EndometriosisTAEDIUMVITAENCT07204093
Ultra-Safe Hormonal Strategy: Transdermal Estradiol Added to Progestins for Endometriosis
An observational study of Endometriosis, run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico at 1 site in Italy.
Trial summary
Endometriosis is a chronic, estrogen-dependent disease affecting women of reproductive age, associated with pelvic pain, infertility, and reduced quality of life. Progestins are the standard first-line therapy, but long-term treatment requires well-tolerated regimens that balance efficacy with patient satisfaction. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women only
- Conditions the study is for
- Endometriosis
- What is being tested?
- Drospirenone 4 mg orally and Dienogest 2 mg orally
- Type of treatment
- Pill or oral medicine
- How many people
- 138 participants
- Where
- 1 siteItaly
- Study dates
- 11 Aug 2025to Feb 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- No healthy volunteers
- Adult
Study population: Women with endometriosis referred to the endometriosis outpatient clinic of the Gynaecology SC of the Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico in Milan between October 2024 and September 2025 will be included in the study. The diagnosis of endometriosis is made on the basis of the combination of symptomatology + gynaecological examination, transvaginal/transrectal ultrasound or previous surgical visualisation of the disease.
Who may be able to join
- women who have been on combination therapy for at least 6 months with progestin and transdermal natural oestrogen (Dienogest + transdermal oestradiol or Drospirenone + transdermal oestradiol);
- women who have performed follow-up at least 6 months after the start of treatment and for whom data on the primary endpoint of the study (treatment satisfaction) are available.
Who cannot join
- absence of surgical diagnosis or imaging indicative of endometriosis or adenomyosis;
- women who have taken GnRH analogue therapy within 6 months prior to treatment with dienogest + transdermal oestradiol vs. drospirenone + transdermal oestradiol
- women who have taken only progestogen therapy without transdermal oestradiol or with contraindications to oestrogen use;
- women who received surgical indications during the treatment period, including obstructive uropathy or symptomatic bowel stricture; evidence of complex ovarian cysts or ovarian endometriomas with a diameter greater than 5 cm on transvaginal ultrasound.
Trial locations and contacts
1 site in 1 country.
Italy1 site
Gynecology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan, 20122
About this study
Official title: Transdermally Applied Estradiol Delivery In Ultra-Safe Medications Valuable In Treatment Against Endometriosis
Endometriosis is a chronic, estrogen-dependent disease affecting women of reproductive age, associated with pelvic pain, infertility, and reduced quality of life. Progestins are the standard first-line therapy, but long-term treatment requires well-tolerated regimens that balance efficacy with patient satisfaction.
This study will compare two combinations of progestins with natural transdermal estradiol-dienogest versus drospirenone-to evaluate which regimen provides greater patient satisfaction after 6 months of therapy.
Read the detailed description
Endometriosis is a chronic, estrogen-dependent disorder characterized by the presence of endometrial tissue outside the uterine cavity. This ectopic tissue induces chronic inflammation, fibrosis, and adhesions, often resulting in pelvic pain, dysmenorrhea, dyspareunia, infertility, and impaired quality of life. The condition affects an estimated 6-10% of women of reproductive age, with peak prevalence between 25 and 35 years, making it one of the most common gynecological diseases with significant social and economic impact.
Available treatments for endometriosis are symptomatic rather than curative. Medical management is considered the cornerstone of therapy, especially in women who are not seeking immediate pregnancy. Current guidelines recommend progestins as first-line treatment due to their proven efficacy in suppressing endometriosis-associated pain and their favorable safety and tolerability profile. However, because therapy is usually long-term until menopause and continuous, optimal regimens must combine efficacy with good tolerability and sustained patient satisfaction.
Dienogest is an established fourth-generation progestin widely used in endometriosis management, with well-documented efficacy and safety. Drospirenone, another fourth-generation progestin, combines progestogenic, anti-androgenic, and anti-mineralocorticoid activities. Although marketed primarily as a contraceptive, drospirenone has shown promising results in controlling endometriosis symptoms and improving patient-reported outcomes.
Progestin-only regimens may lead to hypoestrogenic adverse effects, including vaginal dryness, mood disturbances, reduced libido, irregular bleeding, and bone loss. For this reason, the addition of natural estradiol is considered advantageous, as it may prevent atrophic changes, support bone metabolism, and improve overall quality of life. Transdermal estradiol, in particular, avoids hepatic first-pass metabolism, does not induce prothrombotic liver factors, and is associated with a lower risk of thromboembolic events compared with ethinyl estradiol.
