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Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2007-0267
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The Journal of Clinical Endocrinology & Metabolism Vol. 92, No. 7 2739-2743
Copyright © 2007 by The Endocrine Society

Anti-Müllerian Hormone Levels in Peripubertal Daughters of Women with Polycystic Ovary Syndrome

Nicolás Crisosto, Ethel Codner, Manuel Maliqueo, Bárbara Echiburú, Fernando Sánchez, Fernando Cassorla and Teresa Sir-Petermann

Endocrinology and Metabolism Laboratory (N.C., M.M., B.E., F.S., T.S.-P.), West Division, and Institute of Maternal and Child Research (E.C., F.C.), School of Medicine, University of Chile, Casilla 33052, Correo 33, Santiago, Chile

Address all correspondence and requests for reprints to: Teresa Sir-Petermann, M.D., Laboratory of Endocrinology, Department of Medicine W. Division, School of Medicine, Las Palmeras 299, Interior Quinta Normal, Casilla 33052, Correo 33, Santiago, Chile. E-mail: tsir{at}med.uchile.cl.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Context: We have previously observed increased anti-Müllerian hormone (AMH) levels in prepubertal daughters of polycystic ovary syndrome (PCOS) women, suggesting that these girls may have an altered follicular development. However, it is not known whether AMH levels remain increased during puberty.

Objective: The aim was to establish whether the increased AMH levels observed in prepubertal daughters of PCOS women persist during the peripubertal period, a stage during which the gonadal axis is activated and PCOS may become clinically manifested.

Design: We studied 28 daughters (8–16 yr old) of PCOS women (PCOSd) and 33 daughters (8–16 yr old) of control women (Cd). In both groups, an oral glucose tolerance test was performed. Gonadotropins, sex hormones, and AMH were determined in a fasting sample.

Results: Both groups were comparable in age, body mass index, and breast Tanner stage. Free androgen index, testosterone, AMH (Cd 14.4 ± 8.0 pMvs. PCOSd 24.0 ± 19.0 pM; P = 0.012), and 2-h insulin levels were significantly higher in the PCOSd group compared with the control group. The average ovarian volume was significantly higher in the PCOSd group. In both groups a positive correlation between 2-h insulin and AMH concentrations was observed (PCOSd: r = 0.530, P = 0.007; Cd: r =0.561, P = 0.008).

Conclusions: AMH concentrations are increased in peripubertal PCOSd. These findings, along with the results of our previous study, suggest that PCOSd appear to show an increased follicular mass that is established during early development, and persists during puberty.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
POLYCYSTIC OVARY SYNDROME (PCOS) is a highly prevalent (5–10%) endocrine-metabolic dysfunction in premenopausal women, and is the most frequent cause of anovulatory infertility and hyperandrogenism in women. In addition, most women with PCOS also have peripheral insulin resistance (1, 2, 3). Insulin resistance and pancreatic ß-cell dysfunction, with increased risk for type 2 diabetes mellitus, are frequent comorbidities in PCOS patients (4, 5, 6).

Clinical signs of PCOS may emerge during the peripubertal period, and premature pubarche may constitute an early manifestation in some girls (7, 8, 9). However, in most girls, PCOS usually becomes clinically apparent during adolescence and early adulthood. Nevertheless, the clinical features that are used to diagnose PCOS in adult women are difficult to apply during adolescence. Furthermore, biochemical markers such as increased androgen and insulin secretion, typical of PCOS, may be observed in normal adolescents (10, 11, 12, 13). In this situation, a biochemical marker that might discriminate between normal and PCOS pubertal girls is not yet available.

