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Horm Metab Res 2009; 41(5): 408-413
DOI: 10.1055/s-0028-1105918
Humans, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Assessment of Pituitary and Steroid Hormones and Members of the TGF-β Superfamily for Ovarian Function in Patients with Congenital Uterus and Vaginal Aplasia (MRKH Syndrome)

P. L. Strissel 1 , P. Oppelt 1 , S. Cupisti 1 , E. Stiegler 1 , M. W. Beckmann 1 , R. Strick 1
  • 1University-Clinic Erlangen, Department of Gynaecology and Obstetrics, Laboratory for Molecular Medicine, Erlangen, Germany
Further Information

Publication History

received 07.01.2008

accepted 06.11.2008

Publication Date:
19 December 2008 (online)

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Abstract

Patients with Mayer–Rokitanski–Kuster–Hauser (MRKH) syndrome have congenital uterine and vaginal aplasia. The main question of this study was, if the absence of a uterus along with other genital and organ malformations could contribute to hormone or other growth factor protein fluctuations involved in communication between the hypothalamus-pituitary axis, ovaries and uterus. Serum from 56 MRKH patients (mean 27.6 years) and 22 female controls (mean 30.7 years) were analyzed using ELISA to determine levels of pituitary and steroid hormones (LH, FSH, estradiol, progesterone), growth factors of the TGF-β superfamily like activin A, inhibin B, and anti-Müllerian hormone (AMH). All serum levels were analyzed in relation to other organ malformations. Compared to controls, all 56 patients, including 5% with streak ovaries or unilateral ovarian aplasia, were generally similar in hormone and growth factor levels and could be grouped into hormonal phases. However, compared to controls LH/FSH and FSH/LH ratios of patients had significantly higher and lower mean values, of 2.75-fold (p=0.015) and 1.9-fold (p=0.002), respectively. Undetectable inhibin B levels of<10 pg/ml (p=0.05) were noted in 41.1% of MRKH patients, resulting in significantly higher activin A/inhibin B ratios (p<0.001). MRKH patients have hormonal phases supporting ovarian function, but patients with low FSH/LH ratios and undetectable inhibin B levels (<10 pg/ml) could represent cycle phasing irregularities. A model is discussed regarding our findings and the loss of ovarian-uterine communication.

Key words

uterine anomalies - pituitary and steroid hormones - β-hCG - AMH - activin - inhibin

