Oral Contraceptive Use In Women Research Articles

Synergistic Effects of Hypofibrinolysis and Genetic and Acquired Risk Factors on the Risk of a First Venous Thrombosis

BackgroundPreviously, we demonstrated that hypofibrinolysis, a decreased capacity to dissolve a blood clot as measured with an overall clot lysis assay, increases the risk of venous thrombosis. Here, we investigated the combined effect of hypofibrinolysis with established risk factors associated with hypercoagulability.Methods and FindingsFibrinolytic potential was determined with a plasma-based clot lysis assay in 2,090 patients with venous thrombosis and 2,564 control participants between 18 and 70 y of age enrolled in the Multiple Environmental and Genetic Assessment (MEGA) of risk factors for venous thrombosis study, a population-based case-control study on venous thrombosis. Participants completed a standardized questionnaire on acquired risk factors.Hypofibrinolysis alone, i.e., clot lysis time (CLT) in the fourth quartile (longest CLT) (in absence of the other risk factor of interest) increased thrombosis risk about 2-fold relative to individuals with CLT in the first quartile (shortest CLT). Oral contraceptive use in women with CLT in the first quartile gave an odds ratio (OR) of 2.6 (95% confidence interval [CI] 1.6 to 4.0), while women with hypofibrinolysis who used oral contraceptives had an over 20-fold increased risk of venous thrombosis (OR 21.8, 95% CI 10.2 to 46.7). For immobilization alone the OR was 4.3 (95% CI 3.2 to 5.8) and immobilization with hypofibrinolysis increased the risk 10.3-fold (95% CI 7.7 to 13.8). Factor V Leiden alone increased the risk 3.5-fold (95% CI 2.3 to 5.5), and hypofibrinolysis in factor V Leiden carriers gave an OR of 8.1 (95% CI 5.3 to 12.3). The combination of hypofibrinolysis and the prothrombin 20210A mutation did not synergistically increase the risk. All ORs and 95% CIs presented are relative to individuals with CLT in the first quartile and without the other risk factor of interest.ConclusionsThe combination of hypofibrinolysis with oral contraceptive use, immobilization, or factor V Leiden results in a risk of venous thrombosis that exceeds the sum of the individual risks.

Relationship between Leptin and C-Reactive Protein in Young Finnish Adults

Leptin and C-reactive protein (CRP) concentrations are increased in inflammation, and both have been linked to increased risk for cardiovascular diseases. The objective of the study was to explore in a population-based sample whether the relation between leptin and CRP is independent of obesity level and whether genetic causes of CRP elevation contribute to leptin levels. This was a population-based study including 1862 young adults (971 women; 891 men) aged 24-39 yr. The study was conducted at five centers in Finland. Associations between leptin and CRP adjusted for obesity indices, risk factors, genetic variables, and lifestyle variables were measured. Women had 3.0-fold higher median concentrations of leptin (12.5 vs. 4.1 ng/ml) and 1.3-fold higher median concentrations of CRP (0.75 vs. 0.56 mg/liter) than men (P < 0.0001 in both comparisons). In univariate analyses, CRP and leptin were significantly intercorrelated (r = 0.47, P < 0.0001 for women; r = 0.46, P < 0.0001 for men). In multiple regression analysis including age, body mass index, waist circumference, insulin, lipids, systolic and diastolic blood pressures, smoking status, and use of oral contraceptives in women, leptin was the main determinant of CRP in men (P < 0.0001) and the second most important determinant in women (P < 0.0001). A Mendelian randomization test based on genetic variants in the CRP gene (five single nucleotide polymorphisms) provided no support for CRP as a causal agent for leptin. Leptin, obesity, and oral contraceptive use in women were the main factors related to CRP. The relation between leptin and CRP was independent of obesity and cardiovascular risk factors.

