Assessment of Sensitivity of the Hypothalamic GnRH Pulse Generator to Estradiol and Progesterone Inhibition

Assessment of Sensitivity of the Hypothalamic GnRH Pulse Generator to Estradiol and Progesterone Inhibition in Early Pubertal Girls (JCM026)

Gonadotropin-releasing hormone (GnRH) is a hormone that regulates the ability of the pituitary to secrete two hormones, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). LH and FSH control the production of female hormones (such as estrogen and progesterone) and the development of eggs by the ovary. Progesterone and estrogen then decrease the number of GnRH pulses produced by the brain (and therefore the number of LH pulses from the pituitary). The ability to decrease GnRH pulses seems to be very important for normal menstrual function in adult women. The purpose of this study is to learn more about how GnRH and LH pulses are controlled during puberty. The information gathered in this study will hopefully allow us to learn more about how menstrual cycles are normally established in girls during puberty.

In this study, the investigators will aim to discover the effect of 7 days of estrogen and progesterone on GnRH pulses in girls in early and mid puberty. Ultimately, if the investigators understand these normal processes, the investigators may be able to better understand abnormalities of puberty.

Inclusion Criteria:

• Girls ages 8 to 14
• Tanner 1-3 pubertal stage
• Pre-menarchal
• Normal screening labs

Exclusion Criteria:

• Abnormal screening labs
• Congenital adrenal hyperplasia
• Hyperandrogenism (e.g., hirsutism, elevated free testosterone level)
• Hemoglobin <12 mg/dL or hematocrit < 36% (Subjects will be offered the opportunity to take iron supplementation for 60 days if their hematocrit is slightly low (33-36%) (suggestive of iron deficiency anemia) and will then return for retesting of their hemoglobin/hematocrit.)
• Weight < 31 kg
• History of peanut allergy, deep venous thrombosis, breast cancer, endometrial cancer, or cervical cancer
• On hormonal medications (including oral contraceptive pills) or on medications known to affect the reproductive axis within 3 months of the study
• Pregnant or breast feeding
• Participation in a research study within the past 30 days that involved taking a study drug.
• Participation in a research study that involved taking up to or greater than 473 ml's of blood within the past 60 days.
• Cigarette smoking
• History of surgery that required bedrest within the past 30 days
• Family history of hypercoagulability or unexplained thromboembolic disease (not in setting of bedrest, surgery, or malignancy)
• In order to ensure an adequate number of younger girls, no more than 4 enrolled subjects will be Tanner stage 3