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The Journal of Clinical Endocrinology & Metabolism Vol. 89, No. 6 2741-2744
Copyright © 2004 by The Endocrine Society

The Investigation of Insulin Resistance in Patients with Idiopathic Hirsutism

Kürsad Ünlühizarci, Yesim Karababa, Fahri Bayram and Fahrettin Kelestimur

Department of Endocrinology, Erciyes University Medical School, 38039 Kayseri, Turkey

Address all correspondence and requests for reprints to: Prof. Fahrettin Kelestimur, Department of Endocrinology, Erciyes University Medical School, 38039 Kayseri, Turkey. E-mail: fktimur{at}erciyes.edu.tr.


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Discussion
 References
 
Hirsutism, which is characterized by excessive growth of terminal hair in a male pattern, is a common clinical condition in women. It may result from various causes including polycystic ovary syndrome, nonclassic adrenal hyperplasia, adrenal or ovarian tumors, or it may be idiopathic. Idiopathic hirsutism (IH) is considered to be one of the most common forms of hirsutism. Although not universal, insulin resistance and hyperinsulinemia have been demonstrated in women with polycystic ovary syndrome. Because there are not enough data showing whether patients with IH also have insulin resistance, we intended to investigate the presence/absence of insulin resistance in women with IH. Thirty-two women with IH [mean age, 24.8 ± 1.2 yr; body mass index (BMI), 24.6 ± 0.8 kg/m2] and 17 healthy women (mean age, 25.8 ± 0.6 yr; BMI, 22.5 ± 0.6 kg/m2) were included in the study. Eight of 32 patients with IH had BMI higher than 30 kg/m2. The presence of insulin resistance was investigated by using basal insulin levels, the oral glucose tolerance test, the iv insulin tolerance test, and the homeostasis model assessment (HOMA) score in both groups. Six (18.7%) patients had impaired glucose tolerance (IGT). Overall, patients with IH had significantly (P < 0.05) higher basal insulin levels (10.5 ± 1.1 mU/liter vs. 5.7 ± 0.9 mU/liter) and HOMA scores (2.0 ± 0.2 vs. 1.1 ± 0.2) and lower plasma glucose disappearance rate values (5.2 ± 0.2 vs. 6.0 ± 0.3) than control subjects. However, patients with IGT were notably more obese than the patients with a normal glucose tolerance test. Analyses after omitting the patients with IGT showed that there was still a significant (P < 0.05) difference in terms of basal insulin levels and HOMA scores. Six of eight (75%) obese patients with IH showed IGT. These data suggest that IH is associated with insulin resistance and an increased prevalence of IGT in obese patients.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Discussion
 References
 
HIRSUTISM, WHICH IS characterized by excessive growth of terminal hair in a male pattern, is a common clinical condition in women (1). It may result from various causes including polycystic ovary syndrome (PCOS), nonclassic adrenal hyperplasia, adrenal or ovarian tumors, or it may be idiopathic. Idiopathic hirsutism (IH) is considered to be one of the most common forms of hirsutism (2, 3). Because the definition of IH has varied during the last three decades, it is difficult to establish the estimate of its prevalence. Currently, IH is defined as hirsutism associated with normal ovulatory function and normal circulating serum androgen concentrations. In other words, the current diagnosis of IH depends on the exclusion of ovulatory dysfunction, hyperandrogenemia, and other androgen excess disorders (4).

The pathogenesis of IH is not clear. Increased peripheral 5{alpha}-reductase activity (5) and androgen receptor gene polymorphisms (6, 7) have been postulated to explain the pathogenesis of this disorder. Insulin resistance and hyperinsulinemia are now well known features of PCOS, and insulin-sensitizer drugs improve the hirsutism in patients with PCOS, however, there are not enough data whether patients with IH also have insulin resistance. Thus, our aim was to investigate the presence/absence of insulin resistance and hyperinsulinemia in women with IH.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Discussion
 References
 
Thirty-two women with IH and 17 healthy women were included in the study. None of the control subjects had ovarian dysfunction, hirsutism, or hyperandrogenemia. The purpose of the protocol was explained both to the patients and control subjects, and informed consent was obtained before beginning the study. The subjects were recruited sequentially from the clinic practice. The study was approved by the local Ethics Committee.

The diagnosis of IH was based on the presence of hirsutism (modified Ferriman-Gallwey score, >8) (8), regular ovulatory menstrual cycles, and a normal serum androgen profile including free testosterone, androstenedione, and dehydroepiandrosterone sulfate (DHEAS). Normal androgen levels were defined according to the reference values of the commercial kits. Thyroid dysfunction, hyperprolactinemia, nonclassic adrenal hyperplasia due to 21-hydroxylase and 11ß-hydroxylase deficiency, PCOS, and adrenal/ovarian tumors were excluded by appropriate tests and ultrasonography of the ovaries and the adrenal glands.

The presence of insulin resistance was investigated by using basal insulin levels, the oral glucose tolerance test (OGTT), the iv insulin tolerance test (ITT), and homeostasis model assessment (HOMA) score in both groups. The OGTT was performed after 10–12 h of fasting between 0800 and 1000 h. A 300-g carbohydrate diet was given for 3 d before the OGTT. After a basal blood sample was obtained, a 75-g glucose load was administered orally, and blood samples were obtained at 30-min intervals for 2 h for the measurement of glucose and insulin. Glucose tolerance was evaluated by using the criteria of the American Diabetes Association, and impaired glucose tolerance (IGT) was defined as a 2-h postload glucose of 140 mg/dl or greater and less than 200 mg/dl (9). The glucose and insulin responses to the OGTT were also expressed as area under the curve (AUC) estimated by the trapezoidal rule. The ITT was also used for the assessment of insulin sensitivity, as described by Bonora et al. (10). Briefly, the rate constant for the plasma glucose disappearance rate (KITT) was calculated from the formula (0.693/t1/2). The plasma glucose t1/2 was calculated from the slope of least square analysis of the plasma glucose concentrations from 3–15 min after iv insulin injection. The estimate of insulin resistance by HOMA score was calculated with the formula: fasting serum insulin (µU/ml) x fasting plasma glucose (mmol/liter)/22.5 (11).

None of the patients had used any medication known to interfere with carbohydrate metabolism and hirsutism. The patients and the healthy women were studied in the follicular phase (d 2–9) of their cycles. Ovulation was confirmed by d 24 serum progesterone levels (>8 nmol/liter) in the patients and healthy women before the follicular phase study.

Serum samples for hormone levels were drawn after an overnight fast in the follicular phase of the menstrual cycle. Serum samples were stored at –20 C until assayed. Serum FSH (ACS 180; Bayer, Tarrytown, NY), LH (ACS 180; Bayer), and estradiol (ACS 180; Bayer) levels were determined by an automated chemiluminescence system; free testosterone (DSL-4900; Diagnostic Systems Laboratories, Inc., Webster, TX), DHEAS (Immunotech, Marseille, France), androstenedione (Immunotech), and insulin (Diagnostic Products Corp., Los Angeles, CA) levels were measured by RIA; and the SHBG level was measured by immunoradiometric assay (Orion Diagnostica, Espoo, Finland), using commercial kits. The intraassay and interassay coefficients of variation were: 2.8 and 4.6% for FSH, 4.7 and 6.3% for LH, 7.2 and 7.5% for estradiol, 3.7 and 7.9% for free testosterone, 5.6 and 4.1% for DHEAS, 9.3 and 10.0% for insulin, 4.7 and 7.6% for androstenedione, and 4.0 and 5.5% for SHBG.

The results are reported as means ± SEM. The results of women with IH and healthy women were compared by using unpaired t test. P < 0.05 was regarded as statistically significant.


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Discussion
 References
 
Patients and control subjects did not differ in mean age (24.8 ± 1.2 and 25.8 ± 0.6 yr, respectively) and body mass index (BMI) (24.6 ± 0.8 and 22.5 ± 0.6 kg/m2, respectively; range, 18–33 for patients and 18–29 for control subjects) values, whereas the modified Ferriman-Gallwey score was significantly (P < 0.001) higher in the patients with IH (13.9 ± 0.7) than in the healthy women (1.6 ± 0.2). BMI was not an inclusion/exclusion criterion, and eight patients had a BMI higher than 30 kg/m2.

The hormonal profile of the patients and the control group is shown in Table 1Go. By definition, all the patients and healthy women had normal serum-free testosterone (<3.18 pg/ml), androstenedione (<3 ng/ml), and DHEAS (<3330 ng/ml) levels. However, patients with IH had significantly (P < 0.05) higher serum-free testosterone levels and lower serum estradiol levels than healthy women. The ratio of estradiol to testosterone was significantly lower (36.7 ± 7.9) in patients with IH than in the control subjects (81.8 ± 24.4). Serum LH, FSH, SHBG, androstenedione, and DHEAS levels were similar between the patients and control subjects (Table 1Go).


