Understanding menstrual cycle development in girls after their first period

Reproductive Axis Maturation in the Early Post-Menarchal Years: A Pilot Study

This study looks at how girls aged 8-14 experience changes in their menstrual cycles in the two years after their first period to help understand normal puberty and identify early signs of hormonal problems.

Quick facts

• Study type: Observational
• Enrollment: 400 (estimated)
• Ages: 8 Years to 65 Years
• Sex: Female
• Sponsor: National Institutes of Health Clinical Center (CC) (nih)
• Locations: 1 site (Research Triangle Park, North Carolina)
• Trial ID: NCT03986021 on ClinicalTrials.gov

What this trial studies

This observational study aims to investigate how girls' menstrual cycles evolve in the two years following their first period. It focuses on healthy girls aged 8-14 who are either pre-menarche or have recently started menstruating, as well as those at risk for polycystic ovarian syndrome (PCOS). The study will monitor physiological changes and menstrual regularity to better understand normal puberty and identify early signs of hormonal issues. By comparing these girls with women aged 18-34 with and without PCOS, researchers hope to uncover critical insights into reproductive health.

Who should consider this trial

Good fit: Ideal candidates include healthy girls aged 8-14 who are either showing signs of puberty or have recently started their menstrual cycles.

Not a fit: Patients who are outside the age range or have chronic medical conditions affecting reproductive hormones may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to earlier detection and intervention for hormonal issues in adolescent girls, potentially improving long-term reproductive health.

How similar studies have performed: While studies on menstrual cycle irregularities exist, this specific focus on early post-menarcheal development and its implications for future health is relatively novel.

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, 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:

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 \< 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, 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

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
* 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, 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:

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, 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)

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, inflammatory bowel 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, 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)

Inclusion Criteria:

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

Exclusion Criteria:

* 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

Where this trial is running

Research Triangle Park, North Carolina

• NIEHS Clinical Research Unit (CRU) — Research Triangle Park, North Carolina, United States (RECRUITING)

Study contacts

• Principal investigator: Natalie D Shaw, M.D. — National Institute of Environmental Health Sciences (NIEHS)
• Study coordinator: NIEHS Join A Study Recruitment Group

Conditions: Reproductive Physiological Processes, Pediatrics, Adolescent Health, Adolescent Development, Menarche, Adolescent, Physiology, Hormones