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Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2005-2693
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The Journal of Clinical Endocrinology & Metabolism Vol. 91, No. 8 3105-3109
Copyright © 2006 by The Endocrine Society

Increased Anti-Müllerian Hormone Serum Concentrations in Prepubertal Daughters of Women with Polycystic Ovary Syndrome

Teresa Sir-Petermann, Ethel Codner, Manuel Maliqueo, Bárbara Echiburú, Catalina Hitschfeld, Nicolás Crisosto, Francisco Pérez-Bravo, Sergio E. Recabarren and Fernando Cassorla

Endocrinology and Metabolism Laboratory (T.S.-P., M.M., B.E., C.H., N.C.), West Division, School of Medicine; Institute of Maternal and Child Research (E.C., F.C.), School of Medicine; and Institute of Nutrition and Food Technology (F.P.-B.), University of Chile, Casilla O52 Correo 33, Santiago, Chile; and Laboratory of Animal Physiology and Endocrinology (S.E.R.), School of Veterinary Medicine, University of Concepción, 380-1061 Chillán, Chile

Address all correspondence and requests for reprints to: Prof. T. Sir-Petermann, Laboratory of Endocrinology, Department of Medicine West 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: Anti-Müllerian hormone (AMH) is produced by the granulosa cells and reflects follicular development. Adult women with polycystic ovary syndrome (PCOS) have increased levels of AMH associated with an excessive number of growing follicles. However, it is not known whether these abnormalities are present before the clinical onset of PCOS.

Objective: Our objective was to investigate whether prepubertal daughters of women with PCOS have increased AMH levels.

Design: Fourteen female infants (2–3 months old) and 25 prepubertal girls (4–7 yr old) born to PCOS mothers were studied. As a control group, we studied 21 female infants and 24 prepubertal girls born to mothers with regular menses and without hyperandrogenism. The group with PCOS mothers and the control group had normal birth weight and were born from spontaneous singleton pregnancies. Circulating concentrations of gonadotropins, testosterone, androstenedione, estradiol, 17-OH-progesterone, SHBG, inhibin B, and AMH were determined by specific assays.

Results: Serum concentrations of AMH were significantly higher in the PCOS group compared with the control group during early infancy (20.4 ± 15.6 vs. 9.16 ± 8.6 pmol/liter; P = 0.024) and during childhood (14.8 ± 7.7 vs. 9.61 ± 4.4 pmol/liter; P = 0.007). Gonadotropin and serum sex steroid concentrations were similar in both groups during the two study periods, except for FSH, which was lower during childhood in girls born to PCOS mothers.

Conclusions: We conclude that serum AMH concentrations are increased in prepubertal daughters of PCOS women, suggesting that these girls appear to show evidence of an altered follicular development during infancy and childhood.


   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. Ovarian morphology, assessed by ultrasound and by histological examination, has shown that polycystic ovaries are characterized by an excessive number of growing follicles compared with normal ovaries (1, 2, 3), suggesting an altered folliculogenesis in this syndrome.

Anti-Müllerian hormone (AMH), a dimeric glycoprotein member of the TGFß superfamily (4), may constitute a marker of follicular development. AMH is produced exclusively in the gonads (5), and its dimorphic expression in ovary and testis is crucial for the normal differentiation of reproductive structures (6, 7). During early fetal development, Sertoli cell expression of AMH results in Müllerian duct regression in the male (5). In contrast, in the female fetus, granulosa cell expression of AMH occurs during late gestation, after the Müllerian ducts have lost sensitivity to AMH (8). Serum AMH levels seem to be correlated with the development of preantral and small antral follicles, from puberty to the end of reproductive life (9). During this period, AMH expression in the human ovary is similar to that observed in the mouse and rat (10), suggesting an important role for AMH in the regulation of early follicle growth.