This observational study is designed to directly compare two therapeutic strategies for women with endometriosis: Dienogest + transdermal estradiol or Drospirenone + transdermal estradiol.
The primary endpoint is patient satisfaction after 6 months of treatment, reflecting the central importance of patient-centered outcomes in a chronic disease that impacts multiple aspects of daily life. Secondary endpoints include sexual function, psychological well-being, and health-related quality of life, assessed with validated questionnaires.
By comparing two modern progestin-based regimens combined with natural estradiol, this study aims to generate evidence that will help clinicians tailor hormonal therapy to improve not only symptom control but also the long-term well-being and quality of life of women with endometriosis.
- Conditions
- Endometriosis
- Being tested
- Drospirenone 4 mg orally, Dienogest 2 mg orally
- Medical subject headings
- Endometriosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Drospirenone 4 mg orallyDrug
Also called Slinda
Daily oral administration of Drospirenone 4 mg + Transdermal estradiol; continuous administration for at least 6 months.
Dienogest 2 mg orallyDrug
Also called Visanne, Dienogest, Zafrilla
Daily oral administration of Dienogest 2 mg + Transdermal estradiol; continuous administration for at least 6 months.
| Study group | Role | What they receive |
|---|---|---|
| Women with endometriosis undergoing medical management | This cohort will include women of reproductive age with a confirmed diagnosis of endometriosis, either by laparoscopy/histology or by validated imaging techniques (e.g., transvaginal ultrasound, MRI). Receives: Drug: Drospirenone 4 mg orally; Drug: Dienogest 2 mg orally |
What is being measured
The primary outcome is the main question the study is designed to answer.
Patients' statisfaction
Therapy satisfaction will be assessed by means of a 5-level Likert scale (very satisfied; satisfied; neither satisfied nor dissatisfied; dissatisfied; very dissatisfied). Women expressing the judgement 'very satisfied' and 'satisfied' will be considered to be globally satisfied, similarly to reported in the study on which the calculation of the sample size is based. The outcome will be dichotomised (very satisfied + satisfied versus neither satisfied nor dissatisfied + dissatisfied + very dissatisfied).
The level of statisfaction in the two groups will be compared as the proportion of satisfied women in each treatment group, reported as frequencies and percentages and analyzed accordingly.
Measured: This outcome will be evaluated after at least 6 months of treatment
Secondary outcomes (11)
Therapeutic efficacy - symptoms control (NRS)
Symptoms control, measured by Numeric Rating Scale (NRS), 11-point (0 = no pain; 10 = worst imaginable pain) for the following symptoms: dysmenorrhea, deep dyspareunia, superficial dyspareunia, non-menstrual pelvic pain, pain during defecation, pain during urination.
Measured: This outcome will be evaluated after at least 6 months of treatment
Therapeutic efficacy - symptoms control (use of analgesics)
Symptoms control, measured by use of analgesic therapy for pain symptoms, as reported during clinical evaluation (0 = no, 1 = yes).
Measured: This outcome will be evaluated after at least 6 months of treatment
Therapeutic efficacy - ovulation suppression
Confirmation of ovulation suppression, the therapeutic goal in endometriosis management, through serum measurement of 17β-estradiol, progesterone, and follicle-stimulating hormone (FSH), according to clinical practice.
Measured: This outcome will be evaluated after at least 6 months of treatment
Therapeutic efficacy - amenorrhea achievement and bleeding pattern
Bleeding pattern during treatment, with number achieving amenorrhea (therapeutic goal in endometriosis medical management). Unexpected uterine bleeding will be recorded as: spotting, menstrual-like bleeding, or heavy bleeding. The cumulative number of bleeding days and the number of treatment interruptions lasting one week (tailored cycling) to manage irregular bleeding will be collected.
Measured: This outcome will be evaluated after at least 6 months of treatment
Global Impression of Change
Patients' Global Impression of Change (PGIC) Scale, single-item, 7-point Likert scale (very much improved; much improved; minimally improved; no change; minimally worse; worse; very much worse).
Measured: This outcome will be evaluated after at least 6 months of treatment
Sexual function
Measured by the Female Sexual Function Index (FSFI), 19-item questionnaire with 5-point Likert scale. The final score will be interpreted as continuous (lower scores indicating worse sexual function)
Measured: This outcome will be evaluated after at least 6 months of treatment
Mood changes
Measured by the Hospital Anxiety and Depression Scale (HADS), 14-item, 4-point Likert scale. The total score will be interpreted as continuous (lower scores indicating better psychological status).