Anti-Müllerian hormone (AMH), also called Müllerian-inhibiting substance, is a dimeric glycoprotein, member of the TGF superfamily (14, 15). AMH is produced exclusively in the gonads by Sertoli and granulosa cells (16), and its dimorphic expression in ovary and testis is crucial for the normal differentiation of reproductive structures (17). During fetal development, AMH is secreted by the immature Sertoli cells. The main role of AMH in the male fetus is to cause Müllerian ducts regression (15), but AMH is also involved in testicular development (18). AMH expression by granulosa cells is evident at the end of gestation, when it is secreted in small amounts by early developing follicles, allowing the differentiation of the Müllerian ducts (19). During postnatal life, gonadal AMH secretion shows a clear-cut sexual dimorphism in prepubertal children, when serum AMH is significantly lower in females (20, 21, 22). Mean serum AMH levels increase during late puberty (23) and then show a progressive decline along reproductive life in women (23, 24).

Serum AMH levels seem to correlate with the development of preantral and small antral follicles during reproductive life (21). It has been established that AMH levels are 2- to 3-fold higher during reproductive life in women with PCOS compared with healthy women (25, 26). This is related to the increased number of growing follicles that secrete AMH (27).

Recently, our group documented higher serum levels of AMH in daughters of PCOS women (PCOSd) compared with control girls (Cd) during two stages of sexual development, early infancy (2–3 months of age) and childhood (4–7 yr of age), suggesting the presence of an increased growing follicular pool in these girls (28).

The aim of the present study was to establish whether the increased AMH levels observed in prepubertal PCOSd persist during the peripubertal period, a stage during which the gonadal axis is activated, and PCOS may become clinically manifested.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Subjects

We studied 28 PCOSd (8–16 yr old). As a control group, we studied 33 daughters (8–16 yr old) of women with regular menses and without hyperandrogenism, history of infertility, or diabetes. The control group (Cd) was recruited from public schools, and we excluded girls with diabetes mellitus or glucose intolerance, hepatic, cardiac, pulmonary, or renal disease, and use of any medications.

Both groups of girls were matched for age, Tanner stage, and body mass index (BMI) at the beginning of the study.

PCOS mothers were recruited from patients attending the Unit of Endocrinology and Reproductive Medicine, University of Chile. Diagnosis of PCOS was made according to the National Institutes of Health consensus criteria (29). At the moment of diagnosis, all of the PCOS mothers exhibited chronic oligomenorrhea or amenorrhea, hirsutism, serum testosterone (T) more than 0.6 ng/ml, and/or free androgen index (FAI) more than 5.0, androstenedione ({Delta}4A) more than 3.0 ng/ml. In addition, PCOS women showed the characteristic ovarian morphology of polycystic ovaries on ultrasound, based on the criteria described by Adams et al. (30). PCOS mothers were normoglycemic, with varying degrees of hyperinsulinemia that were evaluated by an oral glucose tolerance test. All patients had an elevated waist-to-hip ratio greater than 0.85.

We excluded patients with hyperprolactinemia, androgen-secreting neoplasm, Cushing’s syndrome, and late-onset 21-hydroxylase deficiency, as well as thyroid disease.

We selected as control mothers, 33 women of similar socioeconomic level, with a history of singleton pregnancies, regular 28- to 32-d menstrual cycles, absence of hirsutism and other manifestations of hyperandrogenism, and no history of infertility or pregnancy complications.

The protocol was approved by the institutional review boards of the San Juan de Dios and San Borja Arriarán Hospitals, and the University of Chile. All parents signed informed consents before entering the study.

Study protocol

The girls were admitted with their mothers to the pediatric unit of our Clinical Research Center at approximately 0830 h. We performed a complete physical examination on each girl, including Tanner stage score determination for breast development and anthropometric measurements: weight, height, waist, hip, BMI, and BMI SD score (SDS), using current Centers for Disease Control and Prevention standard curves (31). Postmenarchal girls were studied in the early follicular phase of the menstrual cycle (d 3–7). In the premenarchal girls, the study was performed whenever feasible.