It has been established that AMH levels are 2- to 3-fold higher during reproductive life in women with PCOS compared with healthy women (11, 12). Increased serum AMH concentrations in PCOS women are related to the increased number of growing follicles that secrete AMH (13). However, it is not known whether AMH increases before the clinical onset of PCOS, as defined by the Rotterdam ESHRE/ASRM-sponsored PCOS consensus (14). Phenotypic and family aggregation studies in different populations have demonstrated that hyperandrogenic symptoms and polycystic ovaries assessed by ultrasound are more frequent in first-degree relatives of PCOS patients compared with controls (15, 16, 17, 18, 19). Therefore, we investigated whether daughters of women with PCOS have increased AMH levels during early infancy or during childhood.


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

As the PCOS group (PCOSG), we studied 14 female infants (2–3 months old) and 25 prepubertal girls (4–7 yr old) born to PCOS mothers. As a control group, we studied 21 female infants and 24 prepubertal girls (CG) born to mothers with regular menses and without hyperandrogenism. PCOSG and CG had normal birth weight and were born from spontaneous singleton pregnancies. Both groups of girls were matched for age 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 (20). PCOS mothers were evaluated before pregnancy, and all of them exhibited chronic oligomenorrhea or amenorrhea, hirsutism, serum testosterone concentration more than 0.6 ng/ml and/or free androgen index more than 5.0, and androstenedione concentration more than 3.0 ng/ml. In addition, PCOS women showed the characteristic ovarian morphology of PCOS on ultrasound, based on the criteria described by Adams et al. (21). PCOS mothers were normoglycemic, with different 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.

PCOS patients included in this study were selected from a group of 39 PCOS patients who were seeking treatment for infertility and were placed on a 6-month diet and an exercise program consisting of a low-fat diet and a daily 30-min walk. During this program, 12 patients ovulated and became pregnant. Another 25 patients became pregnant with the addition of metformin at a dose of 1500 mg, which was immediately discontinued when they became pregnant. Only two patients became pregnant after pharmacological induction of ovulation with clomiphene citrate, 100 mg/d from cycle d 5–9.

As control mothers, we selected 45 women of similar age and socioeconomic level with singleton pregnancies. Control mothers had a history of 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

All girls were admitted with their mothers to the pediatric unit of the Clinical Research Center at approximately 0830 h. We performed a complete physical examination on each girl, including anthropometric measurements. Girls were excluded if we observed signs of a genetic disorder or pubertal development. In the female infants of both groups, weight, length, and head circumference were recorded at birth. Weight and length were transformed into SD scores (SDS) using Chilean normative data for newborns (22), adjusting for differences in gestational age and gender. SDS were calculated using the formula SDS = (x – mean)/SD percentile). For the prepubertal girls (4–7 yr) of both groups, anthropometric birth data were obtained retrospectively from the clinical history.

A fasting sample (3 ml) was obtained by venipuncture of an antecubital vein. Circulating concentrations of gonadotropins, testosterone, androstenedione, estradiol, 17-OH-progesterone (17-OHP), SHBG, inhibin B, and AMH were determined by specific assays.

Assays

Serum AMH was assayed by enzyme immunoassay (Immunotech-Beckman Coulter, Marseille, France) (23). Analytical sensitivity was 2.1 pmol/liter, and intra- and interassay coefficients of variation were 5.3 and 8.7%, respectively.

Serum LH, FSH, and estradiol were determined by electrochemiluminescence (Roche, Basel, Switzerland). Assay sensitivities were 0.1 IU/liter, 0.1 IU/liter, and 5.0 pg/ml, respectively. Intra- and interassay coefficients of variation were 1.1 and 2.1% for LH, 1.67 and 3.7% for FSH, and 2.7 and 5.0% for estradiol, respectively.

Serum testosterone was assayed by RIA (Diagnostic Systems Laboratories, Inc., Webster, TX), and androstenedione, 17-OHP, and SHBG were determined by radioimmunometric assay (DPC, Los Angeles, CA). Assay sensitivities were 0.1 ng/ml, 0.1 ng/ml, 0.1 ng/ml, and 0.04 nmol/liter, respectively. Intra- and interassay coefficients of variation were 7.0 and 11.0% for testosterone, 3.7 and 4.9% for androstenedione, 3.5 and 5.0% for 17-OHP, and 3.8 and 7.9% for SHBG. Serum inhibin B was assayed by ELISA (Diagnostic Systems Laboratories) with an assay sensitivity of 7.0 pg/ml and intra- and interassay coefficients of variation of 6.3 and 4.6%, respectively.

Statistical evaluation

Data were normally distributed and were expressed as means and SD. Differences between groups were assessed by Student’s t test. The correlation between continuous variables was assessed by Spearman regression analysis. Statistical analysis was performed using the Statistical Package for Social Science software (SPSS 10.0). A P value of <0.05 was considered statistically significant.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
As expected, PCOS mothers had increased serum testosterone and insulin concentrations and free androgen index. In addition, they had decreased levels of SHBG. Table 1Go shows the clinical and endocrine characteristics of the PCOS mothers, compared with a group of 71 normal women studied by us (24).


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  		TABLE 1. Clinical and endocrine characteristics of PCOS mothers

 
Both groups of girls were comparable in gestational age (control, 38.9 ± 1.7, vs. PCOS, 38.6 ± 1.2 wk; P = 0.327) and birth weight (control, 3370 ± 550, vs. PCOS, 3334 ± 481 g; P = 0.756). Table 2Go shows the clinical and biochemical characteristics of CG and PCOSG during early infancy (2–3 months of age). No difference was observed in age, weight, height, or weight SDS between both groups. In addition, no significant differences were observed in serum concentrations of sex steroids, SHBG, or inhibin B.


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  		TABLE 2. Clinical and biochemical characteristics of CG and PCOSG during infancy

 
Table 3Go shows the endocrine and biochemical characteristics of CG and PCOSG during childhood (4–7 yr of age). We did not observe any significant differences in age, weight, or height. Waist circumference and waist-to-hip ratio, as well as serum concentrations of sex steroids, inhibin B, and SHBG, were similar in both groups. However, during this period, FSH concentrations were significantly lower in the PCOSG compared with the CG.


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  		TABLE 3. Clinical and biochemical characteristics of CG and PCOSG during childhood

 
Serum AMH concentrations in CG and PCOSG during the two study periods are shown in Fig. 1Go. Serum concentrations of AMH were significantly higher in the PCOSG compared with the CG during early infancy (PCOSG, 20.4 ± 15.6, vs. CG, 9.16 ± 8.6 pmol/liter; P = 0.024) and during childhood (PCOSG, 14.8 ± 7.7, vs. CG, 9.61 ± 4.4 pmol/liter; P = 0.007). AMH levels were not different between early infancy and childhood in the PCOSG (P = 0.140) or in the CG (P = 0.830). No correlation between AMH and FSH or estradiol in the PCOSG or CG was observed during infancy or childhood by Spearman analysis. Moreover, there was no association between the infertility treatment of the PCOS mothers and the AMH levels in their daughters.


Figure 1
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  		FIG. 1. Comparison of AMH serum concentrations in infant girls 2–3 months of age (A) and prepubertal girls 4–7 yr of age (B). •, Daughters of PCOS women; {circ}, daughters of control women.

 

   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
The present study shows that AMH levels are increased in prepubertal daughters of women with PCOS, suggesting that the ovarian preantral follicular pool may be increased in these girls. AMH is synthesized by granulosa cells of preantral and small antral follicles (25, 26). Therefore, the increased serum AMH levels observed in prepubertal daughters of women with PCOS suggest that the ovarian follicle pool is increased from an early age in these girls and persists elevated during childhood (4–7 yr), at a time when the gonadal axis is relatively quiescent.

In this study, we selected only appropriate-for-gestational-age infants born to PCOS and control mothers, to avoid the possible effect of fetal size on gonadal function. A relationship between reduced fetal size and PCOS has been suggested (27, 28). In addition, we have recently demonstrated that PCOS mothers show a significantly higher prevalence of small-for-gestational-age newborns (29).

