Study Background

The broad goal of this study is to determine the cause of irregular menstrual cycles in teenage girls. We will examine reproductive hormones and will also look at the potential role of lifestyle and environmental factors (for example, insulin resistance, body composition, microbiome, sleep schedules, physical activity).

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.

The aim of this cohort is to obtain a better understanding of normal hormonal dynamics during the transition from menarche to the establishment of mature ovulatory cycles – a prerequisite for fertility. This will permit the more precise differentiation of girls with anovulatory cycles who will go on to establish regular cycles from those who may be at high-risk for long term oligomenorrhea and infertility. The interval from menarche to regular ovulatory cycles also deserves particular attention as it represents a time of unopposed estrogen exposure (i.e., estrogen [E] without P), an established risk factor for endometrial cancer, even among adolescents, and a potential risk factor for breast cancer.

We therefore propose the following objectives: To determine the normal reproductive axis developmental trajectory from menarche to regular ovulatory cycles (defined as at least two ovulatory cycles during the first two post-menarchal years) in a contemporary cohort of adolescent girls. 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).