Chen-Patterson et al (of the CALICO consortium) [1] are to be complimented for describing the contemporary phenotype of polycystic ovary syndrome (PCOS) in adolescent girls (age range, 14-18 years) across the United States, and for unravelling how PCOS features may differ between adolescents with a body mass index (BMI) below the 85th percentile (“lean”) vs those with a BMI above the 95th percentile (“with obesity”) [1]. The relevance of this paper can be raised by elaborating on its epidemiological, developmental, and therapeutic implications.
By definition, there are supposed to be 17-fold more adolescent girls with a BMI below the 85th percentile than with a BMI above the 95th percentile. In the CALICO database, however, the PCOS cases with obesity outnumbered the lean PCOS cases more than 4-fold, namely 4.5-fold (373 vs 82) before the exclusion of patients on medications, and 4.2-fold (286 vs 68) after their exclusion [1]. These unique numbers suggest that girls with obesity are approximately at a 75-fold higher risk of developing adolescent PCOS than lean girls. Such obesity-linked risk fits into the emerging concept that adolescent PCOS is essentially driven by ectopic fat and/or insulin resistance, both of which may ensue from a mismatch between the capacity and the demand to store lipids in subcutaneous adipose tissue [2, 3].
Under “data collection,” Chen-Patterson et al mention that “medical information included birthweight” but they appear to share no results on this variable [1]. Birthweight data from lean girls with adolescent PCOS would be welcome, given that their average weight at term birth may have been below the mean for girls in a contemporary US cohort [2, 3]. Birthweight data from adolescents with PCOS and obesity would also be welcome, given that these girls are at an 18-fold higher risk of developing type 2 diabetes [4], and that such development depends on interactions among genetic risk, prenatal weight gain, and postnatal BMI [5].
Chen-Patterson et al state that “combined oral contraceptive pills remain the first-line pharmacological treatment for PCOS based on current guidelines,” and that their identification of distinct subgroups within adolescent PCOS provides a rationale “for individualized treatment approaches” [1]. Distinct approaches are still under investigation (reviewed in [3]) but pilot evidence suggests that medications targeting a loss of ectopic fat and/or a gain of insulin sensitivity are capable of reversing the adolescent PCOS phenotype [6, 7]. The first results are so promising that they may even suffice to concur that regulatory agencies should refrain from approving combined oral contraceptive pills as the first-line pharmacological treatment for adolescent PCOS, certainly in lean girls [3, 6].
Disclosures
The authors have nothing to disclose.
Abbreviations
- BMI
body mass index
- PCOS
polycystic ovary syndrome
Contributor Information
Francis de Zegher, Leuven Research & Development, University of Leuven, 3000 Leuven, Belgium.
Lourdes Ibáñez, Email: lourdes.ibanez@sjd.es, Endocrinology Department, Institut de Recerca Sant Joan de Déu, University of Barcelona, 08950 Esplugues, Barcelona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029 Madrid, Spain.
References
- 1. Chen-Patterson A, Bernier A, Burgert T, et al. Distinct reproductive phenotypes segregate with differences in body weight in adolescent polycystic ovary syndrome. J Endocr Soc 2024;8(2):bvad169. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. de Zegher F, Lopez-Bermejo A, Ibáñez L. Adipose tissue expandability and the early origins of PCOS. Trends Endocrinol Metab 2009;20(9):418‐423. [DOI] [PubMed] [Google Scholar]
- 3. Ibáñez L, de Zegher F. Adolescent PCOS: a postpubertal central obesity syndrome. Trends Mol Med 2023;29(5):354‐363. [DOI] [PubMed] [Google Scholar]
- 4. Hudnut-Beumler J, Kaar JL, Taylor A, et al. Development of type 2 diabetes in adolescent girls with polycystic ovary syndrome and obesity. Pediatr Diabetes 2021;22(5):699‐706. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Wibaek R, Andersen GS, Linneberg A, et al. Low birthweight is associated with a higher incidence of type 2 diabetes over two decades independent of adult BMI and genetic predisposition. Diabetologia 2023;66(9):1669‐1679. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Ibáñez L, Díaz M, García-Beltrán C, et al. Toward a treatment normalizing ovulation rate in adolescent girls with polycystic ovary syndrome. J Endocr Soc 2020;4(5):bvaa032. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Morelli N, Lo J, Ware M, et al. Four months of oral semaglutide on clinical measures in adolescents with obesity and PCOS (TEAL study). Program of the Annual Meeting of the Obesity Society; October 14-17, 2023 (Abstract 216), Dallas, TX.