Ovarian EndometriomaPhase 4ERASENCT05837624
Estetrol/Drospirenone to Reduce the Average Size of Endometriomas
A Phase 4 study testing Estetrol/Drospirenone in people with Ovarian Endometrioma and Endometrioma, run by Andrew Zakhari at 1 site in Canada.
Trial summary
Endometriosis, a chronic gynecological disorder associated with pain and infertility, is a common condition affecting approximately one in ten women. Up to 50% of patients with endometriosis have ovarian endometriomas (or "chocolate cysts"). These cysts directly impact fertility and ovarian reserve (ie. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Ovarian Endometrioma, Endometrioma
- What is being tested?
- Estetrol/Drospirenone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteCanada
- Study dates
- 3 Dec 2024to Aug 2027
- Phase
- Phase 4
- 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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Equal to or greater than 18 years old
- Has at least one ovarian endometrioma, of at least 3 cm
- Seeking a hormonal treatment for their endometrioma(s)
Who cannot join
- Any allergy or contraindication to the study drug
- Inability to provide informed consent
- Any hormone use, from the following list, within last 3 months (excluding hormones used for ovarian stimulation for fertility treatments): Estrogen (agonist or antagonist), Progestogen (agonist or antagonist), Androgen (agonist or antagonist), GnRH (agonist or antagonist), Cabergoline
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Cassandra Della Rocca, BSc. contact
Canada1 site, 1 recruiting
- Recruiting
McGill University Health Center
Montreal, Quebec, H4A 3J1
Andrew Zakhari, M.D., (514) 228-8889, andrew.zakhari@mcgill.ca
Andrew Zakhari, M.D.
About this study
Endometriosis, a chronic gynecological disorder associated with pain and infertility, is a common condition affecting approximately one in ten women. Up to 50% of patients with endometriosis have ovarian endometriomas (or "chocolate cysts"). These cysts directly impact fertility and ovarian reserve (ie. ability to have children) and can cause additional symptoms in women such as added pain, discomfort, and surgical emergencies (cyst rupture, or more rarely twisting). While endometriomas tend to require surgical excision as a solution, medical management with a variety of medications has been shown to be effective in reducing their size.
Medical management (ie. medications and treatments that don't involve surgery) to reduce cyst size can help relieve symptoms either as a long term solution, before fertility treatments, or temporarily until surgery can be offered. Because the COVID-19 pandemic caused significantly reduced access to surgery and resources, medical management has become important for relief of the overburdened healthcare network.
Read more
The purpose of this study is to see how effective Estetrol/drospirenone, a combined oral contraceptive (COC), is in the reduction of ovarian endometriomas after a 3- and 6-month period of treatment.
This single arm interventional study will recruit women 18 years or older with an ovarian endometrioma of at least 3cm, who are seeking a hormonal treatment for their endometrioma(s). Consenting participants of the study will take Estetrol/drospirenone once daily, orally, for a 6 month duration. An ultrasound assessment of ovarian endometrioma(s) will be performed before starting the drug (0 months), and will be repeated at 3-months and 6-months time. At each of these hospital visits (0, 3 \& 6 months), participants will have their weight and blood pressure measured, and they will complete questionnaires regarding their endometriosis symptoms, incidence of amenorrhea, compliance and incidence of any adverse effects.
Read the detailed description
Ovarian endometriomas (or "chocolate cysts") are present in up to 50% of patients with endometriosis - a chronic gynecological disorder associated with pain and infertility. These cysts directly impact fertility and ovarian reserve and can cause additional symptoms in women such as added pain, discomfort, and surgical emergencies (cyst rupture, or more rarely torsion).
While endometriomas tend to require surgical excision for definitive resolution, medical management with a variety of agents has been shown to be effective in reducing their size; these agents include combined oral contraceptives (COC), aromatase inhibitors, progestins, androgens, cabergoline, and gonadotropin-releasing hormone agonists (GnRH-a). Medical management to reduce their size can help alleviate symptoms indefinitely without damaging ovarian reserve prior to fertility treatments, or to temporize until surgical management can be offered. Medical management has become particularly important in light of the COVID-19 pandemic, with significantly reduced access to surgery, and resource allocation to alleviate an overburdened healthcare network.