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  		TABLE 1. Hormonal characteristics of the patients with IH and control subjects

 
Fasting plasma glucose levels were similar in both groups. After the OGTT, six (18.7%) patients had IGT, and none of the patients was aware of this condition formerly. The AUCGlucose value was significantly (P < 0.05) higher in women with IH, and although it did not reach a significant level, the AUCinsulin value was also higher in women with IH than in the healthy women. Patients with IH had significantly (P < 0.05) higher basal insulin levels, HOMA scores, and lower KITT values than the control subjects (Table 2Go).


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  		TABLE 2. BMI-adjusted insulin resistance parameters in women with IH and control subjects

 
Analyses after omitting the patients with IGT showed that there was still a significant difference in terms of basal insulin levels (P < 0.05) and HOMA scores (P < 0.05). KITT was still lower in patients with IH, although it did not reach a significant level (P = 0.09). Data of the patients with IH and normal glucose tolerance are shown in Table 3Go. Patients with IGT were apparently more obese (32.1 ± 0.4 kg/m2) than the patients (22.8 ± 0.6 kg/m2) with a normal glucose tolerance test, and six of eight (75%) obese patients with IH showed IGT. The insulin resistance parameters of women with IH and IGT are shown in Table 4Go.


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  		TABLE 3. Hormonal characteristics and BMI-adjusted insulin resistance parameters of the patients with IH (excluding IGT subjects) and control subjects

 

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  		TABLE 4. The insulin resistance parameters of women with IH and IGT (n = 6)

 

   Discussion
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
References
 
Hirsutism is a sign of an underlying endocrine abnormality, namely, androgen excess or exaggerated androgen responsiveness. Not all hirsute patients have evidence of detectable androgen excess or endocrine imbalance, as in women with IH. The criteria used to diagnose IH have changed over the last years. Early reports defined IH as "hirsutism of unknown cause" regardless of whether they had elevated serum androgen levels (12, 13, 14). However, in conjuction with our understanding of various androgen excess disorders, the definition of IH has changed. IH can be easily diagnosed in hirsute patients who have normal serum androgen levels and regular menstrual cycles. By using these strict criteria, the prevalence of IH has been reported as 6% in Italy (15) and 17% in Alabama (16). In our population, IH is also a relatively common (16%) cause of hirsutism (17).

Until now, the pathogenesis of IH could not be established clearly. This deficiency is due to the fact that most previous studies have included patients in whom the diagnosis of IH was not strictly established. Although IH is thought to be caused by the increased sensitivity of the pilosebaceous unit to the circulating androgens, recently Rossi et al. (18) evaluated the adrenal and ovarian function in 48 young hirsute women by using GnRH analog and the ACTH stimulation test. The authors demonstrated that milder forms of functional ovarian and/or adrenal hyperandrogenism, similar to those found in hyperandrogenic women, were observed and could be an underlying mechanism of IH. Currently, the pathophysiology of IH is presumed to be a primary increase in skin 5{alpha}-reductase activity and possibly an alteration in androgen receptor function (4).

The two common disorders frequently associated with insulin resistance are PCOS and type 2 diabetes mellitus. It has been suggested that insulin plays an important role in the development of ovarian hyperandrogenism and related metabolic abnormalities (19). Ehrmann et al. (20) showed that women with PCOS have a substantially higher IGT and diabetes mellitus than age- and body weight-matched healthy women. Similarly, a higher prevalance of IGT (17.4%) has been found in young Turkish women with PCOS (21) than in young Turkish women overall (5.3%) (22). In contrast, there is not enough study regarding the abnormalities of insulin action in patients with IH. Paoletti et al. (23) noted that patients with IH have hyperinsulinemia and that it can be reversed by flutamide treatment. However, there is no universal agreement regarding the effect of flutamide on hyperinsulinemia (24, 25).

In the present study, we found a higher prevalance (18.7%) of IGT among women with IH, and patients with IH showed a more insulin-resistant state than control subjects. In contrast, analysis of the data after excluding the patients with IGT showed that patients with IH and normal glucose tolerance still exhibit an insulin-resistant state, whereas the presence of obesity notably increases glucose intolerance. Therefore, we suggest that insulin resistance and glucose intolerance may be associated with hirsute women regardless of whether they have PCOS or IH. In addition to metabolic consequences, insulin resistance may have a role in the clinical expression of hirsutism. The effect of insulin and the IGF system have been investigated in in vitro systems (26), and Itami et al. (27) showed that they have a role in stimulating hair follicle growth. It is possible that the insulin/IGF-I system may act in concert with androgens to stimulate hair growth.

The main purpose of this study was to investigate the presence or absence of insulin resistance and to determine the prevalence of glucose intolerance among women with IH. On the other hand, our results showed that patients with IH had significantly higher free testosterone levels and lower estradiol levels than healthy women. In other words, the ratio of estradiol to testosterone, which is the product of aromatase activity, is lower in patients with hirsutism. The skin, especially the pilosebaceous unit composed of sebaceous glands and hair follicles, can synthesize androgens de novo from cholesterol or by locally converting circulating weaker androgens to more potent ones. Aromatase, which is localized in fat cells and follicles, may play a "detoxifying" role by removing excess androgens (28). Although free testosterone and estradiol levels were within normal limits, our results indicate that an unbalance between these hormones may have a pathogenic role.

In conclusion, IH is associated with some degree of insulin resistance and an increased tendency for glucose intolerance notably in obese women with IH. Decreased aromatase activity may contribute to the pathogenesis of IH. More studies in larger numbers of patients should be performed to investigate the role of insulin resistance in women with IH. By establishing the pathogenetic mechanisms underlying IH, new therapeutic strategies may play an important role in offering more effective therapies.


   Footnotes
 
This study was presented in part at the 6th European Congress of Endocrinology, Lyon, France, 2003.

Abbreviations: AUC, Area under the curve; BMI, body mass index; DHEAS, dehydroepiandrosterone sulfate; HOMA, homeostasis model assessment; IH, idiopathic hirsutism; IGT, impaired glucose tolerance; ITT, iv insulin tolerance test; KITT, plasma glucose disappearance rate; OGTT, oral glucose tolerance test; PCOS, polycystic ovary syndrome.

Received September 17, 2003.

Accepted February 23, 2004.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
 References
 

