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Objective To evaluate the association between migraine and cardiovascular disease, including stroke, myocardial infarction, and death due to cardiovascular disease.Design Systematic review and meta-analysis.Data sources Electronic databases (PubMed, Embase, Cochrane Library) and reference lists of included studies and reviews published until January 2009.Selection criteria Case-control and cohort studies investigating the association between any migraine or specific migraine subtypes and cardiovascular disease.Review methods Two investigators independently assessed eligibility of identified studies in a two step approach. Disagreements were resolved by consensus. Studies were grouped according to a priori categories on migraine and cardiovascular disease.Data extraction Two investigators extracted data. Pooled relative risks and 95% confidence intervals were calculated.Results Studies were heterogeneous for participant characteristics and definition of cardiovascular disease. Nine studies investigated the association between any migraine and ischaemic stroke (pooled relative risk 1.73, 95% confidence interval 1.31 to 2.29). Additional analyses indicated a significantly higher risk among people who had migraine with aura (2.16, 1.53 to 3.03) compared with people who had migraine without aura (1.23, 0.90 to 1.69; meta-regression for aura status P=0.02). Furthermore, results suggested a greater risk among women (2.08, 1.13 to 3.84) compared with men (1.37, 0.89 to 2.11). Age less than 45 years, smoking, and oral contraceptive use further increased the risk. Eight studies investigated the association between migraine and myocardial infarction (1.12, 0.95 to 1.32) and five between migraine and death due to cardiovascular disease (1.03, 0.79 to 1.34). Only one study investigated the association between women who had migraine with aura and myocardial infarction and death due to cardiovascular disease, showing a twofold increased risk.Conclusion Migraine is associated with a twofold increased risk of ischaemic stroke, which is only apparent among people who have migraine with aura. Our results also suggest a higher risk among women and risk was further magnified for people with migraine who were aged less than 45, smokers, and women who used oral contraceptives. We did not find an overall association between any migraine and myocardial infarction or death due to cardiovascular disease. Too few studies are available to reliably evaluate the impact of modifying factors, such as migraine aura, on these associations.

Objectives To evaluate the risk of venous thromboembolic events associated with the use of progestin-only contraception and whether that risk differs with the mode of drug delivery (oral, intrauterine, or depot injection).Design Systematic review and meta-analysis of randomised controlled trials and observational studies.Data sources Pubmed, Embase, Cochrane Library, and reference lists of relevant reviews.Study selection Randomised controlled trials and case-control, cohort, and cross sectional studies with venous thromboembolic outcome for progestin-only contraception reported relative to a non-hormone comparator group.Data extraction Data were extracted by two independent investigators, and consensus for inclusion was reached after assessment by additional investigators.Results Among the 2022 unique references identified by all searches, eight observational studies fulfilled inclusion criteria. A total of 147 women across all studies were diagnosed with a venous thromboembolic event while taking progestin-only contraception, and the summary measure for the adjusted relative risk of a venous thromboembolic episode for users versus non-users of a progestin-only contraceptive was, based on the random effects model, 1.03 (95% CI 0.76 to 1.39). Subgroup analysis confirmed there was no association between venous thromboembolic risk and progestin-only pills (relative risk 0.90 (0.57 to 1.45)) or a progestin intrauterine device (0.61 (0.24 to 1.53)). The relative risk of a venous thromboembolic event for users of an injectable progestin versus non-users was 2.67 (1.29 to 5.53).Conclusions Published data assessing the risk of venous thromboembolism in women prescribed progestin-only contraception are limited. In this meta-analysis of eight observational studies, the use of progestin-only contraception was not associated with an increased risk of venous thromboembolism compared with non-users of hormonal contraception. The potential association between injectable progestins and thrombosis requires further study.