A 2 h, 1.75 g/kg, oral glucose tolerance test was performed with measurements of glucose and insulin in each sample. In the fasting sample, circulating concentrations of gonadotropins, T, {Delta}4A, estradiol (E2), 17-OH-progesterone (17-OHP), SHBG, and AMH were determined by specific assays.

On the following day, ultrasonography was performed and analyzed by a single observer (F.S.), who was blinded to the condition of the subject. The examination was performed transabdominally with a 5 MHz abdominal probe, using Medison Sonoace 6000C equipment (Medison Co., Ltd., Seoul, Korea). Ovarian volume was calculated using the simplified formula for a prolate ellipsoid.

Assays

Serum AMH was assayed by enzyme immunoassay (Immunotech-Beckman Coulter, Marseille, France) (32). Analytical sensitivity was 2.1 pM, and intraassay and interassay coefficients of variation were 5.3 and 8.7%, respectively.

Serum LH, FSH, and E2 were determined by electrochemiluminescence (Roche, Basel, Switzerland). Assay sensitivities were 0.1 IU/liter, 0.1 IU/liter, and 5.0 pg/ml, respectively. Intraassay and interassay coefficients of variation were 1.1 and 2.1% for LH, 1.7 and 3.7% for FSH, and 2.7 and 5.0% for E2.

Serum T and insulin were assayed by RIA (Diagnostic System Laboratories, Inc., Webster, TX), and {Delta}4A, 17-OHP, and SHBG were determined by radioimmunometric assay (Diagnostic Products Corp., Los Angeles, CA). Assay sensitivities were 0.1 ng/ml, 5 µIU/ml, 0.1 ng/ml, 0.1 ng/ml, and 0.04 nmol/liter, respectively. Intraassay and interassay coefficients of variation were 7.0 and 11.0% for T, 5 and 8% for insulin, 3.7 and 4.9% for {Delta}4A, 3.5 and 5.0% for 17-OHP, and 3.8 and 7.9% for SHBG. Plasma glucose levels were determined by the glucose oxidase method (Photometric Instrument 4010; Roche).

Statistical evaluation

Data were normally distributed, and expressed as means and SD values. Differences between groups were assessed by the Student’s t test. The correlation between continuous variables was assessed using Pearson’s correlation coefficient. Statistical analysis was performed using the Statistical Package for the Social Sciences software (version 10.0; SPSS, Inc., Chicago, IL). A P value < 0.05 was considered statistically significant.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
Both groups of girls were comparable in age (Cd 11.5 ± 2.2 yr vs. PCOSd 11.4 ± 2.5 yr; P = 0.984), BMI (Cd 21.1 ± 2.4 kg/m2 vs. PCOSd 22.5 ± 4.5 kg/m2; P = 0.146), and BMI SDS (Cd 1.0 ± 0.6 SD vs. PCOSd 1.1 ± 0.8 SD; P = 0.382). The distribution of Tanner stage scores for breast development and menarchal status were comparable between the two groups (Tanner stage distribution {chi}2; P = 0.979, menarchal status {chi}2; P = 0.754) (Table 1Go).


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  		TABLE 1. Clinical characteristics of peripubertal control daughters (Controld) and PCOS daughters (PCOSd)

 
Table 2Go shows the main biochemical characteristics and ovarian volumes of both groups. AMH levels were significantly higher in the PCOSd group (Cd 14.4 ± 8.0 pM vs. PCOSd 24.0 ± 19.0 pM; P = 0.012; Fig. 1Go) compared with the control group. Basal T levels (Cd 0.4 ± 0.2 ng/ml vs. PCOSd 0.6 ± 0.4 ng/ml; P = 0.006) and FAI (Cd 4.5 ± 4.0 vs. PCOSd 12.6 ± 12.7; P = 0.001) were significantly higher in the PCOSd group. E2 levels (Cd 38.6 ± 26.2 pg/ml vs. PCOSd 23.7 ± 16.3 pg/ml; P = 0.027) were significantly lower in the PCOSd group. There were no differences in gonadotropin or the other sex steroid concentrations.


