Keywords
dysmenorrhea - dienogest - endometriosis - migraine disorders - combined oral contraceptives
Schlüsselwörter
Dysmenorrhö - Dienogest - Endometriose - Migräne - kombinierte orale Kontrazeptiva
Introduction
Painful menstruation cramps (dysmenorrhea) are common in women. Prevalence rates of
women with dysmenorrhea in studies with representative samples range from 16.8 to
81% [1]
[2]
[3], with a meta-analysis showing an estimated overall prevalence of 71.1% [4].
Chronic pelvic pain (which is often associated with endometriosis and includes dysmenorrhea
in particular) can severely affect women’s health and have a negative impact on quality
of life. Labor productivity/absenteeism also causes costs with a socioeconomic burden
on the healthcare system and society [1]
[5]
[6]. Therefore, appropriate treatment of severe, disruptive and disabling dysmenorrhea
is crucial for society. Differential diagnoses for dysmenorrhea include primary dysmenorrhea,
endometriosis, adenomyosis, pelvic inflammatory disease, and uterine fibroids. Endometriosis,
a chronic, hormone-dependent condition, often requires long-term management.
Signs of endometriosis can be detected by gynecological examination and imaging techniques
such as transvaginal ultrasound. However, the histological diagnosis of endometriosis
is made by surgery, particularly laparoscopy [7]. Literature shows that endometriosis is confirmed by surgery in about 70% of the
patients with endometriosis symptoms [8]
[9]. Surgery is invasive and may be associated with morbidity and mortality, but the
removal of endometriosis lesions may be associated with a reduction of overall pain
[7]
[10]. Especially if hydronephrosis is present due to compression/infiltration of the
ureter by deep infiltrating endometriosis, surgical treatment is required to prevent
kidney damage. Surgical detection, resection, histological proof of endometriosis
and the resulting visualization of this hidden disease can further be an important
psychological factor for these patients and their environment [7]. However, a risk/benefit assessment should always be carried out before surgery
[7]
[10]
[11]
[12]. Residual dysmenorrhea after endometriosis surgery or prophylaxis for endometriosis/pain
recurrence can be treated with endocrine therapy e.g. dienogest, hormonal contraceptives
or GNRH-analogues and antagonists in combination with estrogen add-back.
Pragmatic empirical treatment of dysmenorrhea can be carried out with hormonal contraceptives
or progestogens when clinical and sonographic evaluation suggests endometriosis or
in the absence of other identifiable pathology [7]
[13]. It is known that hormonal contraceptives can reduce dysmenorrhea, especially when
taken continuously compared to standard cyclical usage [13].
Despite the potential benefits of hormonal contraceptives or progestogens in endometriosis
and dysmenorrhea, many patients show a negative attitude towards these therapies,
which leads to lower compliance [14]
[15]. Notably, hormonal treatment is also frequently rejected in the presence of endometriomas,
although this refusal is not consistent with current medical evidence, as it entails
a considerable risk of recurrence and, in young women, may compromise future fertility
[16]. Negative associations and a decline in the use of oral contraception are also observed
in patients without endometriosis [17]
[18].
In this analysis of a cross-sectional study, we investigate the prevalence of endocrine
treatment of dysmenorrhea and the use of pain medication in a cohort of dysmenorrhea
patients without a history of surgical endometriosis treatment and histologically
proven diagnosis of endometriosis.
Material and Methods
Study design and setting
A cross-sectional multi-center study was conducted from May to November 2023 via an
online survey platform (https://www.umfrageonline.com). Patients were recruited via an e-mail invitation to patients from two university
hospital endometriosis centers with patient visits between January 2017 and March
2023 and permission for e-mail follow-up in May 2023 (UKSH Kiel, UKSH Lübeck, Germany).
Further recruitment was carried out by the German Endometriosis Association via the
homepage and social media channels.
Inclusion criteria and questionnaire design
Inclusion criteria for the survey were postmenarcheal and premenopausal women with
a history of menstrual pain or endometriosis – regardless of severity, as assessed
by self-report –, who were able to understand German language. The study questionnaire
was developed by the research team, pilot-tested in a sample of patients for clarity.
