Androgen receptor gene polymorphism and sexual function in midlife women

  • Barbara Sutter
  • Manuela Fehr
  • Conny Hartmann
  • Stefan Schmid
  • Michael Zitzmann
  • Petra StuteEmail author
Gynecologic Endocrinology and Reproductive Medicine



To assess the impact of serum androgen levels and androgen receptor CAG polymorphism on sexual function in 45 healthy midlife women living in a heterosexual relationship.


Cross-sectional study [Cantonal Ethics Committee Bern (Ref.-Nr. KEK-BE: 087/13)]. Main outcome measures: Association between androgen serum levels, androgen receptor CAG polymorphism and sexual function was assessed by the FSFI-d questionnaire.


In our cohort of healthy, midlife, well-educated, middle-class, mostly postmenopausal women living in a heterosexual satisfying partnership, sexual function was perceived to remain stable or to decline during menopausal transition with sexual desire scoring lowest (FSFI-d 3.3 ± 0.9). Androgen serum levels did not correlate with sexual function. Mean CAG repeat number was 21.6 ± 1.9. There was a highly inverse though non-significant correlation between female sexual function and AR CAG repeat polymorphism with specifically higher numbers of CAG repeats being significantly positively correlated to more frequent or more severe pain during or after sexual intercourse.


The AR polymorphism is a non-negligible factor in female sexual function. Future studies on female sexual (dys)function should incorporate its assessment.


Androgen receptor gene polymorphism CAG repeat Sexual function Libido Serum testosterone Healthy midlife women 



The authors would like to thank D. Gafner and J. D. Wanner, study nurses, for their administrative assistance during the study. Furthermore, we would like to thank Unilabs SA, Bern, especially H. Frey and D. Gerber, for their financial and administrative support for blood chemistry analysis.

Author contributions

BS, MF, CH: data collection and manuscript writing; SS: providing the questionnaire about health, life satisfaction and sexuality in middle-aged women; MZ: protocol development, data analysis, and manuscript writing; PS: protocol/project development, funding, and manuscript writing.


Blood chemistry analysis was financially supported and performed by Unilabs SA, Bern.

Conflict of interest

B Sutter, M. Fehr, C. Hartmann, S. Schmid, M. Zitzmann and P. Stute declare to have no conflict of interest in context of this manuscript.

Data statement

Due to the sensitive nature of the questions asked in this study, survey respondents were assured raw data would remain confidential and would not be shared.

Supplementary material

404_2019_5052_MOESM1_ESM.docx (45 kb)
Supplementary material 1 (DOCX 44 kb)
404_2019_5052_MOESM2_ESM.docx (31 kb)
Supplementary material 2 (DOCX 31 kb)