Objective To assess the risk of venous thrombosis in current users of different types of hormonal contraception, focusing on regimen, oestrogen dose, type of progestogen, and route of administration.Design National cohort study.Setting Denmark, 1995-2005.Participants Danish women aged 15-49 with no history of cardiovascular or malignant disease.Main outcome measures Adjusted rate ratios for all first time deep venous thrombosis, portal thrombosis, thrombosis of caval vein, thrombosis of renal vein, unspecified deep vein thrombosis, and pulmonary embolism during the study period.Results 10.4 million woman years were recorded, 3.3 million woman years in receipt of oral contraceptives. In total, 4213 venous thrombotic events were observed, 2045 in current users of oral contraceptives. The overall absolute risk of venous thrombosis per 10 000 woman years in non-users of oral contraceptives was 3.01 and in current users was 6.29. Compared with non-users of combined oral contraceptives the rate ratio of venous thrombembolism in current users decreased with duration of use (<1 year 4.17, 95% confidence interval 3.73 to 4.66, 1-4 years 2.98, 2.73 to 3.26, and >4 years 2.76, 2.53 to 3.02; P<0.001) and with decreasing dose of oestrogen. Compared with oral contraceptives containing levonorgestrel and with the same dose of oestrogen and length of use, the rate ratio for oral contraceptives with norethisterone was 0.98 (0.71 to 1.37), with norgestimate 1.19 (0.96 to 1.47), with desogestrel 1.82 (1.49 to 2.22), with gestodene 1.86 (1.59 to 2.18), with drospirenone 1.64 (1.27 to 2.10), and with cyproterone 1.88 (1.47 to 2.42). Compared with non-users of oral contraceptives, the rate ratio for venous thromboembolism in users of progestogen only oral contraceptives with levonorgestrel or norethisterone was 0.59 (0.33 to 1.03) or with 75 μg desogestrel was 1.12 (0.36 to 3.49), and for hormone releasing intrauterine devices was 0.90 (0.64 to 1.26).Conclusion The risk of venous thrombosis in current users of combined oral contraceptives decreases with duration of use and decreasing oestrogen dose. For the same dose of oestrogen and the same length of use, oral contraceptives with desogestrel, gestodene, or drospirenone were associated with a significantly higher risk of venous thrombosis than oral contraceptives with levonorgestrel. Progestogen only pills and hormone releasing intrauterine devices were not associated with any increased risk of venous thrombosis.

Very severe intrahepatic cholestasis of pregnancy (ICP) characterised by total serum bile acid (TSBA) >100 umol/L is associated with an increased stillbirth risk of 3.4%. Patients exposed to thiopurines may be at increased risk of ICP. We report a case of a mid-30-year-old primigravida who presented at 27+2/40 with a 7-week history of pruritus and jaundice and was diagnosed with very severe ICP (TSBA=117 µmol/L). She had inflammatory bowel disease, controlled on azathioprine 200 mg daily. Thiopurine metabolites ratio, 6-methylmercaptopurine: 6-thioguanine nucleotide (6MMP:TGN) was 34 at 12/40 and 21 at 27/40. Cessation of azathioprine precipitated a TSBA fall to 31 µmol/L within 7 days. A multidisciplinary plan was made in conjunction with the patient for delivery between 35 and 36 weeks. This case highlights the risks of thiopurine use in pregnancy and supports ceasing azathioprine treatment immediately at the onset of ICP, avoiding TSBA levels rising.

Leuprolide acetate is commonly used to reduce the size of myomas before surgery. Initially, it stimulates pituitary gonadotropin secretion, followed by sustained suppression of gonadal function. However, the impact on pregnancy outcomes from inadvertent exposure remains unclear. This case involves a woman in her 30s, multiparous, with a 20-week-sized leiomyoma, who received two doses of 3.75 mg subcutaneous leuprolide acetate, 15 days after menstruation, 4 weeks apart. An ultrasound, conducted 2 weeks after the last dose, accidentally revealed a viable intrauterine pregnancy at 8+6 weeks gestation. Her pregnancy progressed without complications, culminating in a term caesarean delivery without fetal anomalies. She opted for a total hysterectomy with bilateral salpingectomy 6 months later. Despite unclear teratogenic effects, evidence suggests that leuprolide acetate does not significantly impact pregnancy outcomes.

Objective To see if the mortality risk among women who have used oral contraceptives differs from that of never users.Design Prospective cohort study started in 1968 with mortality data supplied by participating general practitioners, National Health Service central registries, or both.Setting 1400 general practices throughout the United Kingdom.Participants 46 112 women observed for up to 39 years, resulting in 378 006 woman years of observation among never users of oral contraception and 819 175 among ever users.Main outcome measures Directly standardised adjusted relative risks between never and ever users for all cause and cause specific mortality.Results 1747 deaths occurred in never users of oral contraception and 2864 in ever users. Compared with never users, ever users of oral contraception had a significantly lower rate of death from any cause (adjusted relative risk 0.88, 95% confidence interval 0.82 to 0.93). They also had significantly lower rates of death from all cancers; large bowel/rectum, uterine body, and ovarian cancer; main gynaecological cancers combined; all circulatory disease; ischaemic heart disease; and all other diseases. They had higher rates of violent deaths. No association between overall mortality and duration of oral contraceptive use was observed, although some disease specific relations were apparent. An increased relative risk of death from any cause between ever users and never users was observed in women aged under 45 years who had stopped using oral contraceptives 5-9 years previously but not in those with more distant use. The estimated absolute reduction in all cause mortality among ever users of oral contraception was 52 per 100 000 woman years.Conclusion Oral contraception was not associated with an increased long term risk of death in this large UK cohort; indeed, a net benefit was apparent. The balance of risks and benefits, however, may vary globally, depending on patterns of oral contraception usage and background risk of disease.

