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CompletedNCT07928024ClinicalTrials.gov record

Impact of Oral vs. Transdermal Oestrogen on Cortisol & CBG Before SST

Cortisol · Cortisol Binding Globulin

THE QUICK READ

What this study involves

The registry does not currently label this study as recruiting. Ask about its status before planning a screening visit.

Study type
Observational
Phase
Not applicable / not listed
Age range
18 years - 90 years
Sex eligible
Female
Healthy volunteers
Not reported
Participants
1 Actual

These are starting points, not an eligibility decision. The research team must review the full requirements.

About the research

Cortisol is a hormone that helps the body handle stress and maintain blood pressure. Doctors check if the adrenal glands (which make cortisol) are working correctly using a Synacthen test (SST). This test involves giving a drug that stimulates cortisol production and measuring how much is released.

For women taking oestrogen pills (found in birth control and hormone replacement therapy), the test results can be misleading. Oestrogen increases a substance in the blood called cortisol-binding globulin (CBG), which attaches to cortisol and makes some of it inactive. When doctors measure cortisol, they check both active and inactive forms. If CBG is high, the test can falsely suggest cortisol levels are normal, making it harder to tell if the adrenal glands are working correctly.

To avoid this problem, women taking oestrogen pills and gels/patches (transdermal) are asked to stop for 6 weeks before the test so that CBG/cortisol levels return to normal. However, this can cause uncomfortable symptoms like hot flushes, mood swings, and headaches.

Some women use transdermal oestrogen, which is absorbed through the skin instead. Unlike pills, there is some evidence that transdermal oestrogen doesn't affect CBG levels meaning women using them may not need to stop before an SST. This study will provide more evidence confirming that transdermal oestrogen is safe to continue before testing.

We will study three groups: women taking oestrogen pills, women using gel/patches, and women not taking oestrogen. By measuring CBG and cortisol every week, we aim to find out exactly when CBG returns to normal after stopping oestrogen pills. If it happens before 6 weeks, doctors may be able to shorten the break, making testing more manageable and more comfortable.

This research could improve testing for women taking oestrogen, potentially allowing those on gel/patches to continue treatment and those on pills to pause for a shorter time before testing.

Who may be able to participate?

The list below is the sponsor’s full registry wording. It can include conditions, prior treatment, test results and other requirements. A match in search does not mean you qualify.

Inclusion Criteria:

  • Female patients aged 18 to 70 years.
  • Scheduled to undergo a Short Synacthen Test (SST) as part of routine clinical care.
  • Currently taking oral or transdermal oestrogen therapy for ≥3 months, or not on oestrogen (control group).
  • Willing and able to provide informed consent.
  • Willing and able to discontinue oestrogen therapy (if applicable) for 6 weeks.
  • Willing and able to provide weekly blood and saliva samples over a 6-week period.

Exclusion Criteria:

  • Pregnant or breastfeeding women.
  • Significant liver dysfunction, defined as ALT or AST \>2× the upper limit of normal, or low albumin (\<25 g/L).
  • Currently taking glucocorticoids above replacement dose or have done so in the past 6 months.
  • Recent intra articular steroid injection (within 12 weeks)
  • Unable to comply with study procedures or follow-up schedule.
  • Individuals who were not assigned female sex at birth
  • Women using oestrogen hormone-modulating medications
  • Chronic kidney disease affecting hormone metabolism
  • Diagnosed with adrenal insufficiency or any known pituitary or adrenal disorder that could affect cortisol production.
  • Any endocrine disorder (e.g., Cushing's syndrome, uncontrolled thyroid disease) that could interfere with the study results
  • Use of drugs that significantly alter liver metabolism (e.g., anticonvulsants, rifampicin), as they may impact CBG levels.

Study population

Norfolk and Norwich University Hospitals NHS Foundation Trust

Understand screening

Treatment, groups and participation

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Assignment
Not reported
Masking
Not reported
Oral oestrogen group

Women taking oestrogen pills - They will stop taking them for up to six weeks, as required for standard care.

Transdermal oestrogen group

Women using oestrogen gel or patches - They will stop taking them for up to six weeks, as required for standard care.

Control group

Women not taking any oestrogen - This control group will help compare results.

Prepare your questions

What researchers are measuring

Outcome measures describe what is being studied. They are not proof that a treatment works.

Primary measures

Changes in cortisol binding globulin (CBG) concentration and serum cortisol levels

Time frame: 6 weeks

The primary outcome measures are the changes in cortisol binding globulin (CBG) concentration and serum cortisol levels over a six-week period following the discontinuation of oral or transdermal oestrogen therapy. These will be assessed through weekly blood samples, with additional comparison to salivary cortisol levels.

The aim is to evaluate the impact of oestrogen route on CBG and cortisol levels, and to determine whether the current 6-week cessation period for oral oestrogen prior to the Short Synacthen Test (SST) can be safely shortened. This could improve test accuracy, patient experience, and potentially support the continued use of transdermal oestrogen without interruption.

Secondary measures

Salivary cortisol and cortisone levels

Time frame: 6 weeks

Salivary cortisol and cortisone levels measured weekly over the 6-week period, to evaluate their potential as non-invasive alternatives to serum cortisol for assessing adrenal function.

No results are flagged as posted.

Review the complete result tables and limitations in the official record.

Open official results ↗

Research locations (1)

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1 locations

Norfolk and Norwich University Hospitals NHS Foundation TrustNorwich, Norfolk, United KingdomStatus unknown

Study team and timeline

Lead sponsor
Norfolk and Norwich University Hospitals NHS Foundation Trust
Study start
Feb 16, 2026 Actual
Primary completion
Aug 12, 2026 Actual
Study completion
Aug 12, 2026 Actual
First posted
Nov 10, 2026 Actual
Last updated
Nov 10, 2026 Actual

Official study contacts

No central contact is listed. Check the locations and the official record.

Official study title

Comparing the Impact of Oral and Transdermal Oestrogen on Cortisol Binding Globulin and Cortisol Levels Before Short Synacthen Test

A HUMAN NEXT STEP

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Source: ClinicalTrials.gov API v2. Information is submitted by sponsors and investigators. NLM does not approve the safety or science of all listed studies. Registry disclaimer.

Retrieved: Nov 12, 2026 · Last registry update: Nov 10, 2026