During early infancy, daughters of PCOS women exhibited a normal pituitary gonadal profile (30, 31), except for the fact that serum AMH levels were elevated. It is likely that the detection of an elevated AMH concentration in female infants of PCOS mothers at 2–3 months of age reflects an increase in the ovarian follicular pool (32) that is already present during intrauterine life. This phenomenon could be explained by genetic or environmental factors. It has been suggested that PCOS may have a genetic etiology (33), and numerous candidate genes have been proposed (34). However, given the large number of genetic variants found in association with this syndrome, it has been recently suggested that PCOS is a complex multigenic trait, subject to environmental influences that may play an important role in the expression of the hyperandrogenic phenotype (35). In addition, it has been proposed that the endocrine, nutritional, and metabolic milieu of the fetus may have a programming effect, which may persist into adult life (36, 37, 38, 39). Recently, it has been established that prenatal androgen exposure in females born to androgenized sheep or monkey mothers is associated with growth retardation, infertility, obesity, and insulin resistance during adulthood, even though some of these characteristics could have been already expressed early during extrauterine life (40, 41, 42, 43, 44). Moreover, prenatal exposure to androgens in rhesus monkeys and sheep produces endocrine changes that are similar to PCOS (45, 46).

We have recently demonstrated that women with PCOS exhibit a significant increase in androgen concentrations during pregnancy, which could provide a potential source of androgens to the fetus (47). Therefore, it is possible that the high androgen levels observed in pregnant PCOS women may influence fetal physiology, leading to changes in ovarian morphology and function as described in experimental models. Data from rhesus monkeys strongly suggest that intraovarian androgens promote granulosa cell proliferation and inhibit apoptosis, especially in small follicles whose granulosa cells are rich in androgen receptors (48). Accordingly, polycystic ovaries are characterized by an excessive number of growing follicles of up to 2–5 mm in size (preantral and small antral follicles) (1). Based on these observations, Jonard and Dewailly (49) postulate that the follicular dysfunction in PCOS is 2-fold, with two abnormalities that are linked. First, intraovarian hyperandrogenism may promote early follicular growth, leading to an excess of 2- to 5-mm follicles. Second, the ensuing excessive number of growing follicles may inhibit the selection process, presumably through follicle-follicle interaction involving granulosa cell products such as AMH. Recently, Stubbs et al. (50) showed that AMH is expressed in primordial and transitional follicles. However, in PCOS patients, a lower AMH expression was observed. These authors suggest that the relative deficiency in AMH results in an enhanced primordial follicle recruitment, which is in agreement with the notion that AMH inhibits the recruitment of primordial follicles into the pool of growing follicles (51). As a consequence, more growing follicles will be present, resulting in increased serum AMH levels. According to our data, these abnormalities may be present during the early stages of postnatal life.

The presence of elevated serum AMH concentrations in daughters of PCOS women during childhood, at a time when the gonadal axis is relatively quiescent and other hormonal markers of ovarian function such as estradiol and inhibin B are very low, suggests that AMH may be used as an early marker of ovarian follicular development. This assumption is in agreement with previous studies in adult women with PCOS. According to the study by Laven et al. (52), inhibin B was elevated in only 20% of the PCOS cases, and a recent study by Fanchin et al. (53) demonstrated that serum AMH levels were better correlated with follicular number than inhibin B, estradiol, FSH, and LH on cycle d 3.

FSH levels were lower in our PCOS girls during childhood compared with controls, but inhibin B levels were similar in both groups. Assuming that AMH levels reflect the follicular mass, lower FSH levels in the PCOS group could indirectly reflect the effect of other FSH-regulatory peptides of follicular origin on FSH levels (54). We did not find lower FSH levels in the PCOS group compared with controls during infancy. However, the present study was not designed to find differences in FSH concentrations, so the statistical power of this observation is low.

In children, AMH determination has been used to investigate gonadal development and differentiation (23, 55). To our knowledge, this is the first study of AMH serum concentrations in a cohort of prepubertal daughters of PCOS women. Our study shows that serum AMH concentrations are increased in these girls, suggesting that they may show evidence of altered follicular development during infancy and childhood. Prospective studies are needed to establish the clinical significance of elevated AMH levels during the prepubertal period in these girls and its possible relationship with the subsequent development of PCOS.


   Acknowledgments
 
We express our gratitude to Dr. Vasantha Padmanabhan for her editorial comments.