This case report describes an uncommon case of a woman who developed fixed drug eruption (FDE) on her vulval area secondary to trimethoprim use. She had no known history of drug allergy. Some common culprit medications that cause FDE include antimicrobials such as co-trimoxazole and non-steroidal anti-inflammatory agents. Vulval FDE is uncommon and should remain as an important differential diagnosis in women presenting with severe vulval pain accompanied by erythema and swelling, particularly after the introduction of a new medication. Discontinuation of trimethoprim along with the adjunct use of a steroid cream led to complete resolution of the patient’s symptoms.

Ovarian hyperstimulation syndrome (OHSS) in patients on tamoxifen therapy is a rare but potentially serious complication. This patient underwent a laparoscopic unilateral salpingo-oophorectomy due to persistent pelvic pain and received a gonadotropin-releasing hormone (GnRH) agonist injection with normalisation of her oestradiol level, previously elevated to 956 pg/mL. Management options of OHSS include medical therapy with GnRH agonists or surgical intervention. Studies have shown that GnRH agonists can effectively normalise oestradiol levels and induce the resolution of cysts in these patients. Additionally, combined therapy with tamoxifen and GnRH agonists may reduce the risk of OHSS. Risk factors for OHSS during tamoxifen treatment include younger age and absence of chemotherapy. Monitoring of oestradiol levels and close clinical follow-up are essential in managing patients on tamoxifen therapy to prevent and promptly address OHSS.

Gestational alloimmune liver disease (GALD) is a rare pregnancy complication involving maternal antibody-mediated fetal liver injury that recurs in 90% of affected pregnancies. The fetal and neonatal mortality rate is high, up to 82%, and affected fetuses can develop fetal hydrops, growth restriction, and oligohydramnios. Intravenous immunoglobulin (IVIG) administration can prevent GALD recurrence.We present a patient whose three live births were impacted by GALD. Her first pregnancy was an elective termination. Her second pregnancy resulted in neonatal demise due to autopsy-proven GALD. Her third pregnancy was complicated by liver injury secondary to biopsy-proven drug-induced liver injury (DILI) after IVIG administration and resulted in precipitous preterm twin delivery. In her fourth pregnancy, she received IVIG and high-dose steroids and did not develop DILI; the infant, delivered preterm due to GALD, died due to complications of prematurity.GALD is a highly recurrent condition that results in significant neonatal mortality. In this rare case of DILI due to IVIG administration, high-dose steroids treated DILI recurrence and prevented acute liver injury and may be beneficial to patients who are unable to tolerate IVIG due to liver injury.

Objective To assess the risk of venous thromboembolism from use of combined oral contraceptives according to progestogen type and oestrogen dose.Design National historical registry based cohort study.Setting Four registries in Denmark.Participants Non-pregnant Danish women aged 15-49 with no history of thrombotic disease and followed from January 2001 to December 2009.Main outcome measures Relative and absolute risks of first time venous thromboembolism.Results Within 8 010 290 women years of observation, 4307 first ever venous thromboembolic events were recorded and 4246 included, among which 2847 (67%) events were confirmed as certain. Compared with non-users of hormonal contraception, the relative risk of confirmed venous thromboembolism in users of oral contraceptives containing 30-40 µg ethinylestradiol with levonorgestrel was 2.9 (95% confidence interval 2.2 to 3.8), with desogestrel was 6.6 (5.6 to 7.8), with gestodene was 6.2 (5.6 to 7.0), and with drospirenone was 6.4 (5.4 to 7.5). With users of oral contraceptives with levonorgestrel as reference and after adjusting for length of use, the rate ratio of confirmed venous thromboembolism for users of oral contraceptives with desogestrel was 2.2 (1.7 to 3.0), with gestodene was 2.1 (1.6 to 2.8), and with drospirenone was 2.1 (1.6 to 2.8). The risk of confirmed venous thromboembolism was not increased with use of progestogen only pills or hormone releasing intrauterine devices. If oral contraceptives with desogestrel, gestodene, or drospirenone are anticipated to increase the risk of venous thromboembolism sixfold and those with levonorgestrel threefold, and the absolute risk of venous thromboembolism in current users of the former group is on average 10 per 10 000 women years, then 2000 women would need to shift from using oral contraceptives with desogestrel, gestodene, or drospirenone to those with levonorgestrel to prevent one event of venous thromboembolism in one year.Conclusion After adjustment for length of use, users of oral contraceptives with desogestrel, gestodene, or drospirenone were at least at twice the risk of venous thromboembolism compared with users of oral contraceptives with levonorgestrel.