Introduction
Migraine and endometriosis are disabling conditions with
chronic pain affecting women during the reproductive
years. Oestrogens play a pivotal role in the pathophysiol-
ogy of both conditions and symptoms typically dissolve
with menopause.
1 Some newer studies indicate in addition,
that both conditions are associated with breast cancer. 2,3
Today there is high evidence, that there is a shared genetic
background, especially related to polymorphisms of sex
hormones.
4–6 Migraine prevalence was significantly higher
in endometriosis patients compared with controls in a pop-
ulation-based study (1.7 fold).
7 Survey-based case-control
Menstrual migraine prevalence and
features in women with endometriosis: A
common disabling comorbidity
Gabriele S Merki-Feld1 , Maria S Neumeier2,
Hanna Dietrich1, Angela Niggli1 , Brigitte Leeners1,
Christoph J. Schankin3 , Gantenbein Andreas4,5 and
Peter Sandor4
Abstract
Introduction: Endometriosis is a highly prevalent disabling comorbidity of women with migraine. The aim of the
current study was to identify menstrual migraine prevalence and features in women with endometriosis.
Methods
This observational study included data from patients visiting our outpatient clinic from 2015 to 2021.
Information was collected from charts and through structured phone interviews. Patients with surgically confirmed
endometriosis and migraine were included.
Results
A total of 92 from 344 endometriosis patients suffered from migraine and a subset of 35 from menstrual
migraine (MM). From the subset of women with MM 42.9% reported to have auras. Groups did not differ with regard
to rASRM stage. Women with MM reported significantly more pain days/month at present and 5 years ago and more
often a MIDAS Grade 4 (p < 0.01). Both groups had less migraine attacks/month now, compared with monthly attacks
5 years ago. All women experienced endometriosis surgery in this interval. There was a trend towards more severe
dysmenorrhoea with onset at menarche and towards higher use of analgesics for menstrual pain during the bleeding in
the MM group. Less deliveries were noted in the group with MM.
Conclusion
In women with similar endometriosis stages MM is associated with a higher migraine frequency, more
dysmenorrhoea days and a higher burden of disease. Future studies are needed to better understand a potential influence
of menstrual migraine on the number of deliveries. Our findings suggest, that close collaboration of neurologists with
gynaecologists and shared treatment decisions might be of advantage for patients with the comorbidity.
Keywords
Migraine, endometriosis, medical treatment, ASRM stage, disability, dysmenorrhoea, menstrual migraine
Date received: 8 December 2023; accepted: 25 August 2024
1 Department of Reproductive Endocrinology, University Hospital
Zurich, Zurich, Switzerland
2 Department of Neurology, University Hospital Zurich, Zurich,
Switzerland
3 Department of Neurology, Inselspital, Bern University Hospital,
University of Bern, Bern, Switzerland
4 Department of Neurology and Pain, Zurzach Care, Bad Zurzach,
Switzerland
5Private Practice, Neurologie am Untertor, Bülach, Switzerland
Corresponding author:
Gabriele S. Merki-Feld, Department of Gynaecologic Endocrinology,
University Hospital Zurich, Frauenklinikstrasse 26, Zurich 8091,
Switzerland.
Email:
[email protected]
1283520 PEV0010.1177/22840265241283520Journal of Endometriosis and Pelvic Pain DisordersMerki-Feld et al.
research-article2024
Original Research Article
4 Journal of Endometriosis and Pelvic Pain Disorders 17(1)
studies reported migraine in 29%–69% of endometriosis
patients, which is far higher than the expected prevalence
in the general female population.
8–10 Endometriosis is an
inflammatory proliferative chronic disease affecting 5%–
10% of women of reproductive age.
11–13 A combination of
immunological, environmental and anatomical factors are
discussed as pathomechanisms for the ectopic growth of
endometrial tissue.
11 Endometrial tissue in affected patients
may release Calcitonin Gene-Related Peptide (CGRP) and
shows an increased density of CGRP-positive sensory
nerve fibres.
14,15 Endometriosis pain is strongly related to
the period of menstrual bleeding with dysmenorrhoea and
pelvic pain being the most disabling symptoms.
16 Other
endometriosis associated symptoms may occur at any type
of the cycle. Menstrual migraine (MM) is a special sub-
type of migraine occurring at days 1 ± 2 in at least two of
three cycles and associated with oestrogen withdrawal in
the natural cycle or in the pill break in users of combined
hormonal contraceptives.
17 MM attacks are more severe,
of longer duration and less responsive to acute therapy
with, for example, triptans or short-term prevention.
18–27
Their high negative impact on quality of life has been
described many times.
28 Between 18% and 25% of women
with migraine report MM, while the prevalence and fea-
tures of MM in endometriosis patients with migraine as a
comorbidity is unknown.
