Neuropeptides in Human Reproduction

Study Overview
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Brief Summary
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The investigators are seeking healthy volunteers and volunteers with reproductive disorders for the study of the role of dynorphin in the reproductive system. Dynorphin is a naturally occurring opioid hormone that is blocked by naloxone. We hypothesize that naloxone, by blocking dynorphin, will stimulate production of gonadotropin-releasing hormone (GnRH) and kisspeptin, two other naturally occurring reproductive hormones.

Official Title
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Neuropeptides in Human Reproduction

Conditions
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Hypogonadotropic Hypogonadism

Intervention / Treatment
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* Drug: Kisspeptin 112-121
* Drug: Naloxone
* Drug: GnRH


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages 21-40 (healthy men and regularly cycling women) OR ages 18-75 (men and women with hypogonadotropic hypogonadism (HH)) Normal blood pressure (systolic BP <140 mm Hg, diastolic BP <90 mm Hg) White blood cell, platelets, prolactin, and thyroid stimulating hormone (TSH)within 90%-110% of laboratory reference range Negative urine drug screen panel Hemoglobin: For healthy men and healthy regularly cycling women: normal For men and women with HH: No less than 0.5 gm/dL below the lower limit of the reference range for normal women Blood urea nitrogen (BUN), creatinine, liver function tests not elevated For healthy subjects: Normal reproductive function and history For healthy subjects: Body Mass Index (BMI) 18.5-30kg/m2 For subjects with HH: All medical conditions stable and well controlled Exclusion Criteria: History of medication reaction requiring emergency medical attention Illicit drug use Consumption of more than 10 alcoholic drinks per week Difficulty with blood draws Currently seeking fertility, breastfeeding, or pregnant For healthy subjects: history of chronic disease and prescription medication use (with the exception of seasonal allergy medication) For subjects with HH: prescription medications known to affect reproductive endocrine function except for those used to treat the subject's reproductive condition

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Naloxone, Kisspeptin, GnRH<br>Intravenous (IV) administration of kisspeptin 112-121, GnRH, and naloxone | Drug: Kisspeptin 112-121<br>* Subjects will receive up to 10 IV doses of kisspeptin 112-121<br>* Other names: Metastin 45-54;Drug: Naloxone<br>* Subjects will receive one IV dose of naloxone followed by an IV infusion of naloxone.<br>Drug: GnRH<br>* Subjects will receive up to 10 doses of IV GnRH<br>* Other names: Gonadotropin-releasing hormone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average difference in luteinizing hormone (LH) concentration before and after kisspeptin | Compares response to kisspeptin on and off naloxone infusion | Within 30 minutes of administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Reproductive disorders, Hypogonadotropic hypogonadism, Kisspeptin, GnRH, Naloxone