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Background and Purpose-Epidemiological studies have shown an increased risk of venous thrombosis in women takingthird-generation oral contraceptives, ie, those containing the progestogens desogestrel or gestodene. This study assesses the risk of ischemic stroke with several types of oral contraceptives. Methods-A multicenter, population-based, case-control study was performed in 9 Dutch centers in women aged 18 to 49 years. Women with a first ischemic stroke were compared with control women without vascular diseases. The control subjects were recruited by random-digit dialing and were stratified by age, area of residence, and year of stroke. All patients and control subjects filled in a questionnaire about the use of oral contraceptives and risk factors for ischemic stroke. Odds ratios were adjusted for the stratification factors. Results-Two hundred three women with an ischemic stroke and 925 control women were included. The risk of stroke in women using any type of oral contraceptives versus none was 2.3 (95% CI 1.6 to 3.3). Current users of first-generation oral contraceptives had an odds ratio of 1.7 (95% CI 0.7 to 4.4). Low-dose second-generation oral contraceptives increased the risk of stroke 2.4 times (95% CI 1.6 to 3.7), and third-generation oral contraceptives increased the risk of stroke 2.0 times (95% CI 1.2 to 3.5). The risk of stroke in women using third-generation oral contraceptives was not different from that in women using second-generation oral contraceptives (odds ratio 1.0, 95% CI 0.6 to 1.8). Conclusions-Third-generation oral contraceptives (containing desogestrel or gestodene) confer the same risk of first ischemic stroke as second-generation oral contraceptives (containing levonorgestrel).

Summary.  Hundreds of millions of women worldwide use either oral contraceptives or postmenopausal hormone replacement. The use of oral contraceptives leads to an increased risk of venous thrombosis, of myocardial infarction, of stroke and of peripheral artery disease, the risks of which are highest during the first year of use. Women with coagulation abnormalities have a higher risk of venous thrombosis when they use oral contraceptives (or postmenopausal hormones) than women without these abnormalities. The risk of venous thrombosis is also higher for preparations containing desogestrel or gestodene (third‐generation progestogens) than for those containing levonorgestrel (second‐generation progestogens). A previous thrombosis as well as obesity also increase the risk of oral contraceptive‐related thrombosis. Hormone replacement therapy increases the risk of venous thrombosis, and has no beneficial, and possibly even a detrimental, effect on the risk of arterial disease. The risk of arterial disease in oral contraceptive users and users of hormone replacement therapy is at most weakly affected by the presence of prothrombotic abnormalities.

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Back-ground An association between the use of oral contraceptives and the risk of myocardial infarction has been found in some, but not all, studies. We investigated this association, according to the type of progestagen included in third-generation (i.e., desogestrel or gestodene) and second-generation (i.e., levonorgestrel) oral contraceptives, the dose of estrogen, and the presence or absence of prothrombotic mutations. Methods In a nationwide, population-based, casecontrol study, we identified and enrolled 248 women 18 through 49 years of age who had had a first myocardial infarction between 1990 and 1995 and 925 control women who had not had a myocardial infarction and who were matched for age, calendar year of the index event, and area of residence. Subjects supplied Information on oral-contraceptive use and major cardiovascular risk factors. An analysis for factor V Leiden and the G20210A mutation in the prothrombin gene was conducted in 217 patients and 763 controls.Results The odds ratio for myocardial infarction among women who used any type of combined oral contraceptive, äs compared with nonusers, was 2.0 (95 percent confidence interval, 1.5 to 2.8). The adjusted odds ratio was 2.5 (95 percent confidence interval, 1.5 to 4.1) among women who used second-generation oral contraceptives and 1.3 (95 percent confidence interval, 0.7 to 2.5) among those who used third-generation oral contraceptives. Among women who used oral contraceptives, the odds ratio was 2.1 (95 percent confidence interval, 1.5 to 3.0) for those without a prothrombotic mutation and 1.9 (95 percent confidence interval, 0.6 to 5.5) for those with a mutation. Conclusions The risk of myocardial infarction was increased among women who used second-generation oral contraceptives. The results with respect to the use of third-generation oral contraceptives were inconclusive but suggested that the risk was Iower than the risk associated with second-generation oral contraceptives. The risk of myocardial infarction was similar among women who used oral contraceptives whether or not they had a prothrombotic mutation. Later studies established the use of oral contraceptives äs a risk factor for venous äs well äs arterial thrombosis. 2 7 Various modifications were made in an attempt to Iower these risks, including a reduction in the estrogen dose and changes in the progestagen compound. Oral contraceptives containing an estrogen and the progestagen desogestrel or gestodene, available since the 1980s, are associated with at least a doubling of the risk of venous thrombosis äs compared with other combined oral contraceptives. 812 It has been suggested that these third-generation contraceptives protect against myocardial infarction by having a favorable effect on the lipid profile, 131S because studies showed that women who used these types had a slight increase in the level of high-density lipoprotein cholesterol. 15 · 16 Only a few studies of the association between oral contraceptives and myocardial infarction have included a direct compar...

