Reproductive Physiological ProcessesNCT03986021
Reproductive Axis Maturation in the Early Post-Menarchal Years
An observational study of Reproductive Physiological Processes and Pediatrics, run by National Institute of Environmental Health Sciences (NIEHS) at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 8 to 65 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Reproductive Physiological Processes, Pediatrics, Adolescent Health
- How many people
- 400 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Dec 2019to 1 Jul 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 65 years
- Women only
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Healthy early post-menarchal girls age 8-<15 years; PCOS women and girls with first degree relatives with PCOS; Healthy women 18-34 years; Late post-menarchal girls age 11-<17.5; healthy pre-menarchal girls age 8-<14.5; mothers of pediatric participants age 18-65
Who may be able to join
- 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
Show all 23Show fewer
- 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
Who cannot join
- 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
Show all 45Show fewer
- 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
- 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)
- 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 for 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
NIEHS Clinical Research Unit (CRU)
Research Triangle Park, North Carolina, 27709
NIEHS Join A Study Recruitment Group, 855-696-4347, myniehs@nih.gov
About this study
Official title: Reproductive Axis Maturation in the Early Post-Menarchal Years: A Pilot Study
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.
Read more
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).
Read the detailed description
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
- Reproductive Physiological Processes, Pediatrics, Adolescent Health, Adolescent Development
- Keywords
- Menarche, Adolescent, Physiology, Hormones, Natural History
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| At-risk girls | Girls with first degree relative diagnosed with Polycystic Ovary Syndrome (PCOS) age 8-<15 | |
| early post-menarche girls | Healthy, early post-menarchal girls age 8-<15 | |
| Healthy control women | Women age >18-34 without PCOS at least 3-years post-menarchal with regular menstrual cycles every 21-35 days | |
| late post-menarche girls | Late post-menarchal girls age 11-<17.5 (gynecological age 2-5) | |
| Mothers of pediatric study participants | Mothers age 18-65 whose daughter has provided at least one vaginal swab sample for the First Period study. | |
| pre-menarche girls | Healthy, pre-menarchal girls age 8-<14.5 | |
| Women with PCOS | Women diagnosed with PCOS >18-34 at least 3-years post-menarchal with irregular menstrual cycles |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the time from menarche to regular ovulatory cycles, defined as two consecutive ovulatory cycles in girls of variable genetic risk for PCOS
We hypothesize that the temporal sequence of reproductive maturation will consist of anovulatory cycles (representing a time of unopposed estrogen exposure), ovulatory cycles with a short luteal phase (estrogen with low progesterone exposure), and finally, ovulatory cycles with a normal luteal phase length (estrogen action fully counterbalanced by progesterone action)
Measured: Defined as two consecutive ovulatory cycles with normal (10-14 day) luteal phase length during the first two post-menarchal years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2019
- Study start19 Dec 2019
- Primary completion1 Jul 2029 (estimated)
- Study completion1 Jul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Reproductive Physiological ProcessesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Institute of Environmental Health Sciences (NIEHS)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Natalie D Shaw, M.D., Principal investigator, National Institute of Environmental Health Sciences (NIEHS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03986021
- Sponsor's protocol ID
- 190110
- Other IDs
- 19-E-0110
- Status last verified
- 3 Nov 2026
- First submitted
- 13 Jun 2019
- Last updated
- 5 Nov 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: It is not yet known if there will be a plan to make IPD available
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reproductive Axis Maturation in the Early Post-Menarchal Years: A Pilot Study
- ClinicalTrials.gov ID
- NCT03986021
- Acronym / sponsor ID
- 190110
- Conditions
- Reproductive Physiological Processes, Pediatrics, Adolescent Health, Adolescent Development
- Keywords
- Menarche, Adolescent, Physiology, Hormones, Natural History
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- National Institute of Environmental Health Sciences (NIEHS)US National Institutes of Health
- Study start
- 19 Dec 2019 (actual)
- Primary completion
- 1 Jul 2029 (estimated)
- Study completion
- 1 Jul 2029 (estimated)
- First posted
- 14 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| At-risk girls | – | –Girls with first degree relative diagnosed with Polycystic Ovary Syndrome (PCOS) age 8-<15 |
| early post-menarche girls | – | –Healthy, early post-menarchal girls age 8-<15 |
| Healthy control women | – | –Women age >18-34 without PCOS at least 3-years post-menarchal with regular menstrual cycles every 21-35 days |
| late post-menarche girls | – | –Late post-menarchal girls age 11-<17.5 (gynecological age 2-5) |
| Mothers of pediatric study participants | – | –Mothers age 18-65 whose daughter has provided at least one vaginal swab sample for the First Period study. |
| pre-menarche girls | – | –Healthy, pre-menarchal girls age 8-<14.5 |
| Women with PCOS | – | –Women diagnosed with PCOS >18-34 at least 3-years post-menarchal with irregular menstrual cycles |
Who may qualify
- Ages
- 8 to 65 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Healthy early post-menarchal girls age 8-<15 years; PCOS women and girls with first degree relatives with PCOS; Healthy women 18-34 years; Late post-menarchal girls age 11-<17.5; healthy pre-menarchal girls age 8-<14.5; mothers of pediatric participants age 18-65
Key inclusion criteria (23 listed)
- 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
Key exclusion criteria (45 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
To determine the time from menarche to regular ovulatory cycles, defined as two consecutive ovulatory cycles in girls of variable genetic risk for PCOS
Time frame: Defined as two consecutive ovulatory cycles with normal (10-14 day) luteal phase length during the first two post-menarchal years
We hypothesize that the temporal sequence of reproductive maturation will consist of anovulatory cycles (representing a time of unopposed estrogen exposure), ovulatory cycles with a short luteal phase (estrogen with low progesterone exposure), and finally, ovulatory cycles with a normal luteal phase length (estrogen action fully counterbalanced by progesterone action)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. It is not yet known if there will be a plan to make IPD available
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Natalie D Shaw, M.D. principal investigator
National Institute of Environmental Health Sciences (NIEHS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Reproductive Physiological Processes and Pediatrics, run by National Institute of Environmental Health Sciences (NIEHS) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 45 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact NIEHS Join A Study Recruitment Group ((855) 696-4347, myniehs@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the time from menarche to regular ovulatory cycles, defined as two consecutive ovulatory cycles in girls of variable genetic risk for PCOS (time frame: Defined as two consecutive ovulatory cycles with normal (10-14 day) luteal phase length during the first two post-menarchal years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.