Measured: This outcome will be evaluated after at least 6 months of treatment
Health-related quality of life (HRQoL)
Calculated using the 12-Item Short Form Health Survey (SF-12) questionnaire, with Physical Component Summary (PCS-12) and Mental Component Summary (MCS-12). The total score will be interpreted as continuous (lower scores indicating worse health status).
Measured: This outcome will be evaluated after at least 6 months of treatment
Acceptance of transdermal therapy
Measured by:
- 11-point numeric scale (0 = no discomfort; 10 = worst imaginable discomfort).
- 5-level categorical scale (1 = no discomfort; 5 = intolerable discomfort).
Measured: This outcome will be evaluated after at least 6 months of treatment
Adverse events
Assessed globally through a single-item question on side effects reported during treatment (as previously used in the sample size reference study). Reported side effects will be collected, and, if present, their impact on quality of life will be evaluated using a 10-point numeric scale (1 = minimal impact; 10 = maximum impact).
Measured: This outcome will be evaluated after at least 6 months of treatment
Treatment adherence
Measured by the Morisky Medication-Taking Adherence Scale (MMAS-4), single-item, with scores ranging from 0 = excellent adherence to 4 = poor adherence.
Measured: This outcome will be evaluated after at least 6 months of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2025
- Study start11 Aug 2025
- Primary completionFeb 2026 (estimated)
- Study completionFeb 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EndometriosisStudies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 138 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07204093
- Sponsor's protocol ID
- 0021423-U
- Other IDs
- TAEDIUMVITAE
- Acronym
- TAEDIUMVITAE
- Status last verified
- Jul 2025
- First submitted
- 8 Sep 2025
- Last updated
- 2 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transdermally Applied Estradiol Delivery In Ultra-Safe Medications Valuable In Treatment Against Endometriosis
- ClinicalTrials.gov ID
- NCT07204093
- Acronym / sponsor ID
- TAEDIUMVITAE / 0021423-U
- Conditions
- Endometriosis
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 138 participants (estimated)
- Lead sponsor
- Fondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoUniversity, hospital or other
- Study start
- 11 Aug 2025 (actual)
- Primary completion
- Feb 2026 (estimated)
- Study completion
- Feb 2026 (estimated)
- First posted
- 2 Oct 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Endometriosis is a chronic, estrogen-dependent disease affecting women of reproductive age, associated with pelvic pain, infertility, and reduced quality of life. Progestins are the standard first-line therapy, but long-term treatment requires well-tolerated regimens that balance efficacy with patient satisfaction.
This study will compare two combinations of progestins with natural transdermal estradiol-dienogest versus drospirenone-to evaluate which regimen provides greater patient satisfaction after 6 months of therapy.
Detailed description
Endometriosis is a chronic, estrogen-dependent disorder characterized by the presence of endometrial tissue outside the uterine cavity. This ectopic tissue induces chronic inflammation, fibrosis, and adhesions, often resulting in pelvic pain, dysmenorrhea, dyspareunia, infertility, and impaired quality of life. The condition affects an estimated 6-10% of women of reproductive age, with peak prevalence between 25 and 35 years, making it one of the most common gynecological diseases with significant social and economic impact.
Available treatments for endometriosis are symptomatic rather than curative. Medical management is considered the cornerstone of therapy, especially in women who are not seeking immediate pregnancy. Current guidelines recommend progestins as first-line treatment due to their proven efficacy in suppressing endometriosis-associated pain and their favorable safety and tolerability profile. However, because therapy is usually long-term until menopause and continuous, optimal regimens must combine efficacy with good tolerability and sustained patient satisfaction.
Dienogest is an established fourth-generation progestin widely used in endometriosis management, with well-documented efficacy and safety. Drospirenone, another fourth-generation progestin, combines progestogenic, anti-androgenic, and anti-mineralocorticoid activities. Although marketed primarily as a contraceptive, drospirenone has shown promising results in controlling endometriosis symptoms and improving patient-reported outcomes.
Progestin-only regimens may lead to hypoestrogenic adverse effects, including vaginal dryness, mood disturbances, reduced libido, irregular bleeding, and bone loss. For this reason, the addition of natural estradiol is considered advantageous, as it may prevent atrophic changes, support bone metabolism, and improve overall quality of life. Transdermal estradiol, in particular, avoids hepatic first-pass metabolism, does not induce prothrombotic liver factors, and is associated with a lower risk of thromboembolic events compared with ethinyl estradiol.
This observational study is designed to directly compare two therapeutic strategies for women with endometriosis: Dienogest + transdermal estradiol or Drospirenone + transdermal estradiol.