Thyroid substitution treatment in patients with hypercholesterolaemia and subclinical hypothyroidism decreases total plasma cholesterol by 0.4 mmol/l, but plasma levels remain elevated in most patients. Further treatment with dietary restriction and cholesterol synthesis inhibitors should then be considered.

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Background Increasing evidence suggests that severe skeletal muscle index (SMI) loss (sarcopenia) is associated with poor overall survival in metastatic colorectal cancer patients, but its mechanisms are unknown. We recently found, using data of the randomized phase 3 CAIRO3 study, that SMI loss was related with shorter time to disease progression and overall survival during first‐line maintenance treatment with capecitabine + bevacizumab (CAP‐B) or observation and during more intensive capecitabine + oxaliplatin + bevacizumab (CAPOX‐B) reintroduction treatment. As a potential risk factor for reduced survival, we explored whether sarcopenia and SMI loss were associated with dose‐limiting toxicities (DLTs) during CAP‐B and CAPOX‐B. Methods Sarcopenia status and SMI loss were assessed by using consecutive computed tomography scans. DLTs were defined as any dose delay/reduction/discontinuation of systemic treatment because of reported CTCAE (version 3.0) toxicities at the start or during treatment. Poisson regression models were used to study whether sarcopenia and body mass index (BMI) at the start of treatment and SMI and BMI loss during treatment were associated with DLTs. Results One hundred eighty‐two patients (mean age 63.0 ± 8.8 years, 37% female) received CAP‐B, and 232 patients (mean age 63.0 ± 9.0 years, 34% female) received CAPOX‐B. At the start of CAP‐B and CAPOX‐B, 54% and 46% of patients were sarcopenic, respectively. Mean BMI was lower in sarcopenic patients, although patients were on average still overweight (sarcopenic vs. non‐sarcopenic at the start of CAP‐B 25.0 ± 3.9 vs. 26.7 ± 4.1 and CAPOX‐B 25.8 ± 3.8 vs. 27.1 ± 3.8 kg/m 2 ). Sarcopenia at the start of CAP‐B was not associated with DLTs [relative risk 0.87 (95% confidence interval 0.64–1.19)], whereas patients with >2% SMI loss had a significantly higher risk of DLTs [1.29 (1.01–1.66)]. At the start of subsequent CAPOX‐B, 25% of patients received a dose reduction, and the risk of dose reduction was significantly higher for patients with preceding SMI loss [1.78 (1.06–3.01)] or sarcopenia [1.75 (1.08–2.86)]. After the received dose reductions, sarcopenia or SMI loss was not significantly associated with a higher risk of DLTs during CAPOX‐B [sarcopenia vs. non‐sarcopenic: 0.86 (0.69–1.08) and SMI loss vs. stable/gain: 0.83 (0.65–1.07)]. In contrast, BMI (loss) at the start or during either treatment was not associated with an increased risk of DLTs. Conclusions In this large longitudinal study in metastatic colorectal cancer patients during palliative systemic treatment, sarcopenia and/or muscle loss was associated with an increased risk of DLTs. BMI was not associated with DLTs and could not detect sarcopenia or SMI loss. Prospective (randomized) studies should reveal whether normalizing chemotherapeutic doses to muscle mass or muscle mass preservation (by exercise and nutritional interventions)...