Metabolic Mediation of the Association Between Hyperandrogenism and Paratubal Cysts in Polycystic Ovary Syndrome: A Structural Equation Modeling Approach
Abstract
1. Introduction
2. Methods
2.1. Study Population
2.2. PCOS Diagnosis Criteria
2.3. Clinical and Laboratory Measures
2.4. Assessment of PTCs
2.5. Statistical Analysis
3. Results
3.1. Comparison of Baseline Characteristics with and Without PTCs in Women with PCOS
3.2. Characteristics of Women Diagnosed with PTCs
3.3. Direct and Indirect Relationship Between Androgen Levels and PTC Occurrence
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Goodarzi, M.O.; Dumesic, D.A.; Chazenbalk, G.; Azziz, R. Polycystic ovary syndrome: Etiology, pathogenesis and diagnosis. Nat. Rev. Endocrinol. 2011, 7, 219–231. [Google Scholar] [CrossRef] [PubMed]
- Ojaniemi, M.; Pugeat, M. An adolescent with polycystic ovary syndrome. Eur. J. Endocrinol. 2006, 155, S149–S152. [Google Scholar] [CrossRef]
- Rosenfield, R.L. Identifying children at risk for polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 2007, 92, 787–796. [Google Scholar] [CrossRef]
- Liang, S.-J.; Hsu, C.-S.; Tzeng, C.-R.; Chen, C.-H.; Hsu, M.-I. Clinical and biochemical presentation of polycystic ovary syndrome in women between the ages of 20 and 40. Hum. Reprod. 2011, 26, 3443–3449. [Google Scholar] [CrossRef]
- Jones, H.; Sprung, V.S.; Pugh, C.J.; Daousi, C.; Irwin, A.; Aziz, N.; Adams, V.L.; Thomas, E.L.; Bell, J.D.; Kemp, G.J. Polycystic ovary syndrome with hyperandrogenism is characterized by an increased risk of hepatic steatosis compared to nonhyperandrogenic PCOS phenotypes and healthy controls, independent of obesity and insulin resistance. J. Clin. Endocrinol. Metab. 2012, 97, 3709–3716. [Google Scholar] [CrossRef]
- Sanchez-Garrido, M.A.; Tena-Sempere, M. Metabolic dysfunction in polycystic ovary syndrome: Pathogenic role of androgen excess and potential therapeutic strategies. Mol. Metab. 2020, 35, 100937. [Google Scholar] [CrossRef]
- Xu, Y.; Qiao, J. Association of insulin resistance and elevated androgen levels with polycystic ovarian syndrome (PCOS): A review of literature. J. Healthc. Eng. 2022, 2022, 9240569. [Google Scholar] [CrossRef]
- Parker, J.; Briden, L.; Gersh, F.L. Recognizing the role of insulin resistance in polycystic ovary syndrome: A paradigm shift from a glucose-centric approach to an insulin-centric model. J. Clin. Med. 2025, 14, 4021. [Google Scholar] [CrossRef] [PubMed]
- Diamanti-Kandarakis, E.; Dunaif, A. Insulin resistance and the polycystic ovary syndrome revisited: An update on mechanisms and implications. Endocr. Rev. 2012, 33, 981–1030. [Google Scholar] [CrossRef]
- Baranova, A.; Tran, T.P.; Birerdinc, A.; Younossi, Z.M. Systematic review: Association of polycystic ovary syndrome with metabolic syndrome and non-alcoholic fatty liver disease. Aliment. Pharmacol. Ther. 2011, 33, 801–814. [Google Scholar] [CrossRef] [PubMed]
- Muolokwu, E.; Sanchez, J.; Bercaw, J.L.; Sangi-Haghpeykar, H.; Banszek, T.; Brandt, M.L.; Dietrich, J.E. The incidence and surgical management of paratubal cysts in a pediatric and adolescent population. J. Pediatr. Surg. 2011, 46, 2161–2163. [Google Scholar] [CrossRef]
- Skaff, B.; Zoorob, D.; El Assaad, R.; Abou-Baker, M. Minimally Invasive Excision of a Giant Paratubal Cyst: Case Report and Management Review. Case Rep. Obstet. Gynecol. 2019, 2019, 3458230. [Google Scholar] [CrossRef]