Use of oral contraceptives in the treatment of women with polycystic ovary syndrome

In addition to the benefits of contraception, oral contraceptives (OCs) are commonly prescribed for women with polycystic ovary syndrome (PCOS) to improve the clinical and metabolic parameters associated with this disorder. However, women with PCOS are at increased risk of insulin resistance and the metabolic syndrome and, therefore, may also be at increased risk of both diabetes and cardiovascular disease. OCs are contraindicated in women at increased risk of both venous and cardiovascular events; therefore, we must reconsider the routine use of OCs in women with PCOS who may also be at increased risk of either venous or arterial events. Furthermore, some studies have shown that the use of OCs is associated with impaired insulin sensitivity. Therefore, OCs should not be used as a monotherapy in women with impaired glucose tolerance. Finally, weight loss and lifestyle changes, including exercise and reducing caloric and saturated fat intake, are important in the treatment of obese patients with PCOS.

The use of oral contraceptives in women alters the differences in substrate oxidation between phases of the menstrual cycle

We previously reported that women in the luteal (LUT) phase oxidize less leucine, lipid and lipid relative to CHO as a fuel source, whereas they have a more advantageous protein balance, at rest and during exercise as compared with the follicular (FOL) phase ( Hamadeh, et al, Physiologist 2004; 47: 306– 7). Moreover, FOL and LUT women oxidize less leucine and have a less negative protein balance at rest and during exercise as compared with men. To investigate whether this is maintained in women taking oral contraceptives (OC), we measured whole body leucine kinetics using the stable isotope L-[1-13C]leucine in 6 women taking triphasic OC and compared the results with those for 12 men at rest and during moderate intensity endurance exercise. The women were tested in the FOL (day 9 ± 2; mean ± SEM) and LUT phases (day 21 ± 1) of the menstrual cycle. Following a primed continuous infusion of L-[1-13C]leucine in the postabsorptive state, VCO2 and steady state breath 13CO2 and plasma [13C]α-KIC enrichments were measured at rest and 60, 75 and 90 min during cycling at an intensity of 65% VO2max. Menstrual phase had no effect on any outcome measure. Men had higher leucine Ra (P < 0.004), leucine oxidation (P < 0.005) and protein breakdown (P < 0.004), but lower estimated protein balance (P < 0.005), than women. Men had higher protein synthesis (P = 0.046) as compared with FOL women only. We conclude that OC use in women abolishes the differences in substrate oxidation observed in non-OC users. Studies measuring substrate oxidation should account for the use of OC in women. (Funded by the Hamilton Health Sciences Foundation and NSERC Canada).

Hormone-Related Headache

Epidemiological data suggest a link between migraine and the female sex hormones. Indeed, it is known that estrogen affects various brain functions, including pain perception. The prevalence of migraine is similar in boys and girls before puberty, but is 3-fold higher in postpubertal females compared with males. Migraine attacks in women are more likely to occur in the perimenstrual period and occur exclusively so in some women. The acute treatment of menstrual migraine is similar to that of non-menstrually related attacks, but the response to treatment may be less favourable. Perimenstrual prophylaxis, with NSAIDs, triptans or estradiol, is effective in decreasing attack frequency and severity. The use of oral contraceptives (OCs) may change migraine frequency and severity. Since both migraine and hormonal contraceptive use are risk factors for ischaemic stroke, the use of OCs in women who experience migraine should be made only after consideration of the benefit-risk ratio. Migraine typically, but not invariably, improves during the last two trimesters of pregnancy, and may worsen in the postpartum period. When using drugs to treat migraine during pregnancy, potential risks to the mother and fetus should be considered. The prevalence of migraine decreases with advancing age and it improves in many, but not all, women after the menopause. However, in the perimenopausal period, migraine may worsen as a result of fluctuations in estrogen levels. Reducing the estrogen dose and changing the estrogen type or the route of administration of hormone replacement therapy (HRT) from oral to transdermal may reduce headache. Migraine is not a risk factor for stroke in postmenopausal women. When considering symptomatic HRT for postmenopausal migraneurs, the usual indications and contraindications should be applied. HRT may also exacerbate migraine.

