ESPE Abstracts

Background: Minipuberty is considered an essential period for early diagnosis of endocrine disorders and reproductive organ maturation. While the complex dynamics of female reproductive hormones during minipuberty was recently described, detailed evaluation of ovarian and uterine morphology in relation to circulating levels of reproductive hormones remains to be elucidated.

Aim: Report normative values of ovarian and uterine morphology using transabdominal ultrasound (TAUS) and evaluate on the association to reproductive hormones at minipuberty.

Methods: The present study is a secondary analysis from The Copenhagen Analgesic Study (COPANA) (ClinicalTrials.gov NCT04369222) primarily designed to evaluate if prenatal exposure to paracetamol is associated with ovarian function and uterine morphology. Healthy, singleton pregnant women, enrolled during the first trimester of pregnancy (n = 685), 589 (302 girls) infants completed follow-up. Girls examined (age 3.4 months (0.4) mean (±SD)) including breast tissue palpation and measurement of diameter with a ruler (mm), n = 300. TAUS by a single examiner: ovarian volume n = 189, number of follicles (two groups: 2-4mm and ≥ 5mm), n = 192, uterine volume (n = 204) and endometrial thickness, n = 247. Blood samples (n = 269/302=89%) for analyzes of reproductive hormones were drawn (AMH, FSH, LH, Inhibin B (immunoassays), E2, Androstenedione (LC/MS-MS)). Statistics: Pearson correlation coefficient (parametric data), Spearman’s rho (non-parametric data).

Results: Ovarian and uterine volume were 0.29cm3 (0.17-0.48) (median (IQR)) and 1.23cm3 (9.72-1.53), respectively. Follicle count total: 2 (1-6), 2-4mm: 1 (0-3.5), >5mm: 1 (0-5) (median (min-max)). Total follicle count correlated positively with ovarian volume, serum AMH concentrations, Inhibin B and E2: r = 0.606, P <0.001; r =0.347, P <0.001; r =0.283, P <0.001, and r =0.160, P = 0.032, respectively, and negatively with serum FSH concentrations; r =-0.327, P <0.001. Subgrouping the follicles in small and larger follicle sizes, serum AMH concentrations correlated positively with number of small follicles (2-4mm) as well as larger follicles (≥ 5mm): r =0.163, P = 0.031 and r =0.331, P <0.001. Number of follicles ≥ 5mm correlated negatively with FSH: r =-0.298, P <0.001 and positively with Inhibin B, E2 and Androstenedione: r =0.254, P <0.001; r =0.242, P <0.001, and r =0.204, P = 0.007 respectively. Uterine volume, endometrial thickness and breast tissue diameter correlated positively with serum E2 concentrations; r =0.148, P = 0.045; r =0.170, P = 0.012; r =0.202, P = 0.002, respectively.

Conclusion: The study confirms the early activation of the HPG axis during female minipuberty. Similarly to adult women, small antral follicles contribute to circulating AMH levels in infancy, while circulating inhibin B, E2 and Androstenedione concentrations are primarily associated with the number of large follicles. E2 concentrations were associated with the size of target organs: uterus, endometrium, and breast tissue.