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

This work was presented in part at the Seventh European Society for Pediatric Endocrinology/Lawson Wilkins Pediatric Endocrine Society Joint Meeting Pediatric Endocrinology, Lyon, France, 2005.

First Published Online May 23, 2006

Abbreviations: AMH, Anti-Müllerian hormone; BMI, body mass index; CG, girls born to control mothers; 17-OHP, 17-OH-progesterone; PCOS, polycystic ovary syndrome; PCOSG, girls born to PCOS mothers; SDS, SD score.

Received December 12, 2005.

Accepted May 17, 2006.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Hughesdon PE 1982 Morphology and morphogenesis of the Stein Leventhal ovary and of so-called "hyperthecosis". Obstet Gynecol Surv 37:59–77[Medline]
  2. Jonard S, Robert Y, Cortet-Rudelli C, Pigny P, Decanter C, Dewailly D 2003 Ultrasound examination of polycystic ovaries: is it worth counting the follicles? Hum Reprod 18:598–603[Abstract/Free Full Text]
  3. Webber LJ, Stubbs S, Stark J, Trew GH, Margara R, Hardy K, Franks S 2003 Formation and early development of follicles in the polycystic ovary. Lancet 362:1017–1021[CrossRef][Medline]
  4. Josso N, di Clemente N 1999 TGF-ß family members and gonadal development. Trends Endocrinol Metab 10:216–222[CrossRef][Medline]
  5. Lee MM, Donahoe PK 1993 Mullerian inhibiting substance: a gonadal hormone with multiple functions. Endocr Rev 14:152–164[Abstract]
  6. 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]
  7. 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]
  8. Rajpert-De Meyts E, Jorgensen N, Graem N, Muller J, Cate R, Skakkebaek N 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]
  9. 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]
  10. Weenen C, Laven JS, Von Bergh AR, Cranfield M, Groome NP, Visser JA, Kramer P, Fauser BC, Themmen AP 2004 Anti-Mullerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment. Mol Hum Reprod 10:77–83[Abstract/Free Full Text]
  11. 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]
  12. Laven JS, Mulders A, Visser J, Themmen A, Jong F, Fauser B 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]
  13. Piltonen T, Morin-Papunen L, Koivunen R, Perheentupa A, Ruokonen A, Tapanainen JS 2005 Serum anti-Mullerian 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]
  14. The Rotterdam ESHRE/ASRM-sponsored PCOS Consensus Workshop Group 2003 Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 19:41–47
  15. Cooper HE, Spellacy WN, Prem KA, Cohen WD 1968 Hereditary factors in the Stein-Leventhal syndrome. Am J Obstet Gynecol 100:371–387[Medline]
  16. Givens JR 1988 Familial polycystic ovarian disease. Endocrinol Metab Clin North Am 17:771–783[Medline]
  17. 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]
  18. Hague WM, Adams J, Reeders ST, Peto TE, Jacobs HS 1988 Familial polycystic ovaries: a genetic disease? Clin Endocrinol (Oxf) 29:593–605[Medline]
  19. Lunde O, Magnus P, Sandvik L, Hoglo S 1989 Familial clustering in the polycystic ovarian syndrome. Gynecol Obstet Invest 28:23–30[Medline]
  20. Zawadzki JK, Dunaif A 1992 Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. In: Hershmann JM, ed. Current issues in endocrinology and metabolism. Boston: Blackwell; 377–384
  21. 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]
  22. Juez G, Lucero E, Ventura-Junca P, Gonzalez H, Tapia JL, Winter A 1989 [Intrauterine growth in Chilean middle class newborn infants]. Rev Chil Pediatr 60:198–202 (Spanish)[Medline]
  23. 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]
