree to which the pain reported by the patients is due to features of
the myomas versus other possible factors.
2016 Elsevier Ireland Ltd. All rights reserved.

Introduction
Myomas are the most frequent benign neoplasias of the female
reproductive system. They probably occur in about 2040% of all
women of reproductive age [1]. In more precise processing of
hysterectomy preparations, leiomyomas of various sizes are found
* Corresponding author at: Charite Universitatsmedizin Berlin, Campus
Virchow-Klinikum, Klinik fur Gynakologie, Augustenburger Platz 1, D 13353
Berlin, Germany. Tel.: +49 30 450564142; fax: +49 30 450564932.
E-mail address: matthias.david@charite.de (M. David).
in up to 80% [2]. Most myomas are asymptomatic and do not need
any treatment. Yet 2050% of women with myomas have
complaints that encroach upon their quality-of-life and make
treatment necessary [3]. The following symptoms can typically be
caused by myomas: heavy and prolonged menstrual bleeding,
dysmenorrhea, dyspareunia, feelings of pressure or foreign bodies
in the underbelly, and bladder pressure [4,5].
These myoma-associated complaints have negative effects on
both the quality-of-life and the ability to work of the affected
patients, and they are associated with an increased utilization of the
healthcare system [6,7]. Patients with similar or identical myoma
pathology ndings report different complaints, individually or in

http://dx.doi.org/10.1016/j.ejogrb.2016.02.026
0301-2115/ 2016 Elsevier Ireland Ltd. All rights reserved.
138 M. David et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 199 (2016) 137140
combinations, and also of varying intensity [8,9]. In a large internet-
based survey in eight countries, 43% of the women who had reported
both a diagnosis of uterine broids and a mild to severe impact of
their symptoms on their daily life in the past 12 months then also
stated that their sexual life was negatively affected [11].
There are surprisingly few studies in which the relations
between myoma (or resulting uterine enlargement) and pain have
been systematically investigated. Such investigations would
enable clinicians to better determine which patients reported
pain is, might be, or is not due to the myoma. And that insight
would in turn be helpful for the indication of myoma therapy or the
selection of a treatment approach. So the aim of the current
retrospective study was to answer the following three questions:
(1) What is the frequency and intensity of pain in women seeking
medical care at an outpatient myoma clinic?
(2) Does the pain intensity depend on the number, size, or location
of the myomas?
(3) Is there an association of premenstrual pain, pain during
menstruation, and pain during sexual intercourse?
Methods
Study design and ethics
The current study was designed as a retrospective review of
these medical records. This retrospective evaluation received
advising from the Institutional Board of Charite University
Hospital, to ensure good scientic practice and adherence to data
privacy regulations.
Patients
All patients who came to the myoma outpatient clinic,
regardless of their reason, between February 2009 and January
2013, were included in the analysis. Repeat visits by the same
patient within that time period were not considered. Patients who
had either an incomplete questionnaire or lacked a clearly
evaluable ultrasound record or documentation were not included
in the study. Patients were excluded from the analysis if they were
pregnant or had ultrasound signs of adenomyosis.
Clinical measures
All patients who attended the myoma outpatient clinic lled
out a 28-item questionnaire on their symptoms and history that
we had developed. For the possible myoma symptoms, the
questionnaire had a visual 11-point Likert scale, where 0 repre-
sented no trouble and 10 represented extreme trouble. The
following eight symptoms that might be myoma-associated were
covered: (1) bleeding intensity, (2) premenstrual pain, (3)
menstrual pain, (4) pain during sexual intercourse, (5) back pain,
(6) bladder pressure, (7) pressure or feelings of a foreign mass in
the lower belly, (8) atulence or constipation.
All patients underwent a vaginal ultrasound (8 MHz receiving
transducer), and some also underwent an abdominal ultrasound
(5 MHz receiving transducer). All ultrasound examinations were
done with a Siemens Sonoline G40, and nearly all were performed
by the same clinician (MD). Each patients myoma size was
dened as the largest diameter of any myoma on the sonographs.
Statistics
The database consisted of 51 variables from the questionnaire
and the medical records. To simplify the analysis, some variables
were condensed into categories. Results are expressed as medians
with interquartile ranges (IQR) or as frequencies in percentages.