- Kiseli, M.; Caglar, G.S.; Cengiz, S.D.; Karadag, D.; Yılmaz, M.B. Clinical diagnosis and complications of paratubal cysts: Review of the literature and report of uncommon presentations. Arch. Gynecol. Obstet. 2012, 285, 1563–1569. [Google Scholar] [CrossRef] [PubMed]
- Magistrado, L.; Dorland, J.; Sangi-Haghpeykar, H.; Patil, N.; Dietrich, J.E. Paratubal Cyst Recurrence in Children and Adolescents. J. Pediatr. Adolesc. Gynecol. 2020, 33, 649–651. [Google Scholar] [CrossRef]
- Genadry, R.; Parmley, T.; Woodruff, J.D. The origin and clinical behavior of the parovarian tumor. Am. J. Obstet. Gynecol. 1977, 129, 873–880. [Google Scholar] [CrossRef]
- Department of Child and Adolescent Health Development; WHO. Orientation Programme on Adolescent Health for Health Care Providers; World Health Organization: Geneva, Switzerland, 2019; pp. B5–B8. [Google Scholar]
- Azziz, R.; Carmina, E.; Dewailly, D.; Diamanti-Kandarakis, E.; Escobar-Morreale, H.F.; Futterweit, W.; Janssen, O.E.; Legro, R.S.; Norman, R.J.; Taylor, A.E.; et al. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: The complete task force report. Fertil. Steril. 2009, 91, 456–488. [Google Scholar] [CrossRef]
- The Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil. Steril. 2004, 81, 19–25. [Google Scholar] [CrossRef]
- Legro, R.S.; Arslanian, S.A.; Ehrmann, D.A.; Hoeger, K.M.; Murad, M.H.; Pasquali, R.; Welt, C.K. Diagnosis and treatment of polycystic ovary syndrome: An Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 2013, 98, 4565–4592. [Google Scholar] [CrossRef] [PubMed]
- Keskin, M.; Kurtoglu, S.; Kendirci, M.; Atabek, M.E.; 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, 115, e500–e503. [Google Scholar] [CrossRef] [PubMed]
- Vuguin, P.; Saenger, P.; Dimartino-Nardi, J. Fasting glucose insulin ratio: A useful measure of insulin resistance in girls with premature adrenarche. J. Clin. Endocrinol. Metab. 2001, 86, 4618–4621. [Google Scholar] [CrossRef]
- Legro, R.S.; Finegood, D.; Dunaif, A. A fasting glucose to insulin ratio is a useful measure of insulin sensitivity in women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 1998, 83, 2694–2698. [Google Scholar] [CrossRef] [PubMed]
- Practice Committee of the American Society for Reproductive Medicine. Diagnostic evaluation of the infertile female: A committee opinion. Fertil. Steril. 2015, 103, e44–e50. [Google Scholar] [CrossRef]
- Kim, J.J.; Chae, S.J.; Choi, Y.M.; Hwang, S.S.; Hwang, K.R.; Kim, S.M.; Yoon, S.H.; Moon, S.Y. Assessment of hirsutism among Korean women: Results of a randomly selected sample of women seeking pre-employment physical check-up. Hum. Reprod. 2011, 26, 214–220. [Google Scholar] [CrossRef]
- Won, Y.B.; Seo, S.K.; Yun, B.H.; Cho, S.; Choi, Y.S.; Lee, B.S. Non-alcoholic fatty liver disease in polycystic ovary syndrome women. Sci. Rep. 2021, 11, 7085. [Google Scholar] [CrossRef]
- Grundy, S.M.; Brewer, H.B., Jr.; Cleeman, J.I.; Smith, S.C., Jr.; Lenfant, C. Definition of metabolic syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 2004, 109, 433–438. [Google Scholar] [CrossRef]
- Zeng, X.; Xie, Y.-J.; Liu, Y.-T.; Long, S.-L.; Mo, Z.-C. Polycystic ovarian syndrome: Correlation between hyperandrogenism, insulin resistance and obesity. Clin. Chim. Acta 2020, 502, 214–221. [Google Scholar] [CrossRef]
- Brookhart, C.; Boehler-Tatman, M.; Malekyan, C.; Tucker, L.-Y.; Shirazi, A.; Cizek, S.; Woo, V. 88. Paratubal Cysts, PCOS, and Obesity in Adolescence: A Retrospective Cohort Study from a Large Integrated Health System. J. Pediatr. Adolesc. Gynecol. 2025, 38, 273. [Google Scholar] [CrossRef]
- Savelli, L.; Ghi, T.; De Iaco, P.; Ceccaroni, M.; Venturoli, S.; Cacciatore, B. Paraovarian/paratubal cysts: Comparison of transvaginal sonographic and pathological findings to establish diagnostic criteria. Ultrasound Obstet. Gynecol. 2006, 28, 330–334. [Google Scholar] [CrossRef] [PubMed]
- Rosseel, Y. lavaan: An R Package for Structural Equation Modeling. J. Stat. Softw. 2012, 48, 1–36. [Google Scholar] [CrossRef]
- MacKinnon, D.P.; Lockwood, C.M.; Williams, J. Confidence Limits for the Indirect Effect: Distribution of the Product and Resampling Methods. Multivar. Behav. Res. 2004, 39, 99–128. [Google Scholar] [CrossRef]
- Preacher, K.J.; Hayes, A.F. Asymptotic and resampling strategies for assessing and comparing indirect effects in multiple mediator models. Behav. Res. Methods 2008, 40, 879–891. [Google Scholar] [CrossRef]
- Huang-Doran, I.; Kinzer, A.B.; Jimenez-Linan, M.; Thackray, K.; Harris, J.; Adams, C.L.; de Kerdanet, M.; Stears, A.; O’Rahilly, S.; Savage, D.B.; et al. Ovarian hyperandrogenism and response to gonadotropin-releasing hormone analogues in primary severe insulin resistance. J. Clin. Endocrinol. Metab. 2021, 106, 2367–2383. [Google Scholar] [CrossRef]
- Muolokwu, E.; Sanchez, J.; Bercaw, J.L.; Sangi-Haghpeykar, H.; Banszek, T.; Brandt, M.L.; Dietrich, J.E. Paratubal cysts, obesity, and hyperandrogenism. J. Pediatr. Surg. 2011, 46, 2164–2167. [Google Scholar] [CrossRef]
- Dietrich, J.E.; Adeyemi, O.; Hakim, J.; Santos, X.; Bercaw-Pratt, J.L.; Bournat, J.C.; Chen, C.H.; Jorgez, C.J. Paratubal cyst size correlates with obesity and dysregulation of the Wnt signaling pathway. J. Pediatr. Adolesc. Gynecol. 2017, 30, 571–577. [Google Scholar] [CrossRef]
- Samaha, M.; Woodruff, J.D. Paratubal cysts: Frequency, histogenesis, and associated clinical features. Obstet. Gynecol. 1985, 65, 691–694. [Google Scholar]
- Darwish, A.M.; Amin, A.F.; Mohammad, S.A. Laparoscopic management of paratubal and paraovarian cysts. JSLS J. Soc. Laparoendosc. Surg. 2003, 7, 101–106. [Google Scholar]
- Guerriero, S.; Ajossa, S.; Piras, S.; Angiolucci, M.; Marisa, O.; Melis, G.B. Diagnosis of paraovarian cysts using transvaginal sonography combined with CA 125 determination. Ultrasound Obstet. Gynecol. 2006, 28, 856–858. [Google Scholar] [CrossRef]
- Stefanopol, I.A.; Baroiu, L.; Neagu, A.I.; Danila, D.M.; Nechifor, A.; Miulescu, M.; Balan, G.; Vasile, C.I.; Niculet, E.; Tatu, A.L. Clinical, imaging, histological and surgical aspects regarding giant paraovarian cysts: A systematic review. Ther. Clin. Risk Manag. 2022, 18, 513–522. [Google Scholar] [CrossRef]
Variables | With PTCs (n = 16) | Without PTCs (n = 561) | p-Value |
---|---|---|---|
Age at PCOS Dx (year) | 20.5 [17.0;23.5] | 24.0 [21.0;29.0] | 0.004 |
BMI (kg/m2) | 28.0 [24.9;31.3] | 22.4 [19.9;26.4] | 0.003 |
Obesity (n) | 12 (75%) | 183 (32.6%) | 0.001 |
Total cholesterol (mg/dL) | 195.0 [165.0;225.5] | 180.0 [161.0;204.0] | 0.191 |
Triglycerides (mg/dL) | 146.5 [87.5;207.0] | 81.5 [58.0;121.0] | 0.002 |
HDL (mg/dL) | 46.0 [37.0;61.0] | 57.0 [47.0;67.5] | 0.031 |
LDL (mg/dL) | 115.2 [95.5;149.7] | 101.0 [85.0;121.8] | 0.127 |
Fasting glucose (mg/dL) | 91.0 [87.0;103.0] | 91.0 [86.0;96.0] | 0.443 |
