Opioid Antagonism in Hypogonadotropic Hypogonadism

Study Overview
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Brief Summary
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The goal of this study is to evaluate the effects of opioid antagonists on the hypothalamic-pituitary-gonadal axis in subjects with idiopathic hypogonadotropic hypogonadism (HH).

Detailed Description
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Assignment: Each study subject will serve as their own control. Delivery of Interventions: Prior to the study visit, subjects will undergo a review of their medical history and screening laboratories. During the inpatient study, the subjects will Period 1: Undergo q10 min blood sampling for up to 13 hours Receive 3 kisspeptin intravenous (IV) boluses Receive 1 gonadotropin-releasing hormone (GnRH) IV bolus Period 2: Undergo q10 min blood sampling for up to 13 hours Receive a naloxone bolus followed by a naloxone infusion Receive 3 kisspeptin IV boluses Receive 1 GnRH IV bolus

Official Title
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Opioid Antagonism in Hypogonadotropic Hypogonadism

Conditions
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Hypogonadotropic Hypogonadism

Intervention / Treatment
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* Drug: kisspeptin, GnRH, naloxone
* Drug: GnRH
* Drug: Naloxone


Participation Criteria
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Eligibility Criteria
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Confirmed diagnosis of HH with Low testosterone or estradiol Low or low-normal gonadotropin levels Thyroid Stimulating Hormone (TSH) and prolactin within the reference range Absence of abnormal pituitary or hypothalamic findings on Magnetic Resonance Imaging (MRI) All other medical conditions stable and well controlled No prescription medications known to affect reproductive endocrine function for at least 2 months or for 5 half-lives of the drug (whichever is shorter) except for medications used to treat the subject's reproductive condition No history of a medication reaction requiring emergency medical care No opiate drug use No excessive alcohol consumption (<10 drinks/week) Not currently seeking fertility If applicable, able to undergo appropriate washout from hormone therapy Normal blood pressure (BP), (systolic BP < 140 mm Hg, diastolic < 90 mm Hg) White blood cell, platelet counts, and TSH between 90% of the lower limit and 110% of the upper limit of the reference range Hemoglobin Women: no less than 0.5 gm/dL below the lower limit of the reference range for normal women Men: on adequate testosterone replacement therapy: normal male reference range; off testosterone replacement therapy: no lower than 0.5 gm/dL below the lower limit of the reference range for normal women Blood urea nitrogen (BUN), creatinine, aspartate aminotransferase (AST), alanine transaminase (ALT) not elevated Negative urine drug screening panel For women Negative serum human chorionic gonadotropin (hCG) pregnancy test at the time of screening (additional urine pregnancy test will be conducted prior to drug administration) Not breastfeeding and not pregnant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: kisspeptin, GnRH, naloxone<br>IV administration of kisspeptin 112-121; six boluses in up to a 26-hour period. IV administration of GnRH; two boluses in up to a 26-hour period. IV administration of naloxone; one bolus and an infusion over an up to 13-hour period. | Drug: kisspeptin, GnRH, naloxone<br>* Six IV doses of kisspeptin 112-121<br>* Other names: metastin 45-54;Drug: GnRH<br>* Two IV doses of GnRH<br>* Other names: gonadotropin-releasing hormone;Drug: Naloxone<br>* One bolus and one infusion of naloxone<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average change in Luteinizing Hormone (LH) pulse frequency | Change in LH pulse frequency before and during naloxone infusion | Before and during treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average change in LH pulse amplitude | change in LH pulse amplitude before and during naloxone infusion | Before and during treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypogonadotropic Hypogonadism, kisspeptin, naloxone