Objectives and Design: Endometriosis-related pain can be caused by anatomical distortions as well as environmental factors such as inflammation and oxidative stress. The aim of this study is to investigate the relationship between the severity of dysmenorrhea in patients with ovarian endometrioma (OMA) and cyst fluid (CF) concentrations of irons, including total iron, heme iron, and free iron. Method: Eighty-three patients who were histologically diagnosed with OMA were enrolled in the Department of Gynecology, Nara Medical University Hospital, between 2013 and 2019. The patients were divided into 4 groups according to the severity of dysmenorrhea: no pain, mild, moderate, and severe. Iron concentration was measured by the inductively coupled plasma optical emission spectrometry method. Results: There were no significant differences among the 4 groups in variables such as age at diagnosis, preoperative CA125, preoperative CA19-9, cyst size, and tumor laterality (unilateral or bilateral). There was a positive correlation between the severity of dysmenorrhea and total iron (p < 0.001) and heme iron (p = 0.016) concentrations. Multiple regression analyses revealed that the CF concentration of total iron (hazard ratio 18.75, 95% confidence interval: 2.26–155.35, p = 0.007) was a significant independent variable associated with the severity of dysmenorrhea. A receiver operating characteristic curve analysis showed that a total iron exceeding 290.8 mg/L was associated with severe dysmenorrhea with a sensitivity of 90.9% and a specificity of 65.7%. Limitations: This study excluded patients with adenomyosis, superficial endometriosis, or deep endometriosis, resulting in a smaller number of cases. Iron levels could not be compared to the endometriosis stage using the r-ASRM score. Conclusions: There is no clear evidence that iron predicts the severity of endometriosis-related pain. However, iron may be closely associated with dysmenorrhea.

1.
Koninckx
PR
,
Ussia
A
,
Adamyan
L
,
Wattiez
A
,
Gomel
V
,
Martin
DC
.
Pathogenesis of endometriosis: the genetic/epigenetic theory
.
Fertil Steril
.
2019 Feb
;
111
(
2
):
327
40
. .
2.
Nisenblat
V
,
Bossuyt
PM
,
Farquhar
C
,
Johnson
N
,
Hull
ML
.
Imaging modalities for the non-invasive diagnosis of endometriosis
.
Cochrane Database Syst Rev
.
2016 Feb 26
;
2
(
2
):
CD009591
. .
3.
Fraser
MA
,
Agarwal
S
,
Chen
I
,
Singh
SS
.
Routine vs. expert-guided transvaginal ultrasound in the diagnosis of endometriosis: a retrospective review
.
Abdom Imaging
.
2015 Mar
;
40
(
3
):
587
94
. .
4.
Muzii
L
,
Marana
R
,
Pedulla
S
,
Catalano
G
,
Caruana
P
,
Rizzi
M
, et al.
Endometriosis-associated dysmenorrhea is not related to typical or atypical peritoneal implants
.
J Am Assoc Gynecol Laparosc
.
1996 Aug
;
3
(
4
):
S32
. .
5.
Chopin
N
,
Ballester
M
,
Borghese
B
,
Fauconnier
A
,
Foulot
H
,
Malartic
C
, et al.
Relation between severity of dysmenorrhea and endometrioma
.
Acta Obstet Gynecol Scand
.
2006
;
85
(
11
):
1375
80
. .
6.
Porpora
MG
,
Koninckx
PR
,
Piazze
J
,
Natili
M
,
Colagrande
S
,
Cosmi
EV
.
Correlation between endometriosis and pelvic pain
.
J Am Assoc Gynecol Laparosc
.
1999 Nov
;
6
(
4
):
429
34
. .
7.
Vercellini
P
,
Fedele
L
,
Aimi
G
,
Pietropaolo
G
,
Consonni
D
,
Crosignani
PG
.
Association between endometriosis stage, lesion type, patient characteristics and severity of pelvic pain symptoms: a multivariate analysis of over 1000 patients
.
Hum Reprod
.
2007 Jan
;
22
(
1
):
266
71
. .