C-reactive protein and cardiorespiratory fitness in young adults

Fitness and obesity are both independently associated with cardiovascular events and mortality. C-reactive protein (CRP), a predictor of cardiovascular events is associated with obesity; but its association with cardiorespiratory fitness in early adulthood is uncertain. The aim of this study was to examine the relationship between cardiorespiratory fitness and CRP, controlling for obesity in an unselected cohort of young adults. A cross-sectional study in a representative birth cohort. We measured CRP levels, cardiorespiratory fitness, anthropometric variables, blood pressure and smoking in 26-year-old men (n=400) and women (n=315). Log CRP levels were compared across cardiorespiratory fitness with adjustment for body mass index (BMI), sex, blood pressure, smoking and combined oral contraceptive use. Geometric mean CRP levels were higher in women (3.23 mg/l, 95% CI 2.85-3.64) compared with men (1.70 mg/l, 1.52-1.89). Regression analysis adjusting for sex and weight showed an inverse association between fitness and CRP (beta=-0.16, P<0.001). This association held after statistical controls were added for BMI, systolic blood pressure and smoking and combined oral contraceptive use (P< or =0.01). Cardiorespiratory fitness levels are inversely associated with CRP levels in young adults independent of obesity, blood pressure, smoking and combined oral contraceptive use in women. Physical fitness may decrease the risk of cardiovascular events by reducing inflammation.

Fatty acid reesterification but not oxidation is increased by oral contraceptive use in women

We evaluated the hypothesis that fatty acid reesterification would be increased during rest and exercise in the midluteal menstrual cycle phase and during oral contraceptive use, when ovarian hormone concentrations are high, compared with the early follicular phase. Subjects were eight moderately active, weight-stable, eumenorrheic women (24.8 +/- 1.2 yr, peak oxygen consumption = 42.0 +/- 2.3 ml.kg(-1).min(-1)) who had not taken oral contraceptives for at least 6 mo. Plasma free fatty acid (FFA) kinetics were assessed in the 3-h postprandial state by continuous infusion of [1-(13)C]palmitate and [1,1,2,3,3-(2)H]glycerol during 90 min of rest and 60 min of exercise at 45% and 65% peak oxygen consumption in the early follicular and midluteal menstrual cycle phases and during the inactive- and high-dose phases following 4 mo of oral contraceptive use. Plasma FFA rates of appearance, disappearance, and oxidation increased significantly from rest to exercise with no differences noted between menstrual cycle or oral contraceptive phases or exercise intensities. Compared with either menstrual cycle phase, oral contraceptive use resulted in an increase in plasma-derived fatty acid reesterification and a decrease in the proportion of plasma FFA rate of disappearance that was oxidized at rest and during exercise. Endogenous and exogenous synthetic ovarian hormones do not exert a measurable influence on plasma FFA turnover or oxidation at rest or during moderate-intensity exercise in the 3-h postprandial state when carbohydrate use predominates. The increase in whole body lipolytic rate during exercise noted previously with oral contraceptive use is not matched by an increase in fatty acid oxidation and results in an increase in reesterification. Synthetic ovarian hormones contained in oral contraceptives increase lipolytic rate, but fatty acid oxidation during exercise is determined by exercise intensity and its metabolic and endocrine consequences.

Oral contraceptive use in women with poor anticoagulant response to activated protein C but not carrying the factor V Leiden mutation increases the risk of venous thrombosis.

The factor V Leiden mutation (FVL), associated with reduced sensitivity to activated Protein C (APC), is a risk factor for venous thromboembolism (VTE) and displays a strong interaction with oral contraceptives (OC). The aim of this study was to evaluate the risk of VTE in OC users with reduced APC sensitivity unrelated to the FVL. APC sensitivity was measured by an original aPTT-based test (without sample pre-dilution in factor V-deficient plasma) in 195 women who suffered from VTE in reproductive age and in 487 healthy women with results being expressed as normalized ratio. Subjects with currently known clinically relevant thrombophilic alterations were excluded. APC normalized ratios were stratified into quartiles. The adjusted ORs of subjects in the lower quartile (>/= 0.90) was 2.46 (95%CI: 1.02-5.95). Of the 195 patients, 89 had suffered VTE during OC. The 181 healthy women who had used OC for at least 6 months in the two year period before presentation but who had stopped OC at least 3 months before blood sampling were considered OC users. The risk of VTE in subjects using OC with APC normalized ratio in the lower quartile was increased 4.9-fold (95% CI: 1.92-12.6). In conclusion, our results showed that altered APC resistance in women not carrying the FVL significantly increased the VTE risk, albeit to a lesser extent than in women also carrying the FVL. Our data also showed that OC use in women with altered APC resistance further increased the risk of VTE in a way that exceeded the additive expectation.

Age- and sex-related reference values for serum insulin concentration and its biological determinants in a French healthy population. The STANISLAS cohort

Insulin is involved in coronary heart disease through diabetes and metabolic syndrome. A great deal is known about insulin and its correlates, as well as factors related to changes in insulin. However, few studies consider the broad variety of correlates simultaneously. Therefore, the aims of the present study were to characterize the main factors of biological variation affecting serum insulin concentration and to establish reference limits of insulinemia in a presumably healthy French population. Insulin was measured using a microparticular enzymatic immunoassay. A total of 646 subjects aged 11-58 years from the STANISLAS cohort and divided into four groups of 162 males, 157 females, 163 boys and 164 girls, were included in the statistical analyses. In the whole population, serum insulin concentration varied from 0.80 to 54.60 microU/ml. Significant factors affecting insulin were age, gender, body mass index and glucose, in addition to alanine aminotransferase and high-density lipoprotein cholesterol in men, triglycerides and oral contraceptive use in women, and alkaline phosphatase in girls. In summary, we presented biological correlates of insulin in both healthy French male and female adults and children/adolescents and determined reference limits for insulin for each group. These results will contribute to a better interpretation of insulin data in further studies and laboratory investigations.

Oral contraception over the age of 40.

Scientific data from the past decade have proved that the age of 35 years is not an obligatory border at which to stop taking oral contraceptives (OCs). Combined OC formulations (COCs) are safe and effective for healthy women up to the age of the menopause. The use of OCs in women who do not smoke does not result in an increased risk of cardiovascular disease. Since the risk of thromboembolism increases with age and the level of obesity in women of 40 and over, it is wise to prescribe the lowest available dose of ethinyl-estradiol in the COCs. Some authors prefer levonorgestrel to any third-generation progestogen in COCs, but the excess risk of venous thromboembolism associated with the use of third-generation products can be balanced by the reduced risk of myocardial infarction associated with the same products. When OCs are considered for perimenopausal women, it is important to take into account progestogen-only pills. In consequence of the reduced fecundity, these have a better contraceptive efficacy in this age group than in women aged below 35 years. Their only important possible adverse effect is an unpredictable bleeding pattern; further, they do not alleviate climacteric symptoms if these are present. In such cases, progestogen-only pills can be combined with cyclic hormone replacement therapy.

Poster 200: Severe headache in a woman using oral contraceptives: a case report.

