LBMON237 Predictors Of Postmenarchal Progression Of Pcos Phenotypes In At-risk Girls

Physiologic and genetic analyses implicate hyperandrogenemia (HA) as a core causal pathway in PCOS. Both daughters of women with PCOS (PCOS-d) and overweight/obese girls (OW-g) have HA beginning in childhood suggesting that they are at increased risk for PCOS. Accordingly, we performed a prospective study of girls in the early postmenarchal transition until the diagnosis of PCOS can be established according to clinical guidelines at 2 or more yrs after menarche. | PCOS-d, OW-g and lean control girls (LC), ages 11-16 yrs at baseline, were studied within 0.2-1.2 yrs of menarche and returned after 1-3 years. Two PCOS-d, 2 OW-g, and 4 LC could not be assessed at follow up because they were taking hormonal contraception, which was most often prescribed for irregular menses. Baseline and follow up sample sizes were: PCOS-d 16, 12; OW-g 13, 9; LC 18, 14. A fasting morning blood sample was obtained. | Age was similar but BMI differed by design. The change in BMI from baseline to follow up did not differ between the groups. At baseline, DHEAS levels were increased (P=0. 009) and SHBG levels decreased (P<0. 001) in PCOS-d and OW-g. In contrast, LH levels were higher only in PCOS-d (P=0. 03), whereas insulin levels were increased only in OW-g (P=0. 01). At baseline, the prevalence of HA (T, fT or DHEAS > LC mean + 1 SD) was increased (χ2 P=0. 04) in PCOS-d (69%) compared to OW-g (62%) and LC (28%). The prevalence of ovulatory dysfunction (OD, menses >45 d or <21 d) was also increased (χ2 P=0. 04) in PCOS-d (63%) compared with OW-g (15%) and LC (18%). All PCOS-d and 75% OW-g and LC had persistent HA at follow-up. Thirty-eight percent of PCOS-d had persistent OD, while 1 of 2 LC had persistent OD. Neither OW-g with OD at baseline returned for follow up. Two PCOS-d, 2 OW-g and 1 LC fulfilled PCOS criteria at follow up. One of these PCOS-d also had HA and OD at baseline, one OW-g developed both HA and OD. A model that included BMI, SHBG, fasting insulin and LH levels at baseline predicted PCOS diagnosis after 2-yrs of follow up with a Receiver-Operator-Curve area-under-the-curve of 0.98. | There was an increased prevalence of HA in PCOS-d and OW-g early postmenarche that persisted after 2-yrs postmenarche. PCOS-d also had an increased prevalence of OD early postmenarche, which aligns with their increased LH levels at baseline. These findings suggest neuroendocrine dysfunction in PCOS-d, which appears to improve with pubertal maturation, since in the majority of PCOS-d, OD resolved. In contrast, OW-g were hyperinsulinemic. There were no significant differences in the prevalence of PCOS at follow up, although there may have been bias because of preferential exclusion of girls with OD due to hormonal contraception. A model of biomarkers in early postmenarchal girls, that included both reproductive and metabolic parameters, was highly predictive of PCOS diagnosis at follow up. Girls with HA should still be considered at risk for PCOS and require ongoing monitoring. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.