The survey assessed sociodemographic and clinical characteristics, comorbidities,
menstrual and endometriosis-related symptoms, quality of life, surgical diagnosis/treatment,
and hormonal and analgesic management, including type and regimen of hormone therapy.
Premenopausal status was defined as self-reported time between menarche and menopause,
confirmed by current menstruation or ongoing hormonal treatment; other causes of amenorrhea,
such as previous hysterectomy or current pregnancy, were also assessed in this context.
However, in this analysis we focus only on subjects with dysmenorrhea and non-surgically
treated endometriosis (no-STE). Surgical treatment of endometriosis was defined as
removal of at least some endometriosis tissue. Subjects with incomplete questionnaires
and/or who did not fulfil the inclusion criteria were excluded from the analysis.
Only patients who completed and submitted the full online questionnaire were included;
however, single unanswered items were left blank and excluded from analysis on a per-item
basis. Patients with no-STE and no menstrual bleeding within the last three months,
which could not be explained with an active hormonal treatment were excluded (see
[Fig. 1]).
Fig. 1
Flowchart of participant enrolment and analysis.
Ethical approval and consent
Before participation in the study, information was provided on the average expected
response time, the objectives of the study and the voluntary nature of participation.
In order to start the survey, the subjects had to agree on study participation and
anonymized data storage. Ethics approval for this study was issued by the Ethics Committee
of University of Lübeck (AZ2023–287) prior to recruitment in 2023.
Statistical analyses
For statistical analysis Statistical Package for Social Sciences (IBM SPSS Statistics
for MAC, Version 22.0. Armonk, NY: IBM Corp) was used. Statistical significance was
set at p < 0.05 (two-sided). One-way analysis of variance (one-way ANOVA) was used
for comparisons between groups who
-
utilized endocrine dysmenorrhea treatment (EDT) and
-
those that were not using EDT.
Descriptive analyses were expressed as mean ± standard deviation (SD). Absolute numbers
and percentages are additionally stated. The Shapiro-Wilk test was performed to determine
whether variables were normally distributed.
Results
Descriptive analysis
A total of 969 subjects responded to the questionnaire and 821 subjects stated dysmenorrhea
(all women, mean age 30.68 ± 6.92 years, range 15–54 years). Further details of the
study participants are shown in [Fig. 1]. A total 266 patients had no surgical treatment of endometriosis (no-STE) (all women,
mean age 28.10, range 15–43). Among them, 42 patients (7%) underwent surgery for endometriosis
symptoms, but endometriosis diagnosis could not be made surgically.
Usage of endocrine treatment for dysmenorrhea (EDT)
Ninety-five subjects (35.7%) were currently receiving EDT. Of these, nine reported
that their hormonal therapy was not prescribed for dysmenorrhea or endometriosis,
although the treatment may still alleviate dysmenorrhea symptoms. 171 subjects (64.3%)
were currently not using EDT. The sociodemographic data are shown in [Table 1]. Subjects receiving EDT were significantly younger than patients not receiving EDT
(mean age 26.58 [95% CI 25.22–27.94] vs. 28.95 [95% CI 28.08–29.82] years; p = 0.003).
Patients not receiving EDT did not significantly differ from patients who received
EDT in terms of
-
intensity of dysmenorrhea (7.35 [95% CI 7.08–7.62] vs. 7.52 [95% CI 7.18–7.87] VAS),
-
degree of impairment caused by dysmenorrhea and
-
restrictions in work, family and leisure time (see [Table 1]).
Table 1
Variables assessed in patients with dysmenorrhea and no surgically treated endometriosis
(no-STE), including sociodemographic data, menstrual pain characteristics and type
of hormone treatment. Sample size (absolute numbers and percentage), mean and 95%
confidence interval (CI) and statistical test (ANOVA) are stated for all studied subjects.
