Influence of Body Mass Index on Measured and Calculated Androgen Parameters in Adult Women with Hirsutism and PCOS

 

 Buy Article Permissions and Reprints

Abstract

There is growing evidence that obesity in women lead to a more severe form of hyperandrogenism and other endocrine abnormalities which may have some health implications later in life. Obese females are at higher risk for metabolic syndrome due to severe hyperandrogenemia. Calculated values for free testosterone are equivalent to those obtained by equilibrium dialysis, which is one of the reference measurement procedures (RMP) for estimation of free testosterone and may be capable of replacing values estimated using RMP's. For adult women correlations of body mass index (BMI) with calculated free (cFT) and bioavailable testosterone (cBT) are still rare, while these data are reported for peripubertal and adolescent girls. In this study we aimed to investigate the association between BMI and different androgen parameters (including calculated free and bioavailable testosterone, free androgen index, and sex hormone-binding globulin [SHBG]) in adult women with Hirsutism and with PCOS. In hirsute women with BMI ≥25 kg/m2 measured total testosterone (TT) was significantly higher, SHBG was significantly lower and the calculated androgen parameter (FAI, cFT and cBT) were significantly higher compared to women with BMI <25 kg/m2. In PCOS women with BMI ≥25 kg/m2 TT was significantly higher, SHBG was significantly lower and the calculated androgen parameter (FAI, cFT and cBT) were also significantly higher compared to women with BMI <25 kg/m2. In both the Hirsutism and PCOS-group there was a positive correlation between BMI and TT, cFT, and cBT, while BMI was negatively correlated with SHBG. In summary, in adult women with Hirsutism and PCOS obesity is associated with increased levels of TT and decreased levels of SHBG resulting in significant elevated calculated free and bioavailable testosterone levels. Obesity might lead to a more severe form of hyperandrogenism with elevated calculated free and bioavailable testosterone in the study population.

