Abstract
Purpose
Women with polycystic ovary syndrome (PCOS) have an increased ovarian responsiveness to exogenous recombinant follicle stimulating hormone (rFSH) but also have high rates of obesity, which is known to affect serum FSH concentrations following exogenous injection. The purpose of this study was to compare rFSH absorption and ovarian response between lean and overweight/obese PCOS subjects and normo-ovulatory controls.
Methods
Fourteen women with PCOS aged 18–42 years old with a BMI of 18.5–24.9 kg/m2 (normal) or 25.0–40.0 kg/m2 (overweight/obese) and eleven normo-ovulatory controls matched by age and BMI were included. After downregulation with oral contraceptives, participants were administered a single subcutaneous injection of 225 IU rFSH and underwent serial blood draws over 72 h.
Results
Lean PCOS subjects exhibited a significantly higher area under the curve (AUC) of baseline-corrected serum FSH over 72 h when compared with overweight/obese PCOS subjects (183.3 vs 139.8 IU*h/L, p = 0.0002), and lean, normo-ovulatory women had a significantly higher AUC FSH when compared with overweight/obese, normo-ovulatory women (193.3 vs 93.8 IU*h/L, p < 0.0001). Within overweight/obese subjects, those with PCOS had a significantly higher AUC FSH compared with normo-ovulatory controls (p = 0.0002). Lean PCOS subjects similarly had the highest AUC of baseline-corrected estradiol (6095 pg h/mL), compared with lean normo-ovulatory subjects (1931 pg h/mL, p < 0.0001) and overweight/obese PCOS subjects (2337 pg h/mL, p < 0.0001).
Conclusion
Lean PCOS subjects exhibited significantly higher baseline-corrected FSH and estradiol levels following rFSH injection compared with overweight/obese PCOS subjects with similar ovarian reserve markers. Amongst overweight/obese subjects, those with PCOS had significantly higher FSH and E2 levels when compared with normo-ovulatory controls.
Similar content being viewed by others
References
Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004;89(6):2745–9. https://doi.org/10.1210/jc.2003-032046.
Knochenhauer ES, Key TJ, Kahsar-Miller M, Waggoner W, Boots LR, Azziz R. Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study. J Clin Endocrinol Metab. 1998;83(9):3078–82. https://doi.org/10.1210/jcem.83.9.5090.
Diamanti-Kandarakis E, Kouli CR, Bergiele AT, Filandra FA, Tsianateli TC, Spina GG, et al. A survey of the polycystic ovary syndrome in the Greek Island of Lesbos: hormonal and metabolic profile. J Clin Endocrinol Metab. 1999;84:4006–11.
Goldzieher JW, Axelrod LR. Clinical and biochemical features of polycystic ovarian disease. Fertil Steril. 1963;14:631–53. https://doi.org/10.1016/s0015-0282(16)35047-6.
Ben-Rafael Z, Levy T, Schoemaker J. Pharmacokinetics of follicle-stimulating hormone: clinical significance. Fertil Steril. 1998;69:40S–9S.
Mannaerts B, de Leeuw R, Geelen J, Van Ravestein A, Van Wezenbeek P, Schuurs A, et al. Comparative in vitro and in vivo studies on the biological characteristics of recombinant human follicle-stimulating hormone. Endocrinology. 1991;129(5):2623–30. https://doi.org/10.1210/endo-129-5-2623.
Coffler MS, Patel K, Dahan MH, Malcom PJ, Kawashima T, Deutsch R, et al. Evidence for abnormal granulosa cell responsiveness to follicle stimulating hormone in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2003 Apr;88(4):1742–7. https://doi.org/10.1210/jc.2002-021280.
Rosencrantz MA, Wachs DS, Coffler MS, Malcom PJ, Donohue M, Chang RJ. Comparison of inhibin B and estradiol responses to intravenous FSH in women with polycystic ovary syndrome and normal women. Hum Reprod. 2010 Jan;25(1):198–203. https://doi.org/10.1093/humrep/dep373.
Erickson GF, Magoffin DA, Cragun JR, Chang RJ. The effects of insulin and insulin-like growth factors-I and -II on estradiol production by granulosa cells of polycystic ovaries. J Clin Endocrinol Metab. 1990 Apr;70(4):894–902. https://doi.org/10.1210/jcem-70-4-894.
Azziz R, Sanchez LA, Knochenhauer ES, Moran C, Lazenby J, Stephens KC, et al. Androgen excess in women: experience with over 1000 consecutive patients. J Clin Endocrinol Metab. 2004;89:453–62.
Steinkampf MP, Hammond KR, Nichols JE, Slayden SH. Effect of obesity on recombinant follicle-stimulating hormone absorption: subcutaneous versus intramuscular administration. Fertil Steril. 2003;80:99–102.
Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004 Jan;19(1):41–7. https://doi.org/10.1093/humrep/deh098.
Le Cotonnec JY, Loumaye E, Porchet HC, Beltrami V, Munafo A. Pharmacokinetic and pharmacodynamic interactions between recombinant human luteinizing hormone and recombinant human follicle-stimulating hormone. Fertil Steril. 1998 Feb;69(2):201–9. https://doi.org/10.1016/s0015-0282(97)00503-7.
Luke B, Brown MB, Morbeck DE, Hudson SB, Coddington CC, Stern JE. Factors associated with ovarian hyperstimulation syndrome (OHSS) and its effect on assisted reproductive technology (ART) treatment and outcome. Fertil Steril. 2010;94:1399–404.
Swanton A, Storey L, McVeigh E, Child T. IVF outcome in women with PCOS, PCO and normal ovarian morphology. Eur J Obstet Gynecol Reprod Biol. 2010;149:68–71.
Lee TH, Liu CH, Huang CC, Wu YL, Shih YT, Ho HN, et al. Serum anti-Müllerian hormone and estradiol levels as predictors of ovarian hyper stimulation syndrome in assisted reproduction technology cycles. Hum Reprod. 2008 Jan;23(1):160–7. https://doi.org/10.1093/humrep/dem254.
Jayaprakasan K, Chan Y, Islam R, Haoula Z, Hopkisson J, Coomarasamy A, et al. Prediction of in vitro fertilization outcome at different antral follicle count thresholds in a prospective cohort of 1,012 women. Fertil Steril. 2012;98:657–63.
Aramwit P, Pruksananonda K, Kasettratat N, Jammeechai K. Risk factors for ovarian hyperstimulation syndrome in Thai patients using gonadotropins for in vitro fertilization. Am J Health Syst Pharm. 2008;65:1148–53.
Ciampelli M, Fulghesu AM, Cucinelli F, Pavone V, Ronsisvalle E, Guido M, et al. Impact of insulin and body mass index on metabolic and endocrine variables in polycystic ovary syndrome. Metabolism. 1999 Feb;48(2):167–72. https://doi.org/10.1016/s0026-0495(99)90028-8.
Wachs DS, Coffler MS, Malcom PJ, Shimasaki S, Chang RJ. Increased androgen response to follicle-stimulating hormone administration in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2008 May;93(5):1827–33. https://doi.org/10.1210/jc.2007-2664.
Bergh C, Carlsson B, Olsson JH, Selleskog U, Hillensjö T. Regulation of androgen production in cultured human thecal cells by insulin-like growth factor I and insulin. Fertil Steril. 1993 Feb;59(2):323–31. https://doi.org/10.1016/s0015-0282(16)55675-1.
Nahum R, Thong KJ, Hillier SG. Metabolic regulation of androgen production by human thecal cells in vitro. Hum Reprod. 1995 Jan;10(1):75–81. https://doi.org/10.1093/humrep/10.1.75.
Wachs DS, Coffler MS, Malcom PJ, Chang RJ. Comparison of follicle-stimulating-hormone-stimulated dimeric inhibin and estradiol responses as indicators of granulosa cell function in polycystic ovary syndrome and normal women. J Clin Endocrinol Metab. 2006 Aug;91(8):2920–5. https://doi.org/10.1210/jc.2006-0442.
Acknowledgments
The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources, the National Center for Advancing Translational Science, or the National Institutes of Health.
Funding
This work was conducted with support from the Department of Obstetrics and Gynecology, Brigham and Women’s Hospital, Expanding the Boundaries Grant; EMD Serono; and Harvard Catalyst, The Harvard Clinical and Translational Science Center (the project was supported by Grant Number 1UL1TR002541-01, Harvard Clinical and Translational Science Center, from the National Center for Advancing Translational Science and Grant Number 1UL1TR001102). Research reported in this publication was supported in part by the Office of the Director, National Institutes of Health under Award Number P51OD011106 to the Wisconsin National Primate Research Center, University of Wisconsin-Madison.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee (Partners Healthcare Institutional Review Board) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Disclosure statement
MSL, AL, AVD, AB have nothing to disclose. ESG receives royalties from UpToDate.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Lee, M.S., Lanes, A., Dolinko, A.V. et al. The impact of polycystic ovary syndrome and body mass index on the absorption of recombinant human follicle stimulating hormone. J Assist Reprod Genet 37, 2293–2304 (2020). https://doi.org/10.1007/s10815-020-01865-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10815-020-01865-9