After verifying the normality of data distribution, patients with
severe pain versus non-severe pain were compared for differences
in terms of the three kinds of pain and the clinical parameters
(number of myomas, size of myomas, and location of the myomas),
using the non-parametric MannWhitney test. Tests were carried
out in an exact version, if there were small samples, large
differences in sample sizes, large but unbalanced groups, data sets
containing ties, or sparse data. Spearmans rho was used to
calculate the pairwise correlation between the three pain items
from the questionnaire. The statistical analysis was performed
with SPSS 22.0 (IBM). A value of p < 0.05 was considered
signicant. Because of the retrospective character of the study,
no adjustments for multiple testing have been made.
Results
From the 1936 visits to the myoma outpatient clinic during the
study timeperiod, 1548 (80%) were retained for analysis after
applying the exclusion criteria listed above in the Methods. The
median age was 42.5 years, and 542 patients (41.5%) were under
the age of 40 at the time of their visit. There were 887 patients
(58.5%) who had already been pregnant at least once. There were
551 patients (39.2%) who wanted to have another child, though
143 of this subgroup of patients (26%) were already over age 40.
There were 783 patients (50.6%) with one myoma, 415 (26.8%)
with two, and 239 (15.4%) with three or more. Table 1 shows the
size, localization, and the corresponding frequencies of the largest
myoma of each patient, which we dened as the dominant myoma.
Table 2 presents a summary of the patient replies to the eight
questionnaire items on complaints possibly associated with the
myoma. The most frequent complaints were heavy menstrual
bleeding (92.9%), pain during menstrual bleeding (78.8%), and
premenstrual pain (72.6%), though these complaints had various
symptom intensities.
The data evaluation concentrated on the three pain symptoms
(premenstrual pain, menstrual pain, and pain during sexual
intercourse), especially in the subgroup of women who gave the
highest scores (810) on these items. A score of 810 was given by
145 women (9.7%) for premenstrual pain, 269 women (18.0%) for
menstrual pain, and 49 women (3.4%) for pain during sexual
intercourse.
For the analysis of a possible relation between myoma-related
pains (all three kinds above) and the number, size, and location of
myoma, the patients were combined into two groups each: those
with severe pain (scores of 810) vs. all others (scores of 07). For
the variable of premenstrual pain, there was no signicant
difference between these two groups of patients in regards to
the number of myomas (p = 0.740), the size of the myomas
(p = 0.730), or the location of the myomas (p = 0.568). Also for the
variable of pain during sexual intercourse, there was no signicant
difference between these two groups of patients in regards to the
Table 1
Frequency of the size and position of the largest myoma among 1548 patients.
Myoma Frequency (%)
Largest diameter <2 cm 6.8
2 to <5 cm 38.5
5 to <8 cm 27.1
8 to <10 cm 9.7
10 cm 6.1
Location Submucosal 13.3
Intramural 56.3
Subserosal 18.0
Pedunculated 12.4
 M. David et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 199 (2016) 137140
Table 2
Intensity of myoma-associated complaints, listed in the order of frequency of the symptom in the study sample (n = 1548; items rated on an 11-point Likert scale; results given
as %.).
Symptom Frequency (rank)
Heavy menstrual bleeding 92.9 (1)
Menstrual pain 78.8 (2)
Premenstrual pain 72.6 (3)
Bladder pressure 64.1 (4)
Constipation 60.5 (5)
Back problems 59.4 (6)
Pressure in the lower belly 59.4 (6)
Pain during sexual intercourse 47.2 (7)
number of myomas (p = 0.664), the size of the myomas (p = 0.260),
or the location of the myomas (p = 0.286). For women with
severe menstrual pain, there was a signicant difference for the
submucosal location versus all other myoma locations (p = 0.01);
for the submucosal position, severe pain (response scores 810)
was observed signicantly more frequent than mild to moderate
pain (response scores 17). Women with a myoma size <5 cm
reported severe menstrual pain (scores 810) signicantly more
frequently than women with myomas 5 cm (p < 0.001). The
number of myomas (1 vs. 2 or more) had no inuence on
the existence of severe pain (scores of 810 vs. all others),
according to Fischers exact test (p = 0.289).