29–31 This is despite the probable
high burden caused by the combination of disabling symp-
toms from endometriosis and MM during the days of the
menstrual cycle. It is still unknown, if MM onset in women
with endometriosis already occurs with the initiation of
dysmenorrhoea during the early years of puberty. Such a
coincidence could facilitate earlier diagnosis and treatment
potentially contributing to avoiding the development of
central pain sensitisation (CPS). CPS leads in patients with
chronic pain conditions to pain hypersensitivity.
32 Migraine
as well as endometriosis respond to continuous therapy
with some progestins in dosages which inhibit ovula-
tion.
33–36 With the present study we aim to improve to iden-
tify MM features in women with endometriosis, as well as
MM prevalence and burden of disease. Considering not
only the strong genetic background, but also the high influ-
ence of oestrogens on both conditions, we were interested
to evaluate, if certain endometriosis features might differ
in these patients, and if MM onset and dysmenorrhoea
onset are timely connected. Higher awareness of women at
risk for the comorbidity might contribute to earlier diagno-
sis, prevent CPS and decrease burden of disease.
Materials and methods
This cross-sectional study was conducted at the Clinic for
Reproductive Endocrinology in the Department of
Gynaecology of the University Hospital of Zurich. Data
were collected from patient records and supplemented
through telephone interviews. In order to assure correctness
of our data, two persons from medical staff were trained in
50 interviews prior to start of the study. The presented data
derive from a broader study investigating the characteristics
of endometriosis in women with migraine anddepression.
37
Data collection
Patients with the diagnosis of endometriosis and migraine
were preselected by searching charts from all endometrio-
sis patients treated in our outpatient clinic from January
2015 to July 2021. Included were premenopausal patients
aged >18 years with histopathological examination results
confirming endometriosis, who in addition suffered from
migraine (Figure 1). Migraine, menstrual migraine and
pure menstrual migraine diagnosis was clarified during a
telephone interview using the criteria of the International
Classification of Headache Disorders (third version,
ICHD-3).
17 Postmenopausal women and those with adeno-
myosis or scar endometriosis were excluded. We further -
more excluded patients, if no histology was available and
those in which the stage of endometriosis and localisation
were not clearly documented. During a phone contact, we
informed patients about the study and asked if they were
interested in participating. Those willing to participate
received an information sheet and thereafter provided oral
consent. Details about the inclusion process can be found
in Figure 1. During the interview we collected headache
data on age at migraine onset, migraine frequency in the
past and at present, aura, menstrual attacks, duration of
attacks, migraine triggers, acute and prophylactic medica-
tion, family history, history of medication overuse head-
ache, history of status migrainosis and quality of life, using
the Migraine Disability Assessment questionnaire
(MIDAS).
38 Endometriosis stage according to the
American Society for Reproductive Medicine classifica-
tion (rASRM stage) was identified from the surgery
report.
39 Further gynaecological information and informa-
tion on comorbidities was collected in the interview using
a shortened and adapted to our needs version of the
‘Women’s Health Symptom Survey Questionnaire’ recom-
mended from the World Endometriosis Research
Foundation.
40 We collected data on medical conditions,
operations, family history, pregnancies, deliveries, poten-
tial symptoms of endometriosis and medications used at
present. Furthermore, we collected detailed information on
the menstrual cycle, we focussed on menstrual pain days
during adolescence and at present, dysmenorrhoea onset
and intensity, number of pregnancies and deliveries, num-
ber and timing of endometriosis surgery and number of
pain days during the cyclic bleeding as well as use of hor-
mones and analgesics. Pain intensity was rated on a scale
from 0 to 3 with 0 meaning no pain and 3 severe pain. The
study was approved by the cantonal ethics commission of
Zurich (BASEC Nr. 2021-00285) and registered on clini-
cal Trials.gov (NCT04816357).
Merki-Feld et al. 5
Statistical analysis
Data was analysed using SPSS® statistics (IBM®, Armonk,
New York, United States Version 27.0.1.0.). Shares in per-
cent were used for categorical variables and means includ-
ing standard deviation (SD) were used for numeric
variables. To compare categorical variables among groups,
we used Chi-Square or Fisher’s exact test (expected fre-
quencies <5), depending on expected frequencies. To
compare numeric variables between two groups, we used
the independent sample t-test for normally distributed var-
iables and Wilcoxon-Mann-Whitney test for not normally
distributed variables. In addition, binary logistic regres-
sion was used to evaluate a potential association between
age and menarche and migraine onset in both subgroups. A
two-tailed p-value ⩽0.05 was considered statistically
significant.
Results
In this study involving 375 premenopausal patients with
endometriosis and 92 patients suffered from both, endo-
metriosis and migraine (Figure 1). About 38% (n = 35) of
the migraineurs experienced menstrual migraine and 61%
(n = 57) reported non-menstrual migraine (nMM; Table 1).
