Establishment of regular menstrual cycles is a key component of reproductive maturation and a recognized vital sign for health and well-being. Irregular menstrual cycles are especially common for the first 2-3 years after an adolescent's first menstrual period (i.e., menarche), which delays the identification and diagnosis of early reproductive disturbances such as polycystic ovary syndrome (PCOS). The purpose of this research study is to determine whether the ovary can serve as a reliable predictor of normal or abnormal development by following the trajectory of ovarian morphology in conjunction with menstrual cyclicity using 3D transabdominal ultrasound imaging in a prospective cohort study of adolescents. A secondary objective is to identify potential environmental factors such as diet and the gut microbiome which influence the trajectory towards normal or abnormal reproductive development.

Establishment of regular menstrual cycles is a key component of reproductive maturation and a recognized vital sign for health and well-being. Irregular menstrual cycles are especially common for the first 2-3 years after an adolescent's first menstrual period (i.e., menarche), which delays the identification and diagnosis of early reproductive perturbations and subsequent future disease risk. Therefore, the objectives of this study are to determine whether there are distinct aspects of ovarian morphology that predict the likelihood of regular menses or cycle irregularity at 2y post-menarche and to determine whether diet or lifestyle (such as quality of sleep) contribute to changes in the ovaries and period patterns.

A group of up to 60 adolescents will be enrolled into a prospective longitudinal cohort study. Participants will attend four study visits to their location's respective clinical research center. Study visits will occur at four distinct time points post-menarche: 6-10 months, 11-13 months, 17-19 months, and 23-25 months.

Prior to each of the study visits, participants will undergo one planned 24-hr dietary recall by a member of the research team and self-collect a stool sample.* Participants will be asked to fast the night before the study visit. At each study visit, participants will undergo the following assessments:

A 3D transabdominal ultrasound of the ovaries and uterus.

A fasting blood sample, obtained via venipuncture.

A series of anthropometric assessments, including: height, weight, waist and hip circumference, blood pressure, heart rate, and body fat percentage obtained using a bioimpedance scale.

Tanner stage assessment, using a standardized self-report scoring scheme and by a trained member of the research team who is blinded to the results of the self-reported tanner stage.

Acne scoring, using a standardized scoring scheme by a member of the research team.

Hirsutism assessment, obtained by visually inspecting nine pre-defined regions of the body for terminal hair growth using a standardized scoring scheme by a trained member of the research team.

Urine sample, self-collected by the participant after the transabdominal ultrasound.*

24-hour dietary recall.*

Physical activity questionnaire.*

Two sleep questionnaires, including questions about sleep hygiene, sleep quality, and circadian rhythms.*

In between study visits, participants will maintain menstrual cycle diaries and medication diaries.

*Participants at the University of Rochester site will not complete the urine or stool collection, the dietary recalls, or any of the physical activity and sleep questionnaires.

Inclusion Criteria:

• Female adolescents aged 9 to 17 years
• Menarche within 11 months of the enrollment visit
• University of Rochester site only: Family history of PCOS (i.e., mother or aunt)

Exclusion Criteria:

• Current or recent use of medications or supplements known or suspected to interfere with reproductive or metabolic function in the past 2 months (e.g., contraceptives, metformin, steroids, anti-seizure medications)
• Untreated and/or unstable medical or mental health condition known or suspected to interfere with reproductive or metabolic function
• Currently pregnant or breast feeding
• History of ovarian surgery
• Presence of significant acute or chronic illness which may interfere with study participation

Eligibility is limited to biologically female individuals because the primary study endpoints include the ovary and menstrual cycle.

Female adolescents between the ages of 9 and 17 years who achieved menarche (i.e., very first period) within the past 11 months will be recruited.