Longitudinal evaluation of breast tissue in healthy infants: Prevalence and relation to reproductive hormones and growth factors.

Introduction: Breast tissue in infancy is a rather undescribed phenomenon. We aimed to describe the prevalence and progression of palpable breast tissue in healthy boys and girls aged 0-1 years and to evaluate clinical markers, individual serum hormone concentrations as well as combined hormone profiles as determinants of the persistence of breast tissue. Methods: In total, 233 term infants (119 boys, 114 girls) were included and followed from birth until 1 year of age in The COPENHAGEN Minipuberty Study (ClinicalTrials.gov #NTC02784184). Infants were followed up to six times with a clinical examination and serum sampling. Principal component analyses (PCAs) produced combined hormone profiles. Results: A total of 98% of all infants aged 0-1 year exhibited breast tissue at some point. 50% still had breast tissue present at 0.5-0.6 years in girls and 0.3-0.4 years in boys ('persistent'). At one year, more girls than boys had breast tissue present (p=0.010). Most clinical and hormonal markers did not differ in infants with/without persistent breast tissue. However, in those with persistent breast tissue, estradiol (first visit, girls, p=0.034), androstenedione, corticosterone, cortisol (first visit, boys, all p<0.050), length (first visit, boys, p=0.030), and testicular volume (0.3-0.4 years, p=0.040) were higher, while IGF-I (0.3-0.4, boys, p=0.033) was lower. In boys, a combined, PCA-derived hormone profile (first visit) was able to predict the persistence of breast tissue (area under the curve=83%) better than any single marker. Discussion: Palpable breast tissue in infancy is common in both sexes although it persists in significantly more girls than boys at one year of age. Data supports both the early origin of breast tissue (in utero- and early postnatal) as well as a role of endogenous hormone production in later development and maintenance.

Reproductive hormones during pubertal transition in girls with transient Thelarche.

CONTEXT: Transient thelarche (TT), that is, the appearance, regression and subsequent reappearance of breast buds, is a frequent phenomenon, but little is known about pubertal transition in these girls. OBJECTIVE: To describe pubertal progression, growth, genotypes, reproductive hormones and growth factors in girls with TT compared to those who do not present TT (non-TT). DESIGN: Retrospective analysis of a longitudinal population-based study. PATIENTS OR OTHER PARTICIPANTS: Girls (n = 508) of the Chilean Growth and Obesity cohort. MEASUREMENTS: Pubertal progression, reproductive hormones, follicle stimulating hormone (FSH) beta subunit/FSH receptor gene single nucleotide polymorphisms and growth. RESULTS: Thirty-seven girls (7.3%) were presented TT. These girls entered puberty by pubarche more frequently (51%) than girls with normal progression (non-TT; n = 471; 23%, P = .005). Girls with TT who were under 8 years old had lower androgens, anti-Müllerian hormone (AMH), luteinizing hormone (LH) and oestradiol (all P < .05) than older girls with TT. At the time of Tanner breast stage 2 (B2), girls with TT had higher androgens, LH, FSH, IGF1, LH, insulin and oestradiol (P < .01) than at the time of TT. TT girls were older at B2 (10.3 ± 1.1 vs. 9.2 ± 1.2 years, P < .001) and menarche (12.3 ± 0.8 vs. 12.0 ± 1.0 years, P = .040) than their counterparts (non-TT). No differences in anthropometric variables or FSHB/FSHR genotypes were detected. CONCLUSION: Transient thelarche is a frequent phenomenon that does not appear to be mediated by hypothalamic-pituitary-gonadal axis activation or by adiposity. Hormonal differences between earlier TT and later TT suggest that their mechanisms are different.

FSHB -211 G>T Polymorphism as Predictor for TESE Success in Patients With Unexplained Azoospermia.

CONTEXT: Testicular sperm extraction (TESE) followed by assisted reproductive techniques often remains the only therapeutic option for men with azoospermia due to spermatogenic failure. Reproductive parameters, such as gonadotropin levels and testicular volume or histopathology, contribute to the prediction of sperm retrieval rate (SRR) in TESE. However, there is an eminent lack of noninvasive predictive factors for TESE outcome. OBJECTIVE: To clarify the impact of three common genetic variants affecting FSH and its cognate receptor on testicular histopathology patterns and SRR in TESE. DESIGN: We evaluated the association of the single-nucleotide polymorphisms (SNP) FSHB -211G>T (rs10835638), FSHR -29G>A (rs1394205), and FSHR c.2039A>G (rs6166) with testicular histopathology and SRR in patients with azoospermia. SETTING: Tertiary referral center for andrology. PATIENTS OR OTHER PARTICIPANTS: Men (n = 1075) with azoospermia who underwent TESE (grouped by clinical pathologies). INTERVENTION(S): All participants underwent TESE. MAIN OUTCOME MEASURE(S): Testicular histopathology, SRR, and reproductive hormone levels. RESULTS: FSHB -211G>T was significantly associated with reduced chances of sperm retrieval in patients with unexplained azoospermia. Indicating an additional mechanism, the association of the SNP with SSR could not be solely attributed to decreased FSH levels. CONCLUSION: A common genetic factor was significantly associated with SRR in TESE. In perspective, a calculator or score including the noninvasive parameters FSH level, testicular volume, and FSHB haplotype should be considered to estimate the chances for sperm retrieval in men with azoospermia.