Reproductive Axis Maturation in the Early Post-Menarchal Years

• 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 bodymass 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, biotin supplements).

• Planning to move more than 60 miles from the CRU within the next 2 to 3 years

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

• First-degree relative with polycystic ovarian syndrome, premature ovarianinsufficiency, 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 bodymass index (BMI) <99th percentile

• Approximately < 6 months post-menarchal (will typically have completed 4 or fewermenstrual 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, biotin supplements).

• Planning to move more than 60 miles from the CRU within the next 2 to 3 years

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

• First-degree relative with polycystic ovarian syndrome, premature ovarianinsufficiency, 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 participateby providing dried blood spots, or no more than 18 ml of blood during any giveninterval.

• Pregnancy

Part 3 - Intensive monitoring of ovarian follicle growth

Inclusion Criteria:

• Age at menarche 10-14.5 years old

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

• Within 1 year of menarche

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

Exclusion Criteria:

• Taking or planning to take medications that affect reproductive hormones in the next 1-2 years (e.g. birth control pills, biotin supplements).

• Planning to move more than 60 miles from the CRU within the next year

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

• First-degree relative with polycystic ovarian syndrome, premature ovarianinsufficiency, 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 participateby providing dried blood spots, or no more than 18 ml of blood during any giveninterval.

• Pregnancy

Part 4 - Late Post-menarche cycle tracking:

Inclusion Criteria:

• Age 11-17.5 years old

• Approximately 2-5 years post-menarchal

• Biochemical criteria: normal thyroid hormone and prolactin

Exclusion Criteria:

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

• Planning to move more than 60 miles from the CRU within the next 6 months

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

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

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

• Pregnancy

Adolescent girls, at-risk daughters, or sisters of women with PCOS

The girls with mothers or sisters with PCOS group will complete the Screening Visit and Parts 1-3. The same inclusion and exclusion criteria apply for Parts 1, 2, and 3 as stated above except that these individuals must have a first-degree relative with PCOS and they can have high androgen levels, excess body hair, and severe acne at screening.

Women with known PCOS (activities for 8 weeks only)

Inclusion Criteria:

• Age >=18-34 years old

• PCOS diagnosis

• at least 3-years post-menarchal with irregular menstrual cycles

• Biochemical (blood) or clinical signs of high androgen levels

Exclusion Criteria:

• Cannot be taking any medications that affect reproductive or metabolic hormones (e.g. birth control pill, biotin supplements, spironolactone, metformin).

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

• Pregnancy

Healthy control women (Activities x 2 menstrual cycles)

Inclusion Criteria:

• Age >=18-34 years old

• at least 3-years post-menarchal with regular menstrual cycles every 21-35 days

Exclusion Criteria:

• Cannot be taking any medications that affect reproductive or metabolic hormones (e.g. birth control pill, biotin supplements, spironolactone, metformin).

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

• PCOS diagnosis or first-degree relative with disorder

• Pregnancy