TOPLINE

Serum corticosteroid-binding globulin (CBG) and total cortisol levels decreased significantly and normalised by 4 weeks in women after discontinuation of combined oral contraceptives (COCs), suggesting that the standard clinical waiting period required before testing the hypothalamic-pituitary-adrenal axis can be safely reduced from 6 to 4 weeks.

METHODOLOGY

• Researchers in Netherlands conducted a prospective single-arm observational study to determine the minimum time required for serum CBG and total cortisol levels to normalise after discontinuation of COCs.
• They included 24 healthy adult women (median age, 29.5 years) who had used COCs for at least 3 consecutive weeks and planned to stop them for at least 6 weeks.
• Participants provided eight weekly fasting morning blood samples: The first sample was collected at week 1 before the cessation of COCs, the second sample was collected on the day the final pill was taken, and the following six samples were collected weekly after the cessation of COCs.
• CBG and total cortisol levels were assessed using validated immunoassays.

TAKEAWAY

• From baseline (a mean value of samples 1 and 2) to 6 weeks after stopping COCs, mean CBG levels reduced from 133 to 60 mg/L, and total cortisol levels declined from 855 to 370 nmol/L.
• CBG levels kept dropping significantly each week from baseline through week 3 (P < .001); after that, levels levelled off, with no meaningful change observed between weeks 4 and 5 or between weeks 5 and 6 — showing that CBG levels had stabilised. Similar results were observed for total cortisol levels.
• By week 4, CBG levels dropped to 49% from baseline and total cortisol levels dropped to 46%.

IN PRACTICE

"The findings of our study lead to a better understanding of the CBG and, consequently, the total cortisol decline following the cessation of oral estrogens. This also facilitates a better interpretation of laboratory results," the authors wrote.

"Reducing the required discontinuation period for women on COCs from six to four weeks will decrease inconvenience for women and minimize diagnostic delay," they added.

SOURCE

This study was led by Karlijn Koops, Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam, Netherlands. It was published online on June 24, 2026, in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS

Only one woman used an oestradiol-containing oral contraceptive, potentially limiting the generalisability of the findings to oestradiol users. The study lacked a control group. Different oestrogen preparations and routes of administration may have affected serum CBG levels.

DISCLOSURES

This study did not disclose any specific funding. The authors disclosed having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.