BACKGROUND: Validity of oral contraceptive pill (OCP) clinical trial results depends on participant compliance. Ethinyl estradiol (EE2) induces increases in hepatic binding globulin (BG) levels. Measuring these BG increases may provide an effective and convenient approach to distinguish noncompliant from compliant OCP users in research settings. This analysis evaluated the usefulness of measuring increases in corticosteroid-, sex-hormone- and thyroxine-binding globulins (CBG, SHBG and TBG, respectively) as measures of OCP compliance. METHODS: We used frozen serum from a trial that compared ovarian suppression between normal-weight and obese women randomized to one of two OCPs containing EE2 and levonorgestrel (LNG). Based on serial LNG measurements during the trial, 17% of participants were noncompliant. We matched noncompliant participants with compliant participants by age, body mass index, ethnicity and OCP formulation. We measured CBG, SHBG and TBG levels and compared change from baseline to 3-month follow-up between the noncompliant and compliant participants. Construction of receiver operator characteristic (ROC) curves allowed comparison of various BG measures. RESULTS: Changes in CBG and TBG distinguished OCP noncompliant users from compliant users [area under the ROC curve (AUROC), 0.86 and 0.89, p<.01]. Changes in SHBG were less discriminating (AUROC 0.69) CONCLUSIONS:EE2-induced increases in CBG and TBG provide a sensitive integrated marker of compliance with an LNG-containing OCP.
RCT Entities:
BACKGROUND: Validity of oral contraceptive pill (OCP) clinical trial results depends on participant compliance. Ethinyl estradiol (EE2) induces increases in hepatic binding globulin (BG) levels. Measuring these BG increases may provide an effective and convenient approach to distinguish noncompliant from compliant OCP users in research settings. This analysis evaluated the usefulness of measuring increases in corticosteroid-, sex-hormone- and thyroxine-binding globulins (CBG, SHBG and TBG, respectively) as measures of OCP compliance. METHODS: We used frozen serum from a trial that compared ovarian suppression between normal-weight and obesewomen randomized to one of two OCPs containing EE2 and levonorgestrel (LNG). Based on serial LNG measurements during the trial, 17% of participants were noncompliant. We matched noncompliant participants with compliant participants by age, body mass index, ethnicity and OCP formulation. We measured CBG, SHBG and TBG levels and compared change from baseline to 3-month follow-up between the noncompliant and compliant participants. Construction of receiver operator characteristic (ROC) curves allowed comparison of various BG measures. RESULTS: Changes in CBG and TBG distinguished OCP noncompliant users from compliant users [area under the ROC curve (AUROC), 0.86 and 0.89, p<.01]. Changes in SHBG were less discriminating (AUROC 0.69) CONCLUSIONS:EE2-induced increases in CBG and TBG provide a sensitive integrated marker of compliance with an LNG-containing OCP.
Authors: Carolyn L Westhoff; Anupama T Torgal; Elizabeth R Mayeda; Noa'a Shimoni; Frank Z Stanczyk; Malcolm C Pike Journal: Contraception Date: 2011-11-12 Impact factor: 3.375
Authors: Carolyn L Westhoff; Andrew Eisenberger; Rosalind Tang; Serge Cremers; Lisa V Grossman; Malcolm C Pike Journal: Contraception Date: 2015-10-09 Impact factor: 3.375