Only two women in the menstrual migraine group suffered
from pure menstrual migraine indicating, that they only
experienced migraine attacks at cycle days 1 ± 2 and never
on any other day. The groups did not differ with regard to
age, but BMI was slightly lower in the MM group. Age at
menarche and age at first severe dysmenorrhoea did not
differ (p = 0.66 and 0.56). A higher percentage of women in
the MM group experienced severe dysmenorrhoea onset
with menarche 48.6% versus 36.8% (p < 0.1). A similar
trend was seen for the number of monthly pain days during
the bleeding and use of analgesics for bleeding-related
pain (p ⩽ 0.1). There were no differences between the two
groups with regard to the ASRM stage or the number of
surgeries (p = 0.28 and 0.22; Table 1). Nevertheless,
women with MM had less pregnancies and significantly
less deliveries (p = 0.09 and 0.04). The groups did not dif-
fer with regard to a history of depression or treatment for a
psychic condition (p = 0.35 and 0.66). Table 2 demon-
strates migraine characteristic for both groups. There were
no differences with regard to age at migraine onset
(p = 0.8). Women with menstrual migraine suffered from a
higher migraine frequency, now and in the past, but not
during adolescence (p = 0.001, 0.002 and 0.36). In both
groups the rate of women having migraine with aura (MA)
was high with (41.2%–42.9%; p = 0.9). Frequency of med-
ication overuse headache, or history of status migrainosus
did not differ between groups (p = 0.44 and 0.3). The only
migraine trigger, which was significantly higher in the
MM group was menstrual bleeding (p > 0.001). In more
than 50% of the women migraine was not present before
starting use of combined hormonal contraceptives (CHC).
This was more pronounced in the group of women without
menstrual migraine (p = 0.057; Table 2). Hormone use at
the time of the interview did not differ between groups
(CHC 6.8 % nMM, 14.3% MM; progestin-only methods
Figure 1. Flow Chart of participants.
6 Journal of Endometriosis and Pelvic Pain Disorders 17(1)
15.3% nMM 2.9% MM, no hormones 77.9% nMM;
82.8%). A correlation between age at menarche and
migraine onset (p = 0.7 and 0.5) or between age at menarche
and onset of severe dysmenorrhoea (p = 0.6 and 0.68)
could not be observed in the whole group, nor in the two
subgroups. Most of MIDAS associated quality of life items
was lower in the women with MM. Both average MIDAS
Grade and MIDAS Score were higher in women with MM
(0.01; Table 3).
Currently, 59% of the patients did not use prophylactic
agents, 37% used magnesium or riboflavin on a regular
basis, while 3.1% used onabotulinumtoxin A or beta-
blockers. Pain medication was prescribed from neurolo-
gists in 18.5% and GPs in 35.1%. Another 35.1% of the
Table 1. Baseline characteristics and endometriosis-related gynaecologic features.
Characteristics Menstrual migraine n = 35 Non menstrual migraine n = 57 p Value=
Mean ± SD/% (n) Mean ± SD/% (n)
Age 37.0 ± 7.5 36.1 ± 7.6 0.57
0 n.r. 0 n.r.
BMI 22.2 ± 2.8 23.7 ± 3.9 0.05
0 n.r 0 n.r.
Age at menarche 12.8 ± 1.6 12.7 ± 1.5 0.66
1 n.r. 0 n.r.
Age at first severe dysmenorrhoea* 18.7 ± 7.4 17.7 ± 7.2 0.56
2 n.r 9 n.r
Severe dysmenorrhoea at menarche (scores 2
and 3)*
48.6 (17) 36.8 (21) 0.10
3 n.r. 0 n.r.
Heavy menstrual bleeding 65.7 (23) 63.2 (36) 0.80
0 n.r. 0 n.r.
Number of pregnancies 0.5 ± 0.7 1.0 ± 1.2 0.09
1 n.r. 1 n.r.
Number of deliveries 0.2 ± 0.4 0.75 ± 1.0 0.04
1 n.r. 1 n.r.
Ever treatment for psychic problems 57.1 (20) 50.9 (29) 0.66
0 n.r. 0.n.r.
Diagnosis of depression 34.4 (10) 27.6 (13) 0.35
6 n.r. 10 n.r.
Maximum of monthly days with endometriosis
pain during menstrual bleeding
4.4 ± 2.3 3.6 ± 2.4 0.10
0 n.r 3 n.r
Monthly days with use of analgesics during the
menstrual bleeding
3.8 ± 3.8 2.7 ± 2.4 0.09
2 n.r. 8 n.r.
rASRM stage 0.28
1 10 (28.6%) 14 (24.6%)
2 6 (17.1%) 14 (24.6%)
3 5 (14.3%) 15 (26.3%)
4 14 (40.0%) 14 (24.6%)
0 n.r. 0 n.r.
rASRM stages 3 or 4 0.75
19 (54.3%) 29 (50.9%)
0 n.r. 0 n.r.
