Using changes in binding globulins to assess oral contraceptive compliance
Open accessAbstract
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.
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Previous studies have demonstrated increases in angiotensinogen and binding globulins during the use of EE-based combined contraceptives, regardless of the administration route.
“Previous studies have demonstrated increases in angiotensinogen and binding globulins during the use of EE-based combined contraceptives, regardless of the administration route (Sitruk-Ware et al., 2007b; Piltonen et al., 2012; Westhoff et al., 2013; Klipping et al., 2021).”
From Ethinylestradiol in combined hormonal contraceptive has a broader effect on serum proteome compared with estradiol valerate: a randomized controlled trial (2023) · cites this paper as Westhoff et al., 2013
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- Authors
- Westhoff, C. L., Petrie, K. A., & Cremers, S.
- Affiliations
- Columbia University Irving Medical Center (US)
- Columbia University (US)
- Corresponding author
- Westhoff, Carolyn L.
- Venue
- Contraception
- Publisher
- Elsevier BV
- Published
- 2013-02
- Volume
- 87
- Issue
- 2
- Pages
- 176-181
- ISSN
- 0010-7824 (ISSN-L)
- PMC
- PMC3494777
- OpenAlex
- W2021195753
- Cited by
- 22
- References
- 32
- Citations by year
- 2025: 1 · 2024: 3 · 2022: 2 · 2021: 1 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 3 · 2015: 2 · 2014: 3 · 2013: 2
- FWCI
- 2.16
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Contraception (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01 HD04578)
- Columbia University (UL1 RR024156)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Health and Contraception
- Health Sciences › Medicine › Family Practice › Medication Adherence and Compliance
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS Research and Interventions
- Keywords
- ethinyl estradiol, corticosteroid-binding globulin, sex hormone-binding globulin, thyroxine-binding globulin, levonorgestrel, ovarian suppression, obesity, clinical trial validity
- MeSH terms
- Adolescent, Adult, Contraceptives, Oral, Educational Status, Ethinyl Estradiol, Ethnicity, Female, Humans, Liver, Patient Compliance, Sex Hormone-Binding Globulin, Transcortin, Case-Control Studies, Levonorgestrel, Thyroxine-Binding Globulin
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