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Normalizing Ovulation Rate by Preferential Reduction of Hepato-Visceral Fat in Adolescent Girls With Polycystic Ovary Syndrome.

Abstract

PURPOSE

Polycystic ovary syndrome (PCOS) is an increasingly prevalent disorder in adolescent girls, commonly presenting with hirsutism/oligomenorrhea, commonly treated with an oral contraceptive (OC), and commonly followed by oligoanovulatory subfertility. We tested whether an intervention targeting the reduction of hepato-visceral adiposity is followed by a higher ovulation rate than OC treatment.

METHODS

This randomized, open-label, single-center, pilot proof-of-concept study (12 months on treatment, then 12 months off) was performed in adolescent girls with hirsutism and oligomenorrhea (PCOS by National Institutes of Health; no sexual activity; N = 36; mean age 16 years, body mass index 23.5 kg/m2; 94% study completion). Compared treatments were OC (ethinylestradiol-levonorgestrel) versus low-dose combination of spironolactone 50 mg/d, pioglitazone 7.5 mg/d, and metformin 850 mg/d (SPIOMET). Primary outcome was post-treatment ovulation rate inferred from menstrual diaries and salivary progesterone (12 + 12 weeks). Secondary outcomes included body composition (dual X-ray absorptiometry), abdominal fat (magnetic resonance imaging), insulinemia (oral glucose tolerance test), and androgenemia (liquid chromatography - tandem mass spectrometry).

RESULTS

SPIOMET was followed by a 2.5-fold higher ovulation rate than OC (p ≤ .001) and by a 6-fold higher normovulatory fraction (71% vs. 12%; p ≤ .001); oligoanovulation risk after SPIOMET was 65% lower (95% confidence interval, 40%-89%) than after OC. Higher post-treatment ovulation rates related to more on-treatment loss of hepatic fat (r2 = .27; p < .005). Visceral fat and insulinemia normalized only with SPIOMET; androgenemia normalized faster with OC but rebounded more thereafter. Body weight, lean mass, and abdominal subcutaneous fat mass remained stable in both groups.

CONCLUSIONS

Early SPIOMET treatment for PCOS normalized post-treatment ovulation rates more than OC. Focusing PCOS treatment on early reduction of hepato-visceral fat may prevent part of later oligoanovulatory subfertility.

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  • Authors+Show Affiliations

    ,

    Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), ISCIII, Madrid, Spain. Electronic address: libanez@hsjdbcn.org.

    ,

    Centro Médico CETIR, Barcelona, Spain.

    ,

    Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), ISCIII, Madrid, Spain.

    ,

    Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), ISCIII, Madrid, Spain.

    ,

    Bioanalysis Research Group, IMIM, Hospital del Mar, Barcelona, Spain.

    ,

    Department of Pediatrics, Dr. Josep Trueta Hospital, Girona Institute for Biomedical Research, Girona, Spain.

    Pediatric & Adolescent Endocrinology, Department of Development & Regeneration, University Hospital Gasthuisberg-University of Leuven, Leuven, Belgium.

    Source

    MeSH

    Adolescent
    Body Mass Index
    Contraceptives, Oral, Combined
    Drug Combinations
    Ethinyl Estradiol
    Female
    Hirsutism
    Humans
    Hypoglycemic Agents
    Infertility, Female
    Intra-Abdominal Fat
    Levonorgestrel
    Metformin
    Oligomenorrhea
    Ovulation
    Pioglitazone
    Polycystic Ovary Syndrome
    Spironolactone
    Thiazolidinediones

    Pub Type(s)