References

  • 1 Nahum GG. Uterine anomalies. How common are they, and what is their distribution among subtypes?.  J Reprod Med. 1998;  43 877-887
    PubMedGoogle Scholar
  • 2 Raga F, Bauset C, Remohi J, Bonilla-Musoles F, Simon C, Pellicer A. Reproductive impact of congenital Mullerian anomalies.  Hum Reprod. 1997;  12 2277-2281
    CrossrefPubMedGoogle Scholar
  • 3 Hauser GA, Schreiner WE. Das Mayer-Rokitanski-Küster-Syndrome.  Schweiz Med Wochenschr. 1961;  61 1-11
    PubMedGoogle Scholar
  • 4 Oppelt P, Renner SP, Kellermann A, Brucker S, Hauser GA, Ludwig KS, Strissel PL, Strick R, Wallwiener D, Beckmann MW. Clinical aspects of Mayer-Rokitansky-Kuester-Hauser syndrome: recommendations for clinical diagnosis and staging.  Hum Reprod. 2006;  21 792-797
    CrossrefPubMedGoogle Scholar
  • 5 Duncan PA, Shapiro LR, Stangel JJ, Klein RM, Addonizio JC. The MURCS association: Mullerian duct aplasia, renal aplasia, and cervicothoracic somite dysplasia.  J Pediatr. 1979;  95 399-402
    PubMedGoogle Scholar
  • 6 Oppelt P, Renner SP, Brucker S, Strissel PL, Strick R, Oppelt PG, Doerr HG, Schott GE, Hucke J, Wallwiener D, Beckmann MW. The VCUAM (Vagina Cervix Uterus Adnex-associated Malformation) classification: a new classification for genital malformations.  Fertil Steril. 2005;  84 1493-1497
    CrossrefPubMedGoogle Scholar
  • 7 Oppelt P, Have M von, Paulsen M, Strissel PL, Strick R, Brucker S, Wallwiener D, Beckmann MW. Female genital malformations and their associated abnormalities.  Fertil Steril. 2007;  87 335-342
    CrossrefPubMedGoogle Scholar
  • 8 Oppelt P, Strissel PL, Kellermann A, Seeber S, Humeny A, Beckmann MW, Strick R. DNA sequence variations of the entire anti-Mullerian hormone (AMH) gene promoter and AMH protein expression in patients with the Mayer-Rokitanski-Kuster-Hauser syndrome.  Hum Reprod. 2005;  20 149-157
    PubMedGoogle Scholar
  • 9 Resendes BL, Sohn SH, Stelling JR, Tineo R, Davis AJ, Gray MR, Reindollar RH. Role for anti-Mullerian hormone in congenital absence of the uterus and vagina.  Am J Med Genet. 2001;  98 129-136
    CrossrefPubMedGoogle Scholar
  • 10 Zenteno JC, Carranza-Lira S, Kofman-Alfaro S. Molecular analysis of the anti-Mullerian hormone, the anti-Mullerian hormone receptor, and galactose-1-phosphate uridyl transferase genes in patients with the Mayer-Rokitansky-Kuster-Hauser syndrome.  Arch Gynecol Obstet. 2004;  269 270-273
    PubMedGoogle Scholar
  • 11 Biason-Lauber A, Konrad D, Navratil F, Schoenle EJ. A WNT4 mutation associated with Mullerian-duct regression and virilization in a 46,XX woman.  N Engl J Med. 2004;  351 792-798
    CrossrefPubMedGoogle Scholar
  • 12 Clement-Ziza M, Khen N, Gonzales J, Cretolle-Vastel C, Picard JY, Tullio-Pelet A, Besmond C, Munnich A, Lyonnet S, Nihoul-Fekete C. Exclusion of WNT4 as a major gene in Rokitansky-Kuster-Hauser anomaly.  Am J Med Genet. 2005;  137 98-99
    PubMedGoogle Scholar
  • 13 Alexander H, Zimmermann G, Wolkersdorfer GW, Biesold C, Lehmann M, Einenkel J, Pretzsch G, Baier D. Utero-ovarian interaction in the regulation of reproductive function.  Hum Reprod Update. 1998;  4 550-559
    CrossrefPubMedGoogle Scholar
  • 14 Jabbour HN, Kelly RW, Fraser HM, Critchley HO. Endocrine regulation of menstruation.  Endocr Rev. 2006;  27 17-46
    CrossrefPubMedGoogle Scholar
  • 15 Visser JA, Themmen AP. Anti-Mullerian hormone and folliculogenesis.  Mol Cell Endocrinol. 2005;  234 81-86
    CrossrefPubMedGoogle Scholar
  • 16 Cupisti S, Dittrich R, Mueller A, Strick R, Stiegler E, Binder H, Beckmann MW, Strissel P. Correlations between Anti-Müllerian Hormone, Inhibin B, and Activin A in follicular fluid in IVF/ICSI Patients for assessing the maturation and developmental potential of oocytes.  Eur J Med Res. 2007;  12 604-608