Age at first EM surgery 0.91
Mean (SD) 31.49 ± 6.26 31.33 ± 8.05
Range 18–42 15–48
0 n.r. 0 n.r.
First surgery at age 0–20 3 (8.6%) 5 (8.8%) 0.97
0 n.r. 0 n..
Number of EM surgeries 0.22
Mean (SD) 1.57 (1.26) 1.86 (1.26)
Range 0 n.r. 0 n.r.
n.r.:no response
Merki-Feld et al. 7
participants bought the medication in the pharmacy with-
out prescription or received it from other sources (11.3%).
Discussion
Endometriosis and migraine are frequent, highly disabling,
oestrogen-dependent comorbidities with a shared genetic
background.
4–6 It is possible that women with endometrio-
sis might differ from those without endometriosis with
regard to MM course and features. Oestrogen interacts
with the local inflammatory process involving sensory
nerve fibres and macrophages produced in the endometrio-
sis lesions.
41 In the present study we found, that 40% of
migraine patients with endometriosis suffered from MM.
Within this subgroup 42% reported migraine with aura. In
comparison with the nMM group the MM group experi-
enced a higher frequency of monthly migraine attacks and
had a significantly lower quality of life with more days
characterised by more days with reduced productivity at
work, missed leisure activities and without the ability to
perform household work. Also, the MIDAS Grade was
significantly higher (Table 3). This was observed despite
no significant differences in the ASRM stage between
women with MM and nMM. Regarding endometriosis
complaints the patients with MM reported more often
severe dysmenorrhoea onset with menarche already
(48.6% vs 35.8% p = 0.1) and more endometriosis-related
pain days during the menstrual bleeding (p = 0.1). The
delivery rate was significantly lower in the MM group
(p = 0.04).
Menstrual migraine frequency, onset and aura
Considering both, the high genetic background of the
comorbidity based amongst others on oestrogen-receptor
polymorphisms, and the relevant role of oestrogens in the
pathophysiology of endometriosis we expected, that the
majority of women might suffer from MM and that
migraine onset might have a relation to age at menarche
and onset of dysmenorrhoea. Insofar we were surprised
Table 2. Migraine characteristics. .
Characteristics Menstrual migraine n = 35 Non menstrual migraine n = 57 p
Mean ± SD/% (n) Mean ± SD/%(n)
Age at migraine onset 20.0 ± 7.9 19.5 ± 8.8 0.80
n.r. 0 n.r. 0.n.r.
Migraine with Aura 42.9 (15) 42.1 (24) 0.9
n.r. 0 n.r. 0 n.r.
Current migraine frequency (attacks/month) 2.7 ± 3.3 0.6 ± 1.7 0.001
n.r. 0 n.r. 0 n.r.
Migraine frequency 5 years ago (attacks /month) 4.4 ± 5.7 1.7 ± 3.4 0.002
n.r. 0 n.r. 0 n.r.
Migraine frequency at age under 20 years (attacks/
month)
1.6 ± 2.3 1.5 ± 3.0 0.36
n.r. 1 n.r 4 n.r
Current migraine frequency >2 attacks/month 40.0 (35) 8.8 (5) 0.001
n.r. 0 n.r. 1 n.r.
Mean duration of migraine attacks/h 19.8 ± 22.3 14.7 ± 17.0 0.43
n.r. 1.n.r. 2.n.r.
Family history first degree relative with migraine 42.9 (15) 40.7 (24)
n.r. 0 n.r. 0 n.r.
Medication overuse headache ever 11.4 (4) 7.0 (4) 0.44
n.r. 0 n.r. 1 n.r.
Status migrainosus ever 28.6 (10) 19.3 (11) 0.30
n.r. 0 n.r. 1 n.r
Migraine was present before CHC start 28.6 (10) 42.1 (24) 0.057
n.r. 0 n.r. 3 n.r.
Migraine trigger
n.r 0 n.r. 0 n.r.
Stress 54.2 (19) 38.6 (22) 0.19
Tiredness 28.5 (10) 43.8 (25) 0.18
Menstruation 100 (35) 26 (15) >0.001
Sleep deficiency 20.0 (7) 24.5 (14) 0.79
Skipping meals 14.2 (5) 7.0 (4) 0.29
Alcohol 11.4 (4) 7.0 (4) 0.47
8 Journal of Endometriosis and Pelvic Pain Disorders 17(1)
that migraine onset also in endometriosis patients is quite
late (age around 20 years) in relation to age at menarche
(12.7–12.8 years) and also age at first severe dysmenor -
rhoea (age 17–18 years). This is around 5–6 years after
menarche. Interesting is, that migraine onset and severe
dysmenorrhoea onset are timely related in both groups.
Further studies are needed to understand if initiation of
severe dysmenorrhoea in endometriosis patients has an
impact on the course of migraine. It is also noteworthy,
that around 50% of our MM patients suffered from severe
dysmenorrhoea already at the time of menarche.
