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Mini-puberty

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Mini-puberty is a transient hormonal activation of the hypothalamic-pituitary-gonadal (HPG) axis that occurs in infants shortly after birth. This period is characterized by a surge in the secretion of gonadotropins (LH and FSH) and sex steroids (testosterone in males and estradiol in females), similar to but less intense than the hormonal changes that occur in puberty during adolescence. Mini-puberty plays a crucial role in the early development of the reproductive system and the establishment of secondary sexual characteristics.

Physiology

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Hypothalamic-pituitary-gonadal axis activation

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Mini-puberty begins within the first few days or weeks of life and typically lasts until 6–12 months of age.[1] The HPG axis is temporarily reactivated, resulting in increased secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus. GnRH stimulates the pituitary gland to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which in turn stimulate the gonads (testes in males and ovaries in females) to produce sex steroids.

Hormonal changes

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  • Males: There is a significant increase in testosterone levels, peaking around 1–3 months of age and leveling off around 6 months.[1][2] This rise in testosterone is essential for the development of male genitalia, testicular descent, and the proliferation of Sertoli and Leydig cells.
  • Females: There is an increase in estradiol and FSH levels, although less pronounced compared to the hormonal changes in males. This rise in estradiol is involved in the maturation of ovarian follicles and the growth of the uterus and levels off around 2 years of life.[1][2] FSH peaks at 1–3 months, similar to boys, but may remain elevated for 3–4 years of life.[1]

Clinical significance

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Developmental role

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Mini-puberty is crucial for several developmental processes, including:

  • Sexual differentiation: In males, the surge in testosterone supports the continued development of male genitalia and other secondary sexual characteristics.[1][2][3]
  • Growth and metabolism: The hormonal changes may have effects on growth patterns, bone maturation, and overall metabolism.[1][2]
  • Neurodevelopment: Sex steroids play a role in brain development and may influence behaviors and cognitive functions, including language development.[1][2]

Diagnostic marker

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Mini-puberty can serve as a valuable diagnostic window for identifying congenital abnormalities of the HPG axis or gonads.[4][5] Conditions such as congenital hypogonadotropic hypogonadism and certain forms of intersex can be diagnosed during this period by evaluating hormone levels and gonadal response.

Potential disorders

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Disruptions in the mini-puberty process can lead to various clinical conditions, including:

  • Delayed or absent mini-puberty: This may indicate underlying issues with the HPG axis or gonads, requiring further investigation and potential intervention.[6][7]

Environmental influences

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Environmental factors, such as exposure to Endocrine Disrupting Chemicals (EDCs), have been shown to impact mini-puberty.[1][8][9] EDCs are widespread in daily life and can be found in products such as pesticides and personal care items. Bisphenol A (BPA)[10] and many phthalates[11] are known to interfere with the earlier HPG axis activation during pregnancy for boys, affecting testosterone levels during mini-puberty, anogenital distance (AGD), and testicular descent.

More recently, BPA and phthalate exposure during mini-puberty have been shown to interfere with HPG axis activation and testosterone levels during that same time frame, suggesting that mini-puberty is a particularly vulnerable window for EDC exposure.[12] Such disruptions may lead to long-term consequences, including delayed or precocious puberty, reproductive health issues, and increased risk of conditions like polycystic ovary syndrome (PCOS),[13] breast cancer[14] and prostate cancer.

In a small study, it was shown that "PCDD/Fs and PCBs measured in breast milk collected within the first 3 weeks following birth were more strongly associated with sexually dimorphic outcomes than exposures measured in maternal blood collected between weeks 28 and 43" of pregnancy,[9] adding evidence that EDC exposure during mini-puberty may interfere with endocrine and neurological development.

Research and future directions

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Although the phenomenon has been known for over 40 years,[2] research into mini-puberty continues to uncover its broader implications for long-term health and development. The potential impact of environmental factors and endocrine disruptors on mini-puberty is an area of active investigation. At the same time, researchers also investigate if mini-puberty may be a window to treat certain disorders, e.g. treating micropenis using gonadotropin (testosterone) injections.[15]