8.
Vercellini
P
,
Trespidi
L
,
De Giorgi
O
,
Cortesi
I
,
Parazzini
F
,
Crosignani
PG
.
Endometriosis and pelvic pain: relation to disease stage and localization
.
Fertil Steril
.
1996 Feb
;
65
(
2
):
299
304
. .
9.
Wright
KR
,
Mitchell
B
,
Santanam
N
.
Redox regulation of microRNAs in endometriosis-associated pain
.
Redox Biol
.
2017 Aug
;
12
:
956
66
. .
10.
Yoshimoto
C
,
Iwabuchi
T
,
Shigetomi
H
,
Kobayashi
H
.
Cyst fluid iron-related compounds as useful markers to distinguish malignant transformation from benign endometriotic cysts
.
Cancer Biomark
.
2015
;
15
(
4
):
493
9
. .
11.
Iwabuchi
T
,
Yoshimoto
C
,
Shigetomi
H
,
Kobayashi
H
.
Cyst fluid hemoglobin species in endometriosis and its malignant transformation: the role of metallobiology
.
Oncol Lett
.
2016 May
;
11
(
5
):
3384
8
. .
12.
Amreen
S
,
Kumar
P
,
Gupta
P
,
Rao
P
.
Evaluation of oxidative stress and severity of endometriosis
.
J Hum Reprod Sci
.
2019 Jan-Mar
;
12
(
1
):
40
6
. .
13.
Baek
JC
,
Jo
JY
,
Lee
SM
,
Cho
IA
,
Shin
JK
,
Lee
SA
, et al.
Differences in 25-hydroxy vitamin D and vitamin D-binding protein concentrations according to the severity of endometriosis
.
Clin Exp Reprod Med
.
2019 Sep
;
46
(
3
):
125
31
. .
14.
Harada
T
.
Dysmenorrhea and endometriosis in young women
.
Yonago Acta Med
.
2013 Dec
;
56
(
4
):
81
4
.
15.
Andersch
B
,
Milsom
I
.
An epidemiologic study of young women with dysmenorrhea
.
Am J Obstet Gynecol
.
1982 Nov 15
;
144
(
6
):
655
60
. .
16.
Tosti
C
,
Pinzauti
S
,
Santulli
P
,
Chapron
C
,
Petraglia
F
.
Pathogenetic mechanisms of deep infiltrating endometriosis
.
Reprod Sci
.
2015 Sep
;
22
(
9
):
1053
9
. .
17.
Ahn
SH
,
Monsanto
SP
,
Miller
C
,
Singh
SS
,
Thomas
R
,
TayadePathophysiology
C
, et al.
Pathophysiology and immune dysfunction in endometriosis
.
Biomed Res Int
.
2015
;
2015
:
795976
. .
18.
McKinnon
B
,
Mueller
M
,
Montgomery
G
.
Progesterone resistance in endometriosis: an acquired property?
Trends Endocrinol Metab
.
2018 Aug
;
29
(
8
):
535
48
. .
19.
Zhu
TH
,
Ding
SJ
,
Li
TT
,
Zhu
LB
,
Huang
XF
,
Zhang
XM
.
Estrogen is an important mediator of mast cell activation in ovarian endometriomas
.
Reproduction
.
2018 Jan
;
155
(
1
):
73
83
. .
20.
Kirchhoff
D
,
Kaulfuss
S
,
Fuhrmann
U
,
Maurer
M
,
Zollner
TM
.
Mast cells in endometriosis: guilty or innocent bystanders?
Expert Opin Ther Targets
.
2012 Mar
;
16
(
3
):
237
41
. .
21.
Liang
Y
,
Liu
D
,
Yang
F
,
Pan
W
,
Zeng
F
,
Wu
J
, et al.
Perineural invasion in endometriotic lesions contributes to endometriosis-associated pain
.
Jpr
.
2018 Sep 25
;
11
:
1999
2009
. .
22.
