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Effect of oral contraceptives containing 20 and 35 μg ethinyl estradiol on urinary prostacyclin and thromboxane levels in smokers and non-smokers
CARDIOVASCULAR, HEMATOLOGIC, AND PULMONARY Methods: A retrospective review of VTE cases occurring between 1978 and 1996 was performed. Cases of deep venous thrombosis (DVT) and pulmonary embolism (PE) were identified by ICD-9 discharge diagnosis code and review of antepartum and coagulation laboratory databases. Study inclusion criteria required the objective diagnosis of VTE with either Doppler ultrasound, impedance plethysmography, pulmonary angiography, ventilation-perfusion scanning, or CT/MRI. Results: Among 268,525 deliveries there were 165 (0.06%) episodes of VTE (1/1627 births). There were 127 cases of DVT and 38 cases of PE. Only 14% (23/165) had a prior history of DVT or PE. Most DVTs occurred in the left leg (104/127, 81.9%). Nearly three quarters of the DVTs (95/127, 74.8%) occurred in the antepartum period. Among the antepartum DVT cases, half were detected prior to 15 weeks of gestation (47/95, 49.5%), with only 28 cases occurring after 20 weeks (P , .0001). The majority of the PEs occurred in the postpartum period (23/38, 60.5%). There were only 3 maternal deaths due to PE, all associated with cesarean section. Only 1 patient developed PE while on heparin therapy for DVT while 11 others had complications attributable to heparin use. Conclusion: Most pregnancy-related VTE occurs in the antepartum period. The risk of deep venous thrombosis appears to begin early in pregnancy, even before the second trimester. The highest risk period for pulmonary embolism is after cesarean delivery. Maternal complications of heparin anticoagulation during pregnancy are rare.
Effect of oral contraceptives containing 20 and 35 mg ethinyl estradiol on urinary prostacyclin and thromboxane levels in smokers and non-smokers Susan Ploszaj, MD, Melvin H. Thornton, MD, Frank Z. Stanczyk, PhD, Daniel R. Mishell, Jr, MD Department of Obstetrics and Gynecology, Los Angeles County and University of Southern California Medical Center, Los Angeles, California Objective: Several observational epidemiological studies have shown an increased risk of myocardial infarction (MI) in
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oral contraceptive (OC) users who smoke cigarettes. Nearly a quarter of all OC users are smokers. The etiology of MI in OC users has been shown to be thrombotic, and the thrombogenic effect of OCs appears to be due to the estrogen component of the formulation. There are epidemiologic data that indicate that decreasing the estrogen dosage in OCs decreases the risk of thrombosis. Smoking may enhance thrombosis in OC users by decreasing prostacyclin levels. The objective of the present study was to investigate the interaction between smoking and OC use with respect to thrombogenesis by studying the effects of OCs and smoking on urinary levels of prostacyclin PGI and thromboxane A2 TX in smokers and non-smokers. Study Design: A total of 60 healthy women, aged 19 –32 years, who were not taking any hormonal treatment for at least 3 months prior to initiating the study were divided into three equal groups: A) OC users who smoked (N 5 20), B) OC users who did not smoke (N 5 20), and a control group of 10 smokers and 10 non-smokers. To be eligible to participate in the study, all smokers had to smoke at least one pack of cigarettes per day. Each OC treatment group was randomized to receive either norethindrone (NET) acetate (1 mg)/ethinyl estradiol (EE2) (0.035 mg) (N 5 10) or NET acetate (1 mg)/EE2 (0.02 mg) (N 5 10) daily for 3 months. Overnight urine collections and fasting blood samples were obtained at baseline and at 3 months prior to taking the last OC. Serum levels of NET and EE2, as well as urinary levels of cotinine and the stable metabolites of prostacyclin and thromboxane A2 (6-keto-prostaglandin F1a and thromboxane B2, respectively), were measured by specific immunoassays. Results: Study subjects showed compliance with respect to smoking and OC use as determined by the levels of serum NET, EE2, and cotinine. Comparing mean levels of PGI metabolites in the two groups of OC smokers, those taking 35 mg EE2 showed a significant decrease in PGI. Comparing the ratio of PGI/TX in all smokers, only the smokers on the 35 mg formulation showed a significant decrease in the ratio, while there was no change in the 20 mg group. No significant changes in the ratio PGI/TX during the same time interval in smoking and non-smoking controls and OC non-smokers were observed. Conclusions: Women smokers taking 20 mg EE2 OC had no thrombophilic changes of PGI and TXA2 metabolites. Women smokers taking 35mg EE2 oral contraceptive had thrombophilic changes in PGI/TXA metabolite ratio. Women smokers who use oral contraceptives may have less thrombotic risk taking formulations with 20mg EE2 than 35mg EE2.
