ESTEEM: A clinical trial testing whether testosterone can help improve the quality of life during menopause
| ISRCTN | ISRCTN21554333 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN21554333 |
| Integrated Research Application System (IRAS) | 1008601 |
| Central Portfolio Management System (CPMS) | 58305 |
| Protocol serial number | SPON 2006-24 |
| Sponsor | Cardiff University |
| Funder | National Institute for Health and Care Research |
- Submission date
- 27/09/2025
- Registration date
- 22/12/2025
- Last edited
- 22/01/2026
- Recruitment status
- Not yet recruiting
- Overall study status
- Ongoing
- Condition category
- Urological and Genital Diseases
Plain English summary of protocol
Background and study aims
The ESTEEM trial is testing whether adding testosterone to standard Hormone Replacement Therapy (HRT) can help improve menopause-related quality of life. Many women still have symptoms such as poor sleep, brain fog, headaches, hot flushes, low mood and low energy even when taking HRT. Testosterone is already used to improve sexual function in post-menopausal women, but its effects on these wider symptoms are not well understood. This trial will also look at any possible side effects, such as acne or hair growth, to weigh up the benefits and risks.
Around 13 million women in the UK are peri- or post-menopausal, and up to a quarter experience severe symptoms that can last for several years. HRT is the most effective treatment, but it does not always fully relieve symptoms. By testing whether testosterone can help with a broader range of symptoms, the trial aims to generate evidence to guide future NHS care.
Who can participate?
The trial is open to peri- and post-menopausal women in the UK who are already on standard doses of HRT for at least 6 months but still have symptoms. Women cannot take part if they have recently used testosterone or certain other hormone medicines.
What does the study involve?
Participants will be randomly allocated to use either testosterone cream or a placebo cream, in addition to their usual HRT, for 12 months. Neither participants nor their doctors will know which treatment they are receiving. They will be asked to complete online questionnaires about their symptoms and quality of life at the start, and again at 3, 6 and 12 months. Blood tests will be taken at the same time points to monitor safety. Some participants and healthcare professionals will also be interviewed to share their views and experiences. The study will run across the UK, with women able to join remotely or through GP practices. Each woman will take part for 12 months.
What are the possible benefits and risks of participating?
By taking part, women will help researchers find out whether testosterone can improve menopause symptoms that are not well managed by HRT, such as sleep problems, brain fog, or lack of energy. This evidence could improve future NHS care for women experiencing the menopause. Some women may also notice an improvement in their own symptoms, although this cannot be guaranteed.
Like all medicines, testosterone cream can have side effects. These may include acne, oily skin, or increased hair growth, and in rare cases, more serious issues. The study includes regular safety monitoring and medical follow-up. Participation also involves a time commitment for blood tests, daily treatment, and completion of questionnaires.
Where is the study run from?
Cardiff University, UK
When is the study starting and how long is it expected to run for?
September 2025 to June 2028
Who is funding the study?
The National Institute for Health and Care Research, NIHR, UK
Who is the main contact?
esteem@cardiff.ac.uk
Contact information
Public
ESTEEM Trial Team, Trial Manager, Centre for Trials Research, Cardiff University
Cardiff
CF14 4YS
United Kingdom
| Phone | +44 (0)29 20687463 ext 7463 |
|---|---|
| esteem@cardiff.ac.uk |
Scientific, Principal investigator
Director, Centre for Trials Research, Cardiff University
Cardiff
CF14 4YS
United Kingdom
| Phone | +44 (0)29 20687463 ext 7177 |
|---|---|
| RoblingMR@cardiff.ac.uk |
Scientific, Principal investigator
Consultant in Sexual & Reproductive Healthcare, Hywel Dda University Health Board
Cardiff
CF14 4YS
United Kingdom
| Phone | +44 (0)29 20687463 |
|---|---|
| Helen.Munro2@wales.nhs.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Randomized placebo-controlled double-blind parallel-group study |
| Secondary study design | Randomised controlled trial |
| Participant information sheet | 48078_PIS_v1.0_16Sept2025.pdf |
| Scientific title | ESTEEM: Evaluating the clinical and cost-effectiveness of testosterone to improve menopause-related quality of life |
| Study acronym | ESTEEM |
| Study objectives | To establish the effectiveness of testosterone in reducing menopausal symptoms, beyond altered sexual function, in women already receiving standard HRT as measured by a validated tool of menopause-specific quality of life 1. Confirm feasibility of adequate and equitable trial recruitment, retention and data quality in an internal pilot 2. Establish the cost-effectiveness of testosterone based on a primary outcome of Quality Adjusted Life Years 3. Assess safety profile and potential harms of testosterone treatment 4. Gain patient consent and link data to allow long-term monitoring of health outcomes using routinely collected data 5. Explore barriers/facilitators amongst service providers and women to future prescribing and uptake of testosterone 6. Work with lay research partners to design, deliver and report a trial that meets the needs of all women who may experience menopausal symptoms |