  1. 1.
    Blümel JE, Chedraui P, Baron G, Belzares E, Bencosme A, Calle A, Espinoza MT, Flores D, Izaguirre H, Leon-Leon P, Lima S, Mezones-Holguin E, Monterrosa A, Mostajo D, Navarro D, Ojeda E, Onatra W, Royer M, Soto E, Vallejo S, Tserotas K (2009) Sexual dysfunction in middle-aged women: a multicenter Latin American study using the Female Sexual Function Index. Menopause (New York, NY) 16(6):1139–1148CrossRefGoogle Scholar
  2. 2.
    Mezones-Holguin E, Córdova-Marcelo W, Lau-Chu-Fon F, Aguilar-Silva C, Morales-Cabrera J, Bolaños-Díaz R, Pérez-López FR, Chedraui P (2011) Association between sexual function and depression in sexually active, mid-aged, Peruvian women. Climacteric 14(6):654–660CrossRefGoogle Scholar
  3. 3.
    Johannes CB, Clayton AH, Odom DM, Rosen RC, Russo PA, Shifren JL, Monz BU (2009) Distressing sexual problems in United States women revisited: prevalence after accounting for depression. J Clin Psychiatry 70(12):1698–1706CrossRefGoogle Scholar
  4. 4.
    Cumming GP, Currie HD, Moncur R, Lee AJ (2009) Web-based survey on the effect of menopause on women’s libido in a computer-literate population. Menopause Int 15(1):8–12CrossRefGoogle Scholar
  5. 5.
    Dennerstein L, Randolph J, Taffe J, Dudley E, Burger H (2002) Hormones, mood, sexuality, and the menopausal transition. Fertil Steril 77:42–48CrossRefGoogle Scholar
  6. 6.
    Burri A, Hilpert P, Spector T (2015) Longitudinal evaluation of sexual function in a cohort of pre- and postmenopausal women. J Sex Med 12(6):1427–1435CrossRefGoogle Scholar
  7. 7.
    Drillich A, Davis SR (2007) Androgen therapy in women: what we think we know. Exp Gerontol 42(6):457–462CrossRefGoogle Scholar
  8. 8.
    Davison SL, Davis SR (2011) Androgenic hormones and aging—the link with female sexual function. Horm Behav 59(5):745–753CrossRefGoogle Scholar
  9. 9.
    Basson R (2010) Testosterone therapy for reduced libido in women. Therap Adv Endocrinol Metab 1(4):155–164CrossRefGoogle Scholar
  10. 10.
    Wylie K, Rees M, Hackett G, Anderson R, Bouloux PM, Cust M, Goldmeier D, Kell P, Terry T, Trinick T, Wu F (2010) Androgens, health and sexuality in women and men. Maturitas 67(3):275–289CrossRefGoogle Scholar
  11. 11.
    Palacios S (2007) Androgens and female sexual function. Maturitas 57(1):61–65CrossRefGoogle Scholar
  12. 12.
    Jones A, Hwang DJ, Duke CB 3rd, He Y, Siddam A, Miller DD, Dalton JT (2010) Nonsteroidal selective androgen receptor modulators enhance female sexual motivation. J Pharmacol Exp Ther 334(2):439–448CrossRefGoogle Scholar
  13. 13.
    Maia H Jr, Casoy J, Valente J (2009) Testosterone replacement therapy in the climacteric: benefits beyond sexuality. Gynecol Endocrinol Off J Int Soc Gynecol Endocrinol 25(1):12–20CrossRefGoogle Scholar
  14. 14.
    Li J, Al-Azzawi F (2009) Mechanism of androgen receptor action. Maturitas 63(2):142–148CrossRefGoogle Scholar
  15. 15.
    Alberts BD, Hopkin K, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2005) Lehrbuch der Molekularen Zellbiologie, 3rd edn. Wiley-VCH Verlag GmbH & Co, WeinheimGoogle Scholar
  16. 16.
    Elaut E, Bogaert V, De Cuypere G, Weyers S, Gijs L, Kaufman JM, T’Sjoen G (2010) Contribution of androgen receptor sensitivity to the relation between testosterone and sexual desire: an exploration in male-to-female transsexuals. J Endocrinol Investig 33(1):37–41CrossRefGoogle Scholar
  17. 17.
    Goldstein AT, Belkin ZR, Krapf JM, Song W, Khera M, Jutrzonka SL, Kim NN, Burrows LJ, Goldstein I (2014) Polymorphisms of the androgen receptor gene and hormonal contraceptive induced provoked vestibulodynia. J Sex Med 11(11):2764–2771CrossRefGoogle Scholar
  18. 18.
    Brum IS, Spritzer PM, Paris F, Maturana MA, Audran F, Sultan C (2005) Association between androgen receptor gene CAG repeat polymorphism and plasma testosterone levels in postmenopausal women. J Soc Gynecol Investig 12(2):135–141CrossRefGoogle Scholar
  19. 19.
    Langdahl BL, Stenkjaer L, Carstens M, Tofteng CL, Eriksen EF (2003) A CAG repeat polymorphism in the androgen receptor gene is associated with reduced bone mass and increased risk of osteoporotic fractures. Calcif Tissue Int 73(3):237–243CrossRefGoogle Scholar
  20. 20.
    Saltiki K, Cimponeriu A, Garofalaki M, Sarika L, Papathoma A, Stamatelopoulos K, Alevizaki M (2011) Severity of coronary artery disease in postmenopausal women: association with the androgen receptor gene (CAG)n repeat polymorphism. Menopause (New York, N.Y.) 18(11):1225–1231CrossRefGoogle Scholar
  21. 21.
    Huang R, Wang G, Song Y, Wang F, Zhu B, Tang Q, Liu Z, Chen Y, Zhang Q, Muhammad S, Wang X (2015) Polymorphic CAG repeat and protein expression of androgen receptor gene in colorectal cancer. Mol Cancer Ther 14(4):1066–1074CrossRefGoogle Scholar
  22. 22.
    Paz YMC, Robles P, Salazar C, Leone PE, Garcia-Cardenas JM, Naranjo M, Lopez-Cortes A (2016) Positive association of the androgen receptor CAG repeat length polymorphism with the risk of prostate cancer. Mol Med Rep 14(2):1791–1798CrossRefGoogle Scholar
  23. 23.
    Zhu T, Yuan J, Xie Y, Li H, Wang Y (2016) Association of androgen receptor CAG repeat polymorphism and risk of epithelial ovarian cancer. Gene 575(2 Pt 3):743–746CrossRefGoogle Scholar
  24. 24.
    Berner M, Kriston L, Zahradnik H-P, Härter M, Rohde A (2004) Überprüfung der gültigkeit und zuverlässigkeit des deutschen Female Sexual Function Index (FSFI-d). Geburtshilfe Frauenheilkd 64(03):293–303CrossRefGoogle Scholar
  25. 25.
    Bucher T, Hornung R, Buddeberg C (2003) Sexualität in der zweiten Lebenshälfte. Zeitschrift für Sexualforschung 16(03):249–270CrossRefGoogle Scholar
  26. 26.
    Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62CrossRefGoogle Scholar
  27. 27.
    McKinlay JB, Feldman HA (1994) Age-related variation in sexual activity and interest in normal men: results from the Massachusetts Male Aging Study. In: Rossi AS (ed) Sexuality across the lifecourse. University of Chicago Press, Chicago, pp 261–85Google Scholar
  28. 28.
    Chedraui P, Perez-Lopez FR, San Miguel G, Avila C (2009) Assessment of sexuality among middle-aged women using the Female Sexual Function Index. Climacteric 12(3):213–221CrossRefGoogle Scholar
  29. 29.
    Stephenson KR, Meston CM (2010) Differentiating components of sexual well-being in women: are sexual satisfaction and sexual distress independent constructs? J Sex Med 7(7):2458–2468CrossRefGoogle Scholar
  30. 30.
    Blumel J, Bravo F, Recavarren M, Sarra S (2003) Sexual function in postmenopausal women using hormone replacement therapy. Revista medica de Chile 131(11):1251–1255Google Scholar
  31. 31.
    Berra M, De Musso F, Matteucci C, Martelli V, Perrone AM, Pelusi C, Pelusi G, Meriggiola MC (2010) The impairment of sexual function is less distressing for menopausal than for premenopausal women. J Sex Med 7(3):1209–1215CrossRefGoogle Scholar
  32. 32.
    Davison SL, Bell R, Donath S, Montalto JG, Davis SR (2005) Androgen levels in adult females: changes with age, menopause, and oophorectomy. J Clin Endocrinol Metab 90(7):3847–3853CrossRefGoogle Scholar
  33. 33.
    Guay A, Jacobson J (2002) Decreased free testosterone and dehydroepiandrosterone-sulfate (DHEA-S) levels in women with decreased libido. J Sex Marital Ther 28(S1):129–142CrossRefGoogle Scholar
  34. 34.
    Turna B, Apaydin E, Semerci B, Altay B, Cikili N, Nazli O (2005) Women with low libido: correlation of decreased androgen levels with female sexual function index. Int J Impot Res 17(2):148–153CrossRefGoogle Scholar
  35. 35.
    Jha S, Thakar R (2010) Female sexual dysfunction. Eur J Obstet Gynecol Reprod Biol 153(2):117–123CrossRefGoogle Scholar
  36. 36.
    Khera M (2015) Testosterone therapy for female sexual dysfunction. Sex Med Rev 3(3):137–144CrossRefGoogle Scholar
  37. 37.
    Braunstein GD (2002) Androgen insufficiency in women: summary of critical issues. Fertil Steril 77:94–99CrossRefGoogle Scholar
  38. 38.