The comorbidity does not seem to be associated with
onset of symptoms already during early adolescence, but
the in general high rate of severe dysmenorrhoea with
menarche could be an indication for the clinician to check
for a history or family history of migraine. Even more rel-
evant might be the choice of a contraceptive or hormone
for endometriosis treatment, if there is an indication for a
bidirectional comorbidity.
In a recent high-quality diary-based study with migraine
patients recruited in a headache centre, the prevalence of
MM was around 15% higher than in our cross-sectional
study, while the , prevalence of migraine with aura did not
differ from ours with 40%.
42 The study did check report if
participants suffered from endometriosis. Another recently
published gene-based study found substantial genetic cor-
relation between migraine with aura and migraine without
aura, suggesting that both conditions might be more alike
than dissimilar.
43 Menstrual migraine has been described
to be typically without aura, however migraines with aura
could occur during the non-menstrual attacks of these
women.
18,24,29 Newer diary-based data confirm the notion,
that typically auras reported from patients with MM do not
occur during the perimenstrual time frame of cycle days
1 ± 2.
42 Prevalence of menstrual migraine did in the latter
study not differ between women with migraine with or
without aura what is in line with our findings.
Still, it is noteworthy, that in our study neither age at
migraine onset was earlier, nor was family history more
frequently positive in women suffering from MM.
44
The percentage of women, who have ever been treated
for a psychological condition (51%–57%) was higher in
our trial including endometriosis patients, than in studies
with migraine patients, but did not differ so much from the
percentages in the Verhagen trial, which reported the per -
centage of lifetime depressions in migraineurs with 38%–
43%.
42,45,46 Major depression rate in our trial was 25% and
did not differ between groups, but there was a high rate of
non-responders.
The monthly migraine frequency (MMF) did not differ
between groups during adolescence. In the later course of
life MMF was significantly higher in women with MM
(Table 2). For the latter group we found in addition a trend
to more days with endometriosis pain days during the men-
strual bleeding, what may contribute to the probably higher
burden of disease. We can only speculate, why for both
groups the MMF was 40%–50% lower at the time of the
interview in comparison to the frequency 5 years earlier
(Table 2). As only 3.1% of the patients used prophylactic
agents apart from magnesium or riboflavin, the observed
decrease in MMF is rather not related to the new-start of
prophylactic agents. All participants in our study underwent
Table 3. MIDAS Parameters in women with Endometriosis and Menstrual or Non-menstrual Migraine.
Women with menstrual
migraine (n = 35)
Women with non-menstrual
migraine (n = 57)
p Value >
Mean/% Standard deviation Mean Standard deviation
MIDAS score 2.23 1.37 0.87 0.12
MIDAS 1 day missed at work 1.67 3.46 0.42 0.86 0.16
MIDAS 2 days with >50% reduced productivity at
work
3.34 4.62 1.49 4.49 0.01
MIDAS 3 days without household work 5.26 9.42 0.84 1.86 0.01
MIDAS 4 days with >50% reduced productivity in
household work
0.89 2.61 1.07 4.28 0.52
MIDAS 5 days when family, social or leisure
activities are missed (60)
4.00 5.80 1.67 4.56 0.01
MIDAS Headache days (61) 6.77 8.27 2.09 4.58 0.001
MIDAS Pain intensity (scale1–10) 5.34 3.16 3.93 3.67 0.01
MIDAS Grade 2.23 1.37 0.87 0.12 0.01
MIDAS Grade >1 55.8% 24.0% 0.002
MIDAS Grade 4 32% 7.0% 0:01
Questions in this table are given in a shortened form. The observation time for MIDAS includes a 90 day interval. Data were compared using non-
parametric Wilcoxon test.
Merki-Feld et al. 9
endometriosis surgery within the recent years. There are two
mechanisms how endometriosis surgery could impact the
course of migraine. On one hand the CGRP release, an
important trigger for migraine attacks, from endometriosis
lesions is diminished. On the other hand, reduction in pelvic
pain might contribute to reverse central pain sensitisation.
Therefore, we hypothesize that endometriosis surgery might
not only reduce dysmenorrhoea and pelvic pain, but also
might have had a positive impact on the course of both types
of migraine.
Burden of disease, surgery and pregnancies
In accordance with findings in migraine patients without
the comorbidity we found for endometriosis patients with
MM that reduction in quality of life was much more pro-
nounced than in those with nMM (Table 3). The high nega-
tive impact of MM on the private life is reflected in the
number of days when family/social activities are missed. If
this burden is the reason, why the pregnancy and delivery
rate in this subgroup is lower requires further investiga-
tion. It is well known, that endometriosis is associated with
infertility.