* Significant results are highlighted.
|
Variable
|
Unit
|
Patients with present endocrine dysmenorrhea treatment
|
Patients with no present endocrine dysmenorrhea treatment
|
Statistics
|
|
n = 95 (100%)
|
Mean (95% CI)
|
n = 171 (100%)
|
Mean (95% CI)
|
F
|
p value
|
|
1 secondary school (Hauptschule) = 1, intermediate school (Mittlere Reife) = 2, high
school (Abitur/Fachabitur) = 3, university degree = 4
2 no menstrual pain = 0, not disturbing = 1, marginally disturbing = 2, moderately
disturbing = 3, severely disturbing = 4, very severely disturbing = 5
3 0 = never, 1 = in less than 2 of 3 menstruations, 2 = in two of three menstruations,
3 = in every menstruation
4 not at all = 0, slightly = 1, moderately = 2, severely = 3, very severely = 4
VAS = visual analogue score
|
|
Sociodemographics
|
|
Age
|
years
|
95 (100%)
|
26.58 (25.22–27.94)
|
171 (100%)
|
28.95 (28.08–29.82)
|
9.208
|
0.003*
|
|
BMI
|
kg/m2
|
95 (100%)
|
23.19 (22.19–24.20)
|
171 (100%)
|
23.86 (23.24–24.48)
|
1.386
|
> 0.05
|
|
Educational level
|
1
|
95 (100%)
|
3.23 (3.06–3.40)
|
171 (100%)
|
3.32 (3.20–3.44)
|
0.751
|
> 0.05
|
|
Migraine as a secondary diagnosis
|
|
Patients with migraine with aura
|
0 = no, 1 = yes
|
14 (14.7%)
|
0.15 (0.07–0.22)
|
29 (17.0%)
|
0.17 (0.11–0.23)
|
0.221
|
> 0.05
|
|
Patients with migraine with never aura
|
0 = no, 1 = yes
|
18 (18.9%)
|
0.19 (0.11–0.27)
|
26 (15.2%)
|
0.15 (0.10–0.21)
|
0.616
|
> 0.05
|
|
Menstrual pain
|
|
VAS score during last 3 months
|
VAS 0–10
|
63 (66.3%)
|
7.52 (7.18–7.87)
|
171 (100%)
|
7.35 (7.08–7.62)
|
0.479
|
> 0.05
|
|
Disturbance of menstruation
|
2
|
94 (98.9%)
|
4.29 (4.13–4.45)
|
171 (100%)
|
4.15 (4.02–4.29)
|
1.557
|
> 0.05
|
|
Usage of pain medication
|
0 = no, 1 = yes
|
87 (91.6%)
|
0.92 (0.86–0.97)
|
154 (90.1%)
|
0.90 (0.86–0.95)
|
0.165
|
> 0.05
|
|
VAS score under pain medication treatment
|
VAS 0–10
|
82 (86.3%)
|
5.06 (4.58–5.55)
|
153 (89.5%)
|
4.63 (4.29–4.98)
|
2.073
|
> 0.05
|
|
Frequency of pain medication intake
|
3
|
81 (85.3%)
|
2.73 (2.59–2.87)
|
144 (84.2%)
|
2.69 (2.58–2.79)
|
0.213
|
> 0.05
|
|
Restriction in job activities
|
4
|
93 (97.9%)
|
2.54 (2.34–2.74)
|
171 (100%)
|
2.44 (2.30–2.59)
|
0.568
|
> 0.05
|
|
Restriction in leisure activities
|
4
|
95 (100%)
|
2.79 (2.61–2.97)
|
2.72 (2.58–2.86)
|
0.364
|
> 0.05
|
|
Restriction in family activities
|
4
|
94 (98.9%)
|
2.44 (2.23–2.65)
|
2.28 (2.12–2.44)
|
1.313
|
> 0.05
|
|
Surgery received due to dysmenorrhea
|
0 = no, 1 = yes
|
20 (21.1%)
|
0.27 (0.16–0.37)
|
22 (12.9%)
|
0.18 (0.11–0.25)
|
2.238
|
> 0.05
|
In the group not receiving EDT, 149 subjects (87.1%) did not undergo surgery due to
dysmenorrhea (see [Table 1]).