Estetrol/drospirenone (Nextstellis™) is a prescription-only COC available in Canada containing two hormones: a progestin (drospirenone - well known as both a standalone contraceptive and in other combined formulations), and an estrogen (estetrol - newly introduced with this product). While ethinyl estradiol (EE) is the most common estrogen currently used in COC, estetrol (E4) has proven safety and tolerability, and emerging evidence points towards a lower risk of thrombosis than traditional EE used in other COC. Studies have documented efficacy and safety for the combination estetrol/drospirenone, with a favourable bleeding profile, and very low rates of adverse reactions. While there exists already encouraging data on drospirenone and drospirenone containing products on alleviating symptoms of endometriosis and reducing the size of endometriomas, there are no studies to date evaluating this novel combination of estetrol/drospirenone in managing ovarian endometriomas.
The primary objective of this study is to determine the effectiveness of Estetrol/drospirenone, a combined oral contraceptive (COC), in the reduction of ovarian endometriomas after a 3- and 6-month period of treatment.
This is a single-center, open label, single arm interventional study that will be performed at the McGill University Health Centre (MUHC) Royal Victoria Hospital (RVH). Women 18 years of age or older with at least one ovarian endometrioma, of at least 3cm, who are seeking a hormonal treatment for their endometrioma(s), will be recruited. The study will aim to recruit 21 women.
Consenting participants will be given a 6-month course of oral estetrol/drospirenone (15 mg estetrol monohydrate / 3 mg drospirenone) once daily for the study duration. An ultrasound assessment of ovarian endometrioma(s) will be performed prior to drug initiation (baseline), and will be repeated at 3-months and 6-months time. All ultrasounds will be performed by the same ultrasonographer using a standardized technique and 3-D volumetric assessment. At each of these hospital visits, participants will have their weight and blood pressure measured and they will complete questionnaires regarding their endometriosis symptoms with a research coordinator. Safety, tolerability, and the incidence of adverse effects will also be monitored at the same time intervals.
- Conditions
- Ovarian Endometrioma, Endometrioma
- Being tested
- Estetrol/Drospirenone
- Keywords
- Estetrol/drospirenone, Nextstellis, Endometriosis, volume reduction, ultrasound, Estetrol-drospirenone
- Medical subject headings
- Endometriosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Estetrol/DrospirenoneDrug
6-month course of oral estetrol/drospirenone (15 mg estetrol monohydrate / 3 mg drospirenone) once daily for the study duration
| Study group | Role | What they receive |
|---|---|---|
| Women with an ovarian endometrioma who will take drospirenone / estetrol | Experimental | Women 18 years of age or older with endometriosis who have at least one ovarian endometrioma, of at least 3 cm in diameter, who will take oral Drospirenone / Estetrol treatment for 6 months Receives: Drug: Estetrol/Drospirenone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in ovarian endometrioma volume at 6-months (from baseline)
Endometrioma volume will be assessed by the same ultrasonographer (Dr. DB Nguyen) at each hospital visit, using a standardized technique, with 3-dimensional volumetric assessment.
Measured: pre-study, 6-months of treatment
Secondary outcomes (9)
Change in endometrioma volume at 3-months (from baseline)
Endometrioma volume will be assessed by the same ultrasonographer (Dr. DB Nguyen) at each hospital visit, using a standardized technique, with 3-dimensional volumetric assessment.
Measured: pre-study, 3-months of treatment
change in endometrioma maximal diameter at 6-months (from baseline)
Endometrioma maximal diameter will be assessed by the same ultrasonographer (Dr. DB Nguyen) at each hospital visit, using a standardized technique, with 3-dimensional volumetric assessment.
