Reproductive Axis Maturation in the Early Post-Menarchal Years

NCT ID: NCT03986021

Last Updated: 2025-11-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

400 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-12-19

Study Completion Date

2029-07-01

Brief Summary

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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. We are also looking at girls who may have a condition called PCOS. 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 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

Girls at risk for PCOS age 8-14 who have a mom or sister with PCOS

Girls with irregular menstrual cycles age 11-17.5

To compare with the girls, we are looking at women \>=18-34 years old with PCOS,

Healthy women \>= 18-34 years old without PCOS,

and Mothers of pediatric participants age 18-65

Design:

Both parents or guardians 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. They have the option to provide DNA samples.

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. There are additional parts that participants may choose to be involved in depending on how involved they want to be.

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

Adults: Women with known PCOS will complete the same Screening Visit as the girls and will collect dried urine specimens at home for 8 weeks;

The Healthy control women group will complete the same Screening Visit as the girls and collect dried urine specimens at home for 2 menstrual cycles;

The Mothers of pediatric participants group will complete a Screening Visit (informed consent, urine pregnancy test) and collect vaginal swab specimens at home for 2 menstrual cycles (approx. 8 weeks)....

Detailed Description

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The broad goal of these studies is to determine the physiologic and pathophysiologic underpinnings of irregular menstrual cycles among adolescents in general and those with increased genetic risk for polycystic ovarian syndrome (PCOS) in the early postmenarchal

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. Importantly, irregular menstrual cycles during the teenage years may be a harbinger of future health risks extending beyond the reproductive system; among the nearly 80,000 female participants the Nurses' Health Study II, those with irregular and long cycles during adolescence and adulthood had a greater risk of premature mortality, particularly related to cardiovascular disease. 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.

Conditions

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Reproductive Physiological Processes Pediatrics Adolescent Health Adolescent Development

Keywords

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Menarche Adolescent Physiology Hormones Natural History

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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At-risk girls

Girls with first degree relative diagnosed with Polycystic Ovary Syndrome (PCOS) age 8-\<15

No interventions assigned to this group

early post-menarche girls

Healthy, early post-menarchal girls age 8-\<15

No interventions assigned to this group

Healthy control women

Women age \>18-34 without PCOS at least 3-years post-menarchal with regular menstrual cycles every 21-35 days

No interventions assigned to this group

late post-menarche girls

Late post-menarchal girls age 11-\<17.5 (gynecological age 2-5)

No interventions assigned to this group

Mothers of pediatric study participants

Mothers age 18-65 whose daughter has provided at least one vaginal swab sample for the First Period study.

No interventions assigned to this group

pre-menarche girls

Healthy, pre-menarchal girls age 8-\<14.5

No interventions assigned to this group

Women with PCOS

Women diagnosed with PCOS \>18-34 at least 3-years post-menarchal with irregular menstrual cycles

No interventions assigned to this group

Eligibility Criteria

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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


* 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 \< 6 months post-menarchal (will typically have completed 4 or fewer menstrual cycles)
* Biochemical criteria: normal thyroid hormone, prolactin, and testosterone levels


* 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
* Within 1 year of menarche
* Biochemical criteria: normal thyroid hormone, prolactin, and testosterone levels


* Age 11-17.5 years old
* Approximately 2-5 years post-menarchal
* Biochemical criteria: normal thyroid hormone and prolactin


* 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


* Age \>=18-34 years old
* at least 3-years post-menarchal with regular menstrual cycles every 21-35 days


* Age \>=18-65 years old
* Biological mother of A Girl's First Period participant

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, 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:


* 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, 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 18 ml of blood during any given interval.
* Pregnancy

Part 3 - Intensive monitoring of ovarian follicle growth


* 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, 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 18 ml of blood during any given interval.
* Pregnancy

Part 4 - Late Post-menarche cycle tracking:


* 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, inflammatory bowel 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 participate by providing dried blood spots, or no more than 18 ml of blood during any given interval.
* Pregnancy

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


Women with known PCOS (activities for 8 weeks only)


* 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, inflammatory bowel disease, juvenile rheumatoid arthritis, and lupus.
* Pregnancy

Healthy control women (Activities x 2 menstrual cycles)


* 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, inflammatory bowel disease, juvenile rheumatoid arthritis, and lupus.
* PCOS diagnosis or first-degree relative with disorder
* Pregnancy

Mothers of pediatric participants (Activities for 8 weeks / 2 menstrual cycles)


* 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.
* Pregnancy
Minimum Eligible Age

8 Years

Maximum Eligible Age

65 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute of Environmental Health Sciences (NIEHS)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Natalie D Shaw, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Institute of Environmental Health Sciences (NIEHS)

Locations

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NIEHS Clinical Research Unit (CRU)

Research Triangle Park, North Carolina, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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NIEHS Join A Study Recruitment Group

Role: CONTACT

Phone: (855) 696-4347

Email: [email protected]

Natalie D Shaw, M.D.

Role: CONTACT

Phone: (984) 287-3716

Email: [email protected]

Facility Contacts

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NIEHS Join A Study Recruitment Group

Role: primary

Related Links

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Other Identifiers

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19-E-0110

Identifier Type: -

Identifier Source: secondary_id

190110

Identifier Type: -

Identifier Source: org_study_id