Tamburro
S
,
Canis
M
,
Albuisson
E
,
Dechelotte
P
,
Darcha
C
,
Mage
G
.
Expression of transforming growth factor beta1 in nerve fibers is related to dysmenorrhea and laparoscopic appearance of endometriotic implants
.
Fertil Steril
.
2003 Nov
;
80
(
5
):
1131
6
. .
23.
Zhao
L
,
Yang
H
,
Xuan
Y
,
Luo
Z
,
Lin
Q
,
Zhao
J
, et al.
Increased expression of fibroblast growth factor receptor 1 in endometriosis and its correlation with endometriosis-related dysmenorrhea and recurrence
.
Eur J Obstet Gynecol Reprod Biol
.
2015 Jan
;
184
:
117
24
. .
24.
McKinnon
B
,
Bersinger
NA
,
Huber
AW
,
Kuhn
A
,
Mueller
MD
.
PPAR-gamma expression in peritoneal endometriotic lesions correlates with pain experienced by patients
.
Fertil Steril
.
2010 Jan
;
93
(
1
):
293
6
. .
25.
Wu
J
,
Xie
H
,
Yao
S
,
Liang
Y
.
Macrophage and nerve interaction in endometriosis
.
J Neuroinflammation
.
2017 Mar 14
;
14
(
1
):
53
. .
26.
Morotti
M
,
Vincent
K
,
Brawn
J
,
Zondervan
KT
,
Becker
CM
.
Peripheral changes in endometriosis-associated pain
.
Hum Reprod Update
.
2014 Sep-Oct
;
20
(
5
):
717
36
. .
27.
Laganà
AS
,
Garzon
S
,
Götte
M
,
Viganò
P
,
Franchi
M
,
Ghezzi
F
, et al.
The pathogenesis of endometriosis: molecular and cell biology insights
.
Ijms
.
2019 Nov 10
;
20
(
22
):
5615
. .
28.
Waelkens
E
,
Peterse
DP
,
Lebovic
D
,
Meuleman
C
,
Tomassetti
C
,
Peeraer
K
, et al.
Evaluation of total, active, and specific myeloperoxidase levels in women with and without endometriosis
.
Gynecol Obstet Invest
.
2018
;
83
(
2
):
133
9
.
29.
Abu-Asab
M
,
Zhang
M
,
Amini
D
,
Abu-Asab
N
,
Amri
H
.
Endometriosis gene expression heterogeneity and biosignature: a phylogenetic analysis
.
Obstet Gynecol Int
.
2011
;
2011
:
719059
. .
30.
Kobayashi
H
,
Yamada
Y
,
Kanayama
S
,
Furukawa
N
,
Noguchi
T
,
Haruta
S
, et al.
The role of iron in the pathogenesis of endometriosis
.
Gynecol Endocrinol
.
2009 Jan
;
25
(
1
):
39
52
. .
31.
Iwabuchi
T
,
Yoshimoto
C
,
Shigetomi
H
,
Kobayashi
H
.
Oxidative stress and antioxidant defense in endometriosis and its malignant transformation
.
Oxid Med Cell Longev
.
2015
;
2015
:
848595
. .
32.
Nassif
J
,
Abbasi
SA
,
Nassar
A
,
Abu-Musa
A
,
Eid
AA
.
The role of NADPH-derived reactive oxygen species production in the pathogenesis of endometriosis: a novel mechanistic approach
.
J Biol Regul Homeost Agents
.
Jan–Mar 2016
;
30
(
1
):
31
40
.
33.
Yamacita-Borin
FY
,
Zarpelon
AC
,
Pinho-Ribeiro
FA
,
Fattori
V
,
Alves-Filho
JC
,
Cunha
FQ
, et al.
Superoxide anion-induced pain and inflammation depends on TNFα/TNFR1 signaling in mice
.
Neurosci Lett
.
2015 Sep 25
;
605
:
53
8
. .
34.
Maioli
NA
,
Zarpelon
AC
,
Mizokami
SS
,
Calixto-Campos
C
,
Guazelli
CF
,
Hohmann
MS
, et al.
