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出境医 / 临床实验 / Reproductive Axis Maturation in the Early Post-Menarchal Years

Reproductive Axis Maturation in the Early Post-Menarchal Years

Study Description
Brief 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. 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.


Condition or disease
Reproductive Physiological Processes Pediatrics Adolescent Health Adolescent Developement

Detailed Description:
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.
Study Design
Layout table for study information
Study Type : Observational
Estimated Enrollment : 75 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Reproductive Axis Maturation in the Early Post-Menarchal Years: A Pilot Study
Actual Study Start Date : December 19, 2019
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2022
Arms and Interventions
Group/Cohort
Post-menarche girls
Healthy, early post-menarchal girls age 10-14
Outcome Measures
Primary Outcome Measures :
  1. To determine the time from menarche to regular ovulatory cycles, defined as two consecutive ovulatory cycles with normal (10-14 day) luteal phase length. [ 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).


Eligibility Criteria
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Ages Eligible for Study:   8 Years to 15 Years   (Child)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Healthy early post-menarchal girls age 8 less than or equal to 15 years.
Criteria
  • 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.

Contacts and Locations

Contacts
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Contact: NIEHS Join A Study Recruitment Group (855) 696-4347 myniehs@nih.gov

Locations
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United States, North Carolina
NIEHS Clinical Research Unit (CRU) Recruiting
Research Triangle Park, North Carolina, United States, 27709
Contact: NIEHS Join A Study Recruitment Group    855-696-4347    myniehs@nih.gov   
Sponsors and Collaborators
National Institute of Environmental Health Sciences (NIEHS)
Investigators
Layout table for investigator information
Principal Investigator: Natalie D Shaw, M.D. National Institute of Environmental Health Sciences (NIEHS)
Tracking Information
First Submitted Date June 13, 2019
First Posted Date June 14, 2019
Last Update Posted Date April 20, 2021
Actual Study Start Date December 19, 2019
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: June 13, 2019)
To determine the time from menarche to regular ovulatory cycles, defined as two consecutive ovulatory cycles with normal (10-14 day) luteal phase length. [ 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).
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Reproductive Axis Maturation in the Early Post-Menarchal Years
Official Title Reproductive Axis Maturation in the Early Post-Menarchal Years: A Pilot Study
Brief 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. 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.

Detailed Description 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.
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population Healthy early post-menarchal girls age 8 less than or equal to 15 years.
Condition
  • Reproductive Physiological Processes
  • Pediatrics
  • Adolescent Health
  • Adolescent Developement
Intervention Not Provided
Study Groups/Cohorts Post-menarche girls
Healthy, early post-menarchal girls age 10-14
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: June 13, 2019)
75
Original Estimated Enrollment Same as current
Estimated Study Completion Date December 31, 2022
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria
  • 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.

Sex/Gender
Sexes Eligible for Study: Female
Ages 8 Years to 15 Years   (Child)
Accepts Healthy Volunteers Yes
Contacts
Contact: NIEHS Join A Study Recruitment Group (855) 696-4347 myniehs@nih.gov
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT03986021
Other Study ID Numbers 190110
19-E-0110
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( National Institute of Environmental Health Sciences (NIEHS) )
Study Sponsor National Institute of Environmental Health Sciences (NIEHS)
Collaborators Not Provided
Investigators
Principal Investigator: Natalie D Shaw, M.D. National Institute of Environmental Health Sciences (NIEHS)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date April 16, 2021