Setting: Academic medical center. Patient: A 37-year-old right-handed woman without significant medical history. Case Description: The patient was in her usual state of good health when she experienced the acute onset of severe left frontal and central headache, present on awakening. She felt nauseated but did not vomit. She noted subtle word-finding difficulties. She reported to the outpatient neurology clinic and had a normal neurologic examination except for inability to correctly recall her telephone area code. An urgent magnetic resonance imaging (MRI) of the brain demonstrated a hyperintense area in the left parietotemporal region. Magnetic resonance angiography was normal. The patient was admitted with the presumptive diagnosis of cerebral infarct or bleed. She underwent magnetic resonance venography (MRV), which demonstrated loss of signal intensity in the straight sinus, left transverse sinus, and left sigmoid sinus. The findings were highly suspicious for venous thrombosis. She was started on heparin after a lumbar puncture was negative. A head computed tomography, to monitor for any hemorrhagic change, was negative except for changes consistent with venous thrombosis. Her neurologic status was stable. Her intense headache continued, and was exacerbated by the lumbar puncture. Her inpatient stay was uncomplicated. She was discharged home on enoxaprin, transitioning to warfarin. She was evaluated by a hematologist for a hypercoagulable disorder and scheduled to follow-up with MRI and MRV after 3 months. Assessment/Results: An exhaustive hypercoaguable work-up was negative. A risk-factor analysis was positive only for the use of oral contraceptives. It was recommended that she permanently discontinue oral contraceptives. Discussion: The medical literature reports cases of venous thrombosis, including cerebral events, but typically in persons with multiple risk factors. Conclusions: It is important to check specifically for oral contraceptive use in women presenting with severe headache. This may herald a more serious central nervous system disorder.

Venous thromboembolism, oral contraceptives and high prothrombin levels

The G20210A prothrombin mutation, associated with elevated prothrombin levels, is a risk factor for venous thromboembolism (VTE) and displays a strong interaction with oral contraceptives (OC). No data are available on VTE risk of OC use in women with high prothrombin levels, either associated or not with the mutation. The aim of this study was to evaluate the risk of VTE in OC users with high prothrombin levels, either including or excluding carriers of the prothrombin mutation. Prothrombin levels were measured by a chromogenic assay in 152 women who suffered from VTE in reproductive age and in 296 healthy women. Subjects carrying thrombophilic alterations other than the G20210A prothrombin mutation were excluded. Prothrombin levels were stratified into quartiles. The OR of subjects in the upper quartile were 3.10 [95% confidence interval (CI) 1.73-5.55] and 2.07 (95% CI 1.11-3.85) in all women and in those not carrying the prothrombin mutation, respectively. Among the 152 patients, 88 had experienced VTE during OC; in the control group we considered as OC users the women who had used OC for at least 6 months in the 2 years before presentation but had stopped the treatment at least 3 months before the time of blood sampling (n = 127). For the interaction between OC and prothrombin levels only the two extreme strata of prothrombin were considered. Women with the lowest prothrombin levels and who did not use OC were used as reference category. The VTE risk of using OC in subjects with prothrombin levels in the upper quartile was increased 5.4-fold (95% CI 2.38-12.3) and 3.5-fold (95% CI 1.48-8.22) in all women and in those not carrying the prothrombin mutation, respectively. We conclude that elevated prothrombin levels, even in women without the G20210A prothrombin mutation, are associated with an increased risk for venous thromboembolism and that oral contraceptive use potentiates such association.

Risk of breast cancer with oral contraceptive use in women with a family history of breast cancer.

Oral contraceptive (OC) use is weakly associated with breast cancer risk in the general population, but the association among women with a familial predisposition to breast cancer is less clear. To determine whether the association between OC use and risk of breast cancer is influenced by family history of the disease. Historical cohort study of 426 families of breast cancer probands diagnosed between 1944 and 1952 at the Tumor Clinic of the University of Minnesota Hospital. Follow-up data on families were collected by telephone interview between 1991 and 1996. A total of 394 sisters and daughters of the probands, 3002 granddaughters and nieces, and 2754 women who married into the families. Relative risk (RR) of breast cancer associated with history of OC use by relationship to proband. After accounting for age and birth cohort, ever having used OCs was associated with significantly increased risk of breast cancer among sisters and daughters of the probands (RR, 3.3; 95% confidence interval [CI], 1.6-6.7), but not among granddaughters and nieces of the probands (RR, 1.2; 95% CI, 0.8-2.0) or among marry-ins (RR, 1.2; 95% CI, 0.8-1.9). Results were essentially unchanged after adjustment for parity, age at first birth, age at menarche, age at menopause, oophorectomy, smoking, and education. The elevated risk among women with a first-degree family history of breast cancer was most evident for OC use during or prior to 1975, when formulations were likely to contain higher dosages of estrogen and progestins (RR, 3.3; 95% CI, 1.5-7.2). A small number of breast cancer cases (n = 2) limited the statistical power to detect risk among women with a first-degree relative with breast cancer and OC use after 1975. These results suggest that women who have ever used earlier formulations of OCs and who also have a first-degree relative with breast cancer may be at particularly high risk for breast cancer. Further studies of women with a strong family history who have used more recent lower-dosage formulations of OCs are needed to determine how women with a familial predisposition to breast cancer should be advised regarding OC use today. JAMA. 2000;284:1791-1798.