References

• 1 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 ((4)) 1929-1935
  CrossrefPubMedGoogle Scholar
• 2 Archer JS, Chang RJ. Hirsutism and acne in polycystic ovary syndrome.  Best Pract Res Clin Obstet Gynecol. 2004;  18 737-754
  PubMedGoogle Scholar
• 3 Azziz R. Diagnostic criteria for polycystic ovary syndrome: a reappraisal.  Fertil Steril. 2005;  83 1343-1346
  CrossrefPubMedGoogle Scholar
• 4 Azziz R, Carmina E, Sawaya ME. Idiopathic Hirsutism.  Endocr Rev. 2000;  21 ((4)) 347-362
  CrossrefPubMedGoogle Scholar
• 5 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;  89 453-462
  Google Scholar
• 6 Bjorntorp P. The regulation of adipose tissue distribution in humans.  Int J Obes Relat Metab Disord. 1996;  20 291-302
  PubMedGoogle Scholar
• 7 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;  91 492-497
  CrossrefPubMedGoogle Scholar
• 8 Dieudonne MN, Pecquery R, Boumediene A, Leneveu MC, Giudicelli Y. Androgen receptors in human preadipocytes and adipocytes: regional specificities and regulation by sex steroids.  Am J Physiol. 1998;  274 1645-1652
  PubMedGoogle Scholar
• 9 Ehrmann DA, Liljenquist DR, Kasza K, Azziz R, Legro RS, Ghazzi MN. PCOS/Troglitazone Study Group . Prevalence and predictors of the metabolic syndrome in women with polycystic ovary syndrome.  J Clin Endocrinol Metab. 2006;  91 ((1)) 48-53
  CrossrefPubMedGoogle Scholar
• 10 Elmlinger MW, Kuhnel W, Wormstall H, Doller PC. Reference intervals for testosterone, androstenedione and SHBG levels in healthy females and males from birth until old age.  Clin Lab. 2005;  51 625-632
  PubMedGoogle Scholar
• 11 Gambineri A, Pelusi C, Genghini S, Morselli-Labate AM, Cacciari M, Pagotto U, Pasquali R. Effect of flutamide and metformin administered alone or in combination in dieting obese women with polycystic ovary syndrome.  Clin Endocrinol (Oxf). 2004;  60 241-249
  CrossrefPubMedGoogle Scholar
• 12 Goodarzi MO, Azziz R. Diagnosis, epidemiology, and genetics of the polycystic ovary syndrome.  Best Pract Res Clin Endocrinol Metab. 2006;  20 193-205
  CrossrefPubMedGoogle Scholar
• 13 Hart R, Hickey M, Franks S. Definitions, prevalence and symptoms of polycystic ovaries and polycystic ovary syndrome.  Best Pract Res Clin Obstet Gynecol. 2004;  18 671-683
  PubMedGoogle Scholar
• 14 Hatch R, Rosenfield Rl, Moon HK, Tredway D. Hirsutism: implications, etiology and management.  Am J Obstet Gynecol. 1981;  140 815-830
  Google Scholar
• 15 Ibanez L, De Zegher F. Flutamide-metformin therapy to reduce fat mass in hyperinsulinemic ovarian hyperandrogenism: effects in adolescents and in women on third-generation oral contraception.  J Clin Endocrinol Metab. 2003;  88 4720-4724
  CrossrefPubMedGoogle Scholar
• 16 Ibanez L, Valls C, Ferrer A, Ong K, Dunger DB, De Zegher F. Additive effects of insulin-sensitizing and anti-androgen treatment in young, nonobese women with hyperinsulinism, hyperandrogenism, dyslipidemia, and anovulation.  J Clin Endocrinol Metab. 2002;  87 2870-2874
  CrossrefPubMedGoogle Scholar
• 17 Karelis AD, St-Pierre DH, Conus F, Rabasa-Lhoret R, Poehlman ET. Metabolic and body composition factors in subgroups of obesity: what do we know?.  J Clin Endocrinol Metab. 2004;  89 2569-2575
  CrossrefPubMedGoogle Scholar
• 18 Korhonen S, Hippelainen M, Vanhala M, Heinonen S, Niskanen L. The androgenic sex hormone profile is an essential feature of metabolic syndrome in premenopausal women: a controlled community-based study.  Fertil Steril. 2003;  79 1327-1334
  CrossrefPubMedGoogle Scholar
• 19 Kumar A, Woods KS, Bartolucci AA, Azziz R. Prevalence of adrenal androgen excess in patients with the polycystic ovary syndrome (PCOS).  Clin Endocrinol (Oxf). 2005;  62 644-649
  CrossrefPubMedGoogle Scholar
• 20 Li X, Lin JF. Clinical features, hormonal profile, and metabolic abnormalities of obese women with obese polycystic ovary syndrome [Abstract].  Zhonghua Yi Xue Za Zhi. 2005;  85 3266-3271
  PubMedGoogle Scholar
• 21 Ly PL, Handelsman DJ. Empirical estimation of free testosterone from testosterone and sex hormone-binding globulin immunoassays.  Eur J Endocrinol. 2005;  152 471-478
  CrossrefPubMedGoogle Scholar
• 22 Mathur RS, Moody LO, Landgrebbe S, Williamson HO. Plasma androgens and sex hormone binding globulin in the evaluation of hirsute patients.  Fertil Steril. 1981;  35 29-37
  PubMedGoogle Scholar
• 23 Marin P, Lonn L, Andersson B, Oden B, Olbe L, Bengtsson BA, Bjorntorp P. Assimilation of triglycerides in subcutaneous and intraabdominal adipose tissues in vivo in men: effects of testosterone.  J Clin Endocrinol Metab. 1996;  81 1018-1022
