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

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

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

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

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

Swiss QUality of life and healthcare impact Assessment in a Real-world Erenumab treated migraine population (SQUARE study): interim results

BACKGROUND The fully human monoclonal antibody erenumab, which targets the calcitonin gene-related peptide (CGRP) receptor, was licensed in Switzerland in July 2018 for the prophylactic treatment of migraine. To complement findings from the pivotal program, this observational study was designed to collect and evaluate clinical data on the impact of erenumab on several endpoints, such as quality of life, migraine-related impairment and treatment satisfaction in a real-world setting. METHODS An interim analysis was conducted after all patients completed 6 months of erenumab treatment. Patients kept a headache diary and completed questionnaires at follow up visits. The overall study duration comprises 24 months. RESULTS In total, 172 adults with chronic or episodic migraine from 19 different sites across Switzerland were enrolled to receive erenumab every 4 weeks. At baseline, patients had 16.6 ± 7.2 monthly migraine days (MMD) and 11.6 ± 7.0 acute migraine-specific medication days per month. After 6 months, erenumab treatment reduced Headache Impact Test (HIT-6™) scores by 7.7 ± 8.4 (p < 0.001), the modified Migraine Disability Assessment (mMIDAS) by 14.1 ± 17.8 (p < 0.001), MMD by 7.6 ± 7.0 (p < 0.001) and acute migraine-specific medication days per month by 6.6 ± 5.4 (p < 0.001). Erenumab also reduced the impact of migraine on social and family life, as evidenced by a reduction of Impact of Migraine on Partners and Adolescent Children (IMPAC) scores by 6.1 ± 6.7 (p < 0.001). Patients reported a mean effectiveness of 67.1, convenience of 82.4 and global satisfaction of 72.4 in the Treatment Satisfaction Questionnaire for Medication (TSQM-9). In total, 99 adverse events (AE) and 12 serious adverse events (SAE) were observed in 62 and 11 patients, respectively. All SAE were regarded as not related to the study medication. CONCLUSIONS Overall quality of life improved and treatment satisfaction was rated high with erenumab treatment in real-world clinical practice. In addition, the reported impact of migraine on spouses and children of patients was reduced. TRIAL REGISTRATION BASEC ID 2018-02,375 in the Register of All Projects in Switzerland (RAPS)

Swiss QUality of life and healthcare impact Assessment in a Real-world Erenumab treated migraine population (SQUARE study): interim results.

BACKGROUND The fully human monoclonal antibody erenumab, which targets the calcitonin gene-related peptide (CGRP) receptor, was licensed in Switzerland in July 2018 for the prophylactic treatment of migraine. To complement findings from the pivotal program, this observational study was designed to collect and evaluate clinical data on the impact of erenumab on several endpoints, such as quality of life, migraine-related impairment and treatment satisfaction in a real-world setting. METHODS An interim analysis was conducted after all patients completed 6 months of erenumab treatment. Patients kept a headache diary and completed questionnaires at follow up visits. The overall study duration comprises 24 months. RESULTS In total, 172 adults with chronic or episodic migraine from 19 different sites across Switzerland were enrolled to receive erenumab every 4 weeks. At baseline, patients had 16.6 ± 7.2 monthly migraine days (MMD) and 11.6 ± 7.0 acute migraine-specific medication days per month. After 6 months, erenumab treatment reduced Headache Impact Test (HIT-6™) scores by 7.7 ± 8.4 (p < 0.001), the modified Migraine Disability Assessment (mMIDAS) by 14.1 ± 17.8 (p < 0.001), MMD by 7.6 ± 7.0 (p < 0.001) and acute migraine-specific medication days per month by 6.6 ± 5.4 (p < 0.001). Erenumab also reduced the impact of migraine on social and family life, as evidenced by a reduction of Impact of Migraine on Partners and Adolescent Children (IMPAC) scores by 6.1 ± 6.7 (p < 0.001). Patients reported a mean effectiveness of 67.1, convenience of 82.4 and global satisfaction of 72.4 in the Treatment Satisfaction Questionnaire for Medication (TSQM-9). In total, 99 adverse events (AE) and 12 serious adverse events (SAE) were observed in 62 and 11 patients, respectively. All SAE were regarded as not related to the study medication. CONCLUSIONS Overall quality of life improved and treatment satisfaction was rated high with erenumab treatment in real-world clinical practice. In addition, the reported impact of migraine on spouses and children of patients was reduced. TRIAL REGISTRATION BASEC ID 2018-02,375 in the Register of All Projects in Switzerland (RAPS)

Hormonale Kontrazeption und Depression – Beratung in der Praxis

Hormonelle Einflüsse im natürlichen Zyklus, aber auch kontrazeptive Hormone haben oft einen gewissen positiven oder negativen Einfluss auf die Stimmung. Das Auslösen einer Depression ist aber ein sehr seltenes Ereignis und nicht dosisabhängig. Einzelfallbeobachtungen sprechen für eine gute Reversibilität der Symptome, falls die Depression wirklich durch das Hormon verursacht wurde. Die Anamnese sollte immer auch die private und die psychische Situation der Patientin erfassen. Haben Patientinnen bereits psychische Probleme, ist ein engmaschiges Follow-up nötig, und Nutzen und Risiko im Vergleich zu einer Kupferspirale sind abzuwägen. Es dürfen aber alle hormonalen Kontrazeptiva verschrieben werden. Auf der Homepage der European Society for Contraception and Reproductive Health findet sich ein aktualisiertes Teaching-Tool zum Thema (Session: Medical condition: Migraine and Depression; https://www.escrh.eu/education/TTTtool-sessions), das Ärzte mit mehr Interesse durchgehen können