    Blümel J, Del Pino M, Aprikian D, Vallejo S, Sarrá S, Castelo-Branco C (2008) Effect of androgens combined with hormone therapy on quality of life in post-menopausal women with sexual dysfunction. Gynecol Endocrinol 24(12):691–695CrossRefGoogle Scholar
  39. 39.
    Krapf JM, Simon JA (2009) The role of testosterone in the management of hypoactive sexual desire disorder in postmenopausal women. Maturitas 63(3):213–219CrossRefGoogle Scholar
  40. 40.
    Bhasin S, Enzlin P, Coviello A, Basson R (2007) Sexual dysfunction in men and women with endocrine disorders. Lancet 369(9561):597–611CrossRefGoogle Scholar
  41. 41.
    Wåhlin-Jacobsen S, Pedersen AT, Kristensen E, Læssøe NC, Lundqvist M, Cohen AS, Hougaard DM, Giraldi A (2015) Is there a correlation between androgens and sexual desire in women? J Sex Med 12(2):358–373CrossRefGoogle Scholar
  42. 42.
    Basson R, Brotto LA, Petkau AJ, Labrie F (2010) Role of androgens in women’s sexual dysfunction. Menopause 17(5):962–971CrossRefGoogle Scholar
  43. 43.
    Zitzmann M, Nieschlag E (2003) The CAG repeat polymorphism within the androgen receptor gene and maleness. Int J Androl 26(2):76–83CrossRefGoogle Scholar
  44. 44.
    Tirabassi G, Corona G, Biagioli A, Buldreghini E, Delli Muti N, Maggi M, Balercia G (2015) Influence of androgen receptor CAG polymorphism on sexual function recovery after testosterone therapy in late-onset hypogonadism. J Sex Med 12(2):381–388CrossRefGoogle Scholar
  45. 45.
    Liu CC, Lee YC, Wang CJ, Yeh HC, Li WM, Wu WJ, Huang CN, Bao BY, Huang CH, Huang SP (2012) The impact of androgen receptor CAG repeat polymorphism on and ropausal symptoms in different serum testosterone levels. J Sex Med 9(9):2429–2437CrossRefGoogle Scholar
  46. 46.
    Rajender S, Singh L, Thangaraj K (2007) Phenotypic heterogeneity of mutations in androgen receptor gene. Asian J Androl 9(2):147–179CrossRefGoogle Scholar
  47. 47.
    Schüring A, Welp A, Gromoll J, Zitzmann M, Sonntag B, Nieschlag E, Greb R, Kiesel L (2012) Role of the CAG repeat polymorphism of the androgen receptor gene in polycystic ovary syndrome (PCOS). Exp Clin Endocrinol Diabetes 120(02):73–79CrossRefGoogle Scholar
  48. 48.
    Baculescu N (2013) The role of androgen receptor activity mediated by the CAG repeat polymorphism in the pathogenesis of PCOS. J Med Life 6(1):18Google Scholar
  49. 49.
    Traish AM, Kim N, Min K, Munarriz R, Goldstein I (2002) Role of androgens in female genital sexual arousal: receptor expression, structure, and function. Fertil Steril 77:11–18CrossRefGoogle Scholar
  50. 50.
    Pelletier G, Ouellet J, Martel C, Labrie F (2012) Effects of ovariectomy and dehydroepiandrosterone (DHEA) on vaginal wall thickness and innervation. J Sex Med 9(10):2525–2533CrossRefGoogle Scholar
  51. 51.
    Francomano D, Greco EA, Lenzi A, Aversa A (2013) CAG repeat testing of androgen receptor polymorphism: is this necessary for the best clinical management of hypogonadism? J Sex Med 10(10):2373–2381CrossRefGoogle Scholar
  52. 52.
    van Anders SM, Goldey KL, Bell SN (2014) Measurement of testosterone in human sexuality research: methodological considerations. Arch Sex Behav 43(2):231–250CrossRefGoogle Scholar
  53. 53.
    Dąbrowska J, Drosdzol A, Skrzypulec V, Plinta R (2010) Physical activity and sexuality in perimenopausal women. Eur J Contracept Reprod Health Care 15(6):423–432CrossRefGoogle Scholar
  54. 54.
    Kim SI, Lee Y, Lim MC, Joo J, Park K, Lee DO, Park S-Y (2015) Quality of life and sexuality comparison between sexually active ovarian cancer survivors and healthy women. J Gynecol Oncol 26(2):148–154CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Internal MedicineHospital of ThunThunSwitzerland
  2. 2.Emergency CenterInselspital BernBernSwitzerland
  3. 3.Institute of Forensic MedicineUniversity of BernBernSwitzerland
  4. 4.Department of Psychosocial and Psychosomatical MedicineUniversity of ZurichZurichSwitzerland
  5. 5.Institute of Reproductive MedicineUniversity Clinic MuensterMuensterGermany
  6. 6.Department of Obstetrics and GynecologyInselspital BernBernSwitzerland

Personalised recommendations