Measured: pre-study, 6-months of treatment
change in endometrioma maximal diameter at 3-months (from baseline)
Endometrioma maximal diameter will be assessed by the same ultrasonographer (Dr. DB Nguyen) at each hospital visit, using a standardized technique, with 3-dimensional volumetric assessment.
Measured: pre-study, 3-months of treatment
Incidence of amenorrhea
Incidence of amenorrhea will be evaluated by having the participant complete a questionnaire at each hospital visit.
- If they have gotten their period in the last 3 months: measured by (yes/no)
- The frequency of spotting in the last month: measured by a 4-point likert scale (Never/Rarely/Occasionally/Often)
Measured: pre-study, 3-months of treatment, 6-months of treatment
Change in patient reported endometriosis symptoms
Change of endometriosis symptoms will be evaluated by monitoring the changes in participants's responses to the modified Biberoglu \& Behrman (B\&B) scale questionnaire. This is a validated scale that evaluates endometriosis pain by patient's self-assessment of three pain symptoms (dysmenorrhea, dyspareunia, and chronic pelvic pain) on a 4-point likert scale (none=0/mild=1/moderate=2/severe=3).
Minimum value: 0 --> best outcome Maximum value: 9 --> worst outcome
Measured: pre-study, 3-months of treatment, 6-months of treatment
Change in weight
Weight will be measured by a research coordinator or nurse at each hospital visit.
Measured: pre-study, 3-months of treatment, 6-months of treatment
Change in blood pressure
Blood pressure will be measured by a research coordinator or nurse at each hospital visit.
Measured: pre-study, 3-months of treatment, 6-months of treatment
Incidence of adverse effects (safety, tolerability)
Incidence of adverse effects (yes/no) including: nausea/vomiting, edema, breast tenderness, headache, cramps/bloating, mood swings (specified), as well as any unexpected adverse effects will be evaluated by having the participant complete a questionnaire at each hospital visit after starting estetrol/drospirenone.
Measured: 3-months of treatment, 6-months of treatment
Compliance
Drug compliance will be evaluated by having the participant complete a questionnaire at each hospital visit after starting estetrol/drospirenone.
- If they have been taking the prescribed dosage of 1 oral tablet of estetrol/drospirenone a day (yes/no)
- If they have been taking the prescribed dosage at the same time every day (yes/no)
- How often they miss a pill, on a 4-point likert scale (Never/Rarely/Occasionally/Often)
Measured: 3-months of treatment, 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 posted1 May 2023
- Study start3 Dec 2024
- Primary completionJul 2027 (estimated)
- Study completionAug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ovarian EndometriomaStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Andrew Zakhari
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Andrew Zakhari, McGill University Health Centre/Research Institute of the McGill University Health Centre
- Investigators
- Andrew Zakhari, M.D., Principal investigator, McGill University Health Centre/Research Institute of the McGill University Health Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05837624
- Sponsor's protocol ID
- 2024-9147
- Acronym
- ERASE
- Status last verified
- Oct 2026
- First submitted
- 12 Apr 2023
- Last updated
- 3 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Liao C, Pal L. Novel Pharmacotherapies for Menopausal Symptoms. Obstet Gynecol. 2025 Oct 1;146(4):473-486. doi: 10.1097/AOG.0000000000006025. Epub 2025 Aug 7.
PubMed 40773756
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Estetrol/Drospirenone to Reduce the Average Size of Endometriomas
- ClinicalTrials.gov ID
- NCT05837624
- Acronym / sponsor ID
- ERASE / 2024-9147
- Conditions
- Ovarian Endometrioma, Endometrioma
- Keywords
- Estetrol/drospirenone, Nextstellis, Endometriosis, volume reduction, ultrasound, Estetrol-drospirenone
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 21 participants (estimated)
- Lead sponsor
- Andrew ZakhariUniversity, hospital or other
- Study start
- 3 Dec 2024 (actual)
- Primary completion
- Jul 2027 (estimated)
- Study completion
- Aug 2027 (estimated)
- First posted
- 1 May 2023 (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, a chronic gynecological disorder associated with pain and infertility, is a common condition affecting approximately one in ten women. Up to 50% of patients with endometriosis have ovarian endometriomas (or "chocolate cysts"). These cysts directly impact fertility and ovarian reserve (ie. ability to have children) and can cause additional symptoms in women such as added pain, discomfort, and surgical emergencies (cyst rupture, or more rarely twisting). While endometriomas tend to require surgical excision as a solution, medical management with a variety of medications has been shown to be effective in reducing their size.