Risk factors for haemorrhagic stroke a case–control study

A hospital based pair-matched case-control study was undertaken to identify risk factors for haemorrhagic stroke. The study took place in the Government Medical College Hospital, Nagpur, India, a tertiary care hospital. The study consisted of 166 hospitalised computerised tomography scan proved cases of haemorrhagic stroke (International Classification Diseases 9, 431-432), and an age and sex matched control per case. The controls were selected from patients who attended the study hospital for conditions other than stroke. The study included hypertension, serum total cholesterol, alcohol intake, smoking, diabetes mellitus, obesity, physical inactivity, type A personality, use of anticoagulants/antiplatelets, family history of stroke, history of cardiac diseases, past history of transient ischaemic attack, history of claudication and oral contraceptive use in women, as risk factors for haemorrhagic stroke. Bivariate analysis included odds ratio (OR), 95% confidence intervals (CI) for OR and McNemar's chi2 test. Multivariate analysis was carried out by conditional multiple logistic regression analysis. Attributable Risk Percent (ARP), Population Attributable Risk Percent (PARP) and their 95% CI were estimated for significant factors. On conditional multiple logistic regression five risk factors-hypertension (OR=1.9, 95% CI 1.5-2.5), serum total cholesterol (OR=2.3, 95% CI 1.4-4.9), use of anticoagulants and antiplatelet agents (OR=3.4, 95% CI 1.1-10.4), past history of transient ischaemic attack (OR=8.4, 95% CI 2.1-33.6) and alcohol intake (OR=2.1, 95% CI 1.3-3.6) were significant. Estimates of ARP and PARP for these factors confirmed their etiological and preventable role respectively. The current study recognised the significance of five risk factors, which are preventable. These risk factors may be considered for devising effective risk factor intervention strategy for haemorrhagic stroke.

Risk factors for haemorrhagic stroke: a case–control study

A hospital based pair-matched case-control study was undertaken to identify risk factors for haemorrhagic stroke. The study took place in the Government Medical College Hospital, Nagpur, India, a tertiary care hospital. The study consisted of 166 hospitalised computerised tomography scan proved cases of haemorrhagic stroke (International Classification Diseases 9, 431–432), and an age and sex matched control per case. The controls were selected from patients who attended the study hospital for conditions other than stroke. The study included hypertension, serum total cholesterol, alcohol intake, smoking, diabetes mellitus, obesity, physical inactivity, type A personality, use of anticoagulants/antiplatelets, family history of stroke, history of cardiac diseases, past history of transient ischaemic attack, history of claudication and oral contraceptive use in women, as risk factors for haemorrhagic stroke. Bivariate analysis included odds ratio (OR), 95% confidence intervals (CI) for OR and McNemar's χ 2 test. Multivariate analysis was carried out by conditional multiple logistic regression analysis. Attributable Risk Percent (ARP), Population Attributable Risk Percent (PARP) and their 95% CI were estimated for significant factors. On conditional multiple logistic regression five risk factors–hypertension (OR=1.9, 95% CI 1.5–2.5), serum total cholesterol (OR=2.3, 95% CI 1.4–4.9), use of anticoagulants and antiplatelet agents (OR=3.4, 95% CI 1.1–10.4), past history of transient ischaemic attack (OR=8.4, 95% CI 2.1–33.6) and alcohol intake (OR=2.1, 95% CI 1.3–3.6) were significant. Estimates of ARP and PARP for these factors confirmed their etiological and preventable role respectively. The current study recognised the significance of five risk factors, which are preventable. These risk factors may be considered for devising effective risk factor intervention strategy for haemorrhagic stroke. Public Health (2000) 114, 177–182

