Safety of Hormonal Contraceptives Therapies in Polycystic Ovary Syndrome (PCOS) Women

Study Overview
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Brief Summary
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The purpose of this study to assess early markers of cardiovascular disease in women with polycystic ovary syndrome in use of oral contraceptive containing ethynilestradiol and chlormadinone acetate alone or associated with Spironolactone.

Detailed Description
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Polycystic ovary syndrome (PCOS) is associated with comorbidities that may contribute to increased risk of cardiovascular disease (CVD). Oral contraceptives (OC) have been the mainstay of PCOS pharmacological therapy for decades. However, in non-hyperandrogenic women, OC use is associated with higher risk of cardiovascular disease, raising concern about a possible worsening of the unfavorable metabolic and cardiovascular profile of PCOS patients. There is lack of evidence about the impact of PCOS pharmacological therapies on cardiovascular risk markers and the long-term safety of these drugs in PCOS has not been established. The aim of this study is to compare the effect of an OC alone or associated with an anti-androgenic drug (spironolactone) on echografic cardiovascular risk markers, metabolic and hemostatic variables.

Official Title
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Metabolic Effects of Multiple Therapies in Polycystic Ovary Syndrome (PCOS) Women

Conditions
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Polycystic Ovary Syndrome

Intervention / Treatment
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* Drug: oral contraceptive
* Drug: Oral contraceptive plus spironolactone
* Drug: Oral contraceptive plus metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age between 18 and 35 years diagnosis of PCOS by Rotterdam Consensus Exclusion Criteria: smoking, alcoholism, drug addiction; current pregnancy; current or previous use (up to two months before the study) of oral, vaginal, monthly injectable, or transdermal combined hormonal contraceptives; current or previous use (up to six months before the study) of a long-lasting hormonal contraceptive method (injectable, implant, or intrauterine device); antiandrogenic or hypoglycemic drugs, anti-inflammatory drugs, or statins; presence of systemic diseases (DM2, cardiovascular disease, autoimmune diseases, liver disease, thyroid disease, or congenital renal hyperplasia); personal history of arterial or venous thrombosis; chronic or acute inflammatory processes; puerperium of 12 weeks or less

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>This group will receive an oral contraceptive containing 0,03mg ethynylestradiol and 2mg chlormadinone acetate | Drug: oral contraceptive<br>* oral contraceptive (0,03mg ethynylestradiol and 2mg chlormadinone acetate)once a day for 12 months<br>* Other names: Belara;|
| Experimental: 2<br>The patient will receive an oral contraceptive (0,03mg ethynylestradiol and 2mg chlormadinone acetate) plus 100 mg spironolactone. One pill each once a day for twelve months. | Drug: Oral contraceptive plus spironolactone<br>* The patient will receive an oral contraceptive (0,03mg ethynylestradiol and 2mg chlormadinone acetate) plus 100 mg spironolactone. One pill each once a day for twelve months.<br>* Other names: Spironolactone;|
| Experimental: 3<br>The patient will receive an oral contraceptive (0,03mg ethynylestradiol and 2mg chlormadinone acetate) plus 850 mg metformin. | Drug: Oral contraceptive plus metformin<br>* Oral contraceptive (0,03mg ethynylestradiol and 2mg chlormadinone acetate) plus 850 mg of metformin<br>* Other names: Metformin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the effect of an oral contraceptive alone or associated with an anti-androgenic drug (spironolactone) or associated with metformin on echografic cardiovascular risk markers. |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to compare the effect of an oral contraceptive alone or associated with an anti-androgenic drug (spironolactone) or associated with metformin on seric cardiovascular risk markers. |  | 12 months | 
| to compare the effect of an oral contraceptive alone or associated with an anti-androgenic drug (spironolactone) or associated with metformin on hemostatic variables. |  | 12 months | 
| to compare the effect of an oral contraceptive alone or associated with an anti-androgenic drug (spironolactone) or associated with metformin on metabolic variables. |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polycystic ovary syndrome, Oral Contraceptives, Hormonal, Cardiovascular Disease, Endothelium