Ethinyl Estradiol-Cyproterone Acetate Versus Low-Dose Pioglitazone-Flutamide-Metformin for Adolescent Girls with Androgen Excess: Divergent Effects on CD163,TWEAK Receptor,ANGPTL4, and LEPTIN Expression in Subcutaneous Adipose Tissue
Abstract
OBJECTIVE: The aim was to compare the effects of a traditional therapy (an oral estroprogestagen) to those of a novel treatment (a low-dose combination of generics) in adolescent girls with androgen excess. STUDY DESIGN AND METHODS: In an open-label trial over 1 yr, 34 adolescents (age, 16 yr; body mass index, 23 kg/m2) with hyperinsulinemic androgen excess and without pregnancy risk were randomized to receive daily ethinyl estradiol-cyproterone acetate (EE-CA; Diane 35 Diario) or a low-dose combination of pioglitazone 7.5 mg/d, flutamide 62.5 mg/d, and metformin 850 mg/d (PioFluMet). Markers of androgen excess, C-reactive protein, high molecular weight adiponectin, lipids, carotid intima media thickness, body composition (absorptiometry), abdominal fat partitioning (magnetic resonance imaging), and gene expression in longitudinal biopsies of sc adipose tissue at the abdominal level (RT-PCR) were assessed at baseline and after 1 yr. RESULTS: EE-CA and low-dose PioFluMet reduced androgen excess comparably, but had divergent effects on C-reactive protein, high molecular weight adiponectin, lipids, carotid intima media thickness, lean mass, abdominal and visceral fat, and on the expression of CD163, leptin, TNF-like weak inducer of apoptosis receptor, and angiopoietin-like protein 4, respectively, related to macrophage activation, fat accretion, inflammation, and lipoprotein metabolism in adipose tissue. All these divergences pointed to a healthier condition on low-dose PioFluMet. CONCLUSION: EE-CA and PioFluMet are similarly effective in reversing androgen excess over 1 yr, but low-dose PioFluMet is superior in reversing inflammatory, metabolic, and cardiovascular anomalies that are often associated with androgen excess.
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Intervention trials in adolescents with polycystic ovary syndrome have also shown improvements related to hirsutism, ovulation, quality of life, sleep, lipid profile, adipocytokine levels, and insulin resistance.
“These trials have also shown improvements related to hirsutism, ovulation, quality of life, sleep, lipid profile, adipocytokine levels, and insulin resistance [148-160]”
From The Diagnosis of Polycystic Ovary Syndrome during Adolescence (2015) · cites this paper as [150]
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- Authors
- Díaz, M., Chacón, M. R., López-Bermejo, A., Maymó-Masip, E., Salvador, C., Vendrell, J., de Zegher, F., & Ibáñez, L.
- Affiliations
- Hospital Sant Joan de Déu Barcelona (ES)
- Instituto de Salud Carlos III (ES)
- Corresponding author
- Ibáñez, Lourdes
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2012-10
- Volume
- 97
- Issue
- 10
- Pages
- 3630-3638
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2011658030
- Cited by
- 21
- References
- 39
- Citations by year
- 2025: 2 · 2023: 2 · 2022: 1 · 2021: 1 · 2019: 2 · 2018: 4 · 2017: 1 · 2016: 2 · 2015: 3 · 2013: 3
- FWCI
- 2.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Dermatology › Acne and Rosacea Treatments and Effects
- Keywords
- hyperandrogenism, adolescent girls, CD163, ANGPTL4, leptin, macrophage activation, adipose tissue inflammation, abdominal fat, carotid intima-media thickness, cardiovascular risk, C-reactive protein, adiponectin
- MeSH terms
- TWEAK Receptor, Angiopoietin-Like Protein 4, Pioglitazone, CD163 Antigen, Adolescent, Androgen Antagonists, Body Composition, Dose-Response Relationship, Drug, Drug Combinations, Ethinyl Estradiol, Female, Flutamide, Humans, Hypoglycemic Agents, Metformin, Receptors, Cell Surface, Antigens, Differentiation, Myelomonocytic, Antigens, CD, Gene Expression, Cyproterone Acetate, Hyperandrogenism, Receptors, Tumor Necrosis Factor, Leptin, Angiopoietins, Thiazolidinediones, Subcutaneous Fat, Abdominal Fat
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