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  		TABLE 2. Biochemical characteristics and ovarian volume of peripubertal control daughters (Controld) and PCOS daughters (PCOSd)

 

Figure 1
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  		FIG. 1. Comparison of AMH serum concentrations in peripubertal girls (8–16 yr old). Control d, Control daughters ({circ}); PCOS d, PCOS daughters (•).

 
Basal glucose and insulin concentrations were similar between both groups. Two-hour insulin was significantly higher in the PCOSd group (Cd 43.3 ± 5.4 µIU/ml vs. PCOSd 71.1 ± 11 µIU/ml; P = 0.046) compared with the control group. The average ovarian volume was significantly higher in the PCOSd group (Cd 5.3 ± 3.6 cc vs. PCOSd 9.3 ± 4.9 cc; P = 0.003). There was no correlation between serum AMH concentrations and ovarian volume.

In both groups, a positive correlation between 2-h insulin and AMH concentrations was observed (Cd r = 0.561, P = 0.008; PCOSd r = 0.530, P = 0.007). After values were adjusted by BMI SDS, this correlation remained significant (Cd r = 0.537, P = 0.01; PCOSd r = 0.39, P = 0.044). No correlation between AMH concentrations and androgen or gonadotropin levels was observed.


   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
The present study shows that AMH serum levels are elevated in peripubertal PCOSd, suggesting that the ovarian growing follicular pool may be increased in these girls.

We have recently demonstrated that AMH is increased from early infancy to childhood (4–7 yr) in PCOSd. Our present results show that AMH remains elevated during puberty in these girls, suggesting that their growing follicular pool may be increased from an early age and may persist elevated until puberty. The fact that AMH concentrations are elevated during childhood (28) (a time when the gonadal axis is relatively quiescent) and puberty (when the gonadal axis is progressively activated until sexual maturation is complete) is in agreement with the notion that AMH may serve as a marker of the growing follicular pool independent of the functional activity of the gonadal axis (24).

During reproductive life, serum AMH levels correlate with the small antral follicle count estimated by transvaginal ultrasound (21). In the present study, although pubertal PCOSd showed increased ovarian volume, it did not correlate with AMH levels. This may be because ovarian volume, estimated by transabdominal ultrasonography, does not have enough sensitivity as transvaginal ultrasound to make an estimate of the number of growing follicles.

In the present study, an elevated 2-h insulin level was observed in the PCOSd group, which is in agreement with the concept that insulin resistance and hyperinsulinemia are early features of PCOS (33, 34). In a study by Lewy et al. (35) in PCOS adolescents, similar basal insulin and glucose concentrations were observed in PCOS and control adolescents, but PCOS girls showed significantly higher first and second-phase insulin levels during hyperglycemic clamp studies. Thus, as previously proposed, insulin resistance seems to be an early feature during the ontogeny of PCOS.

In both groups, a positive correlation between AMH and 2-h insulin levels was observed. This is an interesting finding that links AMH with insulin resistance. A relationship between AMH levels and the homeostatic model assessment index has been previously described by La Marca et al. (36). On the one hand, it is possible that insulin, as a trophic factor for granulosa cells, may be increasing the number of AMH producing cells, although we cannot exclude the possibility that each granulosa cell could be producing more AMH in response to insulin. Conversely, a higher number of follicles reflected by high AMH levels could be determining higher androgen levels that have been related with hyperinsulinemia (37). However, in the present study, we did not observe a correlation between AMH and androgen levels, a finding that does not support this hypothesis.

It has been proposed that an important proportion of the first-degree female relatives of a PCOS woman may be at risk for developing PCOS (38, 39, 40, 41, 42). T levels and FAI were higher in the PCOSd group, which is consistent with the fact that at least a group of these girls may develop PCOS. In addition, lower E2 levels were observed in the PCOSd group, which is not usually observed in adult PCOS women.

