The goal of this study is to see whether kisspeptin, a naturally occurring hormone, can stimulate the release of other reproductive hormones in women with hypothalamic amenorrhea (HA). The investigators are also examining whether kisspeptin can help women release eggs from their ovaries. Kisspeptin will be administered subcutaneously (SC) for two weeks in a pulsatile fashion. Ultrasound monitoring of ovarian follicular growth and frequent blood sampling (every 10 minutes for up to two hours) will be performed to assess the physiologic response to kisspeptin over time.

Assignment: All study subjects will undergo the same interventions.

Delivery of Interventions:

• The subject will undergo a review of their medical history, physical exam, and screening laboratories.

• A pelvic ultrasound will be performed to assess baseline follicular size.

• A pump will be placed to administer pulsatile SC kisspeptin for two weeks.

• During the course of kisspeptin administration, subjects will

  • Undergo q10 min blood sampling (approximately 4 sessions, 2 hours each)
  • Undergo pelvic ultrasounds (approximately 4 sessions)

• Optional q10 min sampling up to 10 hours may take place before and after the course of kisspeptin

Inclusion Criteria:

• Acquired hypogonadotropic hypogonadism (hypothalamic amenorrhea, aka functional hypothalamic amenorrhea)

  • Confirmed diagnosis by medical provider supported by low sex steroids in the setting of low or inappropriately normal gonadotropins]

• Normal blood pressure (systolic BP < 140 mm Hg, diastolic < 90 mm Hg)

• Laboratory Studies:

  • Hemoglobin no less than 0.5 g/dL below the lower limit of the reference range for normal women
  • Negative serum hCG pregnancy test at screening (additional urine pregnancy test will be conducted prior to drug administration)

• No current or recent use of a medication that, in the opinion of a study investigator, can modulate the reproductive axis or willing to complete an appropriate washout for that particular medication and method of administration

Exclusion Criteria:

• Any condition (medical, mental, or behavioral) that, in the opinion of a study investigator, would likely interfere with participation in/completion of the protocol

• Excessive alcohol consumption (>10 drinks/week) and/or active use of illicit drugs

  • Any active use of marijuana will be evaluated by a study medical professional to determine if it may impact study participation.

• Pregnant or trying to become pregnant

• Breast feeding

• History of: bilateral oophorectomy (both ovaries were removed), breast cancer, thromboembolic disease, coronary artery disease, stroke, thrombophilic disorders, or undiagnosed abnormal genital bleeding