Usage of pain medication
Patients taking pain medication (n = 241; 90.6%) for the treatment of dysmenorrhea
had a significantly higher VAS pain level in comparison to those not taking pain medication
(mean pain level of patients using pain medication 7.61 (95% CI 7.41–7.80) versus
non-users 5.15 (95% CI 4.00–6.30), F = 45.961, p < 0.001). Pain medication is taken
by 87 (91.6%) subjects using EDT and by 154 subjects (90.1%) not using EDT during
menstruation due to dysmenorrhea, with no significant difference between the groups
(F = 0.165; p > 0.05; see [Table 1]). Taking pain medication resulted in a lower VAS score of dysmenorrhea in both groups
(5.06 [95% CI 4.58–5.55] VAS vs. 4.63 [95% CI 4.29–4.98] VAS). There was no significant
difference in VAS score when treated with pain medication treatment within groups
(F = 2.073; p > 0.05; see [Table 1]).
Type and characteristics of EDT
The EDT types used are listed in [Table 2]. The active ingredients used are displayed in [Table 3].
Table 2
Type of endocrine dysmenorrhea treatment.
|
Type of hormone treatment
|
N
|
%
|
|
Long-term dienogest intake
|
25
|
26.3
|
|
Combined hormonal contraceptive (cyclical use)
|
14
|
14.7
|
|
Combined hormonal contraceptive (extended/continuous use)
|
27
|
28.4
|
|
Long-term intake of only progestin contraceptive
|
13
|
13.7
|
|
Use of LNG-IUD
|
16
|
16.8
|
|
Total
|
95
|
100
|
Table 3
Type of endocrine endometriosis treatment by active ingredient: total and relative
numbers (%) of patients taking endocrine treatment stated.
|
Active ingredient
|
n
|
%
|
|
Dienogest
|
25
|
26.3
|
|
Ethinylestradiol + dienogest
|
20
|
21.1
|
|
Ethinylestradiol + levonorgestrel
|
11
|
11.6
|
|
Drospirenon
|
5
|
5.3
|
|
Desogestrel
|
4
|
4.2
|
|
Ethinylestradiol + etonogestrel
|
2
|
2.1
|
|
Levonorgestrel
|
1
|
1.1
|
|
Levonorgestrel IUD unknown dosage
|
8
|
8.4
|
|
Levonorgestrel 52 mg IUD
|
4
|
4.2
|
|
Levonorgestrel 13.5 mg IUD
|
2
|
2.1
|
|
Ethinylestradiol + chlormadinon
|
3
|
3.2
|
|
Ethinylestradiol + drospirenon
|
2
|
2.1
|
|
Estetrol + drospirenon
|
2
|
2.1
|
|
Etonogestrel
|
1
|
1.1
|
|
Type of product unknown
|
5
|
5.3
|
|
Total
|
95
|
100
|
63 of the subjects (66.3%) who used EDT reported that they had no amenorrhea during
the last three months. Of these 63 subjects who menstruated or reported vaginal bleeding,
14 subjects were on cyclical combined hormonal contraceptives (100% of cyclical users)
and 16 subjects were on long-term/continuous combined hormonal contraceptives (59.2%
of long-term/continues users). Nineteen patients were on long-term progestogen contraceptives
including long-term dienogest intake (n = 9). Accordingly, 36% of dienogest users
reported vaginal bleeding within the last three months, while 76.9% of patients taking
other progestogens experienced vaginal bleeding within the last three months (F = 7.943,
p < 0.001). 87.5% (n = 14) of LNG-IUD patients reported vaginal bleeding. The comparison
of the different treatment groups is shown in Supplementary Table S1 (online).
Reasons for EDT non-use
86 subjects who do not currently use EDT have used it in the past (90.5%).
The most frequently reported reasons for rejecting endocrine therapy were side effects
(n = 70; 40.9%) and a general refusal to take synthetic hormones (n = 68; 39.8%).
Concerns about thrombosis were mentioned by 29 patients (17.0%). Migraine with aura
was reported as a reason without prior physician advice by 16 patients (9.4%), and
an additional 16 patients (9.4%) stated that their physician recommended avoiding
hormonal treatment due to migraine with aura. Fourteen patients (8.2%) reported a
desire for childbearing as the main reason for declining therapy. Previous thrombosis
(n = 2; 1.2%) and migraine without aura without physician suggestion (n = 1; 0.6%)
were mentioned less frequently. Other reasons were cited by 11 patients (6.4%). Multiple
reasons could be reported (see [Fig. 2]).