Prim Care Update Ob/Gyns
Effect of oral contraceptives containing 20 and 35 mg ethinyl estradiol on urinary prostacyclin and thromboxane levels in smokers and non-smokers Susan Ploszaj, MD, Melvin H. Thornton, MD, Frank Z. Stanczyk, PhD, Daniel R. Mishell, Jr, MD Department of Obstetrics and Gynecology, Los Angeles County and University of Southern California Medical Center, Los Angeles, California Objective: Several observational epidemiological studies have shown an increased risk of myocardial infarction (MI) in
156
oral contraceptive (OC) users who smoke cigarettes. Nearly a quarter of all OC users are smokers. The etiology of MI in OC users has been shown to be thrombotic, and the thrombogenic effect of OCs appears to be due to the estrogen component of the formulation. There are epidemiologic data that indicate that decreasing the estrogen dosage in OCs decreases the risk of thrombosis. Smoking may enhance thrombosis in OC users by decreasing prostacyclin levels. The objective of the present study was to investigate the interaction between smoking and OC use with respect to thrombogenesis by studying the effects of OCs and smoking on urinary levels of prostacyclin PGI and thromboxane A2 TX in smokers and non-smokers. Study Design: A total of 60 healthy women, aged 19 –32 years, who were not taking any hormonal treatment for at least 3 months prior to initiating the study were divided into three equal groups: A) OC users who smoked (N 5 20), B) OC users who did not smoke (N 5 20), and a control group of 10 smokers and 10 non-smokers. To be eligible to participate in the study, all smokers had to smoke at least one pack of cigarettes per day. Each OC treatment group was randomized to receive either norethindrone (NET) acetate (1 mg)/ethinyl estradiol (EE2) (0.035 mg) (N 5 10) or NET acetate (1 mg)/EE2 (0.02 mg) (N 5 10) daily for 3 months. Overnight urine collections and fasting blood samples were obtained at baseline and at 3 months prior to taking the last OC. Serum levels of NET and EE2, as well as urinary levels of cotinine and the stable metabolites of prostacyclin and thromboxane A2 (6-keto-prostaglandin F1a and thromboxane B2, respectively), were measured by specific immunoassays. Results: Study subjects showed compliance with respect to smoking and OC use as determined by the levels of serum NET, EE2, and cotinine. Comparing mean levels of PGI metabolites in the two groups of OC smokers, those taking 35 mg EE2 showed a significant decrease in PGI. Comparing the ratio of PGI/TX in all smokers, only the smokers on the 35 mg formulation showed a significant decrease in the ratio, while there was no change in the 20 mg group. No significant changes in the ratio PGI/TX during the same time interval in smoking and non-smoking controls and OC non-smokers were observed. Conclusions: Women smokers taking 20 mg EE2 OC had no thrombophilic changes of PGI and TXA2 metabolites. Women smokers taking 35mg EE2 oral contraceptive had thrombophilic changes in PGI/TXA metabolite ratio. Women smokers who use oral contraceptives may have less thrombotic risk taking formulations with 20mg EE2 than 35mg EE2.
Prim Care Update Ob/Gyns