Some patients reported more than one of the three time-types
of pain. Both premenstrual and menstrual pain was reported by
39.8% of patients. Both premenstrual pain and pain during sexual
intercourse was reported by in 22.3% of women. Both menstrual
pain and pain during sexual intercourse was reported by 18.8%.
There was a moderate correlation between premenstrual and
menstrual pain (r = 0.542), between premenstrual pain and pain
during sexual intercourse (r = 0.343), and menstrual pain and pain
during sexual intercourse (r = 0.304), and all three of these
correlations were statistically highly signicant (p < 0.001).
Discussion
Although myomas occur relatively frequently among women of
reproductive age, and although 2030% of these women experi-
ence symptoms [12], there are only a few recent studies that focus
on myoma-associated complaints, especially the pain occurring
among myoma patients. Many facts are taken from old studies
without further verication. There is a lack of large, well-designed
investigations, in either clinical myoma patient samples or the
general population, that bring together the (subjective) patient
reports with the ndings of the medical examination.
In the present study of over 1500 myoma patients, heavy
bleeding was the most frequently reported complaint (over 90% of
all patients), followed by menstrual pain and then premenstrual
pain (both in the 7080% range). These frequencies of symptoms
are somewhat higher than those reported in two earlier small
clinical studies [10,13], and much higher than the rates of
symptoms reported in a large, multinational, online survey
[11], probably reecting the specialized clinical setting of our
patient sample. We also found moderate correlations (r-values of
0.3040.542) between premenstrual pain, menstrual pain, and
pain during sexual intercourse.
The intensity of premenstrual complaints and pain during
sexual intercourse was not inuenced by the number, size, or
location of myomas in our study. One previous study has found
that size and location of myoma had no signicant effect on the
prevalence and intensity of dyspareunia [15], while another
previous study has found that the size but not the location of
myomas was relevant to dyspareunia, which was more frequently
139
No symptoms Mild intensity Moderate intensity Severe intensity
(score 0) (scores 13) (scores 47) (scores 810)
7.0 7.6 41.7 41.8
20.9 31.6 27.6 18.0
26.9 35.6 26.0 9.7
36.4 23.7 24.6 9.5
39.2 23.8 22.2 9.3
40.6 25.9 24.8 8.6
41.9 23.1 21.4 7.9
52.3 28.4 13.2 3.4
associated with intramural fundal myomas [14]. Our study also
found strong intensity of dysmenorrhea in women with submu-
cosal myomas and myomas with a diameter less then 5 cm, which
agrees partly with a previous population-based study. Specically,
Lippmann and colleagues found that the size and number of
myomas were not related to the pain intensity, but women with
intramural myoma ndings had moderate or severe pain
symptoms signicantly more often [16].
Our study does have some limitations that must be kept in
mind. First, it is retrospective and therefore the quality of
evidence is not as high as it would be from a prospective study.
Nonetheless, the large sample size of our study make the results a
valuable point of reference for clinicians wishing to put their own
patients symptom complaints into the larger context. Second,
our study sampled women from a clinical setting, not from the
general population. Consequently, our ndings are only about the
myoma characteristics and pain experiences of women seeking
medical treatment. It is important to keep in mind that many
women with myomas in the general population will not seek
medical attention [11], often because their symptoms are less
severe, but possibly also for a variety of other reasons, including
perhaps socioeconomic, geographic, occupational, or health
factors. Women who do not seek medical attention may differ
in important ways from women who do, in terms of myoma
characteristics and pain experiences. Furthermore and third, our
clinical sample was obtained from a single specialized center at a
university hospital, and many of these patients were referred to
us from less specialized providers. Consequently, our sample may
not be representative of all myoma patients seeking medical
treatment in other settings. Fourth and most importantly, our
sample included only patients with myomas and did not have any
kind of comparison group of similar women without myomas. For
this reason, in all scientic rigor, we cannot attribute causality of
the pain frequency or intensity to the pathology of the myomas
observed on the ultrasound. It is theoretically possible that some
(or even all) of the pain and other symptoms reported by the
women in our sample were due to entirely other unrelated factors
besides the myomas. Only a comparison to otherwise similar
women without myomas would enable us to determine how
much of the pain and other symptoms is scientically attribut-
able to the myomas, and not to other general factors.