In summary, we have found significantly higher AMH levels in a group of peripubertal PCOSd carefully matched by age, Tanner stage, and BMI with a control group. These findings, along with the results of our previous work, suggest that PCOSd may show an increased follicular mass that is established early during development and persists until the complete activation of the gonadal axis. Prospective studies with a greater number of subjects are needed to establish whether the postmenarchal girls of the present study, with elevated AMH levels, ultimately develop PCOS.


   Footnotes
 
This work was supported by Fondo Nacional del Desarrollo Científico y Tecnológico Grant 1030487 and by the Alexander von Humboldt Foundation.

This work was presented in part at the 4th Meeting of the Androgen Excess Society, receiving the Young Investigators Award, and at the 88th Annual Meeting of The Endocrine Society in Boston, Massachusetts, June 2006.

Disclosure Statement: N.C., E.C., M.M., B.E., F.S., and T.S.-P. have nothing to disclose. F.C. has given lectures for Pfizer and Novo Nordisk.

First Published Online May 8, 2007

Abbreviations: {Delta}4A, Androstenedione; AMH, anti-Müllerian hormone; BMI, body mass index; Cd, daughters of control women; E2, estradiol; FAI, free androgen index; 17-OHP, 17-OH-progesterone; PCOS, polycystic ovary syndrome; PCOSd, daughters of PCOS women; T, testosterone.

Received February 6, 2007.

Accepted April 27, 2007.