2-h 75 g GTT glucose (mg/dL) | 110.0 [97.5;140.0] | 104.0 [89.0;124.0] | 0.149 |
Fasting insulin (µU/mL) | 15.9 [11.4;24.1] | 8.9 [5.4;14.3] | 0.002 |
2-h 75 g GTT insulin (µU/mL) | 77.6 [45.4;150.6] | 51.1 [30.5;94.0] | 0.081 |
FGIR | 6.7 [3.7;9.0] | 10.1 [6.5;16.8] | 0.005 |
HOMA-IR | 3.6 [2.5;8.3] | 2.0 [1.2;3.3] | 0.002 |
Total testosterone (ng/dL) | 34.0 [25.8;59.4] | 41.5 [30.7;54.4] | 0.636 |
SHBG (nmol/L) | 22.9 [18.9;39.4] | 44.9 [26.7;70.4] | 0.014 |
FAI (%) | 5.0 [4.2;6.8] | 3.2 [1.7;6.2] | 0.038 |
DHEAS (µU/dL) | 205.0 [153.0;326.0] | 219.5 [164.0;289.0] | 0.728 |
LH (mIU/mL) | 10.2 [7.7;13.0] | 8.8 [5.5;13.9] | 0.599 |
FSH (mIU/mL) | 5.8 [5.0;6.6] | 6.2 [5.0;7.3] | 0.375 |
Estradiol (pg/mL) | 39.5 [28.0;73.0] | 45.0 [29.0;62.0] | 0.808 |
AMH (ng/mL) | 8.6 [5.8;11.8] | 11.0 [7.0;16.8] | 0.088 |
Clinical HA (n) | 12 (75%) | 370 (66.0%) | 0.627 |
NAFLD (n) † | 4 (25%) | 46 (8.2%) | 0.042 |
HTN (n) † | 1 (6.2%) | 37 (6.6%) | 1.000 |
Number of MetS components (n) † | |||
0 | 2 (12.5%) | 269 (48%) | |
1 | 4 (25%) | 138 (24.6%) | |
2 | 3 (18.8%) | 77 (13.7%) | |
≥3 | 7 (43.8%) | 77 (13.7%) | 0.004 |
Overall | 0.002 |
PTC Cases (%) | |
---|---|
Age at PCOS diagnosis | |
Adolescent | 5 (31) |
Adult (≥20 years old) | 11 (59) |
Method of diagnosis | |
Surgery | 10 (63) |
ultrasonography | 6 (38) |
Obesity | 12 (75) |
FAI > 4.5 | 10 (63) |
Clinical hyperandrogenism | 12 (75) |
Metabolic syndrome | 7 (44) |
Insulin resistance | |
FGIR < 7 for adolescents, <4.5 for adults | 7 (44) |
HOMA-IR > 3.16 for adolescents, >2.5 for adults | 11 (59) |
Pathway | Effect Type | Standardized Coefficient | p-Value |
---|---|---|---|
FAI → BMI | Direct | 0.47 | <0.001 |
BMI → PTC | Direct | 0.174 | 0.006 |
FAI → PTC | Direct | −0.092 | 0.015 |
FAI → BMI → PTC | Indirect | 0.082 | 0.010 |
FAI → PTC (Total effect) | Total | −0.01 | 0.705 |
Pathway | Effect Type | Standardized Coefficient | p-Value |
---|---|---|---|
FAI → HOMA-IR | Direct | 0.378 | <0.001 |
HOMA-IR → PTC | Direct | 0.156 | 0.042 |
FAI → PTC | Direct | −0.069 | 0.098 |
FAI → HOMA-IR → PTC | Indirect | 0.059 | 0.049 |
FAI → PTC (Total effect) | Total | −0.01 | 0.723 |
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Baek, J.K.; Hong, C.E.; Kim, H.Y.; Yun, B.H. Metabolic Mediation of the Association Between Hyperandrogenism and Paratubal Cysts in Polycystic Ovary Syndrome: A Structural Equation Modeling Approach. J. Clin. Med. 2025, 14, 5545. https://doi.org/10.3390/jcm14155545
Baek JK, Hong CE, Kim HY, Yun BH. Metabolic Mediation of the Association Between Hyperandrogenism and Paratubal Cysts in Polycystic Ovary Syndrome: A Structural Equation Modeling Approach. Journal of Clinical Medicine. 2025; 14(15):5545. https://doi.org/10.3390/jcm14155545
Chicago/Turabian StyleBaek, Jin Kyung, Chae Eun Hong, Hee Yon Kim, and Bo Hyon Yun. 2025. "Metabolic Mediation of the Association Between Hyperandrogenism and Paratubal Cysts in Polycystic Ovary Syndrome: A Structural Equation Modeling Approach" Journal of Clinical Medicine 14, no. 15: 5545. https://doi.org/10.3390/jcm14155545
APA StyleBaek, J. K., Hong, C. E., Kim, H. Y., & Yun, B. H. (2025). Metabolic Mediation of the Association Between Hyperandrogenism and Paratubal Cysts in Polycystic Ovary Syndrome: A Structural Equation Modeling Approach. Journal of Clinical Medicine, 14(15), 5545. https://doi.org/10.3390/jcm14155545