Ultra-Safe Hormonal Strategy: Transdermal Estradiol Added to Progestins for Endometriosis

NCT ID: NCT07204093

Last Updated: 2025-10-02

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 138 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-08-11
• Study Completion Date: 2026-02-28

Brief 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.

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.

Conditions

Endometriosis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

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).

Drospirenone 4 mg orally

Intervention Type: DRUG

Daily oral administration of Drospirenone 4 mg + Transdermal estradiol; continuous administration for at least 6 months.

Dienogest 2 mg orally

Intervention Type: DRUG

Daily oral administration of Dienogest 2 mg + Transdermal estradiol; continuous administration for at least 6 months.

Interventions

Drospirenone 4 mg orally

Daily oral administration of Drospirenone 4 mg + Transdermal estradiol; continuous administration for at least 6 months.

Intervention Type: DRUG

Dienogest 2 mg orally

Daily oral administration of Dienogest 2 mg + Transdermal estradiol; continuous administration for at least 6 months.

Intervention Type: DRUG

Other Intervention Names

Slinda; Visanne; Dienogest; Zafrilla

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Gynecology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, , Italy

Countries

Italy

Other Identifiers

TAEDIUMVITAE

Identifier Type: OTHER

Identifier Source: secondary_id

0021423-U

Identifier Type: -

Identifier Source: org_study_id