Up-to-date review about minipuberty and overview on hypothalamic-pituitary-gonadal axis activation in fetal and neonatal life
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Minipuberty consists of activation of the hypothalamic-pituitary-gonadal (HPG) axis during the neonatal period, resulting in high gonadotropin and sex steroid levels, and occurs mainly in the first 3-6 months of life in both sexes. The rise in the levels of these hormones allows for the maturation of the sexual organs. In boys, the peak testosterone level is associated with penile and testicular growth and the proliferation of gonadic cells. In girls, the oestradiol levels stimulate breast tissue, but exhibit considerable fluctuations that probably reflect the cycles of maturation and atrophy of the ovarian follicles. Minipuberty allows for the development of the genital organs and creates the basis for future fertility, but further studies are necessary to understand its exact role, especially in girls. Nevertheless, no scientific study has yet elucidated how the HPG axis turns itself off and remains dormant until puberty. Additional future studies may identify clinical implications of minipuberty in selected cohorts of patients, such as premature and small for gestational age infants. Finally, minipuberty provides a fundamental 6-month window of the possibility of making early diagnoses in patients with suspected sexual reproductive disorders to enable the prompt initiation of treatment rather than delaying treatment until pubertal failure.
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Gonadal steroidogenesis is active during minipuberty, a short period of hypothalamic-pituitary-gonadal axis activation during neonatal period.
“Gonadal steroidogenesis is also active during ‘minipuberty’, a short period of hypothalamic-pituitary-gonadal axis activation during the neonatal period [24].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [24]
Following full initiation at puberty, gonadal androgen production decreases significantly after menopause in women, while in men the testicular output of testosterone gradually decreases with age, resulting in significantly lower combined androgen levels in men aged 60 and over.
“Following full initiation at puberty gonadal androgen production decreases significantly after menopause in women, while in men the testicular output of testosterone gradually decreases with age, resulting in significantly lower combined androgen levels in men aged 60 and over [24,[280], [281], [282]].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [24]
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de Jong, M., Rotteveel, J., Heijboer, A. C., Cranendonk, A., Twisk, J. W. R., & van Weissenbruch, M. M. (2012) · Early Human Development · doi:10.1016/j.earlhumdev.2012.09.007 · Cited by 13 · see citing works
Nagai, S., Kawai, M., Myowa‐Yamakoshi, M., et al. (2017) · Journal of Perinatology · doi:10.1038/jp.2017.55 · Cited by 13 · see citing works
Feminizing Changes in a Prematurely Born Infant
Marinković, M. D., Rasmussen, M. R., & Jones, K. L. (2009) · Clinical Pediatrics · doi:10.1177/0009922809337624 · Cited by 10 · see citing works
Ovarielles Hyperstimulationssyndrom bei frühgeborenen Mädchen
Vochem, M. (2002) · Zeitschrift für Geburtshilfe und Neonatologie · doi:10.1055/s-2002-33669 · Cited by 8 · see citing works
Atypical case of preterm ovarian hyperstimulation syndrome
Durst, M. A., Wicklow, B. A., & Narvey, M. R. (2017) · BMJ Case Reports · doi:10.1136/bcr-2016-217517 · Cited by 6 · see citing works
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Schiffer, L., Barnard, L., Baranowski, E. S., Gilligan, L. C., Taylor, A. E., Arlt, W., Shackleton, C. H. L., & Storbeck, K.-H. (2019) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2019.105439 · Cited by 450 · see citing works
“Gonadal steroidogenesis is also active during ‘minipuberty’, a short period of hypothalamic-pituitary-gonadal axis activation during the neonatal period [24].”
HUNTER, S. K., S. ANGADI, S., BHARGAVA, A., HARPER, J., HIRSCHBERG, A. L., D. LEVINE, B., L. MOREAU, K., J. NOKOFF, N., STACHENFELD, N. S., & BERMON, S. (2023) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000003300 · Cited by 241 · see citing works
Hilton, E. N., & Lundberg, T. R. (2021) · Sports Medicine · doi:10.1007/s40279-020-01389-3 · Cited by 170 · see citing works
“differences in skeletal muscle likely to influence composition and function beyond the effects of androgenisation [3], while increased testosterone during minipuberty in males aged 1–6 months may be correlated with higher growth velocity and an “imprinting effect” on BMI and bodyweight [20, 21].”
BackgroundHunter, S. K., Angadi, S. S., Bhargava, A., Harper, J., Hirschberg, A. L., Levine, B. D., Moreau, K. L., Nokoff, N. J., Stachenfeld, N. S., & Bermon, S. (2023) · Translational Journal of the American College of Sports Medicine · doi:10.1249/tjx.0000000000000236 · Cited by 43 · see citing works
Shahzad, B., Fatima, B., Bashir, M. K., Waheed, M. R., Zafar, Z., & Zaidi, S. S. H. (2026) · National Journal of Health Sciences · doi:10.21089/njhs.112.0084
- Authors
- Lanciotti, L., Cofini, M., Leonardi, A., Penta, L., & Esposito, S.
- Affiliations
- University of Perugia (IT)
- Corresponding author
- Esposito, Susanna
- Venue
- Frontiers in Endocrinology
- Publisher
- Frontiers Media SA
- Published
- 2018-07-23
- Volume
- 9
- Pages
- 410-410
- ISSN
- 1664-2392 (ISSN-L)
- PMC
- PMC6070773
- OpenAlex
- W2883348341
- Cited by
- 209
- References
- 97
- Citations by year
- 2026: 21 · 2025: 25 · 2024: 36 · 2023: 33 · 2022: 36 · 2021: 22 · 2020: 28 · 2019: 7 · 2018: 1
- FWCI
- 2.19
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Frontiers in Endocrinology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Keywords
- minipuberty, hypothalamic-pituitary-gonadal axis, sex steroids, testosterone, estradiol, preterm infants, small for gestational age, pubertal failure, reproductive disorders, puberty onset
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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