---
title: "Premature adrenarche and long-term metabolic risk: association with insulin resistance and hyperan"
id: "pubmed-42375004"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42375004"
content_type: "clinical_feed_article"
specialty: "Endocrinology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42375004/"
doi: "10.1210/clinem/dgag258"
published_at: "2026-09-16T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Premature adrenarche and long-term metabolic risk: association with insulin resistance and hyperan
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42375004
- **Specialty:** [Endocrinology](https://medichelpline.com/clinical-feed/endocrinology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42375004/)
- **DOI:** [10.1210/clinem/dgag258](https://doi.org/10.1210%2Fclinem%2Fdgag258)
- **Published At:** 2026-09-16T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- This systematic review and meta-analysis evaluated long-term outcomes after **idiopathic premature adrenarche (IPA)** in females, focusing on metabolic syndrome components and reproductive hyperandrogenism. - Databases were searched through February 2025; observational studies reporting outcomes after menarche were pooled using random-effects models. - Twenty-one studies were included, comprising 635 females with IPA and 307 age-matched controls. - Primary outcomes included **body mass index (BMI)**, markers of **insulin resistance** (fasting insulin, HOMA-IR), and clinical/biochemical markers of **hyperandrogenism**. - IPA was associated with higher BMI (mean difference 1.4 kg/m2; 95% CI 1.0–1.9), higher fasting insulin, and higher HOMA-IR, indicating persistent insulin resistance relative to controls. - Clinical and biochemical hyperandrogenism markers — Ferriman-Gallwey score, dehydroepiandrosterone sulfate (DHEA-S), and Free Androgen Index (FAI) — were also elevated in women with prior IPA. - Secondary analyses identified higher triglycerides, lower high-density lipoprotein (HDL), increased leptin, and greater carotid intima-media thickness in the IPA group, consistent with an early adverse cardiometabolic profile. - The authors applied the GRADE approach; most outcomes were graded as **low certainty** of evidence. - The review supports the recommendation for long-term monitoring of metabolic and reproductive outcomes in females with a history of IPA. - Specific methodological details, individual study heterogeneity, and other limitations beyond the abstract were not fully reported in the source summary and would require consultation of the full article for more granular information.
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Affiliations Expand ### Affiliations * 1 Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo (FMRP-USP), Ribeirão Preto, SP 14049-900, Brazil. * 2 Department of Internal Medicine, Medical School, São Paulo State University/UNESP, São Paulo 18618-687, Brazil. * PMID: **42375004** * DOI: [ 10.1210/clinem/dgag258 ](https://doi.org/10.1210/clinem/dgag258) Item in Clipboard Meta-Analysis # From premature adrenarche to adult metabolic risk and hyperandrogenism: a systematic review and meta-analysis Thais Milioni Luciano et al. J Clin Endocrinol Metab. 2026. Show details Display options Display options Format Abstract PubMed PMID J Clin Endocrinol Metab Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22J+Clin+Endocrinol+Metab%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22J+Clin+Endocrinol+Metab%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42375004/) . 2026 Sep 16;111(10):e2300-e2311. doi: 10.1210/clinem/dgag258. ### Authors [Thais Milioni Luciano](https://pubmed.ncbi.nlm.nih.gov/?term=Luciano+TM&cauthor_id=42375004)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42375004/#short-view-affiliation-1 "Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo \(FMRP-USP\), Ribeirão Preto, SP 14049-900, Brazil."), [Mariana Peduti Halah](https://pubmed.ncbi.nlm.nih.gov/?term=Halah+MP&cauthor_id=42375004)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42375004/#short-view-affiliation-1 "Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo \(FMRP-USP\), Ribeirão Preto, SP 14049-900, Brazil."), [Luís Eduardo Cruvinel Pinto](https://pubmed.ncbi.nlm.nih.gov/?term=Pinto+LEC&cauthor_id=42375004)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42375004/#short-view-affiliation-1 "Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo \(FMRP-USP\), Ribeirão Preto, SP 14049-900, Brazil."), [Mayara Souza Ribas Castor](https://pubmed.ncbi.nlm.nih.gov/?term=Castor+MSR&cauthor_id=42375004)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42375004/#short-view-affiliation-1 "Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo \(FMRP-USP\), Ribeirão Preto, SP 14049-900, Brazil."), [Vânia Dos Santos Nunes-Nogueira](https://pubmed.ncbi.nlm.nih.gov/?term=Nunes-Nogueira+VDS&cauthor_id=42375004)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42375004/#short-view-affiliation-2 "Department of Internal Medicine, Medical School, São Paulo State University/UNESP, São Paulo 18618-687, Brazil."), [Sonir Rauber Antonini](https://pubmed.ncbi.nlm.nih.gov/?term=Antonini+SR&cauthor_id=42375004)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42375004/#short-view-affiliation-1 "Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo \(FMRP-USP\), Ribeirão Preto, SP 14049-900, Brazil.") ### Affiliations * 1 Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo (FMRP-USP), Ribeirão Preto, SP 14049-900, Brazil. * 2 Department of Internal Medicine, Medical School, São Paulo State University/UNESP, São Paulo 18618-687, Brazil. * PMID: **42375004** * DOI: [ 10.1210/clinem/dgag258 ](https://doi.org/10.1210/clinem/dgag258) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract **Context:** Idiopathic premature adrenarche (IPA) has been associated with a higher risk of metabolic and reproductive dysfunction, but long-term/adult outcomes remain incompletely known. **Objective:** To assess the relationship between IPA and metabolic syndrome, as well as polycystic ovarian syndrome, in premenarcheal adolescent and adult women. **Methods:** We conducted a systematic review and meta-analysis of observational studies reporting outcomes in females with IPA after menarche. Databases were searched through February 2025. Primary outcomes included body mass index (BMI), insulin resistance markers, and clinical and biochemical markers of hyperandrogenism. Data were pooled using random-effects models. The GRADE approach was applied to assess the certainty of evidence. **Results:** A total of 21 studies comprising 635 females with IPA and 307 age-matched controls were included. Compared to controls, IPA individuals showed significantly higher BMI (mean difference: 1.4; CI: 1.0-1.9), fasting insulin, and homeostasis model assessment of insulin resistance, indicating persistent insulin resistance. Markers of hyperandrogenism, including Ferriman-Gallwey score, dehydroepiandrosterone sulfate, and Free androgenic index, were also elevated. Secondary analyses revealed higher triglycerides, lower high-density lipoprotein, increased leptin, and greater carotid intima-media thickness, supporting an early pattern of cardiometabolic risk. GRADE assessment rated most outcomes as low certainty. **Conclusion:** Women with a history of IPA are at increased risk of long-term insulin resistance and hyperandrogenism, with early signs of adverse cardiometabolic profiles. These findings support the need for long-term monitoring in this population. **Keywords:** adrenarche; long-term outcomes; premature adrenarche. © The Author(s) 2026. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms. 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