Effect of oral contraceptives containing 20 and 35 mu g ethinyl estradiol on urinary prostacyclin and thromboxane metabolite levels in smokers and nonsmokers

The interaction between smoking and oral contraceptive (OC) use with respec t to thrombogenesis was investigated by studying the effects of OC and smok ing on urinary prostacyclin (PGI(2)) and thromboxane A(2) (TxA(2)) metaboli te levels in smokers and nonsmokers. Sixty healthy women, aged 19-32 years, who were not taking any hormonal treatment for at least 3 months before in itiating the study, were divided into three equal groups: OC users who smok ed (N = 20), OC users who did not smoke (N = 20), and a control group of 20 smokers and 10 nonsmokers. Each OC treatment group was randomized to recei ve either norethindrone (NET) acetate (1 mg)/ethinyl estradiol (EE2) (35 mu g) (N = 10) or NET. acetate (1 mg)/EE2 (20 mu g) (N = 10) daily for 3 mont hs. Overnight urine collections and fasting blood samples were obtained at baseline and at the end of the S-month study. Serum levels of NET and EE,, as well as urinary levels of cotinine and the stable metabolites of PGI, an d TkA(2) namely 6-keto-prostaglandin F-1 infinity (6-keto-PGF(1 alpha)) and thromboxane (TxB(2)), respectively, were measured by specific immunoassays . Analysis of pre- to posttreatment changes in mean urinary 6-keto-PGF(1 al pha) and TxB(2) levels for each subgroup, as determined by smoking status a nd EE2 dose, showed no statistically significant differences. Also, no sign ificant differences were found in each subgroup with respect to changes in the 6-keto-PGF(1 alpha)/TxB(2) Patios. Large intersubject variability in ur inary 6-keto-PGF(1 alpha), and TxB(2), levels were observed in all subgroup s. The results of this study indicate that both low-estrogen-dose compounds , when used by smokers or nonsmokers, did not significantly alter the ratio of PGI(2) to TXA(2), metabolites, compared with pretreat ment. However, th e small number of subjects and the large intersubject variability in this s tudy make it difficult to determine if there is a significant difference be tween the 20- and 30-mu g EE2 doses. (C) 1999 Elsevier Science Inc. All rig hts reserved.