The effect of transdermal 17-β-estradiol/progesterone supplementation on glucose regulation in peri- and postmenopausal women with type 1 and type 2 diabetes

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amsterdam UMC Stichting

Participant type

Patients

Age range

18-64 years

Gender

Female

Therapeutic area

Diseases [C] - Hormonal diseases [C19], Phenomena and Processes [G] - Physiological processes [G07]

Trial duration

9 Feb 2026 → ongoing

Decision date (initial)

2025-12-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary objective is to determine the effect of transdermal 17-β-estradiol combined with oral micronized progesterone on glucose regulation in peri- and early postmenopausal women with diabetes mellitus (type 1 or 2) and climacteric symptoms.

Secondary objectives 1

1. Secondary objectives are the influence of menopausal symptoms on glucose regulation and changes in insulin sensitivity, cardiovascular risk factors, liver steatosis, sleep quality and (diabetes related) quality of life.

Conditions and MedDRA coding

Diabetes Mellitus

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Late perimenopausal, defined as changes in the menstrual cycle with an interval of amenorrhea of >= 60 days (STRAW+10 stage –1) OR early postmenopausal (STRAW+10 stage +1), defined as final menstrual cycle more than 1 years prior to inclusion.
2. Final menstrual cycle < 5 years prior to inclusion
3. One or more menopause-associated symptoms. For example: vasomotor symptoms (hot flushes and sweats), musculoskeletal symptoms (joint and muscle pain), effects on mood (low mood), sexual difficulties (low sexual desire)
4. Additionally, for T1DM: Diabetes Mellitus type 1 diagnosed before menopause, and at least 6 months prior to the study
5. Additionally, for T2DM: Diabetes Mellitus type 2 diagnosed before menopause, and at least 6 months prior to the study
6. Additionally, for T2DM: Use of insulin, at least 1 time daily

Exclusion criteria 12

1. Contra-indication for transdermal estrogen and/or progesterone therapy: Presence or sus-picion or history of breast cancer, endometrial cancer, ovarian cancer, presence or history of venous thromboembolism (unless the individual is using anticoagulation therapy), active arterial thrombosis or in the past 6 months (e.g. myocardial infarction, angina pectoris) in-herited or acquired thrombophilia, acute liver disease, or a history of liver disease as long as liver function values have not normalized, untreated endometrial hyperplasia, abnormal vaginal bleeding, porphyria, uncontrolled or severe hypertension.
2. Participants with BRCA1 or 2 gene or PTEN mutation
3. Participants with a first degree relative with (a history of) breast cancer
4. Known hypersensitivity to the excipients in the estradiol patch: acrylate copolymer, poly-ethylene terephthalate, α-tocopherol, or progesterone capsule: soy allergy or peanut aller-gy
5. Hysterectomy
6. Premature menopause (menopause age < 40 years)
7. Hormonal contraception or hormone replacement therapy use (estradiol with or without progesterone) within three months before inclusion
8. Use of systemic glucocorticosteroids less than 1 month prior to the study or anticipated need for systemic steroids during the study period (e.g., for Crohn’s disease or astma/COPD). Incidental use of topical agents is allowed.
9. Active malignancy or history of treated cancer within 24 months of enrollment
10. Chronic kidney disease defined as eGFR < 30 mL/min/1.73m2
11. Additionally, for T1DM: Use of glucose-regulating medications other than insulin, such as metformin, GLP-1/GIP re-ceptor agonists, sulfonylureas, SGLT2 inhibitors, and DPP4 inhibitors
12. Additionally, for T2DM: Changes to glucose-regulating medications (metformin, GLIP-1/GIP receptor agonists, sulfonylureas, SGLT2 inhibitors, DPP4 inhibitors) other than insulin, including starting, stopping or altering the dosage, in three months prior to the study period. (Note that these medications may be used, provided they are not changed three months prior to the study.)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The main endpoint is the difference in the 14-day glucose time-in-range (TIR) during the final two weeks of treatment with estradiol/progesterone compared to the control period.

Secondary endpoints 7

1. Glucose regulation parameters: change in time-below –range (TBR, %), time-above-range (TAR, %), glycaemic variability (coefficient of variation [CV]), and mean glucose measured using 14 days of blinded CGM after 12 weeks of estradiol/progesterone versus 12 weeks of no intervention.
2. Change in serum HbA1c, carbohydrate-insulin ratio (CIR), daily insulin dose
3. Insulin sensitivity (whole body and adipose tissue) measured by hyperinsulinemiceuglycemic clamp. Whole body insulin sensitivity will be expressed as the ratio of M – value and insulin concentration: M / I. M – value in mg / kg / min and I in uIU/uL. Adipose tissue insulin sensitivity will be expressed as the suppression of plasma free fatty acid concentration in %.
4. Cardiovascular risk: change in lipid profile and 24-hour blood pressure
5. Change in liver steatosis using the CAP score assessed with fibroscan and for participants with T2DM total liver fat assessed with MRI-PDFF
6. Change in handgrip strength using handgrip dynamometry
7. Change in climacteric symptoms (Greene Climacteric Scale questionnaire), quality of sleep (Insomnia severity index), depressive symptoms (Hospital Anxiety and Depression Score), diabetes distress (Problem Areas In Diabetes), and quality of life (WHO-5).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amsterdam UMC Stichting

Sponsor organisation

Amsterdam UMC Stichting

Address

De Boelelaan 1117

City

Amsterdam

Postcode

1081 HV

Country

Netherlands

Scientific contact point

Organisation

Amsterdam UMC Stichting

Contact name

Department of endocrinology and metabolism

Public contact point

Organisation

Amsterdam UMC Stichting

Contact name

Department of endocrinology and metabolism

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications