Skip to main content

Advertisement

SpringerLink
Log in

Effect of Three Androgen Indexes (FAI, FT, and TT) on Clinical, Biochemical, and Fertility Outcomes in Women with Polycystic Ovary Syndrome

  • Infertility: Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

This work sought to evaluate the effects of three androgen indexes of free testosterone (FT), total testosterone (TT), and free-androgen index (FAI) on clinical phenotype, endocrine metabolic disorders, and fertility outcomes in women with polycystic ovary syndrome. The data in this study came from a large, multicenter, randomized double-blind controlled clinical trial involving 1000 infertile PCOS patients. Baseline phenotypic, endocrine, and metabolic parameters and fertility outcomes undergoing ovulation induction were collected. FAI is superior to FT, and FT is superior to TT in terms of their correlation with anthropometric parameters and metabolic profile. FT and TT were significantly positively correlated with LH/FSH. FAI and FT were significantly correlated with the incidence of metabolic syndrome. FAI, FT, and TT were significantly positively correlated with polycystic ovary morphology and menstrual period. FAI was significantly related ovulations per cycle, pregnancy, conception, and live birth rates. After adjusting for age, the increased FT level was significantly related to the decreased rates of ovulations per cycle, conception, and pregnancy. FAI is superior to FT and FT is superior to TT in terms of their correlation with phenotypic and metabolic parameters in PCOS patients. FAI and FT are important factors related to the fertility outcomes of infertile PCOS patients. Clinical trial registration number: NCT01573858.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, et al. Position statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an androgen excess society guideline. J Clin Endocrinol Metab. 2006;91:4237–45.

    Article  CAS  Google Scholar 

  2. Fauser BC, Tarlatzis BC, Rebar RW, et al. Consensus on women’s health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Fertil Steril. 2012;97:28–38.

    Article  Google Scholar 

  3. Qiao J, Feng HL. Extra-and intra-ovarian factors in polycystic ovary syndrome: impact on oocyte maturation and embryo developmental competence. Hum Reprod Update. 2011;17:17–33.

    Article  Google Scholar 

  4. Diamanti-Kandarakis E, Christakou C, Kandarakis H. Polycystic ovarian syndrome: the commonest cause of hyperandrogenemia in women as a risk factor for metabolic syndrome. Minerva Endocrinol. 2007;32:35–47.

    CAS  PubMed  Google Scholar 

  5. Dahlgren E, Johansson S, Lindstedt G, Knutsson F, Odén A, Janson PO, et al. Women with polycystic ovary syndrome wedge resected in 1956 to 1965: a long-term follow-up focusing on natural history and circulating hormones. Fertil Steril. 1992;57:505–13.

    Article  CAS  Google Scholar 

  6. Franks S. Polycystic ovary syndrome. N Engl J Med. 1995;333:853–61.

    Article  CAS  Google Scholar 

  7. Cho LW, Kilpatrick ES, Jayagopal V, Diver MJ, Atkin SL. Biological variation of total testosterone, free androgen index and bioavailable testosterone in polycystic ovarian syndrome: implications for identifying hyperandrogenaemia. Clin Endocrinol. 2008;68:390–4.

    Article  CAS  Google Scholar 

  8. Wu XK, Stener-Victorin E, Kuang HY, Ma HL, Gao JS, Xie LZ, et al. Effect of acupuncture and clomiphene in Chinese women with polycystic ovary syndrome: a randomized clinical trial. JAMA. 2017;317:2502–14.

    Article  Google Scholar 

  9. Chen Z, Zhang Y, Liu J. Diagnosis of polycystic ovary syndrome: standard and guideline of Ministry of Health of People’s Republic of China. Zhonghua Fu Chan Ke Za Zhi 2012;47:74–5.

  10. Kuang H, Li Y, Wu X, Hou L, Wu T, Liu J, et al. Acupuncture and clomiphene citrate for live birth in polycystic ovary syndrome: study design of a randomized controlled trial. Evid Based Complement Alternat Med. 2013;2013:1–11.

    Article  Google Scholar 

  11. Zhao X, Ni R, Li L, Mo Y, Huang J, Huang M, et al. Defining hirsutism in Chinese women: a cross-sectional study. Fertil Steril. 2011;96:792–6.

    Article  Google Scholar 

  12. Tan JKL, Tang J, Fung K, Gupta AK, Thomas DR, Sapra S, et al. Development and validation of a comprehensive acne severity scale. J Cutan Med Surg. 2007;11:211–6.

    Article  Google Scholar 

  13. Grundy SM, Brewer HB Jr, Cleeman JI, et al. Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Arterioscler Thromb Vasc Biol. 2004;24:e13–8.

    CAS  PubMed  Google Scholar 

  14. Dumesic DA, Akopians AL, Madrigal VK, Ramirez E, Margolis DJ, Sarma MK, et al. Hyperandrogenism accompanies increased intra-abdominal fat storage in normal weight polycystic ovary syndrome women. J Clin Endocrinol Metab. 2016;101:4178–88.

    Article  CAS  Google Scholar 

  15. Amiri M, Tehrani FR, Nahidi F, et al. Association between biochemical hyperandrogenism parameters and Ferriman–Gallwey score in patients with polycystic ovary syndrome: a systematic review and meta-regression analysis. Clin Endocrinol. 2017;87:217–30.

    Article  CAS  Google Scholar 

  16. Blank SK, McCartney CR, Marshall JC. The origins and sequelae of abnormal neuroendocrine function in polycystic ovary syndrome. Hum Reprod Update. 2006;12:351–61.

    Article  CAS  Google Scholar 

  17. Gilling-Smith C, Willis DS, Beard RW, Franks S. Hypersecretion of androstenedione by isolated thecal cells from polycystic ovaries. J Clin Endocrinol Metab. 1994;79:1158–65.

    CAS  PubMed  Google Scholar 

  18. Yen SSC. Polycystic ovary syndrome. In: Yen SSC, Jaffe RB, Barbieri RL, editors. Reproductive endocrinology. 4th ed. Philadelphia: WB Saunders; 1999. p. 436–78.

    Google Scholar 

  19. Munir I, Yen HW, Geller DH, Torbati D, Bierden RM, Weitsman SR, et al. Insulin augmentation of 17-hydroxylase activity is mediated by phosphatidyl inositol 3-kinase but not extracellular signal-regulated kinase-1/2 in human ovarian theca cells. Endocrinology. 2004;145:175–83.

    Article  CAS  Google Scholar 

  20. Pedersen SB, Fuglsig S, Sjogren P, et al. Identification of steroid receptors in human adipose tissue. Eur J Clin Investig. 1996;26:1051–6.

    Article  CAS  Google Scholar 

  21. Corbould A. Chronic testosterone treatment induces selective insulin resistance in subcutaneous adipocytes of women. J Endocrinol. 2007;192:585–94.

    Article  CAS  Google Scholar 

  22. Corbould A. Effects of spironolactone on glucose transport and interleukin-6 secretion in adipose cells of women. Horm Metab Res. 2007;39:915–8.

    Article  CAS  Google Scholar 

  23. Diamanti-Kandarakis E, Mitrakou A, Raptis S, Tolis G, Duleba AJ. The effect of a pure antiandrogen receptor blocker, flutamide, on the lipid profile in the polycystic ovary syndrome. J Clin Endocrinol Metab. 1998;83:2699–705.

    Article  CAS  Google Scholar 

  24. Maggio M, Lauretani F, Basaria S, Ceda GP, Bandinelli S, Metter EJ, et al. Sex hormone binding globulin levels across the adult lifespan in women - the role of body mass index and fasting insulin. J Endocrinol Investig. 2008;31:597–601.

    Article  CAS  Google Scholar 

  25. Davison SL, Bell R, Donath S, Montalto JG, Davis SR. Androgen levels in adult females: changes with age, menopause, and oophorectomy. J Clin Endocrinol Metab. 2005;90:3847–53.

    Article  CAS  Google Scholar 

  26. Coviello AD, Legro RS, Dunaif A. Adolescent girls with polycystic ovary syndrome have an increased risk of the metabolic syndrome associated with increasing androgen levels independent of obesity and insulin resistance. J Clin Endocrinol Metab. 2006;91:492–7.

    Article  CAS  Google Scholar 

  27. Apridonidze T, Essah PA, Iuorno MJ, Nestler JE. Prevalence and characteristics of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2005;90:1929–35.

    Article  CAS  Google Scholar 

  28. Wu CH, Yang JG, Yang JJ, Lin YM, Tsai HD, Lin CY, et al. Androgen excess down-regulates connexin 43 in a human granulosa cell line. Fertil Steril. 2010;94:2938–41.

    Article  CAS  Google Scholar 

  29. Qureshi AI, Nussey SS, Bano G, Musonda P, Whitehead SA, Mason HD. Testosterone selectively increases primary follicles in ovarian cortex grafted onto embryonic chick membranes: relevance to polycystic ovaries. Reproduction. 2008;136:187–94.

    Article  CAS  Google Scholar 

  30. Younas K, Quintela M, Thomas S, et al. Delayed endometrial decidualisation in polycystic ovary syndrome; the role of AR-MAGEA11. J Mol Med (Berl). 2019;97:1315–27.

    Article  CAS  Google Scholar 

  31. Rahman TU, Ullah K, Guo MX, Pan HT, Liu J, Ren J, et al. Androgen-induced alterations in endometrial proteins crucial in recurrent miscarriages. Oncotarget. 2018;9:24627–41.

    Article  Google Scholar 

  32. Kim ST, Moley KH. Regulation of facilitative glucose transporters and AKT/MAPK/PRKAA signaling via estradiol and progesterone in the mouse uterine epithelium. Biol Reprod. 2009;81:188–98.

    Article  CAS  Google Scholar 

  33. Frolova AI, Moley KH. Glucose transporters in the uterus: an analysis of tissue distribution and proposed physiological roles. Reproduction. 2011;142:211–20.

    Article  CAS  Google Scholar 

  34. Frolova AI, Moley KH. Quantitative analysis of glucose transporter mRNAs in endometrial stromal cells reveals critical role of GLUT1 in uterine receptivity. Endocrinology. 2011;152:2123–8.

    Article  CAS  Google Scholar 

  35. Fornes R, Ormazabal P, Rosas C, Gabler F, Vantman D, Romero C, et al. Changes in the expression of insulin signaling pathway molecules in endometria from polycystic ovary syndrome women with or without hyperinsulinemia. Mol Med. 2010;16:129–36.

    Article  CAS  Google Scholar 

  36. Chang EM, Han JE, Seok HH, Lee DR, Yoon TK, Lee WS. Insulin resistance does not affect early embryo development but lowers implantation rate in in vitro maturation-in vitro fertilization-embryo transfer cycle. Clin Endocrinol. 2013;79:93–9.

    Article  Google Scholar 

  37. Mayama R, Izawa T, Sakai K, et al. Improvement of insulin sensitivity promotes extravillous trophoblast cell migration stimulated by insulin-like growth factor-I. Endocr J. 2013;60:359–68.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The Steering Committee (SC) members: Xiao-Ke Wu, Jiang-Ping Liu, Tai-Xiang Wu, Ernest HY Ng, Elisabet Stener-Victorin, and Heping Zhang and Richard S Legro (Chair). The Data and Safety Monitoring Board (DSMB) members: Esther Eisenberg, Wei-Liang Weng, Su-Lun Sun, Wei Zou, and Zi-Dan Chen and Robert Rebar (Chair). Meanwhile, the authors thank all of participants at each sub-center.

Funding

The National Clinical Trial Base in Chinese Medicine Special Projects (2015B009). National Public Welfare Projects for Chinese Medicine (201107005). The Heilongjiang Natural Science Foundation Project (LH2019H116).

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, 150040, People’s Republic of China

    Duojia Zhang, Jingshu Gao, Huichao Qin & Xiaoke Wu

  2. Department of Endocrinology, Xuzhou Central Hospital, Xuzhou, China

    Xuekui Liu

Authors
  1. Duojia Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jingshu Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xuekui Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Huichao Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiaoke Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Z.-D.J analyzed the data and drafted the manuscript. L.-X.K. and Q.-H.C statistically analyzed the data. X.-K.W. and G.-J.S conceived the study and revised the manuscript.

Corresponding author

Correspondence to Xiaoke Wu.

Ethics declarations

The protocol was approved by the institutional review board of each center. All subjects gave written consent before being enrolled in the trial.

Conflict of Interest

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic Supplementary Material

ESM 1

(DOCX 27 kb).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, D., Gao, J., Liu, X. et al. Effect of Three Androgen Indexes (FAI, FT, and TT) on Clinical, Biochemical, and Fertility Outcomes in Women with Polycystic Ovary Syndrome. Reprod. Sci. 28, 775–784 (2021). https://doi.org/10.1007/s43032-020-00316-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43032-020-00316-1

Keywords

Search

Navigation