ESPE Abstracts (2019) 92 P1-399

Pubertal Events, Reproductive and Growth Hormones and Predictive Factors in Healthy Girls with Transient Thelarche.

Julio Soto 1, Ana Pereira2, Alexander Busch3,4, Kristian Almstrup3,4, Camila Corvalan2, Anders Juul3,4, Veronica Mericq1


1Institute of maternal and Child Health,faculty of medicine, University of Chile, Santiago, Chile. 2Institute of Nutrition and food technology, University of Chile, Santiago, Chile. 3Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 4International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark


Context: Transient thelarche (TT) corresponds to the appearance, regression and subsequent reappearance of the breast bud in girls. Only a single study about its frequency and progression is available (Lindhardt Johansen JCEM 2017).

Objective and Hypotheses: To determine whether girls with TT girls (group 1) compared to girls without TT (group 2) show differences in i) timing/sequence of pubertal events ii) pattern of reproductive hormones and growth factors iii) genotype distribution of genetic polymorphisms associated with pubertal timing and iv) predictive factors (anthropometry since birth,maternal age at menarche).

Methods: The study population consist of the Chilean Growth and Obesity Cohort Study (GOCS, n=507 girls) followed since birth. Annual clinical examination including Tanner assessment until 1 yr postmenarche and fasting blood samples for metabolic, growth and reproductive hormones. Genotyping was performed by competitive and analysis was performed in STATA (version 14).

Results: In 7% (n=37) of the girls (n=507) TT was observed and in 65% of them breast development occurred below 8 years. Once progressive puberty, 51% started with pubarche in group 1 vs. 26% group 2, (P<0.001).During pubertal progression age at breast stage B2 (10.3± 1.1 vs. 9.2 ± 1.2 years, P<0.001) and menarche (12.3 ± 0.8 vs. 12.0± 1.0 years, P<0.05) were later in group 1.No differences in genotypes distribution of FSHβ/FSHR nor in predictive factors were detected. Girls in group 1 who had the event below 8 years had lower DHEAS (P<0.05), Testosterone (T), Androstendione (A) and LH (all P<0.005) than girls with TT at older age. Girls in group 1 at the moment of puberty onset at breast Tanner 2 (B2) had higher DHEAS, IGF-1, LH, Insulin, estradiol, Testosterone and Androstendione (all P<0.01) than at TT. Comparison between group 1 and 2 girls during puberty onset at B2 showed lower DHEAS and IGF-1(P<0.005), T, A,LH and estradiol ( all P<0.05) and higher insulin (P<0.001) in group 1.Hormonal concentrations at B4 and 1 yr postmenarche did not differ.

Conclusion: Transient Thelarche appears to be a frequent event which does not appear to be mediated by hypothalamic-pituitary gonadal axis activation, adiposity, peripheral conversion of androgens to estrogens, or genetic variations in FSHβ/FSHR. These findings suggest that environmental exposure may play a role. We confirmed that TT girls entered puberty more frequently by the pubarche pathway and the subtle differences in hormonal levels at the initiation of puberty later disappeared, which indicates a benign nature of this condition

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