Medical management (ie. medications and treatments that don't involve surgery) to reduce cyst size can help relieve symptoms either as a long term solution, before fertility treatments, or temporarily until surgery can be offered. Because the COVID-19 pandemic caused significantly reduced access to surgery and resources, medical management has become important for relief of the overburdened healthcare network.
The purpose of this study is to see how effective Estetrol/drospirenone, a combined oral contraceptive (COC), is in the reduction of ovarian endometriomas after a 3- and 6-month period of treatment.
This single arm interventional study will recruit women 18 years or older with an ovarian endometrioma of at least 3cm, who are seeking a hormonal treatment for their endometrioma(s). Consenting participants of the study will take Estetrol/drospirenone once daily, orally, for a 6 month duration. An ultrasound assessment of ovarian endometrioma(s) will be performed before starting the drug (0 months), and will be repeated at 3-months and 6-months time. At each of these hospital visits (0, 3 \& 6 months), participants will have their weight and blood pressure measured, and they will complete questionnaires regarding their endometriosis symptoms, incidence of amenorrhea, compliance and incidence of any adverse effects.
Detailed description
Ovarian endometriomas (or "chocolate cysts") are present in up to 50% of patients with endometriosis - a chronic gynecological disorder associated with pain and infertility. These cysts directly impact fertility and ovarian reserve and can cause additional symptoms in women such as added pain, discomfort, and surgical emergencies (cyst rupture, or more rarely torsion).
While endometriomas tend to require surgical excision for definitive resolution, medical management with a variety of agents has been shown to be effective in reducing their size; these agents include combined oral contraceptives (COC), aromatase inhibitors, progestins, androgens, cabergoline, and gonadotropin-releasing hormone agonists (GnRH-a). Medical management to reduce their size can help alleviate symptoms indefinitely without damaging ovarian reserve prior to fertility treatments, or to temporize until surgical management can be offered. Medical management has become particularly important in light of the COVID-19 pandemic, with significantly reduced access to surgery, and resource allocation to alleviate an overburdened healthcare network.
Estetrol/drospirenone (Nextstellis™) is a prescription-only COC available in Canada containing two hormones: a progestin (drospirenone - well known as both a standalone contraceptive and in other combined formulations), and an estrogen (estetrol - newly introduced with this product). While ethinyl estradiol (EE) is the most common estrogen currently used in COC, estetrol (E4) has proven safety and tolerability, and emerging evidence points towards a lower risk of thrombosis than traditional EE used in other COC. Studies have documented efficacy and safety for the combination estetrol/drospirenone, with a favourable bleeding profile, and very low rates of adverse reactions. While there exists already encouraging data on drospirenone and drospirenone containing products on alleviating symptoms of endometriosis and reducing the size of endometriomas, there are no studies to date evaluating this novel combination of estetrol/drospirenone in managing ovarian endometriomas.
The primary objective of this study is to determine the effectiveness of Estetrol/drospirenone, a combined oral contraceptive (COC), in the reduction of ovarian endometriomas after a 3- and 6-month period of treatment.
This is a single-center, open label, single arm interventional study that will be performed at the McGill University Health Centre (MUHC) Royal Victoria Hospital (RVH). Women 18 years of age or older with at least one ovarian endometrioma, of at least 3cm, who are seeking a hormonal treatment for their endometrioma(s), will be recruited. The study will aim to recruit 21 women.
