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 < 0.001) while showing a better response to CHC (OR 2.0 (1.15-3.48, p < 0.001). Patients with EMP in their family reported more current endometriosis symptoms at present (OR 3.72 (1.67-8.30), p = 0.001), more dysmenorrhea (OR 2.13 (1.04-4.35), p = 0.037), more frequent severe dysmenorrhea (OR 2.32 (1.14-4.74), p = 0.019) and suffered significantly more often > 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.

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).

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.

Contraception in adolescents with anorexia nervosa. Is there evidence for a negative impact of combined hormonal contraceptives on bone mineral density and the course of the disease?

Objective: Adolescents with anorexia nervosa (AN) are at increased risk of unplanned pregnancies and bone loss, due to low oestrogen levels and low use of efficient contraception. The negative impact of combined hormonal contraceptives (CHC) on peak bone mass during adolescence might limit wider use in anorexic women. Another issue limiting CHC use is the concern, that CHC-induced cyclic bleeding reduces the motivation for further weight gain and thus exerts a negative impact on recovery. We wanted to find evidence based answers about the impact of CHC use on bone health and course of the disease in adolescents with AN.Methods: We performed a narrative review of the current literature investigating the effect of CHC or progestin-only contraceptives on bone density, body shape and course of disease in young women with anorexia.Results: There is no evidence that CHC use aggravates the bone loss associated with AN. In long-term users CHC exert a protective effect. Anorexic women using CHC showed at least the same or a greater weight gain in comparison with controls. Eating disorder attitudes did not worsen.Conclusion: We conclude, that at present there is no evidence, that use of CHC by AN patients has a negative impact on bone density or the course of disease.

Is there a need for better sexual education of young men? Sexual behaviour and reproductive health in Swiss university students: a questionnaire-based pilot study.

OBJECTIVES: There is evidence that men's perception of contraceptive methods and of their effectiveness and health risks have a major impact on couples contraceptive choices. Engaging men in decision making improves reproductive health outcomes. If they are better informed, men can potentially contribute to more effective use of contraception, thus reducing the rate of sexually transmitted infections and abortion. In Central European countries, few data are available on male contraceptive knowledge and behaviour. METHODS: To collect more data we conducted an anonymous survey among young men studying at Zürich University in Switzerland. A questionnaire was distributed to 1500 male students which included a broad range of items addressing sexual behaviour, condom use and knowledge, and attitudes regarding contraceptive methods. RESULTS: Three hundred and sixty-one questionnaires were eligible for evaluation. Condoms and the combined oral contraceptive pill were the most frequently used methods. However, at last intercourse 15.6% of respondents had not used any method of contraception. Many respondents (37%) had had a one-night stand without protection. Contraceptive methods most regarded as unhealthy for women were the combined oral contraceptive pill, progestin-only methods, intrauterine devices (IUDs) and emergency contraception. Characteristics considered by young men to be important in determining contraceptive method choice were: efficacy, partner satisfaction and no impact on fertility and libido. CONCLUSIONS: Awareness among male Swiss students about contraceptive methods is high, but in-depth knowledge is limited. Myths were expressed about the combined oral contraceptive pill, progestin-only methods, IUDs and the emergency contraceptive pill. High-risk behaviour occurs frequently. The internet was reported to be the most important source of information about contraception.

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. Copyright © 2017 John Wiley & Sons, Ltd.

[Effect of combined hormonal contraceptives on the vascular endothelium und new cardiovascular risk parameters]. / Effekt hormonaler Kontrazeptiva auf das Endothel und neue kardiovaskuläre Risikoparameter.

Epidemiological studies indicate an increased cardiovascular risk in users of combined oral contraceptives (COC) but not progestagen-only preparations. A specially high risk was observed in women older than 35 years with additional cardiovascular risk factors like smoking or hypertension. The mechanisms underlying arterial occlusion can not be explained by hormonal effects on the vascular tonus, nor by effects on newer risk parameters like homocysteine or transforming growth factor-beta. However, CRP increases during oral and transdermal COC use, an effect which can not be observed during use of a progestagen-only implant. Studies concerning the effect of COC on the vasotonus, nitric oxide, homocysteine and CRP usually include young healthy women with intact endothelial function. Females with nicotinabusus, hypertension and hypercholesterolemia have a damaged endothelium. The effect of hormonal treatment on the endothelium in these women might include decreased ability to release the strong vasodilator nitric oxid and as a consequence of that impaired vasodilation.

High survival and developmental rates of vitrified mouse zygotes following polar body biopsy.

The effect of two different methods of polar body biopsy followed by vitrification on the survival and development to blastocyst stage of mouse zygotes was examined. Prior to vitrification, a total of 119 and 124 mouse zygotes were subjected to polar body biopsy using either laser-assisted or partial zona dissection (PZD) techniques, respectively. Vitrification was also applied to 122 zona-intact zygotes that served as a control group. Following vitrification, no differences in the rate of zygote survival (95.8%, 91.9% and 94.3%) or in the rate of development to expanded blastocyst stage (82.3%, 79.8% and 82.0%) were observed between the two groups of biopsied zygotes, or between the biopsied zygotes and control zygotes. The mean total number of cells comprising the blastocysts of controls (77.1 +/- 4.7) was comparable to the mean cell number recorded in the laser (66.4 +/- 4.7) and PZD (69.7 +/- 5.3) groups. Blastocysts developed from laser-treated zygotes hatched much earlier than blastocysts developed from the control and PZD groups of zygotes (P < 0.001). The data obtained in the present study demonstrate that, irrespective of the biopsy method used prior to vitrification, mouse zygotes survive and develop to blastocysts upon warming in proportions similar to those of non-biopsied zygotes.