The effects of metformin on hyperandrogenism and menstrual functions in insulin resistant adolescents with PCOS

Year 2022, Volume: 12 Issue: 3, 449 - 454, 30.05.2022

Müşerref Banu Yılmaz , Recai Pabuçcu

https://doi.org/10.16899/jcm.1065721

Abstract

Aim: To investigate the effects of metformin therapy on hyperandrogenism and menstrual functions in adolescent patients with polycystic ovary syndrome (PCOS) and insulin resistance (IR).
Materials and Methods: In this study, 50 adolescents with PCOS were included. Hormonal and ultrasonographic assessments were done at the early follicular phase. On the day of 19-21 of the cycle, progesterone levels were measured and patients were questioned for menstrual periods. Body-mass-indexes (BMI), waist-hip ratios, and Ferriman-Gallwey scores were calculated for all patients. IR is diagnosed according to HOMA index and insulin-resistant patients were instructed to use 1500 mg/day metformin for 3 months. After treatment ended, measurements were repeated by the same researcher.
Results: Mean age and BMI values were similar between groups. Although the values of BMI and waist/hip ratio decreased after treatment, the decrement didn't reach the values of the IR- group. Free testosterone levels were significantly higher in IR+ subjects compared to IR negatives and significantly decreased after treatment. Sex hormone-binding globulin levels were increased with metformin treatment and as a result, free androgen indexes were decreased. 17 OH progesterone levels were significantly higher in the IR+ group and regressed to similar levels with IR negatives after treatment. While mean levels of fasting insulin were 19.21IU/ml in the IR+ group, it regressed to 13.14IU/ml after treatment. Also fasting glucose/insulin ratios were increased as expected. Finally, a significant improvement in the treatment group was observed at menstrual irregularity.
Conclusion: Consequently, this study supports the conclusion that metformin reduces hyperandrogenism and improves menstrual and ovulatory functions.

Keywords

adolescent, polycystic ovary syndrome, insulin resistance, metformin

Adolesan polikistik over sendromlu hastalarda metformin tedavisinin hiperandrojenizm ve menstruel fonksiyonlar üzerine etkisi

Abstract

Amaç: Çalışmamızda insülin direnci olan adolesan polikistik over sendromlu hastalarda 1500 mg/gün metformin tedavisinin hiperandrojenizm ve menstrüel fonksiyonlar üzerine etkisinin değerlendirilmesi amaçlandı.
Gereç ve Yöntem: Çalışmamıza, polikistik over sendromlu 50 adölesan hasta dahil edildi. Tüm hastaların vücut kitle indeksleri (VKI), bel-kalça oranları ve Ferriman-Gallwey skorları hesaplandı. Erken foliküler fazda hormonal ve ultrasonografik değerlendirmeler yapıldı. Hastalar insülin resistansına (IR) göre gruplara ayrıldı. İnsüline dirençli 25 hastaya 3 ay süreyle 1500 mg/gün metformin kullanması önerildi. Tedavi bitimi tüm ölçümler tekrarlandı. Hastalar menstrüel fonksiyonlar açısından sorgulandı, siklusun 19-21. günlerinde progesteron düzeyi 3 ng/ml’nin üzerindeki değerlerde ovulasyonun gerçekleştiği kabul edildi.
Bulgular: Gruplar arasında ortalama yaş ve VKI açısından anlamlı fark yoktu. İnsülin rezistansı olan grubun bel çevresi kontrol grubuna göre fazla olup, tedavi sonrası kontrollerle benzer seviyelere inemediği gözlendi. DHEA-S ve T testosteron düzeyleri gruplar arasında benzerdi. F testosteron seviyeleri, IR+ hastalarda IR negatiflere kıyasla daha yüksekti ve tedaviden sonra önemli ölçüde azaldı(2.67'ye karşı 1.98 ng/mL, p>0.05) SHBG düzeylerinin metformin tedavisi ile arttığı, dolayısıyla serbest androjen indeksinin azaldığı izlendi(>0.05). 17 OH progesteron seviyeleri IR+ grubunda anlamlı olarak daha yüksekti ve tedavi sonrası IR negatifler ile benzer seviyelere geriledi. IR+ grubunda ortalama açlık insülin düzeyi 19.21IU/ml iken tedavi sonrası 13.14IU/ml'ye geriledi. Ayrıca açlık glukoz/insülin oranı 5,36 iken metforminden sonra 8,35'e kadar arttı. Menstrüel düzensizlikte tedavi grubunda belirgin düzelme gözlendi. Tedavi sonucu ovulatuar siklus oranı artış oldu ancak istatistiksel olarak anlamlı değildi. Hirsutizm skorları gruplar arasında benzerdi ve tedaviden sonra değişmedi.
Sonuç: Bu çalışma, insülin rezistan adolesan PKOS’lu hastalarda üç aylık metformin tedavisinin açlık kan şekeri ve açlık insülin seviyelerinde düşüşe neden olarak insülin rezistansının gerilemesine, buna sekonder olarak da serbest testosteron düzeylerini anlamlı oranda azalttığını göstermektedir. Ayrıca çalışmamız metforminin ovulatuar fonksiyonları iyileştirdiği sonucunu da desteklemektedir.

Keywords

adolesan, polikistik over sendromu, insülin direnci, metformin

References

• Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of polycystic ovary syndrome in an unselected population. JCEM 2004;89:2745-9.
• Bozdag G, Mumusoglu S, Zengin D et al. The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod 2016;31:2841.
• Teede HJ, Misso ML, Costello MF et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Hum Reprod 2018; Sep 1;33(9):1602-1618.
• Ibanez L, Valls C, Poteau N, Marcos MV, De Ziegher F. Sensitization to insulin in adolescent girls to normalize hirsutism, hyperandrogenism, oligomenorrhea, dyslipidemia, and hyperinsulinism after precocious pubarche. J Clin Endocrinol Metab 2000;85(10):3526-3530.
• Jones KL, Arslanian S, Peterokova VA, Park JS, Tomlinson MJ. Effect of metformin in pediatric patients with type 2 diabetes: a randomized controlled trial. Diabetes Care 2002;25:89-94.
• Keskin M, Kurtoglu S, Kendirci M, Atabek ME, Yazici C. Homeostasis model assessment is more reliable than the fasting glucose/insulin ratio and quantitative insulin sensitivity check index for assessing insulin resistance among obese children and adolescents. Pediatrics 2005; Apr;115(4):e500-3.
• Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412-419.
• Taylor HS, Pal L, Seli E. Speroff ’s Clinical Gynecologic Endocrinology and Infertility. 9th Edition. Lippincott Williams & Wilkins: Philadelphia, Pennsylvania, ABD; 2019.
• Wathen NC, Perry L. Interpretation of single progesterone measurement in the diagnosis of anovulation and defective luteal phase: observations on analysis of the normal range. Br Med J 1984;288:7.
• Ferrimann D, Gallway JD. Clinical assessment of body hair growth in women. J Clin Endocrinol Metab 1961;21:1440.
• WHO. 1988. Measuring obesity classification and description of anthropometric data. Copenhagen, Denmark: WHO Regional Office for Europe; Eur/ICP/ NUT 125-0612v.
• Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, Quon MJ. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 2000;85:2402-2410.
• Herter LD, Magalhaes JA, Spritzer PM. Relevance of the evaluation of ovarian volume in adolescent girls with menstrual disorders. J Clin Ultrasound 1996;24:243-8.
• Reinehr, T, Andler, W. Changes in the atherogenic risk factor profile according to the degree of weight loss. Arch Dis Child 2004; 89:419.
• Emoto M, Nishizawa Y, Maekawa K et al. Homeostasis model assessment as a clinical index of insulin resistance in type 2 diabetic patients treated with sulfonylureas. Diabetes Care 1999;22:818-82284.
• Hahn S, Kuehnel W, Tan S, Kramer K, Schmidt M, Roesler S, et al. Diagnostic value of calculated testosterone indices in the assessment of polycystic ovary syndrome. Clin Chem Lab Med 2007;45(2):202-7.
• Rosenfield RL, Ghai K, Ehrmann DA, Barnes RB. Diagnosis of the polycystic ovary syndrome in adolescence: comparison of adolescent and adult hyperandrogenism. J Pediatr Endocrinol Metab 2000;13:1285-9.
• Van Hoff MHA, Voorhorst FJ, Kaptein MBH, et al. Endocrine features of polycystic ovary syndrome in a random population sample of 14-16-year-old adolescents. Hum Reprod 1999;14:2223-2229.
• Gambineri A, Pelusi C, Vicennati V, Pagotto U, Pasquali R. Obesity and the polycystic ovary syndrome. Int J Obes Relat Metab Disord. 2002;26:883-96.
• Michelmore KF, Balen AH, Dunger DB, Vessey MP. Polycystic ovaries and associated clinical and biochemical features in young women. Clin Endocrinology 1999;51:779-86.
• Orsino A, N Van Eyk, J Hamilton. Clinic features, investigations, and management of adolescents with polycystic ovary syndrome. Pediatr Child Health 2005;10(10):602-608.
• Koulouri O, Conway GS. A systematic review of commonly used medical treatments for hirsutism in women. Clin Endocrinol (Oxf). 2008;68:800-5.
• Olutunmbi Y, Paley K, English JC III. Adolescent female acne: etiology and management. J Pediatr Adolesc Gynecol 2008;21:171-6.
• Ibanez L, Vals C, Poteau N, Marcos MV, De Ziegher F. Sensitization to insulin in adolescent girls to normalize hirsutism, hyperandrogenism, oligomenorrhea, dyslipidemia, and hyperinsulinism after precocious pubarche. J Clin Endocrinol Metab 2000;85:3526.
• Unluhizarci K, Kelestimur F, Bayram F, Tutus A. The effects of metformin on insulin resistance and ovarian steroidogenesis in women with polycystic ovary syndrome. Clin Endocrinol(Oxf). 1999;51:231-6.
• De Leo V, Musacchio MC, Morgante G, Piomboni P, Petraglia F. Metformin treatment is effective in obese teenage girls with PCOS. Hum Reprod. 2006;21:2252-6.
• Rosenfield RL, Ghai K, Ehrmann DA, Barnes RB. Diagnosis of the polycystic ovary syndrome in adolescence: comparison of adolescent and adult hyperandrogenism. J Pediatr Endocrinol Metab 2000;13:1285-9.