Functional Study of the Hypothalamus in Magnetic Resonance Imaging (MRI) in Polycystic Ovary Syndrome (PCOS)

Study Overview
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Brief Summary
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The aim to evaluate whether activation of the hypothalamic-pituitary-gonadal axis in PCOS is associated with transient microstructural and metabolic changes in the female hypothalamus using MRI approaches to assess water diffusion and measure proton magnetic resonance spectra.

Official Title
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Functional Study of the Hypothalamus in High-resolution Magnetic Resonance Imaging (MRI) in Women With Polycystic Ovary Syndrome (PCOS): a Comparative Study

Conditions
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Polycystic Ovary Syndrome

Intervention / Treatment
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* Drug: Cyproterone Acetate + estradiol
* Drug: Levonorgestrel, Ethinyl Estradiol 0.1-0.02Mg Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For all subjects Aged from 19 to 30 years Body mass index : 18-25 Informed consent before inclusion Do not smoke the 3 days before the MRI For Healthy volunteers subjects : Regular cycles (between 25 and 35 days) AND ovulatory. No signs of hyperandrogenism. Subjects desirous of taking oral contraceptives (estrogen/progestin combination). For the realization of the 2nd MRI: to be during the 3rd month of a treatment well followed by oestro-progestative monophasic minidose to 0,02mg of Ethinyl-oestradiol / 0,1mg Levonorgestrel. PCOS women: PCOS defined by Rotterdam criteria Needing a treatment with cyproterone acetate To carry out the 2nd MRI: to be in progress during the 3rd month of a treatment well followed by 50 mg of Cyproterone acetate in association with 2mg / day of natural estradiol. Exclusion Criteria: Hormone treatment within 3 months prior to inclusion (including birth control pill ) On-going pregnancy (determined before each MRI scan visit) Claustrophobia Any metal or foreign implants (e.g., aneurysm clips, ear implants, heart pacemakers or defibrillators) Diabetes or known dysthyroidism. Current substance abuse (including smoking more than 5 cigarettes/day; determined using drug screening at the screening visit) Pregnancy or breastfeeding the last 3 months. Practice of intense physical exercise (ex jogging> 10km) the day before the MRI. Person incapable of consenting, or enjoying legal protection (guardianship / curatorship). Unability to understand the treatment protocol

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: PCOS women<br>26 PCOS women who receive consultation for hyperandrogenism needing treatment with Cyproterone Acetate + estradiol will be recruited. | Drug: Cyproterone Acetate + estradiol<br>* PCOS will receive: 50mg cyproterone acetate (Androcur®) in combination with p.o. 2mg estradiol daily<br>* Other names: Androcur, Provames;|
| Other: Healthy volunteers<br>26 Healthy volunteers subjects who receive consultation contemplating oral contraceptives (Levonorgestrel, Ethinyl Estradiol 0.1-0.02Mg Oral Tablet ) will be recruited. | Drug: Levonorgestrel, Ethinyl Estradiol 0.1-0.02Mg Oral Tablet<br>* Healthy volunteers receive combined oral contraceptive (COC) consisting 0.02 mg ethinylestradiol and 0.1mg of progestins (Leeloo Gé®)<br>* Other names: Leeloo Gé®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Apparent Diffusion Coefficient (ADC) | The change in the ADC will be analyzed in healthy volunteers and PCOS women before starting the oral contraceptives, and next during the third sequence of treatment. | Baseline and 3 months after treatment start | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the metabolite concentrations | The change in the metabolite concentrations will be analyzed in the two groups before starting the oral contraceptives, and next during the third sequence of treatment. | Baseline and 3 months after treatment start | 
| Correlation coefficient (Spearman or Pearson) between the ADC and serum hormonal levels (FSH,luteinizing hormone,oestradiol, AMH) | The correlation between ADC and hormonal levels in the two groups will be analysed before starting the contraceptive treatment and during the third processing sequence. | Baseline and 3 months after treatment start | 
| Correlation coefficient (Spearman or Pearson) between the metabolite concentrations and serum hormonal levels (FSH, luteinizing hormone, oestradiol, AMH) | The correlation between metabolite concentrations and hormonal levels in the two groups will be analysed before starting the contraceptive treatment and during the third processing sequence. | Baseline and 3 months after treatment start | 
| Plasma GnRH concentration before and after treatment (PCOS patient and control group) |  | Baseline and 3 months after treatment start | 
| Correlation between brain metabolite concentrations and plasma GnRH concentration before and after contraception. |  | Baseline and 3 months after treatment start | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypothalamus, Diffusion Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy