Administration of Kisspeptin to Healthy Subjects and Subjects With Reproductive Disorders

• FSH levels [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
• testosterone (males) [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
• estradiol (females) [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
• CBC [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
• BUN [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
• creatinine [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
• liver function studies [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]

The investigators are seeking subjects for a study of the role of kisspeptin in the reproductive system. Kisspeptin is a naturally occuring hormone in humans that stimulates the production of reproductive hormones. The investigators hypothesize that kisspeptin administration will be a useful tool for characterizing certain reproductive disorders.

The investigators are seeking men and women with idiopathic hypogonadotropic hypogonadism (IHH). Study participation involves 1-2 outpatient visits and 1-2 12-14-hour hospital admission(s) when subjects will receive kisspeptin and/or gonadotropin-releasing hormone (GnRH). Remuneration is up to $900 for study completion. Individuals interested in learning more may call 617-724-8592.

The master reproductive hormone GnRH (gonadotropin-releasing hormone) is essential for normal reproductive function. Individuals who fail to secrete or respond to GnRH have a condition called hypogonadotropic hypogonadism. These individuals fail to undergo puberty and are infertile. Study of these patients has led to better understanding of the reproductive endocrine system.

Kisspeptin is a peptide hormone that has recently been found to be a potent stimulus for GnRH release. This hormone has several potential applications:

• in research settings, administration of kisspeptin may be used to characterize the precise defect in subjects with hypogonadotropic hypogonadism and, in turn, may lead to better understanding of the reproductive endocrine system
• kisspeptin may have diagnostic applications in the evaluation of delayed puberty and infertility
• kisspeptin may have applications in the treatment of reproductive disorders such as infertility and irregular or absent menstrual periods

This study is to assess the effects of kisspeptin administered in subjects with hypogonadotropic hypogonadism.

• Drug: kisspeptin 112-121
  one or more intravenous doses of kisspeptin 112-121
  Other Name: metastin 45-54
• Drug: GnRH
  One or more intravenous doses of GnRH
  Other Name: gonadotropin-releasing hormone

Inclusion Criteria:

• 18 years or older
• systolic blood pressure <140 mm Hg, diastolic blood pressure <90 mm Hg
• normal ferritin/iron binding studies (ruling out hemochromatosis)
• white blood cell (WBC), platelet counts, prolactin, and thyroid stimulating hormone (TSH) between 90% of the lower limit and 110% of the upper limit of the reference range
• blood urea nitrogen (BUN) and creatinine not elevated
• liver function tests less than 2x upper limit of normal
• for women, negative serum hCG pregnancy test at the time of screening and negative urine hCG pregnancy test at the time of drug administration

Exclusion Criteria:

• use of prescription medications known to affect reproductive endocrine function for at least 2 months
• illicit drug use
• consumption of more than 10 alcoholic drinks per week
• history of anaphylactic reactions
• history of chronic disease, or all medical conditions stable and well controlled
• for women, lack of access of non-hormonal contraception if sexually active with a male partner