47 Infertility rates in migraine patients have not
yet been investigated. As neither ASRM stages nor the age
at first endometriosis operation or the number of endome-
triosis operations differ, we suggest, that the higher burden
of disease in our MM-subpopulation is a main cause for
the lower delivery rate. This hypothesis is in accordance
with a recently published narrative review postulating that
migraine may influence fertility related to the obstacles
patients face stemming the impact of migraine on their
social relationships.
48 Looking at the balanced age distri-
bution of both groups (women >35 years; MM = 52%;
nMM = 54%) we regard it as unlikely that a difference in
the distribution of age between the groups could bias this
result. Staying without children might in addition diminish
psychological well-being.
49 As both migraine and endo-
metriosis are associated with depression we checked in the
interview, if women had ever experienced treatment for
psychic problems or a depression. In spite of the higher
burden of disease reported for our MM patient we did not
find a difference in psychiatric comorbidity between
groups, however the percentage of such a treatment was
strikingly high (>50%) for both groups (Table 1). The
majority of data related to migraine and depression do not
discriminate between migraine subtypes and do not con-
sider fertility or endometriosis, but this topic requires more
attention.
50–53
Finally, we found a trend towards more monthly days
with endometriosis pain during the menstrual bleeding in
MM patients, what could be the cause for the higher num-
ber of days using analgesics in this period (p < 0.1; Table
1). The progestin desogestrel exerts a positive impact on
menstrual and non-menstrual migraine and might insofar
be considered as an important option for the treatment of
both conditions.
35,54,55 It is still not clear today, if the oes-
trogen-induced disabling migraine attacks during the peri-
menstrual phase would also improve with treatment
options like physiotherapy or stress relaxation.
Limitations
Strength of this study are the inclusion of only women
with histologic confirmed endometriosis and a clear stag-
ing, and the collection of migraine data by skilled experts
in a phone interview. However, potentially data related to
pain and migraine frequency in the past might be affected
to recall bias. Insofar our data have to be confirmed in pro-
spective studies. Women were recruited from a specialised
endometriosis clinic and not a headache clinic. This might
explain, why the overall frequency of migraine/month was
rather low. However, we do not expect that the general out-
comes related to high burden, migraine onset in relation to
menarche, low delivery rate and course of MM are much
affected from this.
Conclusions
In women with similar ASRM endometriosis stages MM is
associated with a higher migraine frequency, a lower deliv-
ery rate, more dysmenorrhoea days and a much lower
quality of life in comparison to nMM. In neither group age
of migraine onset correlated with onset of severe dysmen-
orrhoea or age at menarche. Future studies are needed to
better understand a potential influence of menstrual
migraine or its burden on the number of deliveries.
Oestrogen-free hormonal treatment options can be useful
for both conditions and may contribute to reduce the bur -
den of disease. Our findings suggest that collaboration
between neurologists and gynaecologists and shared treat-
ment decisions might be of advantage in endometriosis/
migraine patients.
Acknowledgement
The authors thank all patients who agreed to participate in this
study.
Data Availability Statement
Data sharing not applicable to this article as no datasets were
generated or analysed during the current study.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
10 Journal of Endometriosis and Pelvic Pain Disorders 17(1)
ORCID iDs
Gabriele S Merki-Feld https://orcid.org/0000-0002-8644-
773X
Angela Niggli https://orcid.org/0009-0002-4385-2468
Christoph J Schankin https://orcid.org/0000-0003-4668-
6098
References
1. Somerville BW. The role of estradiol withdrawal in the eti-
ology of menstrual migraine. Neurology 1972; 22: 355–365.
2. Fang T, Zhang Z, Zhou H, et al. Effect of genetic liability
to migraine and its subtypes on breast cancer: a mendelian
randomization study. BMC Cancer 2023; 23: 887.
3. Ye J, Peng H, Huang X, et al. The association between endo-
metriosis and risk of endometrial cancer and breast cancer: a
meta-analysis. BMC Womens Health 2022; 22: 455.
4. van der Vaart JF and Merki-Feld GS. Sex hormone-
related polymorphisms in endometriosis and migraine:
a narrative review. Womens Health (Lond) 2022; 18:
17455057221111315.
5. Adewuyi EO and Sapkota Y
. International Endogene
Consortium I, et al. Shared molecular genetic mechanisms
underlie endometriosis and migraine comorbidity. Genes
(Basel) 2020; 11: 268.
6. Nyholt DR, Gillespie NG, Merikangas KR, et al. Common
genetic influences underlie comorbidity of migraine and
endometriosis. Genetic Epidemiol 2009; 33: 105–113.
7. Yang MH, Wang PH, Wang SJ, et al. Women with endome-
triosis are more likely to suffer from migraines: a popula-
tion-based study. PLoS One 2012; 7: e33941.
8. Maitrot-Mantelet L, Hugon-Rodin J, Vatel M, et al.
Migraine in relation with endometriosis phenotypes: results
from a French case-control study. Cephalalgia 2019 ; 40(6):
606–613.