In conclusion, pain and hypermenorrhea are the most frequent
problems in patients with myomas seeking specialized medical
treatment. In contrast to premenstrual pain and pain during
sexual intercourse, the intensity of menstrual pain is dependent
on the location and size of the myoma. Further research
especially large, prospective, population-based, comparative
research is needed to better understand the degree to which
the pain and other symptoms reported by patients with myomas
is due to the myomas themselves, specic features of the myomas
such as location and size, or other factors unrelated to the
myomas.
140 M. David et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 199 (2016) 137140
Acknowledgements
We are thankful to Prof. Dr. Klaus-D. Wernecke, CRO SOSTANA
GmbH, for statistical advice. We would like to thank Michael
Hanna, PhD, for translating the manuscript from German into
English, providing some suggestions on the presentation of the
results, formatting the manuscript for submission to the journal,
and revising the manuscript after journal peer review, particularly
in regards to the study limitations. We also thank the Journal Editor
and two anonymous Peer Reviewers for providing feedback on the
manuscript.
References
[1] Wallach EE, Vlahos NF. Uterine myomas: an overview of development, clinical
features, and management. Obstet Gynecol 2004;104:393406.
[2] Stewart EA. Uterine broids. Lancet 2001;357:2938.
[3] Vilos GA, Allaire C, Laberge PY, Leyland N. The management of uterine
leiomyomas: SOGC clinical practice guideline. J Obstet Gynaecol Can 2015;37:
157178.
[4] Borah BJ, Nicholson WK, Bradley L, Stewart EA. The impact of uterine leio-
myomas: a national survey of affected women. Am J Obstet Gynecol 2013;209.
319.e1319.e20.
[5] Khan TA, Shehmar M, Gupta JK. Uterine broids: current perspectives. Int J
Womens Health 2014;6:95114.
[6] Williams VS, Jones G, Mauskopf J, Spalding J, DuChane J. Uterine broids: a
review of health-related quality of life assessment. J Womens Health 2006;15:
81829.
[7] Downes E, Sikirica V, Gilabert-Estelles J, et al. The burden of uterine broids in
ve European countries. Eur J Obstet Gynecol Reprod Biol 2010;152:96102.
[8] Wegienka G, Baird DD, Hertz-Picciotto I, et al. Self-reported heavy bleeding
associated with uterine leiomyomata. Obstet Gynecol 2003;101:4317.
[9] Nicholls C, Glover L, Pistrang N. The illness experiences of women with broids:
an exploratory qualitative study. J Psychosom Obstet Gynecol 2004;25:
295304.
[10] Okolo SO, Gentry CC, Perrett CW, Maclean AB. Familial prevalence of uterine
broids is associated with distinct clinical and molecular features. Hum
Reprod 2005;20:23214.
[11] Zimmermann A, Bernuit D, Gerlinger C, Schaefers M, Geppert K. Prevalence,
symptoms and management of uterine broids: an international internet-
based survey of 21,746 women. BMC Womens Health 2012;12:6.
[12] Baird DD, Dunson DB, Hill MC, Cousins D, Schectman JM. High cumulative
incidence of uterine leiomyoma in black and white women: ultrasound
evidence. Am J Obstet Gynecol 2003;188:1007.
[13] Cirkel U, Ochs H, Schneider HP, et al. Experience with leuprorelin acetate
depot in the treatment of broids: a German multicentre study. Clin Ther
1992;14(Suppl. A):3750.
[14] Moshesh M, Olshan AF, Saldana T, Baird D. Examining the relationship
between uterine broids and dyspareunia among premenopausal women
in the United States. J Sex Med 2014;11:8008.
[15] Ferrero S, Abbamonte LH, Giordano M, Parisi M, Ragni N, Remorgida V. Uterine
myomas, dyspareunia, and sexual function. Fertil Steril 2006;86:150410.
[16] Lippman SA, Warner M, Samuels S, Olive D, Vercellini P, Eskenazi B. Uterine
broids and gynecologic pain symptoms in a population-based study. Fertil
Steril 2003;80:148894.