Kontrazeption bei Frauen mit Migräne

Zusammenfassung: Hintergrund: Die Migräne ist eine komplexe, invalidisierende Erkrankung, die überwiegend Frauen im reproduktiven Alter betrifft. Ziel bei betroffenen Frauen muss es sein, eine Verhütungsmethode zu finden, die weder mit einem erhöhten Insultrisiko assoziiert ist noch den Migräneverlauf negativ beeinflusst. Um dies zu erreichen, ist eine sorgfältige Anamnese zum Ausschluss weiterer kardiovaskulärer Risiken erforderlich. Kontrazeption mit Gestagenen: Unter den hormonellen Methoden stehen die Gestagenmethoden an erster Stelle. Sie erhöhen das Risiko für einen Insult nicht. Für Desogestrel 75μg gibt es zudem immer mehr Hinweise, dass es den Verlauf hormonabhängiger und -unabhängiger Migränen bei der Mehrzahl der Frauen positiv beeinflussen kann. Weitere Verfahren: Kombinierte hormonelle Kontrazeptiva (KHK) sollten nur ausnahmsweise verordnet werden. Die Migräne mit Aura ist eine absolute Kontraindikation. Kupferfreisetzende Intrauterinpessare beeinflussen den Verlauf der Migräne nicht. Hormonentzugsmigränen unter KHK kann man mit dem Langzyklus positiv beeinflussen. Es bleibt aber unklar, was dies für das individuelle Risiko eines zerebralen Insults bedeutet. Daher sind Gestagene vorzuziehe

Sex hormone-related polymorphisms in endometriosis and migraine: A narrative review

Some evidence indicates endometriosis and migraine have a common genetic predisposition in sex-hormone genes, which could have important implications for the treatment of these two heterogenous conditions. To date, the genes responsibility remains unknown. Based on the biological hypothesis that polymorphisms of genes involved in sex-hormone pathways may influence estrogen levels and phenotypes of both disorders, we did a literature search for candidate sex-hormone genes and genes involved in the metabolism of estradiol. The aim was to review the evidence for shared sex-hormone-related polymorphisms between endometriosis and migraine and provide an exhaustive overview of the current literature. We included case-control studies investigating associations between candidate sex-hormone-related genes and the disorders endometriosis and migraine, respectively. Results showed three overlapping sex-hormone-associated polymorphisms in estrogen receptor genes that are associated with both conditions. To confirm possible associations with other sex-hormone genes, larger studies are needed. Keywords: endometriosis; migraine; polymorphism; sex hormone genes; sex hormone recepto

Proposal to inform European institutions regarding the regulation of conscientious objection to abortion.

The aim of this paper is to define a set of proposals to inform European institutions in the regulation of Conscientious Objection to abortion. The board of the European Society of Contraception and Reproductive Health Care (ESC) was informed on the elements that should in the opinion of the authors be included in a future regulation of Conscientious Objection to abortion in Europe. These elements are outlined in this paper and the debate about them could form the basis for recommendations to the international scientific community and the European institutions. As current measures governing the principle of conscientious objection result in negative consequences regarding women's access to sexual and reproductive health services, they should be changed. Healthcare services should adopt measures to guarantee that a woman's right to voluntary abortion is not limited by the practitioner's stance on the principle of conscientious objection. In the countries where conscientious objection is allowed, the regulation must clearly delineate the extent of the duties and the exemptions of professionals based on the principles of established social consensus. The recommendations included in this document specify measures on the rights of women, the rights and duties of the practitioner, the role of institutions and the role of professional associations

a consensus statement from the European Headache Federation (EHF) and the European Society of Contraception and Reproductive Health (ESC)

Several data indicate that migraine, especially migraine with aura, is associated with an increased risk of ischemic stroke and other vascular events. Of concern is whether the risk of ischemic stroke in migraineurs is magnified by the use of hormonal contraceptives. As migraine prevalence is high in women of reproductive age, it is common to face the issue of migraine and hormonal contraceptive use in clinical practice. In this document, we systematically reviewed data about the association between migraine, ischemic stroke and hormonal contraceptive use. Thereafter a consensus procedure among international experts was done to develop statements to support clinical decision making, in terms of cardiovascular safety, for prescription of hormonal contraceptives to women with migraine. Overall, quality of current evidence regarding the risk of ischemic stroke in migraineurs associated with the use of hormonal contraceptives is low. Available data suggest that combined hormonal contraceptive may further increase the risk of ischemic stroke in those who have migraine, specifically migraine with aura. Thus, our current statements privilege safety and provide several suggestions to try to avoid possible risks. As the quality of available data is poor further research is needed on this topic to increase safe use of hormonal contraceptives in women with migraine

Investigating migraine phenotype and dynamics in women with endometriosis: an observational pilot study.

