Sub-therapeutic GnRH- Antagonist Treatment to Rectify LH Pulsatility in Lean Women With PCOS.

Study Overview
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Brief Summary
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The clinical study using a sub-therapeutic dose of a GnRH antagonist to reduce overactive LH pulsatility in women with PCOS. With the intervention and lowered LH action we anticipate to decrease androgen levels in women with PCOS. The aim to show for the first time that low-dose GnRH-antagonists can lower LH pulsatility by 20-30% and decrease androgen levels without blunting the hypothalamic-pituitary-gonadal axis and thereby the reproductive functions.

Official Title
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Short-term GnRH- Antagonist Treatment to Lower LH Pulsatility in Women With PCOS Aiming to Improve Hormonal Functions

Conditions
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Polycystic Ovary Syndrome

Intervention / Treatment
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* Drug: Ganirelix
* Drug: Ganirelix


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Minimum weight of 51 kg BMI between 20 and 25 women with PCOS with AMH> 28 pmol / L, LH> 8 IU / mL and testosteronemia > 0.39 ng/mL no hormonal treatment or contraception for 2 months women covered by the Social Security system Exclusion Criteria: hormonal treatment or hormonal contraception Metformin treatment pregnant woman inability to understand the newsletter

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.0625 mg<br>Test the efficacy of Ganirelix administered subcutaneously at single-dose regimen of 0.0625 mg in 10 women with PCOS, in rectifying LH pulse frequency and LH amplitude | Drug: Ganirelix<br>* An intra-venous cannula will be inserted and blood will be sampled at 10-min intervals for a 4-h baseline period commencing at 0800 h. Ganirelix will be then administered subcutaneously at single-dose regimen at 0.025 mg (n = 10 women with PCOS). After Ganirelix administration sampling will continue at 10-min intervals for 4 h.<br>|
| Experimental: 0.025 mg<br>Test the efficacy of Ganirelix administered subcutaneously at single-dose regimen of 0.025 mg in 10 women with PCOS, in rectifying LH pulse frequency and LH amplitude. | Drug: Ganirelix<br>* An intra-venous cannula will be inserted and blood will be sampled at 10-min intervals for a 4-h baseline period commencing at 0800 h. Ganirelix will be then administered subcutaneously at single-dose regimen at 0.0625 mg (n = 10 women with PCOS). After Ganirelix administration sampling will continue at 10-min intervals for 4 h.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum LH level | The degree of gonadotropin suppression will be determined by calculating the percent inhibition from the pre-antagonist period [(mean PRE - nadir)/mean PRE] x 100, where nadir hormone levels will be calculated using a moving average. | every 10 minutes for 8 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Variation in LH secretion amplitude before and after Ganirelix* injection (area under the curve) |  | at the beginning and at the end of the 8 hours | 
| Variation in androgen production | defined by the difference between the measurement at H8 and the measurement at H0 (4 hours before injection) of total testosterone and androstenedione. | at 4 hours after injection | 
| change in FSH levels | defined as the difference between the measurement at H8 and the measurement at H0 (4 hours prior to injection) of FSH | at 4 hours post-injection | 
| change in estradiol levels | defined as the difference between the measurement at H8 and the measurement at H0 (4 hours prior to injection) of estradiol | at 4 hours post-injection | 
| change in AMH levels | defined as the difference between the measurement at H8 and the measurement at H0 (4 hours prior to injection) of AMH. | at 4 hours post-injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LH, PCOS, GnRH antagonist, androgen, testosterone