Fig. 2
Reasons given by patients for refusing hormone treatment. Multiple answers were possible.
Migraine and EDT usage
The prevalence of migraine with and without aura as a secondary diagnosis is shown
in [Table 1]. Migraine with never-occurring aura was a secondary diagnosis in 26 patients who
did not use an EDT. The risk of migraine with never-occurring aura was not increased
in the subgroup of patients who did not use EDT.
Migraine with aura was present in 29 patients who did not use EDT. The risk of migraine
with aura was not increased in the subgroup of subjects without EDT compared to those
with EDT. Four migraine patients with migraine without aura (15.4%) reported that
their physician had not prescribed hormonal treatment due to their migraine, while
19 migraine patients with aura (65.6%) stated that their physician had not prescribed
them hormonal treatment due to their migraine.
Discussion
Our real world data show important potential to improve the management of women with
clinical dysmenorrhea, which have not received surgical treatment either because no
endometriotic lesions have been found and removed surgically – or because they never
have received surgery.
Many of our participants with no-STE do not use EDT (64.3%) and 87.1% of those have
not received surgery for diagnosis and possible treatment of endometriosis. Although
pain medication for dysmenorrhea is used very frequently, pain levels are still high,
so the overall treatment cannot be considered ideal.
Patients undergoing EDT sometimes use it cyclically (14.7% of subjects on EDT). Induced
amenorrhea and thus prevention of menstruation and dysmenorrhea as result of prolonged/continuous
use of EDT only applies to 65.9% of combined hormonal contraceptive users. A small
subgroup of patients reported using hormonal therapy not primarily for dysmenorrhea
or endometriosis (n = 9). Nevertheless, as such treatments may still alleviate menstrual
pain, their inclusion reflects real-world treatment patterns in which hormonal preparations
often serve multiple indications. The main reasons for refusing EDT are (fear of)
negative side effects, refusal to take synthetic hormones, comorbidity with migraine
with or without aura, fear of thrombosis or the desire to become pregnant.
The treatment of dysmenorrhea may, in selected cases, include surgery to locate, visualize,
and remove endometriotic lesions, which can potentially improve symptoms [7]. According to current ESHRE guidelines, both diagnostic laparoscopy with surgical
removal of lesions and an empirical approach with EDT (combined oral contraceptives
or progestogens) are acceptable options in women suspected of endometriosis and are
known to be an effective treatment for dysmenorrhea [7]
[13]. Surgery should therefore be considered as one possible option to reduce endometriosis-associated
pain, taking into account its invasive nature, potential morbidity, and the need for
individualized counselling of patients regarding benefits and risks [7].
Patients receiving hormonal therapy were younger (mean 26.58 vs. 28.95 years, p = 0.003),
which may reflect treatment patterns rather than symptom severity alone. Younger women
typically more often attend gynecological consultations, for example also for contraception
purposes, which may contribute to the prescription of hormonal therapy [19]
Combined oral contraceptives (COCs) are usually used to reduce menstrual pain [13], but progestogens are also an option for empirical first-line treatment of women
with suspected endometriosis [7]
[20]. In the case of endometriosis, progestogens as the first-line treatment are recommended,
as they effectively suppress endometriosis-associated pain and avoid the potential
risk of hidden disease progression that may occur under estrogen-containing combined
oral contraceptives [21]
[22]. Overexpression of the estrogen receptor and underexpression of the progesterone
receptor in ectopic endometrial implants are possible causes [21]
[22].
Dienogest as a progestogen monotherapy which inhibits ovulation at a dose of 2 mg
is not officially a contraceptive pill but is an approved treatment for endometriosis
[23]. It is effective in inhibiting/reducing symptoms associated with endometriosis [24]
[25]. In the past, dienogest has not been used primarily for dysmenorrhea without proven
endometriosis because of the high cost of treatment [22]. Our study now shows that dienogest as a monotherapy appears to be the main progestogen
used to treat dysmenorrhea today.