   References
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 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Franks S 1995 Polycystic ovary syndrome. N Engl J Med 333:853–861[Free Full Text]
  2. Holte J 1996 Disturbances in insulin secretion and sensitivity in women with the polycystic ovary syndrome. Baillieres Clin Endocrinol Metab 10:221–247[CrossRef][Medline]
  3. Dunaif A, Segal KR, Futterweit W, Dobrjansky A 1989 Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes 38:1165–1174[Abstract]
  4. 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]
  5. Legro RS, Kunselman AR, Dodson WC, Dunaif A 1999 Prevalence and predictors of risk for type II diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. J Clin Endocrinol Metab 84:165–169[Abstract/Free Full Text]
  6. O’Meara NM, Blackman JD, Ehrmann DA 1993 Defects in ß-cell function in functional ovarian hyperandrogenism. J Clin Endocrinol Metab 76:1241–1247[Abstract]
  7. Ibanez L, Dimartino-Nardi J, Potau N, Saenger P 2000 Premature adrenarche-normal variant or forerunner of adult disease? Endocr Rev 21:671–696[Abstract/Free Full Text]
  8. Ibanez L, Potau N, Virdis R, Zampolli M, Terzi C, Gussinye M, Carrascosa A, Vicens-Calvet E 1993 Postpubertal outcome in girls diagnosed of premature pubarche during childhood: increased frequency of functional ovarian hyperandrogenism. J Clin Endocrinol Metab 76:1599–1603[Abstract]
  9. DiMartino-Nardi J 2000 Pre- and postpuberal findings in premature adrenarche. J Pediatr Endocrinol Metab 13(Suppl 5):1265–1269
  10. Rosenfield RL 1990 Hyperandrogenism in peripubertal girls. In: Mahoney CP, ed. Current issues in pediatric and adolescent endocrinology. Philadelphia: Saunders; 1333–1358
  11. Franks S 2002 Adult polycystic ovary syndrome begins in childhood. Best Pract Res Clin Endocrinol Metab 16:263–272[CrossRef][Medline]
  12. Homburg R, Lambalk C 2004 Polycystic ovary syndrome in adolescence–a therapeutic conundrum. Hum Reprod 19:1039–1042[Abstract/Free Full Text]
  13. Witchel SF 2006 Puberty and polycystic ovary syndrome. Mol Cell Endocrinol 254–255:146–153
  14. Cate RL, Mattaliano RJ, Heisson C, Tizard R, Farber NM, Cheung A 1986 Isolation of the bovine and human genes for Mullerian inhibiting substance and expression of the human gene in animal cells. Cell 45:685–698[CrossRef][Medline]
  15. Josso N, di Clemente N 1999 TGF-B family members and gonadal development. Trends Endocrinol Metab 10:216–222[CrossRef][Medline]
  16. Lee MM, Donahoe PK 1993 Mullerian inhibiting substance: a gonadal hormone with multiple functions. Endocr Rev 14:152–164[Abstract]
  17. Josso N, Cate RL, Picard JY, Vigier B, di Clemente N, Wilson C, Imbeaud S, Pepinsky RB, Guerrier D, Boussin L, Legeai L, Carré-Eusebe D 1993 Anti-Mullerian hormone: the Jost factor. Recent Prog Horm Res 48:1–59[Medline]
  18. Josso N, Lamarre I, Picard JY, Berta P, Davies N, Morichon N, Peschanski M, Jeny R 1993 Anti-Mullerian hormone in early human development. Early Hum Dev 33:91–99[CrossRef][Medline]
  19. Josso N, Racine C, di Clemente N, Rey R, Xavier F 1998 The role of anti-Mullerian hormone in gonadal development. Mol Cell Endocrinol 145:3–7[CrossRef][Medline]
  20. Rajpert-De Meyts E, Jorgensen N, Graem N, Muller J, Cate RL, Skakkebaek NE 1999 Expression of anti-Mullerian hormone during normal and pathological gonadal development: association with differentiation of Sertoli and granulosa cells. J Clin Endocrinol Metab 84:3836–3844[Abstract/Free Full Text]
  21. Cook CL, Siow Y, Taylor S, Fallat ME 2000 Serum Mullerian-inhibiting substance levels during normal menstrual cycles. Fertil Steril 73:859–861[CrossRef][Medline]
  22. Rey RA, Lhomme C, Marcillac I, Lahlou N, Duvillard P, Josso N, Bidart JM 1996 Antimullerian hormone as a serum marker of granulosa cell tumors of the ovary: comparative study with serum {alpha}-inhibin and estradiol. Am J Obstet Gynecol 174:958–965[CrossRef][Medline]
  23. Lee MM, Donahoe PK, Hasegawa T, Silverman B, Crist GB, Best S, Hasegawa Y, Noto RA, Schoenfeld D, MacLaughlin DT 1996 Mullerian inhibiting substance in humans: normal levels from infancy to adulthood. J Clin Endocrinol Metab 81:571–576[Abstract]
  24. de Vet A, Laven JS, de Jong FH, Themmen AP, Fauser BC 2002 Antimüllerian hormone serum levels: a putative marker for ovarian aging. Fertil Steril 77:357–362[CrossRef][Medline]
