SAT-029 AMH Is Higher Across the Menstrual Cycle in Early Post-Menarchal Girls Than in Ovulatory Women

Ovaries of young girls contain healthy and degenerating follicles from the primordial to antral stage, suggesting coordination of growth and atresia. At age 6 yrs, antral follicle (AF) number and size increase; by late puberty, AF count is higher than at any other life stage. The discovery of AMH, a biomarker of AFs, has facilitated the study of the immature ovary. AMH, a granulosa cell product of pre-antral and small AFs, inhibits primordial follicle growth and AF selection. As a marker of AF count, AMH should be highest during puberty, yet cross-sectional studies suggest that AMH peaks in the mid-20’s. In the current studies we compared AMH levels in early post-menarchal girls and regularly cycling adults. The rich phenotypic data available for this adolescent cohort (Sun 2019) was used to investigate further the relationship between AMH, LH, FSH, and sex steroids, and the propensity for anovulatory cycles (ANOV) in girls. 23 healthy girls (12.8–17.6 yrs;1.7±0.2 yrs post-menarche; 56% overweight/obese [OB]) underwent hormone measurements and pelvic ultrasounds during 2 consecutive menstrual cycles. Cycles were classified as ovulatory (OV) based on an LH and E2 peak and P4 >1.65 ng/mL (Sun 2019). AMH was measured in a random subset of samples (5x/subject) with the Ansh ultrasensitive ELISA. Maximum average ovarian volume (VOL) was calculated in the absence of a dominant follicle. Hormones were compared with data from 32 historic adult controls (18–34 yrs; 44% OB) with regular cycles (Lambert-Messerlian 2016). In adults, AMH was measured during the follicular and luteal phase of an OV (5x/subject) using the Ansh assay. AMH was compared among groups using a mixed model. AMH (in adults), LH (in both) and androgens (in girls) were natural log-transformed (ln) before analysis. 11 girls had 2 OV, 5 girls had 1 OV, and 5 girls had no OV; 2 could not be classified due to loss to follow-up. Girls had higher AMH than women (5.2 ± 0.3 vs. 3.3 ± 0.4 ng/mL; p<0.01) and girls with more OV tended to have lower AMH than those with ANOV (2 OV 4.5 ± 0.2, 1 OV 5.7 ± 1.1, 0 OV 6.8 ± 1.1 ng/mL; p=0.1). In girls, AMH correlated with ln_LH (r=0.4, p=0.02), ln_a’dione (r=0.4, p=0.04), ln_testosterone (r=0.5, p=0.02) and VOL (r=0.6, p=0.01) but not with FSH, E2, or BMI. In women, AMH correlated with E2 (r=-0.4, p=0.03) and not with ln_LH or BMI. Within-person variability in AMH was similar in girls and adults (CV 18%). During the early post-menarchal years, AMH levels exceed those of adults with OV, particularly among girls with ANOV, and correlate with LH and androgens. The finding of higher AMH in adolescents is consistent with previous studies demonstrating a peak in AF count during this stage of development. Investigation into how the normal ovary matures and is pruned of excess AFs, either by increased recruitment and growth or by atresia, may provide insights into the pathogenesis of PCOS, wherein follicles are arrested at the pre-antral and antral stage.