  24. Maliqueo M, Atwater I, Lahsen R, Perez-Bravo F, Angel B, Sir-Petermann T 2003 Proinsulin serum concentrations in women with polycystic ovary syndrome: a marker of ß-cell dysfunction? Hum Reprod 18:2683–2688[Abstract/Free Full Text]
  25. Visser J, Jong F, Laven J, Themmen A 2006 Anti-Mullerian hormone: a new marker for ovarian function. Reproduction 131:1–9[Abstract/Free Full Text]
  26. Durlinger AL, Visser JA, Themmen AP 2002 Regulation of ovarian function: the role of anti-Mullerian hormone. Reproduction 124:601–609[Abstract]
  27. Ibañez L, Potau N, Francois I, de Zegher F 1998 Precocious pubarche, hyperinsulinism, and ovarian hyperandrogenism in girls: relation to reduced fetal growth. J Clin Endocrinol Metab 83:3558–3562[Abstract/Free Full Text]
  28. Ibañez L, Potau N, Ferrer A, Rodriguez-Hierro F, Marcos MV, De Zegher F 2002 Anovulation in eumenorrheic, nonobese adolescent girls born small for gestational age: insulin sensitization induces ovulation, increases lean body mass, and reduces abdominal fat excess, dyslipidemia, and subclinical hyperandrogenism. J Clin Endocrinol Metab 87:5702–5705[Abstract/Free Full Text]
  29. Sir-Petermann T, Hitchsfeld C, Maliqueo M, Codner E, Echiburu B, Gazitua R, Recabarren S, Cassorla F 2005 Birth weight in offspring of mothers with polycystic ovarian syndrome. Hum Reprod 20:2122–2126[Abstract/Free Full Text]
  30. Andersson AM, Toppari J, Haavisto AM, Petersen JH, Simell T, Simell O, Skakkebaek NE 1998 Longitudinal reproductive hormone profiles in infants: peak of inhibin B levels in infant boys exceeds levels in adult men. J Clin Endocrinol Metab 83:675–681[Abstract/Free Full Text]
  31. Quigley CA 2002 The postnatal gonadotropin and sex steroid surge: insights from the androgen insensitivity syndrome. J Clin Endocrinol Metab 87:24–28[Abstract/Free Full Text]
  32. Pigny P, Jonard S, Robert Y, Dewailly D 2006 Serum anti-mullerian hormone as a surrogate for antral follicle count for definition of the polycystic ovary syndrome. J Clin Endocrinol Metab 91:941–945[Abstract/Free Full Text]
  33. Franks S, Gharani N, Waterworth D, Batty S, White D, Williamson R, McCarthy M 1997 The genetic basis of polycystic ovary syndrome. Hum Reprod 12:2641–2648[Abstract/Free Full Text]
  34. Urbanek M, Legro RS, Driscoll DA, Azziz R, Ehrmann DA, Norman RJ, Strauss 3rd JF, Spielman RS, Dunaif A 1999 Thirty-seven candidate genes for polycystic ovary syndrome: strongest evidence for linkage is with follistatin. Proc Natl Acad Sci USA 96:8573–8578[Abstract/Free Full Text]
  35. Escobar-Morreale HF, Luque-Ramirez M, San Millan JL 2005 The molecular-genetic basis of functional hyperandrogenism and the polycystic ovary syndrome. Endocr Rev 26:251–282[Abstract/Free Full Text]
  36. Barker DJP 1994 Programming the baby. In: Mothers, babies, and disease in later life. London: BMJ; 14–36
  37. Holemans K, Aerts L, Van Assche FA 1998 Fetal growth and long-term consequences in animal models of growth retardation. Eur J Obstet Gynecol Reprod Biol 81:149–156[CrossRef][Medline]
  38. Tchernitchin AN, Tchernitchin NN, Mena MA, Unda C, Soto J 1999 Imprinting: perinatal exposures cause the development of diseases during the adult age. Acta Biol Hung 50:425–440[Medline]
  39. Rhind SM, Rae MT, Brooks AN 2001 Effects of nutrition and environmental factors on the fetal programming of the reproductive axis. Reproduction 122:205–214[Abstract]
  40. Eisner JR, Dumesic DA, Kemnitz JW, Abbott DH 2000 Timing of prenatal androgen excess determines differential impairment in insulin secretion and action in adult female rhesus monkeys. J Clin Endocrinol Metab 85:1206–1210[Abstract/Free Full Text]