Contraception in women at high risk or with established cardiovascular disease.

Oral contraceptives are one of the most effective and widely used reversible contraceptive methods. Over 90 million women worldwide, including over 44 million in developing countries, are now using oral contraceptives. Despite their advantages, there is concern about the links between combined oral contraceptives and the risk of cardiovascular disease. The risk attributable to oral contraceptive use in women < 35 years of age is small, even if they smoke, but there are substantially increased risks in older women who both smoke and use oral contraceptives. Differences between oral contraceptive types in the relative risk of venous thromboembolism contribute little to the total cardiovascular mortality associated with oral contraceptive use, even though the total number of cardiovascular events is increased. It is important to consider the user's age and smoking status when determining oral contraceptive-attributable risks. Hormonal oral contraceptives have changed and now contain lower doses of estrogen and progestagen.

Symptomatic fibroids: the need to include low dose OCPs as a treatment option

Symptomatic fibroids are one of the most common reasons women undergo surgical intervention (hysterectomy, myomectomy, endometrial ablation) or other invasive interventions (uterine artery embolization). Although pharmacologic therapy with GnRH analogues, Danazol, RU486 and NSAIDs are occasionally prescribed, rarely are oral contraceptives (OCPs) prescribed for either fibroid prevention or treatment of symptoms. It appears that OCPs are underutilized as a first-line treatment option because of the common belief that OCPs will stimulate fibroid growth and worsen symptoms. This paper reviews the literature on the effects of OCPs on fibroids and evaluates the prevalence of OCP use in a subset of women with fibroids presenting for uterine artery embolization (UAE). From 1/98 through 11/98, women who presented for a UAE were consecutively evaluated under an IRB protocol and data were collected on the reasons for their requesting UAE, the symptoms they were experiencing and what treatment options they had been offered before coming in for UAE. Information was also collected on the number of women who had been treated pharmacologically (ie low dose OCPs) and who had been admitted to a hospital for a surgical procedure (ie myomectomy, D&C, endometrial ablation) before presenting for a UAE. Information also was collected by a MEDLINE search on the effect of OCPs on uterine fibroids. Eighty-four women between the ages of 29 and 60 with symptomatic leiomyoma presented for uterine artery embolization. Three of the women in this cohort had prior surgery. None of the women had been given OCPs as treatment for their pelvic pathology. The literature did not support the association of the use of low dose OCPs and fibroid growth. Women in this cohort with the chief complaint of leiomyomatous uterus had not been offered low dose OCPs. It appears that practitioners are still concerned about possible fibroid growth with low dose OCPs. Education in this area is important to dispel misconceptions about OCP use in women with uterine leiomyoma. As well, there is a need for more research that evaluates the benefits of low dose OCPs in this subset of women.

Are factor V Leiden carriers who use oral contraceptives at extreme risk for venous thromboembolism?