The primary endpoint is patient satisfaction after 6 months of treatment, reflecting the central importance of patient-centered outcomes in a chronic disease that impacts multiple aspects of daily life. Secondary endpoints include sexual function, psychological well-being, and health-related quality of life, assessed with validated questionnaires.
By comparing two modern progestin-based regimens combined with natural estradiol, this study aims to generate evidence that will help clinicians tailor hormonal therapy to improve not only symptom control but also the long-term well-being and quality of life of women with endometriosis.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Women with endometriosis undergoing medical management | – | Drug: Drospirenone 4 mg orally, Drug: Dienogest 2 mg orallyThis cohort will include women of reproductive age with a confirmed diagnosis of endometriosis, either by laparoscopy/histology or by validated imaging techniques (e.g., transvaginal ultrasound, MRI). |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- Women with endometriosis referred to the endometriosis outpatient clinic of the Gynaecology SC of the Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico in Milan between October 2024 and September 2025 will be included in the study. The diagnosis of endometriosis is made on the basis of the combination of symptomatology + gynaecological examination, transvaginal/transrectal ultrasound or previous surgical visualisation of the disease.
Key inclusion criteria (2 listed)
- women who have been on combination therapy for at least 6 months with progestin and transdermal natural oestrogen (Dienogest + transdermal oestradiol or Drospirenone + transdermal oestradiol);
- women who have performed follow-up at least 6 months after the start of treatment and for whom data on the primary endpoint of the study (treatment satisfaction) are available.
Key exclusion criteria (4 listed)
- absence of surgical diagnosis or imaging indicative of endometriosis or adenomyosis;
- women who have taken GnRH analogue therapy within 6 months prior to treatment with dienogest + transdermal oestradiol vs. drospirenone + transdermal oestradiol
- women who have taken only progestogen therapy without transdermal oestradiol or with contraindications to oestrogen use;
- women who received surgical indications during the treatment period, including obstructive uropathy or symptomatic bowel stricture; evidence of complex ovarian cysts or ovarian endometriomas with a diameter greater than 5 cm on transvaginal ultrasound.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Drospirenone 4 mg orallyAlso: SlindaDaily oral administration of Drospirenone 4 mg + Transdermal estradiol; continuous administration for at least 6 months. | Drug | Women with endometriosis undergoing medical management |
| Dienogest 2 mg orallyAlso: Visanne, Dienogest, ZafrillaDaily oral administration of Dienogest 2 mg + Transdermal estradiol; continuous administration for at least 6 months. | Drug | Women with endometriosis undergoing medical management |
Primary outcome
Patients' statisfaction
Time frame: This outcome will be evaluated after at least 6 months of treatment
Therapy satisfaction will be assessed by means of a 5-level Likert scale (very satisfied; satisfied; neither satisfied nor dissatisfied; dissatisfied; very dissatisfied). Women expressing the judgement 'very satisfied' and 'satisfied' will be considered to be globally satisfied, similarly to reported in the study on which the calculation of the sample size is based. The outcome will be dichotomised (very satisfied + satisfied versus neither satisfied nor dissatisfied + dissatisfied + very dissatisfied). The level of statisfaction in the two groups will be compared as the proportion of satisfied women in each treatment group, reported as frequencies and percentages and analyzed accordingly.
11 secondary outcomes
Therapeutic efficacy - symptoms control (NRS)
Time frame: This outcome will be evaluated after at least 6 months of treatment
Therapeutic efficacy - symptoms control (use of analgesics)
Time frame: This outcome will be evaluated after at least 6 months of treatment
Therapeutic efficacy - ovulation suppression
Time frame: This outcome will be evaluated after at least 6 months of treatment
Therapeutic efficacy - amenorrhea achievement and bleeding pattern
Time frame: This outcome will be evaluated after at least 6 months of treatment
Global Impression of Change
Time frame: This outcome will be evaluated after at least 6 months of treatment
Sexual function
Time frame: This outcome will be evaluated after at least 6 months of treatment
Mood changes
Time frame: This outcome will be evaluated after at least 6 months of treatment
Health-related quality of life (HRQoL)
Time frame: This outcome will be evaluated after at least 6 months of treatment
Acceptance of transdermal therapy
Time frame: This outcome will be evaluated after at least 6 months of treatment
Adverse events
Time frame: This outcome will be evaluated after at least 6 months of treatment
Treatment adherence
Time frame: This outcome will be evaluated after at least 6 months of treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Endometriosis, run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 2 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Patients' statisfaction (time frame: This outcome will be evaluated after at least 6 months of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2025.