INTRODUCTION Migraine and endometriosis are chronic disabling pain conditions. There is evidence for a shared genetic background. Migraine phenotype and course in patients with the comorbidity are insufficient investigated. Both conditions can be treated with progestins. METHODS For this observational study we included women with migraine and endometriosis, visiting our clinic from 2015 to 2021. We collected available information from charts and complemented these data by a structured phone interview to collect more specific information on migraine and the course of both diseases. RESULTS From 344 patients fulfilling the inclusion criteria, 94 suffered from both, endometriosis and migraine. Migraine with aura was reported by 41% of the patients and was associated with earlier onset of migraine (age < 17 years (OR 6.54) and with a history of medication overuse headache (OR 9.9, CI 1.6-59.4). Present monthly migraine frequency (1.5 ± 2.6) was significantly lower than five years before the interview (2.9 ± 4.64). There was a correlation between medication overuse headache and use of analgesics more than 3 days/months for dysmenorrhoea (p < 0.03). ASRM endometriosis score was not associated with migraine characteristics. CONCLUSIONS We conclude that the comorbidity of endometriosis is highly linked to migraine with aura. Migraine onset in these patients was earlier. Further studies are needed to explore, if the observed decrease in migraine frequency can be attributed to recent endometriosis surgery and to understand if early diagnosis and treatment of both conditions may contribute to improve the course of both conditions. Trial registration BASEC Nr. 2021-00285

Migraine and Happiness

Objective: To investigate the association between happiness and migraine. Background: Contemporary operationalizations of happiness include the prevailing positive over negative affect and the satisfaction with life. Generally, extreme events and circumstances influence happiness only temporarily. However, how does periodic cycling between being relatively healthy and relatively disabled-as in migraineurs-affect happiness? Migraine is a primary headache disorder, in which headache attacks intermittently interfere with normal living and cause a significant personal, societal, and potentially irreversible disease burden. Methods: In this cross-sectional observational study, migraineurs completed the satisfaction with life scale (SWLS), the Patient Health Questionnaire, and the Generalized Anxiety Disorder scale and reported their headache frequency as well as recent changes in that frequency. Furthermore, participants answered a free text question on how to remain happy despite migraine attacks. We built a regression model with the SWLS score as the dependent variable. Results: Seventy participants completed the questionnaire. The regression model revealed that happiness increases with headache days, and subsequent analysis showed a U-shaped relationship between headache frequency and happiness. The participants' advice on remaining happy focused on upvaluing the pain-free time or relieving the attacks themselves. The latter was increasingly common with longer disease durations. Conclusions: Both high and low headache frequencies facilitate adaptation to the disorder, while intermediate frequencies resulted in lower life satisfaction. The nonlinear relationship between happiness and headache days may be due to "hedonic habituation" and implies that headache calendars do not necessarily correctly reflect patients' difficulty to feel well despite the disorder. Many patients advised other migraineurs to increase happiness by enjoying pain-free time. However, with increasing disease duration, patients' recommendations focused on coping with attacks. Keywords: coping; happy; hedonic habituation; opponent-process theory; satisfaction; satisfaction with life scal

Impact of family history for endometriosis, migraine, depression and early menopause on endometriosis symptoms, localization and stage: A case control study

Introduction Endometriosis is a common disabling pain condition in women of childbearing age, frequently showing familial clustering. Nevertheless, little is known about whether familial predispositions influence its severity or presentation. In this study, we investigate disease characteristics in endometriosis patients with a family history (FH) for endometriosis or the comorbidities migraine, depression and early menopause (EMP). Materials and methods We performed an observational case-control study enrolling women with histologically confirmed endometriosis in a tertiary center. Based on surgical findings, patient records and phone interviews, we examined the relations between a FH for endometriosis, migraine, depression or EMP and endometriotic signs and symptoms, such as response to combined hormonal contraceptives (CHC) and analgesics, disease localization, infiltration depth, Enzian- and rASRM-scores. Results A positive FH for endometriosis, migraine, depression or EMP was reported by 10.2 %, 33.4 %, 32.6 % and 9.9 % of the 344 patients. A positive FH of endometriosis was associated with an increased risk for high rASRM-scores (rASRM 3 + 4: OR 2.74 (95 % CI 1.16–6.49), p = 0.017) and the presence of endometriomas (OR 2.70 (1.22–5.95), p = 0.011). A positive FH for migraine was associated with less response of endometriosis symptoms to CHC (OR 0.469 (0.27–0.82) p = 0.025). Depression in the family was linked to less severe rASRM-scores (rASRM 3 + 4: OR 0.63 (0.39–0.99), p = 0.046) and less endometriomas (OR 0.58 (0.67–0.92), p = 0.02), but increased the risk of both migraine (OR 1.66 (1.01–2.73), p = 0.043) and depression (OR 3.04 (1.89–4.89), p 5 days of non-cyclic pain (OR 3.58 (1.72–7.44), p < 0.001). Conclusions Around 30% reported a positive FH for migraine or depression. Patients with a positive FH for endometriosis, migraine, depression or EMP differ in symptoms and surgical findings when compared to controls. While a FH for endometriosis is associated with higher rASRM scores and more endometriomas, women with a FH for depression had lower rASRM scores and less endometriomas while responding better to CHC. In contrast, women with a FH for migraine showed less response to CHC

Endometriosis features and dienogest tolerability in women with depression: a case-control study

Objective Primary aim of this study was to investigate endometriosis characteristics of patients with psychiatric conditions or depression. The secondary aim was to study tolerability of dienogest in this context. Methods This observational case-control study included endometriosis data from patients visiting our clinic from 2015–2021. We collected information from patient charts and in phone interviews based on a structured survey. Patients with surgical confirmed endometriosis were included. Results 344 patients fulfilled the inclusion criteria: n = 255 no psychiatric disorder, n = 119 any psychiatric disorder and n = 70 depression. Patients with depression (EM-D, p=.018; p=.035) or psychiatric condition (EM-P, p=.020; p=.048) suffered more often from dyspareunia and dyschezia. EM-P patients had more often primary dysmenorrhoea with higher pain scores (p=.045). rASRM stage or localisation of lesions did not differ. EM-D and EM-P patients discontinued dienogest treatment more often related to worsening of mood (p= .001, p=.002). Conclusion EM-D or EM-P had a higher prevalence of pain symptoms. This could not be attributed to differences in rASRM stage or location of endometriosis lesions. Strong primary dysmenorrhoea might predispose to develop chronic pain-based psychological symptoms. Therefore, early diagnosis and treatment are relevant. Gynaecologist should be aware of the potential impact of dienogest on mood. SHORT CONDENSATION Women with endometriosis and psychiatric disorders especially have more dyschezia and dyspareunia, independent from rASRM stage, depth of infiltration and localisation of endometriosis lesions. Dienogest has an impact on mood especially in already prone patients

Piperine decreases binding of drugs to human plasma and increases uptake by brain microvascular endothelial cells

We previously reported that piperine, an active alkaloidal principal of black and long peppers, enhances drug bioavailability by inhibiting drug metabolism. Another mechanism influencing drug availability/uptake is its free fraction. Since piperine is highly lipophilic, we hypothesize that it could also interact with drugs through binding displacement and influence their bioavailability. Accordingly, using equilibrium dialysis, we investigated whether piperine alters the binding of model drug ligands, that is flunitrazepam, diazepam, warfarin, salicylic acid, propranolol, lidocaine, and disopyramide to human plasma (n = 4). Since alterations in binding influence drug disposition, we also studied the effects of piperine on the uptake of plasma bound 3 H-propranolol and 14 C-warfarin by cultured bovine brain microvascular endothelial cells (BMECs). Piperine (1-1000 μM) increased the free fraction (fu) of both albumin and alpha-acid glycoprotein bound drugs in a concentration-dependent manner (p < 0.01). Moreover, piperine (10 μM) increased the uptake of 3 H-propranolol and 14 C-warfarin by BMECs (p < 0.01). In conclusion, our findings provide the first evidence that piperine displaces plasma bound drugs from both albumin and alpha-acid glycoprotein and facilitates drug uptake across biological membranes (e.g. BMEC). Moreover, it is feasible that piperine may similarly facilitate the transport of drugs into tissues, in vivo, and alter both pharmacokinetics and pharmacodynamics of administered drugs

Contraceptive drugs mitigate experimental stroke-induced brain injury

Aims: Effective stroke treatments beyond reperfusion remain scant. The natural steroid hormone progesterone has shown protective effects in experimental models of brain injury and cardiovascular disease. However, unfavorable bioavailability limits its clinical use. Desogestrel and drospirenone are new generation progestins with progesterone-like properties, developed as oral contraceptives with excellent bioavailability and safety profile. We investigated the neuroprotective properties of these progestins in vivo using transient middle cerebral artery occlusion (MCAO) and in vitro using an oxygen-glucose deprivation and reoxygenation (OGD/R) model in primary neuronal cells. Methods and Results: MCAO was induced in female, female ovariectomized (modeling postmenopausal females) and male mice. Treatment with the progestins resulted in less severe strokes after MCAO and less neuronal death in OGD/R. Desogestrel and drospirenone induced higher expression levels of GABAAR α4 and delta subunits within the brain, suggesting changes in GABAAR configuration favoring tonic inhibition as potential mechanism of action. Treatment with the GABAAR blocker picrotoxin abolished the protection afforded by the progestins in vivo and in vitro. Conclusions: For the first time, here we delineate a potential role of desogestrel and drospirenone, both clinically approved and safe drugs in mitigating the consequences of stroke. Contraception with desogestrel and drospirenone in progestin-only preparations may be particularly beneficial for women at risk of stroke