Effects of Dienogest and Dienogest Plus Estradiol Valerate in Ovarian Endometrioma

Study Overview
=================
Brief Summary
-----------------
Progesterone resistance in endometriosis is a known fact. The progestin derivatives used in endometriosis cause decidualization and atrophy of ectopic foci. Moreover, they inhibit neo-angiogenesis, provide suppress expansile/destructive growth facilitated by matrix metalloproteinases, and implantation of ectopic foci. The effect of drugs containing the estrogen-progesterone combination is mainly based on the inhibition of ovulation, decidualization and atrophy of ectopic foci. In estrogen-progesterone mechanism, it is known that estrogen has a progesterone receptor-enhancing effect, which may make progesterone more potent. Based on this, the investigators hypothesized that estrogen added to progesterone could lead to a further reduction in endometrioma size by various mechanisms which probably include the increased progesterone sensitivity in endometriosis. In addition, the investigators hypothesized that this therapy can alleviate the destructive effect of endometriomas on the ovarian reserve.

Official Title
-----------------
Effects of Dienogest and Dienogest Plus Estradiol Valerate on Ovarian Reserve and Endometrioma Size

Conditions
-----------------
Ovarian Reserve

Intervention / Treatment
-----------------
* Drug: Estradiol valerate/dienogest


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Study Group: At least one endometrioma greater than 3 cm, between 18-40 years of age, without surgical indication at the time of diagnosis, occasionally and intermittently controlled pain with NSAIDs or no pain symptom Control Group: Patients with reproductive age without any ovarian cysts Exclusion Criteria: suspicion of malignancy, irregular mentrual period, endocrine diseases, drug intake that may affect ovarian reserve in the last 6 months (i.e GnRH agonists), previous ovarian surgery, AMH levels under 2 ng/ml.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Group (patients with OMA)<br>I) Untreated patients (n=142) II) Dienogest (n=142) III) Dienogest/Estradiol valerate+Dienogest (n=142) | Drug: Estradiol valerate/dienogest<br>* The effects of drugs given for endometrioma and contraception will be observed on ovarian reserve, endometrioma size and pain score.<br>* Other names: Dienogest;|
| Sham Comparator: Control Group(patients without OMA)<br>I) Untreated patients (n=142) II) Dienogest/Estradiol valerate+Dienogest (n=142) | Drug: Estradiol valerate/dienogest<br>* The effects of drugs given for endometrioma and contraception will be observed on ovarian reserve, endometrioma size and pain score.<br>* Other names: Dienogest;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ovarian reserve | The investigators evaluate serum anti-Müllerian hormone (AMH) level(ng/mL) using commercial elisa kits and antral follicle count (number) using ultrasonography. The patients with higher ovarian reserve represent a better outcome. | up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endometrioma Size | The investigators evaluate endometrioma size (centimeter) using ultrasonography. | up to 24 months | 
| Pain Score | Vas score (minimum score:0 and maximum score:10). The patients with lower pain scores represent a better outcome. | up to 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Endometrioma, Estradiol valerate + dienogest, Dienogest, Ovarian reserve