    PubMedGoogle Scholar
  • 17 Kicovic PM, Franchi F, Lusi M. Correlation between incremental changes of oestradiol-17 beta and prolactin during the menstrual cycle by means of multiple plasma sampling.  Reproduction. 1981;  5 43-48
    PubMedGoogle Scholar
  • 18 Mylonas I, Jeschke U, Wiest I, Hoeing A, Vogl J, Shabani N, Kuhn C, Schulze S, Kupka MS, Friese K. Inhibin/activin subunits alpha, beta-A and beta-B are differentially expressed in normal human endometrium throughout the menstrual cycle.  Histochem Cell Biol. 2004;  122 461-471
    PubMedGoogle Scholar
  • 19 Jones RL, Salamonsen LA, Critchley HO, Rogers PA, Affandi B, Findlay JK. Inhibin and activin subunits are differentially expressed in endometrial cells and leukocytes during the menstrual cycle, in early pregnancy and in women using progestin-only contraception.  Mol Hum Reprod. 2000;  12 1107-1117
    PubMedGoogle Scholar
  • 20 Ethier JF, Findlay JK. Roles of activin and its signal transduction mechanisms in reproductive tissues.  Reproduction. 2001;  121 667-675
    CrossrefPubMedGoogle Scholar
  • 21 Thompson TB, Cook RW, Chapmam SC, Jardetzky TS, Woodruff TK. Beta A versus beta B: is it merely a matter of expression?.  Mol Cell Endocrinol. 2004;  225 9-17
    CrossrefPubMedGoogle Scholar
  • 22 Cook RW, Thompson TB, Jardetzky TS, Woodruff TK. Molecular biology of inhibin action.  Semin Reprod Endocrinol. 2004;  22 269-276
    Article in Thieme ConnectPubMedGoogle Scholar
  • 23 Wachs DS, Coffler MS, Malcom PJ, Chang RJ. Comparison of follicle-stimulating-hormone-stimulated dimeric inhibin and estradiol responses as indicators of granulosa cell function in polycystic ovary syndrome and normal women.  J Clin Endocrinol Metab. 2006;  91 2920-2925
    CrossrefPubMedGoogle Scholar
  • 24 Sehested A, Juul AA, Andersson AM, Petersen JH, Jensen TK, Muller J, Skakkebaek NE. Serum inhibin A and inhibin B in healthy prepubertal, pubertal, and adolescent girls and adult women: relation to age, stage of puberty, menstrual cycle, follicle-stimulating hormone, luteinizing hormone, and estradiol levels.  J Clin Endocrinol Metab. 2000;  85 1634-1640
    CrossrefPubMedGoogle Scholar
  • 25 Andersson AM, Toppari J, Haavisto AM, Petersen JH, Simell T, Simell O, Skakkebaek NE. Longitudinal reproductive hormone profiles in infants: peak of inhibin B levels in infant boys exceeds levels in adult men.  J Clin Endocrinol Metab. 1998;  83 675-681
    CrossrefPubMedGoogle Scholar
  • 26 Groome N, Illingworth PJ, O’Brien M, Pai R, Rodger FE, Mather JP, MacNeilly AS. Measurement of dimeric inhibin B throughout the human menstrual cycle.  J Clin Endocrinol Metab. 1996;  81 1401-1405
    CrossrefPubMedGoogle Scholar
  • 27 Burger HG, Cahir N, Robertson DM, Groome NP, Dudley E, Green A, Dennerstein L. Serum inhibins A and B fall differentially as FSH rises in perimenopausal women.  Clin Endocrinol (Oxf). 1998;  48 809-813
    CrossrefPubMedGoogle Scholar
  • 28 Pigny P, Jonard S, Robert Y, Dewailly D. Serum anti-Mullerian hormone as a surrogate for antral follicle count for definition of the polycystic ovary syndrome.  J Clin Endocrinol Metab. 2006;  91 941-945
    CrossrefPubMedGoogle Scholar
  • 29 Lee MM, Donahoe PK, Hasegawa T, Silverman B, Crist GB, Best S, Hasegawa Y, Noto RA, Schoenfeld D, MacLaughlin DT. Mullerian inhibiting substance in humans: normal levels from infancy to adulthood.  J Clin Endocrinol Metab. 1996;  81 571-576
    CrossrefPubMedGoogle Scholar
  • 30 La Marca A, De Leo V, Giulini S, Orvieto R, Malmusi S, Giannella L, Volpe A. Anti-Mullerian hormone in premenopausal women and after spontaneous or surgically induced menopause.  J Soc Gynecol Investig. 2005;  12 545-548
    CrossrefPubMedGoogle Scholar
