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Polikistik over sendromlu obez olmayan kadınlarda progesteron ve progesteron kaynaklı bloke edici faktör (PIBF) düzeyleri

Year 2022, Volume: 47 Issue: 3, 1114 - 1120, 30.09.2022
https://doi.org/10.17826/cumj.1121724

Abstract

Amaç: Bu çalışmanın amacı obez olmayan polikistik over sendromlu (PKOS) hastalarda progesteron ve bir immün mediatör olan progesteron kaynaklı bloke edici faktör (PIBF) düzeylerini değerlendirmektir.
Gereç ve Yöntem: Hastalar iki gruba ayrıldı. Birinci grup PKOS tanısı alan hastalar (n=36), ikincisi sağlıklı kontrol grubu (n=36) idi. Rotterdam tanı kriterlerine göre PKOS tanısı konuldu. Hastalar 18-35 yaşları arasındaydı, obez değildi (Vücut kitle indeksi (VKİ)<25 kg/m2). Menstrual siklusun üçüncü gününde folikül uyarıcı hormon (FSH), luteinize edici hormon (LH), östradiol (E2), tiroid uyarıcı hormon (TSH), prolaktin (PRL), total testosteron ve dehidroepiandrostenedion sülfat (DHEA-S) seviyeleri ölçüldü. Aynı siklusun 21. gününde açlık kan şekeri, insülin, progesteron ve PIBF düzeyleri ölçüldü.
Bulgular: Çalışma gruplar arasında demografik ve klinik özellikleri benzerdi. Serum FSH, E2, TSH, PRL, DHEA-S, toplam testosteron, açlık kan şekeri, açlık insülini, insülin direnci için homeostatik model değerlendirmesi (HOMA-IR) ve hemoglobin A1c değerleri gruplar arasında benzerdi. LH, LH/FSH oranı, serum progesteron ve serum PIBF arasındaki farklar istatistiksel olarak anlamlıydı.
Sonuç: Sonuçlarımız obez olmayan PKOS hastalarında progesteron ve PIBF düzeylerinin düştüğünü gösterdi. PKOS'ta inflamasyonun kaynağı olan ve onu alevlendiren obezitenin yokluğunda bile, altta yatan immünomodülatör olarak düşük PIBF'nin komplikasyonları tetikleyeceğini öneriyoruz.

References

  • 1. Bozdag G, Mumusoglu S, Zengin D, Karabulut E, Yildiz BO. The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod 2016;31:2841-55.
  • 2. Azziz R, Dumesic DA, Goodarzi MO. Polycystic ovary syndrome: an ancient disorder? Fertil Steril 2011;95:1544-8.
  • 3. Amato G, Conte M, Mazziotti G, Lalli E, Vitolo G, Tucker AT et al. Serum and follicular fluid cytokines in polycystic ovary syndrome during stimulated cycles. Obstet Gynecol 2003;101:1177-82.
  • 4. Dabravolski SA, Nikiforov NG, Eid AH, Nedosugova LV, Starodubova AV, Popkova TV et al. Mitochondrial dysfunction and chronic inflammation in polycystic ovary syndrome. Int J Mol Sci 2021;22:3923.
  • 5. Qin L, Xu W, Li X, Meng W, Hu L, Luo Z et al. Differential expression profile of immunological cytokines in local ovary in patients with polycystic ovarian syndrome: analysis by flow cytometry. Eur J Obstet Gynecol Reprod Biol 2016;197:136-41.
  • 6. Gong P, Shi B, Wang J, Cao P, Diao Z, Wang Y et al. Association between Th1/Th2 immune imbalance and obesity in women with or without polycystic ovary syndrome. Gynecol Endocrinol 2018;34:709-14.
  • 7. Cohen RA, Check JH, Dougherty MP. Evidence that exposure to progesterone alone is a sufficient stimulus to cause a precipitous rise in the immunomodulatory protein the progesterone induced blocking factor (PIBF). J Assist Reprod Genet 2016;33:221-9.
  • 8. Szekeres‐Bartho J, Kilaŕ F, Falkay G, Csernus V, Török A, Pacsa A. The Mechanism of the Inhibitory Effect of Progesterone on Lymphocyte Cytotoxicity: I. Progesterone‐Treated Lymphocytes Release a Substance Inhibiting Cytotoxicity and Prostaglandin Synthesis. Am J Reprod Immunol Microbiol 1985;9:15-8.
  • 9. Lachmann M, Gelbmann D, Kalman E, POLGar B, Buschle M, Von Gabain A et al. PIBF (progesterone induced blocking factor) is overexpressed in highly proliferating cells and associated with the centrosome. Int J Cancer 2004;112:51-60.
  • 10. Szekeres-Bartho J, Autran B, Debre P, Andreu G, Denver L, Chaouat G. Immunoregulatory effects of a suppressor factor from healthy pregnant women's lymphocytes after progesterone induction. Cell Immunol 1989;122:281-94.
  • 11. Szekeres‐Bartho J, Faust Z, Varga P, Szereday L, Kelemen K. The immunological pregnancy protective effect of progesterone is manifested via controlling cytokine production. Am J Reprod Immunol 1996;35:348-51.
  • 12. Sahin ME, Madendag IC, Sahin E, Madendag Y, Karakukcu C. The role of serum progesterone induced blocking factor on unexplained infertility. Eur J Obstet Gynecol Reprod Biol 2020;252:15-8.
  • 13. Ferriman D, Gallwey J. Clinical assessment of body hair growth in women. J Clin Endocrinol Metab 1961;21:1440-7.
  • 14. Doshi A, Zaheer A, Stiller MJ. A comparison of current acne grading systems and proposal of a novel system. Int J Dermatol 1997;36:416-8.
  • 15. Akdemir E, Sahin E, Madendag Y, Sahin ME, Madendag IC, Acmaz G et al. Effect of preeclampsia and preeclampsia severity on insulin, HOMA-IR, and betatrophin levels in non-diabetic pregnant women. Placenta 2020;100:54-9.
  • 16. Van Elten T, Karsten M, Geelen A, Gemke R, Groen H, Hoek A et al. Preconception lifestyle intervention reduces long term energy intake in women with obesity and infertility: a randomised controlled trial. Int J Behav Nutr Phys Act 2019;16:1-10.
  • 17. Talukdar S, Bandyopadhyay G, Li D, Xu J, McNelis J, Lu M et al. Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. Nat Med 2012;18:1407-12.
  • 18. Karsten MD, van Oers AM, Groen H, Mutsaerts MA, van Poppel MN, Geelen A et al. Determinants of successful lifestyle change during a 6-month preconception lifestyle intervention in women with obesity and infertility. Eur J Nutr 2019;58:2463-75.
  • 19. Francisco V, Ruiz-Fernández C, Pino J, Mera A, Gonzalez-Gay MA, Gómez R et al. Adipokines: linking metabolic syndrome, the immune system, and arthritic diseases. Biochem Pharmacol 2019;165:196-206.
  • 20. González F, Rote NS, Minium J, Kirwan JP. Increased activation of nuclear factor κB triggers inflammation and insulin resistance in polycystic ovary syndrome. J Clin Endocrinol Metab 2006;91:1508-12.
  • 21. Bukulmez O, Arici A. Leukocytes in ovarian function. Hum Reprod Update 2000;6:1-15.
  • 22. Shi Y, Han T, Cui L, Wu G, Zheng R, Xia M et al. White blood cell differential counts in patients with polycystic ovary syndrome: a pilot study on Chinese women. Eur J Obstet Gynecol Reprod Biol 2013;170:162-4.
  • 23. Jakubowicz DJ, Iuorno MJ, Jakubowicz S, Roberts KA, Nestler JE. Effects of metformin on early pregnancy loss in the polycystic ovary syndrome. J Clin Endocrinol Metab 2002;87:524-9.
  • 24. Sagle M, Bishop K, Ridley N, Alexander F, Michel M, Bonney R et al. Recurrent early miscarriage and polycystic ovaries. BMJ 1988;297:1027.
  • 25. Hudić I, Fatušić Z. Progesterone–induced blocking factor (PIBF) and Th1/Th2 cytokine in women with threatened spontaneous abortion. J Perinat Med 2009;37:338-42.
  • 26. Palomba S, Santagni S, La Sala GB. Progesterone administration for luteal phase deficiency in human reproduction: an old or new issue? J Ovarian Res 2015;8:1-15.
  • 27. Hu S, Leonard A, Seifalian A, Hardiman P. Vascular dysfunction during pregnancy in women with polycystic ovary syndrome. Hum Reprod 2007;22:1532-9.
  • 28. Polgár B, Nagy E, Mikó É, Varga P, Szekeres-Barthó J. Urinary progesterone-induced blocking factor concentration is related to pregnancy outcome. Biol Reprod 2004;71:1699-705.