See also

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References

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  1. ^ a b c d e f g h Lucaccioni, Laura; Trevisani, Viola; Boncompagni, Alessandra; Marrozzini, Lucia; Berardi, Alberto; Iughetti, Lorenzo (2021-01-18). "Minipuberty: Looking Back to Understand Moving Forward". Frontiers in Pediatrics. 8. doi:10.3389/fped.2020.612235. ISSN 2296-2360. PMC 7848193. PMID 33537266.
  2. ^ a b c d e f Becker, Marianne; Hesse, Volker (2020-06-29). "Minipuberty: Why Does it Happen?". Hormone Research in Paediatrics. 93 (2): 76–84. doi:10.1159/000508329. ISSN 1663-2818. PMID 32599600.
  3. ^ Nordenström, Anna (2022-08-01). "Potential impact of mini-puberty on fertility". Annales d'Endocrinologie. 83 (4): 250–253. doi:10.1016/j.ando.2022.06.002. ISSN 0003-4266. PMID 35728696.
  4. ^ Grumbach, Melvin M. (May 2005). "A Window of Opportunity: The Diagnosis of Gonadotropin Deficiency in the Male Infant 1". The Journal of Clinical Endocrinology & Metabolism. 90 (5): 3122–3127. doi:10.1210/jc.2004-2465. ISSN 0021-972X. PMID 15728198.
  5. ^ Quinton, Richard; Mamoojee, Yaasir; Jayasena, Channa N.; Young, Jacques; Howard, Sasha; Dunkel, Leo; Cheetham, Tim; Smith, Neil; Dwyer, Andrew A. (February 2017). "Society for Endocrinology UK guidance on the evaluation of suspected disorders of sexual development: emphasizing the opportunity to predict adolescent pubertal failure through a neonatal diagnosis of absent minipuberty". Clinical Endocrinology. 86 (2): 305–306. doi:10.1111/cen.13257. ISSN 0300-0664. PMID 27749014.
  6. ^ Rohayem, Julia; Alexander, Emma C; Heger, Sabine; Nordenström, Anna; Howard, Sasha R (2024-03-04). "Mini-Puberty, Physiological and Disordered: Consequences, and Potential for Therapeutic Replacement". Endocrine Reviews. 45 (4): 460–492. doi:10.1210/endrev/bnae003. ISSN 0163-769X. PMC 11244267. PMID 38436980.
  7. ^ Dwyer, Andrew A. (January 2020). "Minipuberty: A Primer for Pediatric Nurses". Journal of Pediatric Nursing. 50: 138–139. doi:10.1016/j.pedn.2019.10.012. ISSN 0882-5963. PMID 31874718.
  8. ^ Ünüvar, Tolga; Büyükgebiz, Atilla (2012-04-15). "Fetal and Neonatal Endocrine Disruptors" (PDF). Journal of Clinical Research in Pediatric Endocrinology. 4 (2): 51–60. doi:10.4274/Jcrpe.569. PMC 3386773. PMID 22672860.
  9. ^ a b Winneke, Gerhard; Ranft, Ulrich; Wittsiepe, Jürgen; Kasper-Sonnenberg, Monika; Fürst, Peter; Krämer, Ursula; Seitner, Gabriele; Wilhelm, Michael (March 2014). "Behavioral Sexual Dimorphism in School-Age Children and Early Developmental Exposure to Dioxins and PCBs: A Follow-Up Study of the Duisburg Cohort". Environmental Health Perspectives. 122 (3): 292–298. doi:10.1289/ehp.1306533. ISSN 0091-6765. PMC 3948031. PMID 24273228.
  10. ^ Sun, Xiaowei; Li, Dekun; Liang, Hong; Miao, Maohua; Song, Xiuxia; Wang, Ziliang; Zhou, Zhijun; Yuan, Wei (December 2018). "Maternal exposure to bisphenol A and anogenital distance throughout infancy: A longitudinal study from Shanghai, China". Environment International. 121 (Pt 1): 269–275. Bibcode:2018EnInt.121..269S. doi:10.1016/j.envint.2018.08.055. PMID 30223203.
  11. ^ Muerköster, Anna-Patricia; Frederiksen, Hanne; Juul, Anders; Andersson, Anna-Maria; Jensen, Richard Christian; Glintborg, Dorte; Kyhl, Henriette Boye; Andersen, Marianne Skovsager; Timmermann, Clara Amalie Gade; Jensen, Tina Kold (November 2020). "Maternal phthalate exposure associated with decreased testosterone/LH ratio in male offspring during mini-puberty. Odense Child Cohort". Environment International. 144: 106025. Bibcode:2020EnInt.14406025M. doi:10.1016/j.envint.2020.106025. PMID 32798799.
  12. ^ Lærkeholm Müller, Matilde; Busch, Alexander Siegfried; Ljubicic, Marie Lindhardt; Upners, Emmie N.; Fischer, Margit B.; Hagen, Casper P.; Albrethsen, Jakob; Frederiksen, Hanne; Juul, Anders; Andersson, Anna-Maria (2023-05-01). "Urinary concentration of phthalates and bisphenol A during minipuberty is associated with reproductive hormone concentrations in infant boys". International Journal of Hygiene and Environmental Health. 250: 114166. Bibcode:2023IJHEH.25014166L. doi:10.1016/j.ijheh.2023.114166. ISSN 1438-4639. PMID 37058994.
  13. ^ Palioura, Eleni; Diamanti-Kandarakis, Evanthia (December 2015). "Polycystic ovary syndrome (PCOS) and endocrine disrupting chemicals (EDCs)". Reviews in Endocrine and Metabolic Disorders. 16 (4): 365–371. doi:10.1007/s11154-016-9326-7. ISSN 1389-9155. PMID 26825073.
  14. ^ Burks, Hope; Pashos, Nicholas; Martin, Elizabeth; Mclachlan, John; Bunnell, Bruce; Burow, Matthew (December 2017). "Endocrine disruptors and the tumor microenvironment: A new paradigm in breast cancer biology". Molecular and Cellular Endocrinology. 457: 13–19. doi:10.1016/j.mce.2016.12.010. PMID 28012841.
  15. ^ Avril, Tristan; Hennocq, Quentin; Lambert, Anne-Sophie; Leger, Juliane; Simon, Dominique; Martinerie, Laetitia; Bouvattier, Claire (2023-04-01). "Gonadotropin administration to mimic mini-puberty in hypogonadotropic males: pump or injections?". Endocrine Connections. 12 (4). doi:10.1530/EC-22-0252. ISSN 2049-3614. PMC 10083662. PMID 36724045.
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