Reproductive Axis Maturation in the Early Post-Menarchal Years
Reproductive Axis Maturation in the Early Post-Menarchal Years
Background:

 Most adult women with irregular periods of unknown cause report symptoms dating back to early
 adolescence. This study aims to learn how girls periods change in the 2 years after their
 first period. This will help researchers learn what healthy puberty looks like and how they
 can spot signs of hormone problems early on.

 Objective:

 To learn how long it takes girls to develop regular menstrual cycles after their first
 period.

 Eligibility:

 Healthy girls ages 8-14.5 who either (1) haven t had their first period but show signs of
 puberty, such as breast development and hair in the genital area; or (2) had their first
 period in the past 6 months

 Design:

 A parent or guardian must allow their daughter to participate. They must attend all study
 visits with her.

 Participants will first be screened by phone. Those who qualify will be screened in person.
 They will have a physical exam. They will give blood and urine samples. They will have an
 ultrasound of their abdomen. They will fill out questionnaires. They will sit in a BOD POD
 for 6 minutes: This is an egg-shaped machine that takes body measurements.

 Participants will have sets of visits at home or at the clinic about every 6 months. The
 number of visits in each set will depend on their menstrual cycle. Then they will have a
 final visit. Visits will include repeats of the screening tests.

 At home, participants will collect their urine daily to measure hormones. They will keep a
 diary of their periods.

 The study will last about 2 years.
The broad goal of these studies is to determine the physiologic and pathophysiologic
 underpinnings of irregular menstrual cycles among adolescents in the early post-menarchal
 period. Irregular menstruation affects > 2.5 million reproductive-age women in the US each
 year1. Most adult women with oligomenorrhea of unknown etiology reporting symptoms dating
 back to early adolescence. While a period of cycle irregularity is well-described in the
 first few years after menarche, a lack of understanding of the basic mechanisms of normal
 reproductive axis development in the post-menarchal female has hampered our ability to
 distinguish abnormal from normal developmental trajectories. Moreover, the commonly held
 belief that menstrual irregularity among teenage girls is normal has also delayed detection
 of pathology in reproductive development, precluding institution of early preventative
 strategies to curtail future reproductive morbidity.
-  Part 1-Pre-menarche monitoring (holding pattern):

 INCLUSION CRITERIA:

 -  Age 8-14.5 years old

 -  Healthy weight, defined as having a body weight >85% of expected (EBW) and a body mass
 index (BMI) <99th percentile

 -  Some breast development

 -  Pre-menarche

 EXCLUSION CRITERIA:

 -  Taking or planning to take medications that affect reproductive hormones in the next 2
 to 3 years (e.g. birth control pills).

 -  Planning to move more than 60 miles from the CRU within the next 2 years

 -  Chronic medical condition, including but not limited to diabetes mellitus, congenital
 adrenal hyperplasia, cystic fibrosis, sickle cell disease, inflammatory bowel disease,
 juvenile rheumatoid arthritis, and lupus.

 -  First-degree relative with polycystic ovarian syndrome, premature ovarian
 insufficiency, hypogonadotropic hypogonadism, or other pubertal development disorder

 -  Excessive exercise (defined as running >20 miles per week or its equivalent)

 -  Pregnancy

 Part 2 - Post-menarche cycle tracking:

 INCLUSION CRITERIA:

 -  Age at menarche 10-14.5 years old

 -  Healthy weight, defined as having a body weight >85% of expected (EBW) and a body mass
 index (BMI) <99th percentile

 -  Approximately less than or equal to 6 months post-menarchal (will typically have
 completed 4 or fewer menstrual cycles)

 Biochemical criteria: normal thyroid hormone, prolactin, and testosterone levels

 EXCLUSION CRITERIA:

 -  Taking or planning to take medications that affect reproductive hormones in the next 2
 to 3 years (e.g. birth control pills).

 -  Planning to move more than 60 miles from the CRU within the next 2 years

 -  Chronic medical condition, including but not limited to diabetes mellitus, congenital
 adrenal hyperplasia, cystic fibrosis, sickle cell disease, inflammatory bowel disease,
 juvenile rheumatoid arthritis, and lupus.

 -  First-degree relative with polycystic ovarian syndrome, premature ovarian
 insufficiency, hypogonadotropic hypogonadism, or other pubertal development disorder

 -  Excessive exercise (defined as running >20 miles per week or its equivalent)

 -  Anemia (defined as hemoglobin <12.0 g/dl)

 --Participants with hemoglobin between 11.5 g/dl and 12.0 g/dl may still participate
 by providing dried blood spots, or no more than 18ml of blood during any given
 interval.

 -  Pregnancy

 In some cases, particularly in those participants with short menstrual cycle lengths, the
 participant may have her first cycle monitoring visit before the results from all the
 laboratory tests from the screening visit are available. Some of these tests take > 5-7
 days to complete. The tests are necessary for eligibility but are not related to
 participant safety. If the results are abnormal, the participant will be withdrawn from the
 study at that time.

 If a potential participant meets all eligibility criteria for Part 1 during the initial
 phone screening, she and at least one parent or guardian will verbally assent and consent,
 respectively, to receive regular communications from the study team (i.e. monthly phone
 calls, emails, and text messages. The purpose of these communications is follow-up with the
 participant to determine when she can enroll in Part 2 of the study. She will not
 participate in any clinical study procedures in Part 2 as detailed below until she has her
 first period, at which time she and/or her parent or guardian will notify the study team.
 This will allow study staff to enroll girls at the desired (young) gynecological age and
 allow initial study visits to be scheduled in alignment with the girls' menstrual cycles.