| Ethics approval(s) |
Approved 06/01/2026, London - Fulham Research Ethics Committee (Skipton House, 80 London Road, London, SE1 6LH, United Kingdom; +44 20 7104 8000; fulham.rec@hra.nhs.uk), ref: 25/LO/0770 |
| Health condition(s) or problem(s) studied | Medical condition: Menopause Medical condition in lay language: Menopause Therapeutic areas: Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
| Intervention | • Arm 1 (Intervention): AndroFeme® 1% testosterone cream, transdermal route. The intervention dose uses two pumps (each delivering 0.5 g of 1% testosterone gel, equivalent to 5 mg testosterone per day), applied once daily to the lower abdomen or upper thigh for 12 months in addition to standard HRT. • Arm 2 (Placebo): Matching placebo cream, 2 pumps daily, transdermal route, for 12 months in addition to standard HRT. • Follow-up: Baseline, 3, 6 and 12 months with questionnaires, blood sampling, and app-based safety and treatment adherence monitoring. • Randomisation: Centralised online randomisation system, 1:1 allocation using concealed allocation. |
| Intervention type | Drug |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | AndroFeme® 1% testosterone cream [Testosterone] |
| Primary outcome measure(s) |
Menopause-related quality of life measured using the Menopause-Specific Quality of Life-Intervention (MENQOL-I) questionnaire. Summary scores will be assessed over time, incorporating 3-, 6- and 12-month responses |
| Key secondary outcome measure(s) |
The following secondary outcome measures are assessed at baseline, 3, 6 and 12 months, unless stated: |
| Completion date | 30/06/2028 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Female |
| Target sample size at registration | 416 |
| Key inclusion criteria | 1. Women receiving standard HRT for at least 6 months who remain symptomatic 2. Willing to stay on current standard HRT for duration of trial 3. Able/willing to provide informed consent, including proof of ID 4. At any stage in perimenopause or menopause, including those with Premature Ovarian Insufficiency and medical/surgical menopause already taking standard HRT 5. Able to receive transdermal testosterone 6. Able/willing to adhere to a 12-month follow-up (including regular use of app throughout the trial participation) 7. Able/willing to have blood tests at baseline, 3, 6 and 12 months and as necessary 8. Individuals assigned female sex at birth who are aged > 45 years at the time of consent |
| Key exclusion criteria | 1. Women with altered sexual function as their only symptom attributed to the menopause. 2. High baseline testosterone level outside the pre-menopausal physiological range (above 2.6 nmol/l by immunoassay) 3. Allergy to almonds 4. Pregnant, breastfeeding, planning to become pregnant during the study period, or of childbearing potential and not using a protocol-approved method of contraception. 5. Active malignancy or treatment for malignancy (<6/12); known or suspected carcinoma of the breast; known or suspected androgen-dependent neoplasia 6. Women with nephrotic syndrome 7. History of hypercalcaemia 8. Involvement in another clinical trial for investigational medicinal product (CTIMP) at the time of consent 9. Androgen treatment (testosterone or tibolone) or antiandrogen therapy within the past 6 months (eg. Spironolactone, finasteride, minoxidil, cyproterone) 10. Women who are also using; oral anticoagulants, corticosteroids or adrenocorticotropic hormone (ACTH), oxyphenbutazone, bupropion, ciclosporin, conjugated equine estrogens and any oral contraception containing an estrogenic steroid hormone 11. Less than 1 month use of complementary and/or prescribable non-hormonal alternatives to HRT, which have been shown in trial to be of benefit, such as Fezolinetant, Oxybutinin, Selective Serotonin Reuptake Inhibitor (SSRI), or SNRI/SSRI, Gabapentin, Pregabalin, Clonidine, St Johns Wort, Isoflavones and Black Cohosh. |
| Date of first enrolment | 01/04/2026 |
| Date of final enrolment | 31/07/2027 |
Locations
Countries of recruitment
- United Kingdom
- England
- Wales
Study participating centre
Cardiff
CF10 3AT
Wales
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Available on request |
| IPD sharing plan | The datasets generated during the ESTEEM trial will be available on reasonable request from the Centre for Trials Research (contact: esteem@cardiff.ac.uk), subject to approval by the Trial Management Group (TMG) and Trial Steering Committee (TSC). Data will be fully anonymised. Requests will be considered for scientifically sound proposals addressing questions in line with participant consent and ethical approvals. Access will be provided under a data-sharing agreement. Data will be available from 12 months after publication of the main results for a minimum of 5 years. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version 1.0 | 16/09/2025 | 03/10/2025 | No | Yes |
| Protocol file | version 2.0 | 01/12/2025 | 22/01/2026 | No | No |
Additional files
- 48078_PIS_v1.0_16Sept2025.pdf
- Participant information sheet
- ISRCTN21554333 ESTEEM protocol version 2.0 1st December 2025.pdf
- Protocol file
Editorial Notes
22/01/2026: The following changes were made to the study record:
1. Uploaded protocol (not peer-reviewed) as an additional file.
2. The ethics approval was added.
3. The Date of first enrolment was changed from 12/01/2026 to 01/04/2026
21/01/2026: Internal review.
29/09/2025: Study's existence confirmed by Health Research Authority (HRA) (UK)
