Abstract Disclosure: M. Sofia: None. R. Modarelli: None. S. Molsberry: None. S. Denslow: None. D. Zaccaro: None. C. Kamoun: None. N.D. Shaw: None. Background: Primary dysmenorrhea (PD), or menstrual pain of uterine origin without pelvic pathology, affects up to 93% of adolescents and is a leading cause of school and work absenteeism. The theory that PD only occurs when progesterone levels fall in the late-luteal phase, triggering production of uterine prostaglandins, has dominated the literature. However, recent studies identifying PD among girls with anovulatory cycles cast doubt on this theory. We took advantage of an ongoing longitudinal study of healthy early post-menarchal girls to test the hypothesis that ovulation is associated with increased PD and to explore other participant factors associated with PD. Methods: Participants contributed daily urine samples to measure Cr-corrected LH, estrone conjugates, and pregnanediol-3-glucuronide [PdG], completed menstrual diaries, and reported dysmenorrhea symptoms using the 24-item Menstrual Symptom Questionnaire (MSQ) approximately biannually. A cycle was defined as ovulatory if peak PdG >2500 ng/mg Cr. Scores were natural log-transformed and modeled to assess associations with gynecologic age, ovulation, anxiety, depression, and physical activity exposures using generalized estimating equations with a normal distribution and autoregressive covariance structure. Models were adjusted for age at menarche, baseline BMI Z-score, race, ethnicity, maternal age at menarche, parental education and employment, and gynecologic age (ovulation models only). Results: The 43 participants were 12.38 ± 1.06 years old (mean ± SD) with a gynecologic age of 2.99 ± 2.22 months. The majority were non-Hispanic White and of normal weight. Average maternal age at menarche was 12.64 ± 1.09 years. Among parents of participants, most were both at least college-educated and nearly 50% were both employed. Participants completed 155 MSQs (1-9/participant). Dysmenorrhea scores increased over time (scores 1.14x higher for every 1-year increase in gynecologic age, p<0.001). Dysmenorrhea scores were 1.12x higher (p=0.03) if the preceding cycle was ovulatory vs. anovulatory and 1.11x higher if all cycles in the preceding 6 months were ovulatory vs all anovulatory (p=0.11). Gynecologic age remained significant in models with ovulation-based exposures, and maternal age at menarche was inversely associated with dysmenorrhea score (beta -0.08, p=0.04) in the model with gynecologic age as the exposure. Conclusion: In early-postmenarchal girls, dysmenorrhea scores were higher when associated with ovulatory cycles but also increased over time independent of ovulatory status, suggesting a pathophysiologic role for progesterone and other unknown factors. There was no association between age at menarche, BMI, race/ethnicity, and dysmenorrhea scores whereas maternal age at menarche was inversely associated with dysmenorrhea scores. Presentation: 6/1/2024
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