  • 31 Fraser IS, Baird DT, Hobson BM, Michie EA, Hunter W. Cyclical ovarian function in women with congenital absence of the uterus and vagina.  J Clin Endocrinol Metab. 1973;  36 634-637
    CrossrefPubMedGoogle Scholar
  • 32 Chang RJ, Abraham GG. Peripheral steroid levels in a patient with congenital absence of the uterus.  Obstet Gynecol. 1975;  46 320-322
    PubMedGoogle Scholar
  • 33 Naficy H, Parsa H, Barakat R, Naser H, Hall P. Cyclic hormonal changes in patients with congenital abscence of the uterus.  Acta Med Iran. 1977;  19 120-124
    PubMedGoogle Scholar
  • 34 Carranza-Lira S, Forbii K, Martinez-Chequer JC. Rokitansky syndrome and MURCS association–clinical features and basis for diagnosis.  Int J Fertil Womens Med. 1999;  44 250-255
    PubMedGoogle Scholar
  • 35 Ylikorkala O, Viinikka L. Pituitary and ovarian function in women with congenitally absent uterus.  Obstet Gynecol. 1979;  53 137-139
    PubMedGoogle Scholar
  • 36 Egarter C, Schurz B, Fitz R, Grunberger W. Hormonal situation in patients suffering from Mayer-Rokitanski-Kuster syndrome.  Geburtshilfe Frauenheilkd. 1988;  48 235-239
    Article in Thieme ConnectPubMedGoogle Scholar
  • 37 Farquhar CM, Sadler L, Harvey SA, Stewart AW. The association of hysterectomy and menopause: a prospective cohort study.  BJOG. 2005;  112 956-962
    CrossrefPubMedGoogle Scholar
  • 38 Baccarelli A, Morpurgo PS, Corsi A, Vaghi I, Fanelli M, Cremonesi G, Vaninetti S, Beck-Peccoz P, Spada A. Activin A serum levels and aging of the pituitary-gonadal axis: a cross-sectional study in middle-aged and elderly healthy subjects.  Exp Gerontol. 2001;  36 1403-1412
    CrossrefPubMedGoogle Scholar
  • 39 Berg G, Mesch V, Boero L, Sayegh F, Prada M, Royer M, Muzzio ML, Schreier L, Siseles N, Benencia H. Lipid and lipoprotein profile in menopausal transition. effects of hormones, age and fat distribution.  Horm Metab Res. 2004;  36 215-220
    Article in Thieme ConnectPubMedGoogle Scholar
  • 40 Loria P, Petraglia F, Concari M, Bertolotti M, Martella P, Luisi S, Grisolia C, Foresta C, Volpe A, Genazzani AR, Carulli N. Influence of age and sex on serum concentrations of total dimeric activin A.  Eur J Endocrinol. 1998;  139 487-492
    CrossrefPubMedGoogle Scholar
  • 41 Taylor AE, MacCourt B, Martin KA, Anderson EJ, Adams JM, Schoenfeld D, Hall JE. Determinants of abnormal gonadotropin secretion in clinically defined women with polycystic ovary syndrome.  J Clin Endocrinol Metab. 1997;  82 2248-2256
    CrossrefPubMedGoogle Scholar
  • 42 Banaszewska B, Spaczyñski RZ, Pelesz M, Pawelczyk L. Incidence of elevated LH/FSH ratio in polycystic ovary syndrome women with normo- and hyperinsulinemia.  Rocz Akad Med Bialymst. 2003;  48 131-134
    PubMedGoogle Scholar
  • 43 Rotten D, Vielh JP, Jolivet O, Gautray JP. Predictive value of the FSH: LH ratio on follicular and luteal phase characteristics of the human menstrual cycle.  Eur J Obstet Gynecol Reprod Biol. 1988;  28 229-239
    CrossrefPubMedGoogle Scholar
  • 44 Petrozza JC, Gray MR, Davis AJ, Reindollar RH. Congenital absence of the uterus and vagina is not commonly transmitted as a dominant genetic trait: outcomes of surrogate pregnancies.  Fertil Steril. 1997;  67 387-389
    CrossrefPubMedGoogle Scholar
  • 45 Halket JM, Leidenberger F, Einer-Jensen N, Bendz A. Determination of infused (13C) progesterone in ovarian arterial blood by selected ion monitoring.  Biomed Mass Spectrom. 1985;  8 429-431
    PubMedGoogle Scholar

Correspondence

Dr. R. Strick

Department of Gynaecology and Obstetrics

University-Clinic Erlangen

Laboratory for Molecular Medicine

Universitaetsstr. 21–23

91054 Erlangen

Germany

Phone: +49/9131/85 366 71

Fax: +49/9131/85 366 70

Email: Reiner.Strick@uk-erlangen.de

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