  25. Pigny P, Merlen E, Robert Y, Cortet-Rudelli C, Decanter C, Jonard S, Dewailly D 2003 Elevated serum level of anti-Mullerian hormone in patients with polycystic ovary syndrome: relationship to the ovarian follicle excess and to the follicular arrest. J Clin Endocrinol Metab 88:5957–5962[Abstract/Free Full Text]
  26. Laven JS, Mulders AG, Visser JA, Themmen APN, DeJong FH, Fauser BC 2004 Anti-Mullerian hormone serum concentrations in normoovulatory and anovulatory women of reproductive age. J Clin Endocrinol Metab 89:318–323[Abstract/Free Full Text]
  27. Piltonen T, Morin-Papunen L, Koivunen R, Perheentupa A, Ruokonen A, Tapanainen JS 2005 Serum anti-Müllerian hormone levels remain high until late reproductive age and decrease during metformin therapy in women with polycystic ovary syndrome. Hum Reprod 20:1820–1826[Abstract/Free Full Text]
  28. Sir-Petermann T, Codner E, Maliqueo M, Echiburu B, Hitschfeld C, Crisosto N, Perez-Bravo F, Recabarren SE, Cassorla F 2006 Increased anti-Mullerian hormone serum concentrations in prepubertal daughters of women with polycystic ovary syndrome. J Clin Endocrinol Metab 91:3105–3109[Abstract/Free Full Text]
  29. Zawadski JK, Dunaif A 1992 Diagnostic criteria for polycystic ovary syndrome; towards a rational approach. In: Dunaif A, Givens JR, Haseltine F, eds. Polycystic ovary syndrome. Boston: Blackwell Scientific; 377–384
  30. Adams J, Polson DW, Franks S 1986 Prevalence of polycystic ovaries in women with anovulation and idiopathic hirsutism. Br Med J 293:355–359[Medline]
  31. Ogden CL, Kuczmarski RJ, Flegal KM, Mei Z, Guo S, Wei R, Grummer-Strawn LM, Curtin LR, Roche AF, Johnson CL 2002 Centers for Disease Control and Prevention 2000 growth charts for the United States: improvements to the 1977 National Center for Health Statistics version. Pediatrics 109:45–60[Abstract/Free Full Text]
  32. Rey RA, Codner E, Iniguez G, Bedecarras P, Trigo R, Okuma C, Gottlieb S, Bergada I, Campo SM, Cassorla FG 2005 Low risk of impaired testicular Sertoli and Leydig cell functions in boys with isolated hypospadias. J Clin Endocrinol Metab 90:6035–6040[Abstract/Free Full Text]
  33. Ibañez L, Potau N, Zampolli M, Rique S, Saenger P, Carrascosa A 1997 Hyperinsulinemia and decreased insulin-like growth factor-binding protein-1 are common features in prepubertal and pubertal girls with a history of premature pubarche. J Clin Endocrinol Metab 82:2283–2288[Abstract/Free Full Text]
  34. Ibañez L, Ferrer A, Ong K, Amin R, Dunger D, de Zegher F 2004 Insulin sensitization early after menarche prevents progression from precocious pubarche to polycystic ovary syndrome. J Pediatr 144:23–29[CrossRef][Medline]
  35. Lewy VD, Danadian K, Witchel SF, Arslanian S 2001 Early metabolic abnormalities in adolescent girls with polycystic ovarian syndrome. J Pediatr 138:38–44[CrossRef][Medline]
  36. La Marca A, Orvieto R, Giulini S, Jasonni VM, Volpe A, De Leo V 2004 Mullerian-inhibiting substance in women with polycystic ovary syndrome: relationship with hormonal and metabolic characteristics. Fertil Steril 82:970–972[CrossRef][Medline]
  37. Golden SH, Ding J, Szkio M, Schmidt MI, Duncan BB, Dobs A 2004 Glucose and insulin components of the metabolic syndrome are associated with hyperandrogenism in postmenopausal women: the atherosclerosis risk in communities study. Am J Epidemiol 160:540–548[Abstract/Free Full Text]
  38. Cooper HE, Spellacy WN, Prem KA, Cohen WD 1968 Hereditary factors in the Stein-Leventhal syndrome. Am J Obstet Gynecol 100:371–387[Medline]
  39. Givens JR 1988 Familial polycystic ovarian disease. Endocrinol Metab Clin North Am 17:771–783[Medline]
  40. Ferriman D, Purdie AW 1979 The inheritance of polycystic ovarian disease and a possible relationship to premature balding. Clin Endocrinol (Oxf) 11:291–300[Medline]
  41. Hague WM, Adams J, Reeders ST, Peto TE, Jacobs HS 1988 Familial polycystic ovaries: a genetic disease? Clin Endocrinol (Oxf) 29:593–605[Medline]
  42. Lunde O, Magnus P, Sandvik L, Hoglo S 1989 Familial clustering in the polycystic ovarian syndrome. Gynecol Obstet Invest 28:23–30[Medline]



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Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals