Hyperandrogenemia, Polycystic Ovary Syndrome
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGProgesterone
oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days
DRUGEstrace (estrogen)
oral estrace, 0.5-1 mg once a day for seven days
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
University of Virginia
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
8 Years to 14 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| LH Pulse Frequency as a Function of Day 7 Progesterone | 7 days following oral estrace and progesterone administration | number of LH pulses per 11 hours on Day 7 of progesterone |
Countries
United States
Participant flow
Pre-assignment details
3 subjects enrolled in this study. 2 subjects completed screening procedures only (these 2 subjects were withdrawn from study prior to being assigned to an arm of intervention).
Participants by arm
| Arm | Count |
|---|---|
| Progesterone, Estrace oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr to achieve mean plasma concentrations over the range of 2-8 ng/ml for seven days
oral estrace, 0.5-1 mg once a day for seven days
Progesterone: oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days
Estrace (estrogen): oral estrace, 0.5-1 mg once a day for seven days | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Progesterone, Estrace |
|---|---|
| Age, Categorical <=18 years | 1 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment United States | 1 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1 |
| other Total, other adverse events | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
LH Pulse Frequency as a Function of Day 7 Progesterone
number of LH pulses per 11 hours on Day 7 of progesterone
Time frame: 7 days following oral estrace and progesterone administration
Population: Only one subject completed study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Progesterone, Estrace | LH Pulse Frequency as a Function of Day 7 Progesterone | 0 number of LH pulses/11hr |