  41. Rosser Jr JC, Noyan EL, Herman BS 2003 The surgical treatment of obesity: a personal perspective. J Laparoendosc Adv Surg Tech A 13:207–213[CrossRef][Medline]
  42. Manikkam M, Crespi EJ, Doop DD, Herkimer C, Lee JS, Yu S, Brown MB, Foster DL, Padmanabhan V 2004 Fetal programming: prenatal testosterone excess leads to fetal growth retardation and postnatal catch-up growth in sheep. Endocrinology 145:790–798[Abstract/Free Full Text]
  43. Recabarren SE, Padmanabhan V, Codner E, Lobos A, Duran C, Vidal M, Foster DL, Sir-Petermann T 2005 Postnatal developmental consequences of altered insulin sensitivity in female sheep treated prenatally with testosterone. Am J Physiol Endocrinol Metab 289:801–806
  44. Recabarren SE, Sir-Petermann T, Lobos A, Codner E, Rojas-Garcia PP, Reyes V 2005 Response to the gonadotropin releasing hormone agonist leuprolide in immature female sheep androgenized in utero. Biol Res 38:235–244[Medline]
  45. Abbott DH, Dumesic DA, Franks S 2002 Developmental origin of polycystic ovary syndrome: a hypothesis. J Endocrinol 174:1–1745[Abstract]
  46. Steckler T, Wang J, Bartol FF, Roy SK, Padmanabhan V 2005 Fetal programming: prenatal testosterone treatment causes intrauterine growth retardation, reduces ovarian reserve, and increases ovarian follicular recruitment. Endocrinology 146:3185–3193[Abstract/Free Full Text]
  47. Sir-Petermann T, Maliqueo M, Angel B, Lara HE, Perez-Bravo F, Recabarren SE 2002 Maternal serum androgens in pregnant women with polycystic ovarian syndrome: possible implications in prenatal androgenization. Hum Reprod 17:2573–2579[Abstract/Free Full Text]
  48. Vendola KA, Zhou J, Adesanya OO, Weil SJ, Bondy CA 1998 Androgens stimulate early stages of follicular growth in the primate ovary. J Clin Invest 101:2622–2629[Medline]
  49. Jonard S, Dewailly D 2004 The follicular excess in polycystic ovaries, due to intra-ovarian hyperandrogenism, may be the main culprit for the follicular arrest. Hum Reprod Update 10:107–117[Abstract/Free Full Text]
  50. Stubbs S, Hardy K, Da Silva-Buttkus P, Stark J, Webber L, Flanagan A, Themmen A, Visser J, Groome N, Franks S 2005 Anti-mullerian hormone protein expression is reduced during the initial stages of follicle development in human polycystic ovaries. J Clin Endocrinol Metab 90:5536–5543[Abstract/Free Full Text]
  51. Durlinger A, Kramer P, Karels B, Jong F, Uilenbroek J, Grootegoed JA, Themmen A 1999 Control of primordial follicle recruitment by anti-mullerian hormone in the mouse ovary. Endocrinology 140:5789–5796[Abstract/Free Full Text]
  52. Laven JS, Imani B, Eijkemans MJ, de Jong FH, Fauser BC 2001 Absent biologically relevant associations between serum inhibin B concentrations and characteristics of polycystic ovary syndrome in normogonadotrophic anovulatory infertility. Hum Reprod 16:1359–1364[Abstract/Free Full Text]
  53. Fanchin R, Schonauer LM, Righini C, Guibourdenche J, Frydman R, Taieb J 2003 Serum anti-Mullerian hormone is more strongly related to ovarian follicular status than serum inhibin B, estradiol, FSH and LH on day 3. Hum Reprod 18:323–327[Abstract/Free Full Text]
  54. Foster CM, Olton PR, Racine MS, Phillips DJ, Padmanabhan V 2004 Sex differences in FSH-regulatory peptides in pubertal age boys and girls and effects of sex steroid treatment. Hum Reprod 19:1668–1676[Abstract/Free Full Text]
  55. Lee MM, Donahoe PK, Silverman BL, Hasegawa T, Hasegawa Y, Gustafson ML, Chang YC, MacLaughlin DT 1997 Measurements of serum mullerian inhibiting substance in the evaluation of children with nonpalpable gonads. N Engl J Med 336:1480–1486[Abstract/Free Full Text]



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