Progesterone and progesterone-induced blocking factor (PIBF) levels in non-obese women with polycystic ovary syndrome

Year 2022, Volume: 47 Issue: 3, 1114 - 1120, 30.09.2022
https://doi.org/10.17826/cumj.1121724

Abstract

Purpose: This study aimed to evaluate the level of progesterone and progesterone-induced blocking factor (PIBF), an immune mediator, in non-obese patients with polycystic ovary syndrome (PCOS).
Materials and Methods: Totally 72 patients were recruited into study and divided into 2 groups: The first group was patients diagnosed with PCOS (n = 36) and the second was the healthy control group (n=36). The diagnosis of PCOS was made according to Rotterdam diagnostic criteria. All patients were 18–35 years old and non-obese (body mass index (BMI) < 25 kg/m2). Follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), thyroid-stimulating hormone (TSH), prolactin (PRL), total testosterone, and dehydroepiandrostenedione sulfate (DHEA-S) levels were measured on the third day of the menstrual cycle. On the 21st day of the same menstrual period, fasting blood glucose, insulin, progesterone, and PIBF levels were measured.
Results: Demographic and clinical characteristics of study participants were similar between the two groups. Serum FSH, E2, TSH, PRL, DHEA-S, total testosterone, fasting blood glucose, fasting insulin, homeostatic model assessment for insulin resistance (HOMA-IR), and hemoglobin A1c values were similar between the groups. Differences in LH, LH/FSH ratio, serum progesterone, and serum PIBF were statistically significant.
Conclusion: Progesterone and PIBF levels decreased in non-obese PCOS patients. We suggest that even in the absence of obesity, which is the origin and enhancer of inflammation in PCOS, low PIBF as the underlying immunomodulator will drive complications.

References

  • 1. Bozdag G, Mumusoglu S, Zengin D, Karabulut E, Yildiz BO. The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod 2016;31:2841-55.
  • 2. Azziz R, Dumesic DA, Goodarzi MO. Polycystic ovary syndrome: an ancient disorder? Fertil Steril 2011;95:1544-8.
  • 3. Amato G, Conte M, Mazziotti G, Lalli E, Vitolo G, Tucker AT et al. Serum and follicular fluid cytokines in polycystic ovary syndrome during stimulated cycles. Obstet Gynecol 2003;101:1177-82.
  • 4. Dabravolski SA, Nikiforov NG, Eid AH, Nedosugova LV, Starodubova AV, Popkova TV et al. Mitochondrial dysfunction and chronic inflammation in polycystic ovary syndrome. Int J Mol Sci 2021;22:3923.
  • 5. Qin L, Xu W, Li X, Meng W, Hu L, Luo Z et al. Differential expression profile of immunological cytokines in local ovary in patients with polycystic ovarian syndrome: analysis by flow cytometry. Eur J Obstet Gynecol Reprod Biol 2016;197:136-41.
  • 6. Gong P, Shi B, Wang J, Cao P, Diao Z, Wang Y et al. Association between Th1/Th2 immune imbalance and obesity in women with or without polycystic ovary syndrome. Gynecol Endocrinol 2018;34:709-14.
  • 7. Cohen RA, Check JH, Dougherty MP. Evidence that exposure to progesterone alone is a sufficient stimulus to cause a precipitous rise in the immunomodulatory protein the progesterone induced blocking factor (PIBF). J Assist Reprod Genet 2016;33:221-9.
  • 8. Szekeres‐Bartho J, Kilaŕ F, Falkay G, Csernus V, Török A, Pacsa A. The Mechanism of the Inhibitory Effect of Progesterone on Lymphocyte Cytotoxicity: I. Progesterone‐Treated Lymphocytes Release a Substance Inhibiting Cytotoxicity and Prostaglandin Synthesis. Am J Reprod Immunol Microbiol 1985;9:15-8.
  • 9. Lachmann M, Gelbmann D, Kalman E, POLGar B, Buschle M, Von Gabain A et al. PIBF (progesterone induced blocking factor) is overexpressed in highly proliferating cells and associated with the centrosome. Int J Cancer 2004;112:51-60.
  • 10. Szekeres-Bartho J, Autran B, Debre P, Andreu G, Denver L, Chaouat G. Immunoregulatory effects of a suppressor factor from healthy pregnant women's lymphocytes after progesterone induction. Cell Immunol 1989;122:281-94.
  • 11. Szekeres‐Bartho J, Faust Z, Varga P, Szereday L, Kelemen K. The immunological pregnancy protective effect of progesterone is manifested via controlling cytokine production. Am J Reprod Immunol 1996;35:348-51.
  • 12. Sahin ME, Madendag IC, Sahin E, Madendag Y, Karakukcu C. The role of serum progesterone induced blocking factor on unexplained infertility. Eur J Obstet Gynecol Reprod Biol 2020;252:15-8.
  • 13. Ferriman D, Gallwey J. Clinical assessment of body hair growth in women. J Clin Endocrinol Metab 1961;21:1440-7.
  • 14. Doshi A, Zaheer A, Stiller MJ. A comparison of current acne grading systems and proposal of a novel system. Int J Dermatol 1997;36:416-8.
  • 15. Akdemir E, Sahin E, Madendag Y, Sahin ME, Madendag IC, Acmaz G et al. Effect of preeclampsia and preeclampsia severity on insulin, HOMA-IR, and betatrophin levels in non-diabetic pregnant women. Placenta 2020;100:54-9.
  • 16. Van Elten T, Karsten M, Geelen A, Gemke R, Groen H, Hoek A et al. Preconception lifestyle intervention reduces long term energy intake in women with obesity and infertility: a randomised controlled trial. Int J Behav Nutr Phys Act 2019;16:1-10.
  • 17. Talukdar S, Bandyopadhyay G, Li D, Xu J, McNelis J, Lu M et al. Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. Nat Med 2012;18:1407-12.
  • 18. Karsten MD, van Oers AM, Groen H, Mutsaerts MA, van Poppel MN, Geelen A et al. Determinants of successful lifestyle change during a 6-month preconception lifestyle intervention in women with obesity and infertility. Eur J Nutr 2019;58:2463-75.
  • 19. Francisco V, Ruiz-Fernández C, Pino J, Mera A, Gonzalez-Gay MA, Gómez R et al. Adipokines: linking metabolic syndrome, the immune system, and arthritic diseases. Biochem Pharmacol 2019;165:196-206.
  • 20. González F, Rote NS, Minium J, Kirwan JP. Increased activation of nuclear factor κB triggers inflammation and insulin resistance in polycystic ovary syndrome. J Clin Endocrinol Metab 2006;91:1508-12.
  • 21. Bukulmez O, Arici A. Leukocytes in ovarian function. Hum Reprod Update 2000;6:1-15.
  • 22. Shi Y, Han T, Cui L, Wu G, Zheng R, Xia M et al. White blood cell differential counts in patients with polycystic ovary syndrome: a pilot study on Chinese women. Eur J Obstet Gynecol Reprod Biol 2013;170:162-4.
  • 23. Jakubowicz DJ, Iuorno MJ, Jakubowicz S, Roberts KA, Nestler JE. Effects of metformin on early pregnancy loss in the polycystic ovary syndrome. J Clin Endocrinol Metab 2002;87:524-9.
  • 24. Sagle M, Bishop K, Ridley N, Alexander F, Michel M, Bonney R et al. Recurrent early miscarriage and polycystic ovaries. BMJ 1988;297:1027.
  • 25. Hudić I, Fatušić Z. Progesterone–induced blocking factor (PIBF) and Th1/Th2 cytokine in women with threatened spontaneous abortion. J Perinat Med 2009;37:338-42.
  • 26. Palomba S, Santagni S, La Sala GB. Progesterone administration for luteal phase deficiency in human reproduction: an old or new issue? J Ovarian Res 2015;8:1-15.
  • 27. Hu S, Leonard A, Seifalian A, Hardiman P. Vascular dysfunction during pregnancy in women with polycystic ovary syndrome. Hum Reprod 2007;22:1532-9.
  • 28. Polgár B, Nagy E, Mikó É, Varga P, Szekeres-Barthó J. Urinary progesterone-induced blocking factor concentration is related to pregnancy outcome. Biol Reprod 2004;71:1699-705.
There are 28 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Research
Authors

Mehmet Mete Kırlangıç 0000-0002-9750-1594

Mefkure Eraslan Şahin 0000-0001-6484-9132

Merve Vural Yalman 0000-0001-8933-9112

Esra Akdemir 0000-0002-3776-0674

İlknur Çöl Madendağ 0000-0001-6700-2236

Osman Sertaç Sade 0000-0001-9423-1544

Serhan Kütük 0000-0003-0836-8793

Publication Date September 30, 2022
Acceptance Date August 11, 2022
Published in Issue Year 2022 Volume: 47 Issue: 3

Cite

MLA Kırlangıç, Mehmet Mete et al. “Progesterone and Progesterone-Induced Blocking Factor (PIBF) Levels in Non-Obese Women With Polycystic Ovary Syndrome”. Cukurova Medical Journal, vol. 47, no. 3, 2022, pp. 1114-20, doi:10.17826/cumj.1121724.