9. Wu Y, Wang H, Chen S, et al. Migraine is more prevalent in
advanced-stage endometriosis, especially when co-occuring
with adenomoysis. Front Endocrinol (Lausanne) 2021; 12:
814474.
10. Miller JA, Missmer SA, Vitonis AF, et al. Prevalence of
migraines in adolescents with endometriosis. Fertil Steril
2018; 109: 685–690.
11. Taylor HS, Kotlyar AM and Flores VA. Endometriosis is
a chronic systemic disease: clinical challenges and novel
innovations. Lancet 2021; 397: 839–852.
12. Koninckx PR. Pelvic endometriosis: a consequence of
stress? Contrib Gynecol Obstet 1987; 16: 56–59.
13. Abbey A, Halman LJ and Andrews FM. Psychosocial, treat-
ment, and demographic predictors of the stress associated
with infertility. Fertil Steril 1992; 57: 122–128.
14. Yan D, Liu X and Guo SW. Neuropeptides substance P
and calcitonin gene related peptide accelerate the devel-
opment and fibrogenesis of endometriosis. Sci Rep 2019;
9: 2698.
15. Gupta D, Hull ML, Fraser I, et al. Endometrial biomarkers
for the non-invasive diagnosis of endometriosis. Cochrane
Database Syst Rev 2016; 4: CD012165.
16. Schliep KC, Mumford SL, Peterson CM, et al. Pain typol-
ogy and incident endometriosis. Hum Reprod 2015; 30:
2427–2438.
17. Headache Classification Committee of the International
Headache Society (IHS) the international classification of
headache disorders, 3rd edition. Cephalalgia 2018; 38: 1–211.
18. Granella F, Sances G, Allais G, et al. Characteristics of men-
strual and nonmenstrual attacks in women with menstrually
related migraine referred to headache centres. Cephalalgia
2004; 24: 707–716.
19. Hu Y, Guan X, Fan L, et al. Triptans in prevention of men-
strual migraine: a systematic review with meta-analysis. J
Headache Pain 2013; 14: 7.
20. Pavlovic JM, Stewart WF, Bruce CA, et al. Burden of
migraine related to menses: results from the AMPP study. J
Headache Pain 2015; 16: 24.
21. Nierenburg Hdel C, Ailani J, Malloy M, et al. Systematic
review of preventive and acute treatment of menstrual
migraine. Headache 2015; 55: 1052–1071.
22. Maasumi K, Tepper SJ and Kriegler JS. Menstrual migraine
and treatment options: review. Headache 2017; 57: 194–
208.
23. Couturier EG, Bomhof MA, Neven AK, et al. Menstrual
migraine in a representative Dutch population sample:
prevalence, disability and treatment. Cephalalgia 2003; 23:
302–308.
24. Vetvik KG, Benth JS, MacGregor EA, et al. Menstrual
versus non-menstrual attacks of migraine without aura in
women with and without menstrual migraine. Cephalalgia
2015; 35: 1261–1268.
25. MacGregor EA, Victor TW, Hu X, et al. Characteristics of
menstrual vs nonmenstrual migraine: a post hoc, within-
woman analysis of the usual-care phase of a nonrandomized
menstrual migraine clinical trial. Headache 2010; 50: 528–
538.
26. MacGregor EA. Oestrogen and attacks of migraine with and
without aura. Lancet Neurol 2004; 3: 354–361.
27. Pinkerman B and Holroyd K. Menstrual and nonmen-
strual migraines differ in women with menstrually-related
migraine. Cephalalgia 2010; 30: 1187–1194.
28. Steiner TJ, Terwindt GM, Katsarava Z, et al. Migraine-
attributed burden, impact and disability, and migraine-
impacted quality of life: expert consensus on definitions
from a Delphi process. Cephalalgia 2022; 42: 1387–1396.
29. Vetvik KG, Macgregor EA, Lundqvist C, et al. Prevalence of
menstrual migraine: a population-based study. Cephalalgia
2014; 34: 280–288.
30. Mattsson P. Hormonal factors in migraine: a population-
based study of women aged 40 to 74 years. Headache 2003;
43: 27–35.
31. Russell MB, Iselius L and Olesen J. Migraine without aura
and migraine with aura are inherited disorders. Cephalalgia
1996; 16: 305–309.
32. Latremoliere A and Woolf CJ. Central sensitization: a gen-
erator of pain hypersensitivity by central neural plasticity. J
Pain 2009; 10: 895–926.
33. Merki-Feld GS, Imthurn B, Dubey R, et al. Improvement of
migraine with change from combined hormonal contracep-
tives to progestin-only contraception with desogestrel: how
strong is the effect of taking women off combined contra-
ceptives? J Obstet Gynaecol 2017; 37: 338–341.