It is known that continuous use of COCs leads to a greater reduction in pain than
standard use [13]. This was also seen in our study. 100% of the patients using standard hormonal contraceptives
reported dysmenorrhea and menstruation within the last 3 months, compared with 59.2%
of patients on continuous/extended use. COCs in the treatment of dysmenorrhea also
have the advantage that the tailored cycle in the continuous cycle (4-days treatment
break after 3 consecutive days of vaginal bleeding or spotting) may lead to shorter
periods of bleeding and pain than in those using dienogest [22]
[26].
Continuous/extended use of COCs is considered safe [27]
[28]
[29]. Some preparations have been approved for extended use (91 days to 120 days) [30]
[31]. A preparation containing 90 µg levonorgestrel and 20 µg ethinylestradiol is approved
for 365 days [27]
[28], but is not currently available in some countries. However, off-label continuous
use of COCs is conceivable and is even recommended by the British FSRH guideline [29].
Although EDT is effective in reducing dysmenorrhea and improving quality of life and
reducing absenteeism from work/school [13], women of reproductive age are known to refuse endocrine treatment of endometriosis
symptoms because of side effects, fear of possible side effects, and the desire to
live without synthetic hormones [14]
[15]
[32]
[33]. In addition, women with known ovarian endometriosis have been shown to refuse endocrine
therapy putting their reproductive health at unnecessary risk [16]. Interestingly, it has also been shown that endometrioma patients were significantly
less likely to take hormone therapy in the past and in the present, so the use of
EDT could reduce the risk of ovarian endometriosis formation [16]. Moreover, women with ovarian endometriosis reported in the present comparable levels
of dysmenorrhea and analgesic consumption as those with other forms of the disease
but no endometriomas, indicating that the overall symptom burden does not explain
their lower acceptance of endocrine treatment, as they also take significantly less
hormone therapy in the present [16].
COCs have been reported to increase the likelihood of thrombosis (relative risk 3.5,
95% CI 2.9–4.3) [34]. However, the background risk of thromboembolism in premenopausal women is low (5/10000
per women-year) [35]. Some data show that arterial or venous thrombosis is not significantly increased
using progestin-only hormone therapy compared with no use [36]. However recent data reported that progestin-only pills were associated with a slightly
increased risk of ischemic stroke (adjusted rate ratio 1.6; about 15 extra cases per
100000 person-years) and myocardial infarction (adjusted rate ratio 1.5; about 4 extra
cases per 100000 person-years), while the levonorgestrel-IUD showed no excess risk
[37]. The observed increase in arterial thrombotic risk with progestin-only pills, implants,
and injections in this study should be interpreted with caution, as the number of
events in these subgroups was low and the estimates therefore remain subject to statistical
uncertainty [37]. However also depot medroxyprogesterone acetate (DMPA) is known to increase the
risk of thrombosis [36]. Even in the presence of a history of thromboembolism, the use of progestin-only
hormones does not significantly increase the incidence rate of recurrent venous thromboembolism
[38]. Despite the potential benefits of EDT, patients appear to overestimate the risk
of thrombosis. When discussing this with patients, clinicians should put this into
perspective and remember that progestin-only therapy remains an option in all cases.
Importantly, given the rarity of arterial thrombotic events and the high burden of
dysmenorrhea symptoms, the overall benefit–risk profile remains favorable [37].
Potential adverse effects such as mood changes, depressive symptoms, and libido alterations
must be considered when counseling women with dysmenorrhea regarding hormonal therapy.
While randomized trial evidence does not confirm a causal link with depressive symptoms
[39], large-scale registry data indicate an increased risk of antidepressant use with
several hormonal methods, including combined oral contraceptives (RR 1.23), progestin-only
pills (RR 1.34), and the levonorgestrel IUD (RR 1.4) [40]. Regarding sexual function, data from the Contraceptive CHOICE Project suggest that
lack of sexual desire was more frequently reported with depot medroxyprogesterone
acetate, the vaginal ring, and implants, but not with oral contraceptives or the levonorgestrel
IUD [41]. A meta-analysis investigating treatment of adenomyosis patients showed that dienogest
has a side effect profile comparable to the levonorgestrel IUD [42]. These potential side effects, together with other tolerability concerns, need to
be carefully weighed against the substantial analgesic and overall therapeutic benefits
of hormonal treatment.
Other reasons why patients refused EDT were migraine with and without aura. Screening
instruments, such as the ID Migraine or MS-Q questionnaires, can facilitate the initial
differentiation of migraine with versus without aura based on patient self-reports,
as highlighted in expert consensus guidelines on migraine diagnosis [43]. Migraines with and without aura are known to be associated with an increased risk
of stroke with an incidence of 5.9/100000 and 4.0/100000 per year respectively [44]. Individuals with migraine with aura have a two-fold increased risk of ischemic
stroke compared to those without migraine [45], although the absolute risk remains low [46]. However, some studies cannot confirm increased risk in individuals with migraine
without aura [45]. The different risk may be explained by biological mechanisms, since migraine aura
may change vascular reactivity and endothelial dysfunction by cortical spreading depression,
while migraine without aura does not feature the same vascular and cortical disruptions
[47]. The risk of stroke in migraineurs appears to be further increased by the use of
COCs compared with non-users: 25.4/100000 per year versus 4/100000 for migraine without
aura and 36.9/100000 versus 5.9/100000 for migraine with aura [44]. The consensus working group of the European Headache Federation (EFH) and the European
Society of Contraception and Reproductive Health (ESCRH) stated that – also in the
case of migraine with and without aura – either progestin-only or COCs can be used
for the treatment of endometriosis symptoms on “clinical grounds” [44]. Progestin-only pills are safe in patients with a history of migraine with or without
aura in terms of stroke risk.
One of the solutions to overcome hormone phobia and refusal to use EDT could be that
EDT could be offered to patients with the option to stop or switch immediately if
intolerable side effects occur and the risk-benefit ratio is not positive from the
patient’s perspective. In all cases where further endocrine treatment is not desired
or is not as effective as intended and there is no immediate desire to become pregnant,
surgery for dysmenorrhea should be offered with the intention of diagnosing and treating
endometriosis. Adequate counselling has been shown to significantly reduce anxiety
levels in women with suspected endometriosis, emphasizing the need for structured
patient education to overcome hormone-related concerns [48]. In women who wish to become pregnant, within six months (depending on the patient’s
age and other factors), diagnostic and therapeutic surgery could be offered with the
aim of improving the likelihood of pregnancy, diagnosing infertility and reducing
pain. Early intervention is critical, as a prolonged duration of infertility prior
to surgery significantly reduces postoperative pregnancy rates if endometriosis is
present [49]. In the case of endometriosis diagnosis by imaging and gynecological examination
with suspected infertility a referral to an IVF center should be also discussed [7].
Strengths of our study include its large, multicenter real-world cohort of German-speaking
women with dysmenorrhea and the comprehensive documentation of treatment patterns,
symptom burden, and patient-reported barriers to endocrine therapy. This real-world
perspective highlights discrepancies between guideline recommendations and patient
decision-making.
However, several limitations must be acknowledged. Due to the anonymous nature of
the online survey, patient responses could not be validated against medical records,
and the self-reported information may therefore be subject to recall bias or individual
perception influenced by dysmenorrhea symptoms or prior hormone use. Furthermore,
selection bias is likely, as participation was voluntary and recruitment occurred
mainly via endometriosis centers and the German Endometriosis Association, potentially
attracting women with a higher symptom burden, health awareness or educational level.
Conclusion
As dysmenorrhea and endometriosis have a high prevalence and cause high socioeconomic
costs and reduced quality of life, appropriate treatment of these patients is essential.
Our study demonstrates that endocrine therapy for dysmenorrhea is underutilized, despite
its role as guideline-recommended first-line treatment. Patient attitudes towards
artificial female sex hormones and concerns regarding side effects, thrombosis and
migraine substantially influence treatment choices and highlight the need for structured
counselling and shared decision-making. Many patients therefore refrain from using
endocrine therapy, while surgical treatment should be reserved for selected cases
or when medical management fails.
Supplementary Material
Supplementary Table S1: Endocrine dysmenorrhea treatment; comparison of cyclical use, extended/continuous
use, long term progestogen intake, LNG-IUD.