  CrossrefPubMedGoogle Scholar
• 24 McCartney CR, Prendergast KA, Chhabra S, Eagleson CA, Yoo R, Chang RJ, Foster CM, Marshall JC. The association of obesity and hyperandrogenemia during the pubertal transition in girls: obesity as a potential factor in the genesis of postpubertal hyperandrogenism.  J Clin Endocrinol Metab. 2006;  91 1714-1722
  CrossrefPubMedGoogle Scholar
• 25 Milewicz T, Krzysiek J, Janczak-Saif A, Sztefko K, Krzyczkowska-Sendrakowska M. Age, insulin, SHBG and sex steroids exert secondary influence on plasma leptin level in women.  Endokrynol Pol. 2005;  56 883-890
  PubMedGoogle Scholar
• 26 Mizutani T, Nishikawa Y, Adachi H, Enomoto T, Ikegami H, Kurachi H, Nomura T, Miyake A. Identification of estrogen receptor in human adipose tissue and adipocytes.  J Clin Endocrinol Metab. 1994;  78 950-954
  CrossrefPubMedGoogle Scholar
• 27 Mueller A, Cupisti S, Binder H, Hoffmann I, Beckmann MW, Dittrich R. The role of albumin in the calculation of free and bioavailable testosterone in women with hyperandrogenemia.  In Vivo. 2006a;  20 403-407
  PubMedGoogle Scholar
• 28 Mueller A, Dittrich R, Cupisti S, Beckmann MW, Binder H. Is it necessary to measure free testosterone to assess hyperandrogenemia in women? The role of calculated free and bioavailable testosterone.  Exp Clin Endocrinol Diabetes. 2006b;  114 182-187
  Article in Thieme ConnectPubMedGoogle Scholar
• 29 O'Brien SN, Welter BH, Mantzke KA, Price TM. Identification of progesterone receptor in human subcutaneous adipose tissue.  J Clin Endocrinol Metab. 1998;  83 509-513
  CrossrefPubMedGoogle Scholar
• 30 Price TM, O'Brien SN. Determination of estrogen receptor messenger ribonucleic acid (mRNA) and cytochrome P450 aromatase mRNA levels in adipocytes and adipose stromal cells by competitive polymerase chain reaction amplification.  J Clin Endocrinol Metab. 1993;  77 1041-1045
  CrossrefPubMedGoogle Scholar
• 31 Rotterdam ESHRE/ASRM-sponsored PCOS Consensus Workshop Group . Revised 2003 consensus on diagnostic criteria and long term health risk related to polycystic ovary syndrome (PCOS).  Hum Reprod. 2004;  19 1-7
  CrossrefPubMedGoogle Scholar
• 32 Rotterdam ESHRE/ASRM-sponsored PCOS Consensus Workshop Group . Revised 2003 consensus on diagnostic criteria and long term health risk related to polycystic ovary syndrome (PCOS).  Fertil Steril. 2004;  81 19-25
  PubMedGoogle Scholar
• 33 Souter I, Sanchez LA, Perez M, Bartolucci AA, Azziz R. The prevalence of androgen excess among patients with minimal unwanted hair growth.  Am J Obstet Gynecol. 2004;  191 759-767
  PubMedGoogle Scholar
• 34 Tsujimura A, Matsumiya K, Miyagawa Y, Takao T, Fujita K, Takada S. et al . Comparative study on evaluation methods for serum testosterone level for PADAM diagnosis.  Int J Impot Res. 2005;  23 1-5
  PubMedGoogle Scholar
• 35 Vague J, Meignen JM, Negrin JF. Effects of testosterone and estrogens on deltoid and trochanter adipocytes in two cases of transsexualism.  Horm Metab Res. 1984;  16 380-381
  PubMedGoogle Scholar
• 36 van Hooff MH, Voorhorst FJ, Kaptein MB, Hirasing RA, Koppenaal C, Schoemaker J. Insulin, androgen, and gonadotropin concentrations, body mass index, and waist to hip ratio in the first years after menarche in girls with regular menstrual cycles, irregular menstrual cycles, or oligomenorrhea.  J Clin Endocrinol Metab. 2000;  85 1394-1400
  CrossrefPubMedGoogle Scholar
• 37 Vanky E, Kjotrod S, Salvesen KA, Romundstad P, Moen MH, Carlsen SM. Clinical, biochemical and ultrasonographic characteristics of Scandinavian women with PCOS.  Acta Obstet Gynecol Scand. 2004;  83 482-486
  CrossrefPubMedGoogle Scholar
• 38 Vermeulen A, Verdonck L, Kaufmann JM. A Critical evaluation of simple methods for the estimation of free testosterone in serum.  J Clin Endocrinol Metab. 1999;  84 3666-3672
  CrossrefPubMedGoogle Scholar
• 39 Wabitsch M, Hauner H, Heinze E, Bockmann A, Benz R, Mayer H, Teller W. Body fat distribution and steroid hormone concentrations in obese adolescent girls before and after weight reduction.  J Clin Endocrinol Metab. 1995;  80 3469-3475
  CrossrefPubMedGoogle Scholar
• 40 Weiss R, Dziura J, Burgert TS, Tamborlane WV, Taksali SE, Yeckel CW, Allen K, Lopes M, Savoye M, Morrison J, Sherwin RS, Caprio S. Obesity and the metabolic syndrome in children and adolescents.  N Engl J Med. 2004;  350 2362-2374
  CrossrefPubMedGoogle Scholar

Correspondence

A. Mueller

Department of Obstetrics and Gynecology

Erlangen University Hospital

Universitätsstrasse 21-23

91054 Erlangen

Germany

Phone: +49/9131/853 35 53

Fax: +49/9131/853 35 52

Email: andreas.mueller@gyn.imed.uni-erlangen.de