34. Merki-Feld GS, Imthurn B, Langner R, et al. Headache
frequency and intensity in female migraineurs using
Merki-Feld et al. 11
desogestrel-only contraception: a retrospective pilot
diary study. Cephalalgia 2013; 33: 340–346.
35. Merki-Feld GS, Imthurn B, Langner R, et al. Positive effects
of the progestin desogestrel 75 mug on migraine frequency
and use of acute medication are sustained over a treatment
period of 180 days. J Headache Pain 2015; 16: 522.
36. Sacco S, Merki-Feld GS, KL AE, et al. Effect of exogenous
estrogens and progestogens on the course of migraine during
reproductive age: a consensus statement by the European
Headache Federation (EHF) and the European Society
of Contraception and Reproductive Health (ESCRH). J
Headache Pain 2018; 19: 76.
37. Dietrich H, Knobel C, Portmann L, et al. Endometriosis fea-
tures and dienogest tolerability in women with depression:
a case-control study. Eur J Contracept Reprod Health Care
2023; 28: 198–204.
38. Stewart WF, Lipton RB, Dowson AJ, et al. Development
and testing of the Migraine Disability Assessment (MIDAS)
Questionnaire to assess headache-related disability.
Neurology 2001; 56: S20–S28.
39. Revised American Society for Reproductive Medicine classifi-
cation of endometriosis: 1996. Fertil Steril 1997; 67: 817–821.
40. Anonymous. World endometriosis Research Foundation.
Women’s Health Survey. www.endometriosisfounda-
tion.org/WERF-WHSS-Questionnaire-English.pdf
41. Liang Y, Xie H, Wu J, et al. Villainous role of estrogen in
macrophage-nerve interaction in endometriosis. Reprod
Biol Endocrinol 2018; 16: 122.
42. Verhagen IE, van der Arend BW, van Casteren DS, et al.
Migraine with and without aura in relation to the menstrual
cycle and other hormonal milestones: a prospective cohort
study. Cephalalgia 2023; 43: 3331024231164322.
43. de Boer I, Terwindt GM and van den Maagdenberg A.
Genetics of migraine aura: an update. J Headache Pain
2020; 21: 64.
44. Metzler JM, Imesch P, Dietrich H, et al. Impact of family
history for endometriosis, migraine, depression and early
menopause on endometriosis symptoms, localization and
stage: a case control study. Eur J Obstet Gynecol Reprod
Biol 2023; 293: 36–43.
45. Amoozegar F, Patten SB, Becker WJ, et al. The prevalence
of depression and the accuracy of depression screening
tools in migraine patients. Gen Hosp Psychiatry 2017; 48:
25–31.
46. Song TJ, Cho SJ, Kim WJ, et al. Anxiety and depression in
probable migraine: a population-based study. Cephalalgia
2017; 37: 845–854.
47. de Ziegler D, Borghese B and Chapron C. Endometriosis
and infertility: pathophysiology and management. Lancet
2010; 376: 730–738.
48. Harpe J, Bernstein C and Harriott A. Migraine and infer-
tility, merging concepts in women’s reproductive health: a
narrative review. Headache 2022; 62: 1247–1255.
49. Massarotti C, Gentile G, Ferreccio C, et al. Impact of infer-
tility and infertility treatments on quality of life and levels
of anxiety and depression in women undergoing in vitro fer-
tilization. Gynecol Endocrinol 2019; 35: 485–489.
50. A double-blind study comparing the contraceptive effi-
cacy, acceptability and safety of two progestogen-only pills
containing desogestrel 75 micrograms/day or levonorg-
estrel 30 micrograms/day. Collaborative Study Group on
the Desogestrel-containing Progestogen-only Pill. Eur J
Contracept Reprod Health Care 1998; 3: 169–178.
51. Lee DH, Kim KM, Cho SJ, et al. Impacts of migraine on the
prevalence and clinical presentation of depression: a popu-
lation-based study. J Affect Disord 2020; 272: 215–222.
52. Pisanu C, Lundin E, Preisig M, et al. Major depression sub-
types are differentially associated with migraine subtype,
prevalence and severity. Cephalalgia 2020; 40: 347–356.
53. Buse DC, Reed ML, Fanning KM, et al. Comorbid and
co-occurring conditions in migraine and associated risk
of increasing headache pain intensity and headache fre-
quency: results of the migraine in America symptoms
and treatment (MAST) study. J Headache Pain 2020;
21: 23.
54. Merki-Feld GSIB, Seifert B, Merki LL, et al. Desogestrel-
only contraception reduces headache frequency and
improves quality of life in female migraineurs. Eur J
Contracept Reprod Health Care 2013; 18: 394–400.
55. Morotti M, Remorgida V, Venturini PL, et al. Progestogen-
only contraceptive pill compared with combined oral con-
traceptive in the treatment of pain symptoms caused by
endometriosis in patients with migraine without aura. Eur J
Obstet Gynecol Reprod Biol 2014; 179: 63–68.
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