The superoxide anion donor, potassium superoxide, induces pain and inflammation in mice through production of reactive oxygen species and cyclooxygenase-2
.
Braz J Med Biol Res
.
2015 Apr
;
48
(
4
):
321
31
. .
35.
Lourenco-Gonzalez
Y
,
Fattori
V
,
Domiciano
TP
,
Rossaneis
AC
,
Borghi
SM
,
Zaninelli
TH
, et al.
Repurposing of the nootropic drug vinpocetine as an analgesic and anti-inflammatory agent: evidence in a mouse model of superoxide anion-triggered inflammation
.
Mediators Inflamm
.
2019 Mar
;
31
:
6481812
.
36.
Keyer
K
,
Imlay
JA
.
Superoxide accelerates DNA damage by elevating free-iron levels
.
Proceedings of the National Academy of Sciences
.
1996 Nov 26
;
93
(
24
):
13635
40
. .
37.
Ray
K
,
Fahrmann
J
,
Mitchell
B
,
Paul
D
,
King
H
,
Crain
C
, et al.
Oxidation-sensitive nociception involved in endometriosis-associated pain
.
Pain
.
2015 Mar
;
156
(
3
):
528
39
. .
38.
Wright
KR
,
Mitchell
B
,
Santanam
N
.
Redox regulation of microRNAs in endometriosis-associated pain
.
Redox Biol
.
2017 Aug
;
12
:
956
66
. .
39.
Vitale
SG
,
Capriglione
S
,
Peterlunger
I
,
La Rosa
VL
,
Vitagliano
A
,
Noventa
M
, et al.
The role of oxidative stress and membrane transport systems during endometriosis: a fresh look at a busy corner
.
Oxid Med Cell Longev
.
2018 Mar
;
21
:
7924021
.
40.
Chen
FY
,
Wang
X
,
Tang
RY
,
Guo
ZX
,
Deng
YZ
,
Yu
Q
.
New therapeutic approaches for endometriosis besides hormonal therapy
.
Chin Med J
.
2019 Dec 20
;
132
(
24
):
2984
93
. .
41.
Zheng
W
,
Cao
L
,
Xu
Z
,
Ma
Y
,
Lianganti-angiogenic alternative X, complementary. Medicines for the treatment of endometriosis: a review of potential molecular mechanisms
.
Evid Based Complement Alternat Med
.
2018 Oct
;
1
:
4128984
.
42.
Della Corte
L
,
Noventa
M
,
Ciebiera
M
,
Magliarditi
M
,
Sleiman
Z
,
Karaman
E
, et al.
Phytotherapy in endometriosis: an up-to-date review
.
J Complement Integr Med
.
2020 Sep 23
:
17
(
3
).
43.
Harlev
A
,
Gupta
S
,
Agarwal
A
.
Targeting oxidative stress to treat endometriosis
.
Expert Opin Ther Targets
.
2015
;
19
(
11
):
1447
64
. .
44.
Verlhac
S
,
Morel
M
,
Bernaudin
F
,
Béchet
S
,
Jung
C
,
Vasile
M
.
Liver iron overload assessment by MRI R2* relaxometry in highly transfused pediatric patients: an agreement and reproducibility study
.
Diagn Interv Imaging
.
2015 Mar
;
96
(
3
):
259
64
. .
45.
Yoshimoto
C
,
Takahama
J
,
Iwabuchi
T
,
Uchikoshi
M
,
Shigetomi
H
,
Kobayashi
H
.
Transverse relaxation rate of cyst fluid can predict malignant transformation of ovarian endometriosis
.
Magn Reson Med Sci
.
2017 Apr 10
;
16
(
2
):
137
45
. .
46.
Kobayashi
H
,
Yamada
Y
,
Kawahara
N
,
Ogawa
K
,
Yoshimoto
C
.
Modern approaches to noninvasive diagnosis of malignant transformation of endometriosis
.
Oncol Lett
.
2019 Jan
;
17
(
1
):
1196
202
.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.