Prospective evaluation of the effect of stopping estrogen-containing contraceptives on serum CBG and cortisol levels

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ID: 318626
2026
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Abstract
CONTEXT: Oral estrogens raise corticosteroid-binding globulin (CBG) levels, leading to increased serum total cortisol concentrations. Guidelines advise discontinuation at least six weeks before performing endocrine function tests measuring total serum cortisol concentrations for evaluation of hypothalamus-pituitary-adrenal function in women using combined oral contraceptives (COC). The exact rate of normalization of CBG is unknown. OBJECTIVE: This study aims to identify the duration for CBG and total cortisol levels to normalize after stopping COC. DESIGN, SETTING, PARTICIPANTS: This prospective observational study included 24 healthy adult women discontinuing COC. Eight weekly fasting morning blood samples were collected, starting one week before to six weeks after cessation. CBG and total cortisol concentrations were measured using immunoassays. Data are reported as mean (SD). RESULTS: CBG concentrations were 133 ± 20 mg/L at baseline and 59 ± 10 mg/L six weeks after stopping COC. Total cortisol concentrations were 855 ± 138 nmol/L at baseline and 370 ± 130 nmol/L six weeks after stopping COC. CBG and cortisol concentrations showed an immediate, exponentially shaped decrease after cessation of the COC. The percentage of baseline after four weeks was 49 ± 12% for CBG and 46 ± 11% for total cortisol. Linear mixed model and piecewise linear mixed model showed non-significant changes after four weeks. CONCLUSIONS: CBG and total cortisol concentrations decreased over time following discontinuation of COC. Concentrations of both CBG and total cortisol had normalized by four weeks after discontinuation. Accordingly, the minimum period for discontinuation of COC prior to evaluating HPA-axis measurements may be reduced from six weeks to four weeks.
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Authors Karlijn Koops, Annemieke C. Heijboer, Peter H. Bisschop, Jacquelien J Hillebrand
Journal the journal of clinical endocrinology & metabolism
Year 2026
DOI
10.1210/clinem/dgag249
URL
https://doi.org/10.1210/clinem/dgag249
Keywords Keywords not found

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