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Development of external genitalia during mini-puberty: is it related to somatic growth or reproductive hormones?

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Abstract

Although hypothalamo-pituitary–gonadal axis is active during mini-puberty, its relationship with somatic growth and the role on the development of external genitalia has not been fully elucidated. We aimed to evaluate the effects of somatic growth and reproductive hormones on the development of external genitalia during mini-puberty. Anthropometric data, pubertal assesment, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), sex-hormone binding globulin (SHBG), estradiol (E2) and inhibin-B, testosterone (T), and anti-Mullerian Hormone (AMH) of healthy infants aged 1–4 months were evaluated. Free sex hormone index was calculated as T/SHBG for boys and E2/SHBG for girls. The mean age of 148 (74 female) infants included in the study was 2.31 ± 0.76 months. Tanner stage 2–3 sex steroid and gonadotropin levels were observed. A statistically significant difference was found between the weight, height, BMI, weight gain and serum FSH, LH, and A4 measurements of girls and boys (p < 0.05). Penile length was associated with weight (r = 0.24, p = 0.03), height (r = 0.25, p = 0.02), and AMH (r = 0.3, p = 0.01), but not with testosterone (p = 0.56 respectively). A negative correlation was found between weight and serum LH (r =  − 0.26, p = 0.2) and T/SHBG levels in males (r =  − 0.38, p = 0.015 respectively). Weight-SDS was negatively correlated with testosterone in males (r =  − 0.25, p = 0.02). Testicular size and breast stage did not correlate with any of the hormonal and anthropometric parameters.

  Conclusions: External genitalia in males during mini-puberty is related more to somatic growth rather than reproductive hormones. Similar to pubertal developmental stages, both total and free testosterone are negatively associated with higher weight during mini-puberty.

What is Known:

• Mini-puberty allows early assessment of HPG axis function in infancy.

• There is an inverse relationship between the amount of adipose tissue and circulating testosterone levels in males during puberty and adulthood.

• The potential effect of somatic growth and reproductive hormones on external genital development during mini-puberty remains unclear.

What is New:

• During mini-puberty, males' external genitalia is more related to somatic growth than to reproductive hormones, but this relationship is not observed in girls.

• Both total and free testosterone are negatively associated with higher weight during mini-puberty, similar to the pubertal developmental stages.

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All data generated or analyzed during this study are included in this published article or in the data repositories listed in References.

Abbreviations

A4:

Androstenedione

AMH:

Anti-mullerian hormone

BMI:

Body mass index

DHEAS:

Dehydroepiandrosterone sulfate

E2:

Estradiol

FSH:

Follicle-stimulating hormone

HPG:

Hypothalamic-pituitary–gonadal

LH:

Luteinizing hormone

PC:

Penile circumference

PI:

Ponderal index

SHBG:

Sex-hormone binding globulin

SGA:

Small for gestational age

SPL:

Stretched penile length

T:

Testosterone

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Funding

This work has been supported by the Medical Research Council of Marmara University (Project Grant TTU-2022–10603, TG).

Author information

Authors and Affiliations

  1. Department of Pediatrics, Marmara University School of Medicine, 34841, Istanbul, Turkey

    Hazal Arıkan Gacemer

  2. Department of Pediatric Endocrinology and Diabetes, Marmara University School of Medicine, 34841, Istanbul, Turkey

    Busra Gurpinar Tosun, Didem Helvacioglu, Zehra Yavas Abali, Belma Haliloglu, Serap Demircioglu Turan, Abdullah Bereket & Tulay Guran

  3. Department of Biochemistry, Marmara University School of Medicine, 34841, Istanbul, Turkey

    Ali Yaman & Goncagul Haklar

  4. Department of Pediatric Endocrinology and Diabetes, Marmara University School of Medicine, Fevzi Cakmak Mh, Ustkaynarca/Pendik, Mimar Sinan Cd. No. 41. 34899, Istanbul, Turkey

    Tulay Guran

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  1. Hazal Arıkan Gacemer
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Contributions

H.A.G, A.B. and T.G. wrote the main manuscript text. A.Y and G.H contributed to assessment of laboratory tests. All authors reviewed the manuscript.

Corresponding author

Correspondence to Tulay Guran.

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Ethics approval

The study protocol was approved by the Marmara University School of Medicine Ethics Committee and adhered to the Declaration of Helsinki (Protocol no: 09.2022.263, Date: 11.02.2022).

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Written informed consent was obtained from the participants’parents.

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The authors declare no competing interests.

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Communicated by Peter de Winter

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Gacemer, H.A., Tosun, B.G., Helvacioglu, D. et al. Development of external genitalia during mini-puberty: is it related to somatic growth or reproductive hormones?. Eur J Pediatr 183, 1325–1332 (2024). https://doi.org/10.1007/s00431-023-05393-3

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