    Journal Article
    Randomized Controlled Trial

    Language

    eng

    PubMed ID

    28712591

    Citation

    Ibáñez, Lourdes, et al. "Normalizing Ovulation Rate By Preferential Reduction of Hepato-Visceral Fat in Adolescent Girls With Polycystic Ovary Syndrome." The Journal of Adolescent Health : Official Publication of the Society for Adolescent Medicine, vol. 61, no. 4, 2017, pp. 446-453.
    Ibáñez L, Del Río L, Díaz M, et al. Normalizing Ovulation Rate by Preferential Reduction of Hepato-Visceral Fat in Adolescent Girls With Polycystic Ovary Syndrome. J Adolesc Health. 2017;61(4):446-453.
    Ibáñez, L., Del Río, L., Díaz, M., Sebastiani, G., Pozo, Ó. J., López-Bermejo, A., & de Zegher, F. (2017). Normalizing Ovulation Rate by Preferential Reduction of Hepato-Visceral Fat in Adolescent Girls With Polycystic Ovary Syndrome. The Journal of Adolescent Health : Official Publication of the Society for Adolescent Medicine, 61(4), pp. 446-453. doi:10.1016/j.jadohealth.2017.04.010.
    Ibáñez L, et al. Normalizing Ovulation Rate By Preferential Reduction of Hepato-Visceral Fat in Adolescent Girls With Polycystic Ovary Syndrome. J Adolesc Health. 2017;61(4):446-453. PubMed PMID: 28712591.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Normalizing Ovulation Rate by Preferential Reduction of Hepato-Visceral Fat in Adolescent Girls With Polycystic Ovary Syndrome. AU - Ibáñez,Lourdes, AU - Del Río,Luis, AU - Díaz,Marta, AU - Sebastiani,Giorgia, AU - Pozo,Óscar J, AU - López-Bermejo,Abel, AU - de Zegher,Francis, Y1 - 2017/07/14/ PY - 2017/02/17/received PY - 2017/04/18/revised PY - 2017/04/19/accepted PY - 2017/7/18/pubmed PY - 2018/5/31/medline PY - 2017/7/18/entrez KW - Hepatic fat KW - Metformin KW - Ovulation KW - PCOS KW - Pioglitazone KW - Spironolactone KW - Visceral fat SP - 446 EP - 453 JF - The Journal of adolescent health : official publication of the Society for Adolescent Medicine JO - J Adolesc Health VL - 61 IS - 4 N2 - PURPOSE: Polycystic ovary syndrome (PCOS) is an increasingly prevalent disorder in adolescent girls, commonly presenting with hirsutism/oligomenorrhea, commonly treated with an oral contraceptive (OC), and commonly followed by oligoanovulatory subfertility. We tested whether an intervention targeting the reduction of hepato-visceral adiposity is followed by a higher ovulation rate than OC treatment. METHODS: This randomized, open-label, single-center, pilot proof-of-concept study (12 months on treatment, then 12 months off) was performed in adolescent girls with hirsutism and oligomenorrhea (PCOS by National Institutes of Health; no sexual activity; N = 36; mean age 16 years, body mass index 23.5 kg/m2; 94% study completion). Compared treatments were OC (ethinylestradiol-levonorgestrel) versus low-dose combination of spironolactone 50 mg/d, pioglitazone 7.5 mg/d, and metformin 850 mg/d (SPIOMET). Primary outcome was post-treatment ovulation rate inferred from menstrual diaries and salivary progesterone (12 + 12 weeks). Secondary outcomes included body composition (dual X-ray absorptiometry), abdominal fat (magnetic resonance imaging), insulinemia (oral glucose tolerance test), and androgenemia (liquid chromatography - tandem mass spectrometry). RESULTS: SPIOMET was followed by a 2.5-fold higher ovulation rate than OC (p ≤ .001) and by a 6-fold higher normovulatory fraction (71% vs. 12%; p ≤ .001); oligoanovulation risk after SPIOMET was 65% lower (95% confidence interval, 40%-89%) than after OC. Higher post-treatment ovulation rates related to more on-treatment loss of hepatic fat (r2 = .27; p < .005). Visceral fat and insulinemia normalized only with SPIOMET; androgenemia normalized faster with OC but rebounded more thereafter. Body weight, lean mass, and abdominal subcutaneous fat mass remained stable in both groups. CONCLUSIONS: Early SPIOMET treatment for PCOS normalized post-treatment ovulation rates more than OC. Focusing PCOS treatment on early reduction of hepato-visceral fat may prevent part of later oligoanovulatory subfertility. SN - 1879-1972 UR - https://www.unboundmedicine.com/medline/citation/28712591/Normalizing_Ovulation_Rate_by_Preferential_Reduction_of_Hepato-Visceral_Fat_in_Adolescent_Girls_With_Polycystic_Ovary_Syndrome L2 - https://linkinghub.elsevier.com/retrieve/pii/S1054-139X(17)30202-1 DB - PRIME DP - Unbound Medicine ER -