  1. Zargar AH, Wani AI, Masoodi SR, Laway BA, Bashir MI, Salahuddin M 2002 Epidemiologic and etiologic aspects of hirsutism in Kashmiri women in the Indian subcontinent. Fertil Steril 77:674–678[CrossRef][Medline]
  2. Carmina E, Lobo RA 2001 Polycystic ovaries in hirsure women with normal menses. Am J Med 111:602–606[CrossRef][Medline]
  3. Yen SCC 1991 Chronic anovulation caused by peripheral endocrine disorders. In: Yen SCC, Jaffe RB, eds. Reproductive endocrinology. Philadelphia: Saunders Publishing Co.; 576–630
  4. Azziz R, Carmina E, Sawaya ME 2000 Idiopathic hirsutism. Endocr Rev 21:347–362[Abstract/Free Full Text]
  5. Serafini P, Lobo RA 1985 Increased 5a-reductase activity in idiopathic hirsutism. Fertil Steril 43:74–78[Medline]
  6. Sawaya ME, Shalita AR 1998 Androgen receptor polymorphisms (CAG repeat lengths) in androgenetic alopesia, hirsutism and acne. J Cutan Med Surg 3:9–15[Medline]
  7. Legro RS, Shahbahrami B, Lobo RA, Kovacs BW 1994 Size polymorphisms of the androgen receptor among female Hispanics and correlations with androhenic characteristics. Obstet Gynecol 83:701–706[Medline]
  8. Hatch R, Rosenfield RL, Kim MH, Tredway D 1981 Hirsutism: implications, etiology and management. Am J Obstet Gynecol 140:815–830[Medline]
  9. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus 1998 Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 21(Suppl 1):S5–S19
  10. Bonora E, Moghetti P, Zancarano C, Cigolini M, Quenen M, Cacciatori V, Corgnati A, Muggeo M 1989 Estimates of in vivo insulin action in man: comparison of insulin tolerance test with euglycemic and hyperglycemic glucose clamp studies. J Clin Endocrinol Metab 68:374–378[Abstract]
  11. Bonora E, Targher G, Alberiche M, Bonadonna RC, Saggiani F, Zenere MB, Monauni T, Muggeo M 2000 Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity. Diabetes Care 23:57–63[Abstract]
  12. Kirschner MA, Zucker RI, Jespersen D 1976 Idiopathic hirsutism-an ovarian abnormality. N Engl J Med 294:637–641[Abstract]
  13. Ettinger B, Goldfield EB, Burrill KC, Von Werder K, Forsham PH 1973 Plasma testosterone stimulation-suppression dynamics in hirsute women. Correlation with long term therapy. Am J Med 54:195–200[CrossRef][Medline]
  14. Pugeat M, Forest MG, Nisula BC, Corniau J, De Peretti E, Tourniaire J 1982 Evidence of excessive androgen secretion by both the ovary and the adrenal in patients with idiopathic hirsutism. Obstet Gynecol 59:46–51[Abstract/Free Full Text]
  15. Carmina E 1998 Prevalence of idiopathic hirsutism. Eur J Endocrinol 139:421–423[Abstract]
  16. Azziz R, Waggoner WT, Ochoa T, Knochenhauer ES, Boots LR 1998 Idiopathic hirsutism: an uncommon cause of hirsutism. Fertil Steril 70:274–278[CrossRef][Medline]
  17. Ünlühizarci K, Gökçe C, Atmaca H, Bayram F, Kelestimur F A detailed investigation of etiologies of hirsutism in a Turkish population. Program of the 6th European Congress of Endocrinology, Lyon, France, 2003, p 0011
  18. Rossi R, Tauchmanova L, Luciano A, Valentino R, Savastano S, Battista C Di Martino M, Lombardi G 2001 Functional hyperandrogenism detected by corticotropin and GnRH-analogue stimulation tests in women affected by apparently idiopathic hirsutism. J Endocrinol Invest 24:491–498[Medline]
  19. Baillargeon JP, Iuorno MJ, Nestler JE 2003 Insulin sensitizers for polycystic ovary syndrome. Clin Obstet Gynecol 46:325–340[CrossRef][Medline]
  20. Ehrmann DA, Barnes RB, Rosenfield RL, Cavaghan MK, Imperial J 1999 Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care 22:141–146[Abstract/Free Full Text]
  21. Ünlühizarci K, Çolak R, Sahin Y, Bayram F, Kelestimur F 2000 The prevalence of glucose intolerance in women with polycystic ovary syndrome. Turk J Endocrinol Metab 4:135–137
  22. Kelestimur F, Çetin M, Pasaoglu H, Çoksevim B, Çetinkaya F, Ünlühizarci K, Ünal S, Köker AH 1999 The prevalence and identification of risk factors for type 2 diabetes mellitus and impaired glucose intolerance in Kayseri, Central Anatolia, Turkey. Acta Diabetol 36:85–91[CrossRef][Medline]
  23. Paoletti AM, Cagnacci A, Orru M, Ajossa S, Guerriero S, Melis GB 1999 Treatment with flutamide improves hyperinsulinemia in women with idiopathic hirsutism. Fertil Steril 72:448–453[CrossRef][Medline]
  24. Ibanez L, Potau N, Marcos MV, de Zegher F 2000 Treatment of hirsutism, hyperandrogenism, oligomenorrhea, dyslipidemia, and hyperinsulinism in nonobese, adolescent girls: effect of flutamide. J Clin Endocrinol Metab 85:3251–3255[Abstract/Free Full Text]
  25. Diamanti-Kandarakis E, Mitrakou A, Raptis S, Tolis G, Duleba AJ 1998 The effect of a pure antiandrogen receptor blocker, flutamide, on the lipid profile in the polycystic ovary syndrome. J Clin Endocrinol Metab 83:2699–2705[Abstract/Free Full Text]
  26. Philpott MP, Sanders DA, Kealey T 1994 Effects of insulin and insulin-like growth factors on cultured human hair follicles: IGF-I at physiologic concentrations is an important regulator of hair follicle growth in vitro. J Invest Dermatol 102:857–861[CrossRef][Medline]
  27. Itami S, Kurata S, Takayasu S 1995 Androgen induction of follicular epithelial cell growth is mediated via insulin-like growth factor-I from dermal papilla cells. Biochem Biophys Res Commun 212:988–994[CrossRef][Medline]
  28. Chen W, Thiboutot D, Zouboulis CC 2002 Cutaneous androgen metabolism: basic research and clinical perspectives. J Invest Dermatol 119:992–1007[CrossRef][Medline]



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