Background Major concern was raised by an earlier study regarding oral contraceptive use in women with the factor V Leiden mutation. A more than 30-fold increase in relative risk for venous thromboembolism was reported; for homozygotes, the relative risk was as much as 100-fold or more. Objective To replicate the reported risk estimates with a new population-based case-control study. Methods Eighty women with a diagnosis of venous thromboembolism were consecutively identified and compared with population-based controls (n = 406). Factor V Leiden mutation was identified by genotype analysis. The evaluation was performed with conditional logistic regression (matched for 5-year age group). Results Matched, adjusted odds ratios (OR) for idiopathic venous thromboembolism in women without and with the factor V Leiden mutation who used oral contraceptives were 4.1 (95% confidence interval (CI) 2.1–7.8) and 10.2 (95% CI 1.2–88.4), respectively. The adjusted OR for factor V Leiden carriers was 2.0 (95% CI 1.0–4.4). The OR for women with the factor V Leiden mutation and oral contraceptive use versus no factor V Leiden mutation and no oral contraceptive use was 10.2 (95% CI 3.8–27.6). Conclusion The results confirm the increased relative risk of idiopathic venous thromboembolism for users of oral contraceptives and factor V Leiden carriers. However, we suspect that the true risk for women who are factor V Leiden carriers may be increased two- to four-fold rather than seven-fold or more, and that the risk for the combination of factor V Leiden and oral contraceptive use may be increased in the order often- to 15-fold rather than over 30-fold.

Epidemiology of hepatocellular carcinoma.

Although rare in Canada and the United States, hepatocellular carcinoma (HCC) ranks as the eighth most common cancer in the world. High-risk regions are East and Southeast Asia, and sub-Saharan Africa. Independent of race and geography, rates in men are at least two to three times those in women; this sex ratio is more pronounced in high-risk regions. Rates of HCC in the United States have increased by 70% over the past two decades. Registry data in Canada and Western Europe show similar trends. In contrast, the incidence of HCC in Singapore and Shanghai, China, both high-risk regions, has declined steadily over the past two decades. Among white and black Americans, there is an inverse relationship between social class status and HCC incidence. Chronic infection by the hepatitis B virus (HBV) is by far the most important risk factor for HCC in humans. It is estimated that 80% of HCC worldwide is etiologically associated with HBV. In the United States, although the infection rate in the general population is low, HBV is estimated to account for one in four cases of HCC among non-Asians. Chronic infection by the hepatitis C virus is another important risk factor for HCC in the United States; however, this virus is believed to play a relatively minor role in the development of HCC in Africa and Asia. Dietary aflatoxin exposure is an important codeterminant of HCC risk in Africa and parts of Asia. In Canada and the United States, excessive alcohol intake, cigarette smoking and oral contraceptive use in women also are risk factors for HCC.

Venous Thrombosis, Oral Contraceptives and High Factor VIII Levels

Recently, it has been described that elevated plasma levels of factor VIII are a strong risk factor for venous thrombosis. We analysed the data of the Leiden Thrombophilia Study, a population based case-control study on the causes of venous thrombosis, to verify whether the risk due to oral contraceptive use was higher in women with higher factor VIII levels. Furthermore we investigated the joint risk of high factor VIII levels and oral contraceptive use. We selected 155 premenopausal women with deep-vein thrombosis and 169 control subjects, aged 15-49, who were at the time of their thrombosis (or similar date in control) not pregnant, nor in the puerperium, did not have a recent miscarriage, and were not using injectable progestogens. Of the patients, 109 (70%) women had used oral contraceptives during the month preceding their deep-vein thrombosis, in contrast to 65 (38%) of the control subjects (index date), yielding an odds ratio for oral contraceptive use of 3.8 (95% CI 2.4-6.0). Of the women who suffered a deep-vein thrombosis 56 (36%) had high factor VIII levels (> or =150 IU/dl) as compared with 29 (17%) of the control subjects, yielding an odds ratio for high factor VIII of 4.0 (95% CI 2.0-8.0), relative to factor VIII levels <100 IU/dl. The joint effect of oral contraceptive use and high factor VIII resulted in an odds ratio of 10.3 (95% CI 3.7-28.9), comparing women who had both with women who had neither. We conclude that there is an increase in risk due to oral contraceptive use in women with higher factor VIII levels and that both factors have additive effects.