Consenting participants will be given a 6-month course of oral estetrol/drospirenone (15 mg estetrol monohydrate / 3 mg drospirenone) once daily for the study duration. An ultrasound assessment of ovarian endometrioma(s) will be performed prior to drug initiation (baseline), and will be repeated at 3-months and 6-months time. All ultrasounds will be performed by the same ultrasonographer using a standardized technique and 3-D volumetric assessment. At each of these hospital visits, participants will have their weight and blood pressure measured and they will complete questionnaires regarding their endometriosis symptoms with a research coordinator. Safety, tolerability, and the incidence of adverse effects will also be monitored at the same time intervals.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Women with an ovarian endometrioma who will take drospirenone / estetrol | Experimental | Drug: Estetrol/DrospirenoneWomen 18 years of age or older with endometriosis who have at least one ovarian endometrioma, of at least 3 cm in diameter, who will take oral Drospirenone / Estetrol treatment for 6 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Equal to or greater than 18 years old
- Has at least one ovarian endometrioma, of at least 3 cm
- Seeking a hormonal treatment for their endometrioma(s)
Key exclusion criteria (3 listed)
- Any allergy or contraindication to the study drug
- Inability to provide informed consent
- Any hormone use, from the following list, within last 3 months (excluding hormones used for ovarian stimulation for fertility treatments): Estrogen (agonist or antagonist), Progestogen (agonist or antagonist), Androgen (agonist or antagonist), GnRH (agonist or antagonist), Cabergoline
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 |
|---|---|---|
| Estetrol/Drospirenone6-month course of oral estetrol/drospirenone (15 mg estetrol monohydrate / 3 mg drospirenone) once daily for the study duration | Drug | Women with an ovarian endometrioma who will take drospirenone / estetrol |
Primary outcome
Change in ovarian endometrioma volume at 6-months (from baseline)
Time frame: pre-study, 6-months of treatment
Endometrioma volume will be assessed by the same ultrasonographer (Dr. DB Nguyen) at each hospital visit, using a standardized technique, with 3-dimensional volumetric assessment.
9 secondary outcomes
Change in endometrioma volume at 3-months (from baseline)
Time frame: pre-study, 3-months of treatment
change in endometrioma maximal diameter at 6-months (from baseline)
Time frame: pre-study, 6-months of treatment
change in endometrioma maximal diameter at 3-months (from baseline)
Time frame: pre-study, 3-months of treatment
Incidence of amenorrhea
Time frame: pre-study, 3-months of treatment, 6-months of treatment
Change in patient reported endometriosis symptoms
Time frame: pre-study, 3-months of treatment, 6-months of treatment
Change in weight
Time frame: pre-study, 3-months of treatment, 6-months of treatment
Change in blood pressure
Time frame: pre-study, 3-months of treatment, 6-months of treatment
Incidence of adverse effects (safety, tolerability)
Time frame: 3-months of treatment, 6-months of treatment
Compliance
Time frame: 3-months of treatment, 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 3 Nov 2026.
- Derived from this study: PubMed 40773756Liao C, Pal L. Novel Pharmacotherapies for Menopausal Symptoms. Obstet Gynecol. 2025 Oct 1;146(4):473-486. doi: 10.1097/AOG.0000000000006025. Epub 2025 Aug 7.
- Individual participant dataSharing planned: No
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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.
Cassandra Della Rocca, BSc. contact
Andrew Zakhari, M.D. principal investigator
McGill University Health Centre/Research Institute of the McGill University Health Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Estetrol/Drospirenone in people with Ovarian Endometrioma and Endometrioma, run by Andrew Zakhari at 1 site in Canada.
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 3 inclusion and 3 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: looking for participants now, as of the sponsor's last update on 3 Nov 2026. 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 Canada. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Contact Andrew Zakhari, M.D. (5142288889, andrew.zakhari@mcgill.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in ovarian endometrioma volume at 6-months (from baseline) (time frame: pre-study, 6-months of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05837624, which also lists 1 linked publication.
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 3 Nov 2026.