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Female gonadal functions and ovarian reserve in patients with acromegaly: experience from a single tertiary center

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Abstract

Purpose

To evaluate the gonadal functions and related factors in female patients with acromegaly at the time of diagnosis, the course of gonadal dysfunctions and pregnancies during the follow-up period, and the investigation of ovarian reserve with serum anti-Mullerian hormone (AMH) levels in patients with reproductive age.

Methods

Patients who were not menopausal at the time of acromegaly diagnosis (n = 47) were included in this study. Baseline gonadal status was evaluated retrospectively. Patients were divided into three groups: normal gonadal function (group 1), gonadal dysfunction without central hypogonadism (group 2), and central hypogonadism (group 3). Group 1 and group 2 were compared in terms of clinical and laboratory findings. AMH levels were studied in patients who were ≤ 45 years old (n = 14) at the time of the study. Data related to pregnancies (n = 13) were evaluated retrospectively.

Results

Group 1 included 18 patients (38%), group 2 included 18 patients (38%), and group 3 included 11 patients (24%). The estimated duration of acromegaly was longer, and baseline PRL levels were higher, in group 2 than group 1 (p = 0.002 and p = 0.015, respectively). Gonadal functions recovered in 66% of patients. AMH levels were low in 64% of patients. The frequency of maternal diabetes and hypertension was 7.7%, and there was no tumoral growth in any of the pregnancies.

Conclusion

The most important factors affecting gonadal functions, excluding central hypogonadism, are hyperprolactinemia and the duration of the indolent period before diagnosis of acromegaly. AMH levels in the majority of patients were found to be lower than the expected age. Despite the decreased ovarian reserve, fertilization and normal birth can be achieved with careful surveillance.

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References

  1. L. Katznelson, E.R. Laws Jr, S. Melmed, M.E. Molitch, M.H. Murad, A. Utz, J.A. Wass, Endocrine society, acromegaly: an endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 99(11), 3933–3951 (2014)

    Article  CAS  PubMed  Google Scholar 

  2. S. Melmed, F.F. Casanueva, A. Klibanski, M.D. Bronstein, P. Chanson, S.W. Lamberts, C.J. Strasburger, J.A. Wass JA, A. Giustina, A consensus on the diagnosis and treatment of acromegaly complications. Pituitary 16(3), 294–302 (2013)

    Article  CAS  PubMed  Google Scholar 

  3. G.A. Kaltsas, J.J. Mukherjee, P.J. Jenkins, M.A. Satta, N. Islam, J.P. Monson, G.M. Besser, A.B. Grossman, Menstrual irregularity in women with acromegaly. J. Clin. Endocrinol. Metab. 84, 2731–2735 (1999)

    Article  CAS  PubMed  Google Scholar 

  4. J.D.N. Nabarro, Acromegaly. Clin. Endocrinol. (Oxf.). 26, 481–512 (1987)

    Article  CAS  PubMed  Google Scholar 

  5. M. Grynberg, S. Salenave, J. Young, P. Chanson, Female gonadal function before and after treatment of acromegaly. J. Clin. Endocrinol. Metab. 95(10), 4518–4525 (2010)

    Article  CAS  PubMed  Google Scholar 

  6. G.A. Kaltsas, I.I. Androulakis, K. Tziveriotis, D. Papadogias, A. Tsikini, P. Makras, K. Dimitriou, A. Stathopoulou, G. Piaditis, Polycystic ovaries and the polycystic ovary syndrome phenotype in women with active acromegaly. Clin. Endocrinol. (Oxf.). 67, 917–922 (2007)

    Article  CAS  PubMed  Google Scholar 

  7. L. Katznelson, D. Kleinberg, M.L. Vance, S. Stavrou, K.J. Pulaski, D.A. Schoenfeld, D.L. Hayden, M.E. Wright, C.J. Woodburn, A. Klibanski, Hypogonadism in patients with acromegaly: data from the multi-centre acromegaly registry pilot study. Clin. Endocrinol. (Oxf.). 54, 183–188 (2001)

    Article  CAS  PubMed  Google Scholar 

  8. A. Jadresic, L.M. Banks, D.F. Child, L. Diamant, F.H. Doyle, T.R. Fraser, G.F. Joplin, The acromegaly syndrome. Relation between clinical features, growth hormone values and radiological characteristics of the pituitary tumours. Q. J. Med. 51, 189–204 (1982)

    CAS  PubMed  Google Scholar 

  9. P. Caron, S. Broussaud, J. Bertherat, F. Borson-Chazot, T. Brue, C. Cortet-Rudelli, P. Chanson, Acromegaly and pregnancy: a retrospective multicenter study of 59 pregnancies in 46 women. J. Clin. Endocrinol. Metab. 95(10), 4680–4687 (2010)

    Article  CAS  PubMed  Google Scholar 

  10. The Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group, Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum. Reprod. 19, 41–47 (2004)

    Article  Google Scholar 

  11. D. Ferriman, J.D. Gallwey, Clinical assessment of body hair growth in women. J. Clin. Endocrinol. Metab. 21, 1440–1447 (1961).

    Article  CAS  PubMed  Google Scholar 

  12. A. Giustina, P. Chanson, M.D. Bronstein, A. Klibanski, S. Lamberts, F.F. Casanueva, P. Trainer, E. Ghigo, K. Ho, S. Melmed; Acromegaly Consensus Group, A consensus on criteria for cure of acromegaly. J. Clin. Endocrinol. Metab. 95(7), 3141–3148 (2010)

    Article  CAS  PubMed  Google Scholar 

  13. E. Anckaert, M. Öktem, A. Thies, M. Cohen-Bacrie, N.M. Daan, J. Schiettecatte, C. Müller, D. Topcu, A. Gröning, F. Ternaux, C. Engel, S. Engelmann, C. Milczynski, Multicenter analytical performance evaluation of a fully automated anti-Müllerian hormone assay and reference interval determination. Clin. Biochem. 49(3), 260–267 (2016)

    Article  CAS  PubMed  Google Scholar 

  14. M.E. Molitch, Pathologic hyperprolactinemia. Endocrinol. Metab. Clin. North. Am. 21, 877–901 (1992)

    CAS  PubMed  Google Scholar 

  15. R.V. Lloyd, M. Cano, W.F. Chandler, A.L. Barkan, E. Horvath, K. Kovacs, Human growth hormone and prolactin-secreting pituitary adenomas analyzed by in situ hybridization. Am. J. Pathol. 134, 605–613 (1989)

    CAS  PubMed  PubMed Central  Google Scholar 

  16. D.L. Kleinberg, J. Todd, Evidence that human growth hormone is a potent lactogen in primates. J. Clin. Endocrinol. Metab. 51, 1009–1013 (1980)

    Article  CAS  PubMed  Google Scholar 

  17. R. Abir, R. Garor, C. Felz, S. Nitke, H. Krissi, B. Fisch, Growth hormone and its receptor in human ovaries from fetuses and adults. Fertil. Steril. 90, 1333–1339 (2008)

    Article  CAS  PubMed  Google Scholar 

  18. S.S. Daftary, A.C. Gore, IGF-1 in the brain as a regulator of reproductive neuroendocrine function. Exp. Biol. Med. (Maywood). 230, 292–306 (2005)

    Article  CAS  PubMed  Google Scholar 

  19. V. Chandrashekar, D. Zaczek, A. Bartke, The consequences of altered somatotropic system on reproduction. Biol. Reprod. 71, 17–27 (2004)

    Article  CAS  PubMed  Google Scholar 

  20. H.D. Mason, H. Martikainen, R.W. Beard, V. Anyaoku, S. Franks, Direct gonadotrophic effect of growth hormone on oestradiol production by human granulosa cells in vitro. J. Endocrinol. 126, R1–R4 (1990)

    Article  CAS  PubMed  Google Scholar 

  21. R. Jirge PR, Ovarian reserve tests. J. Hum. Reprod. Sci. 4(3), 108–113 (2001)

    Article  Google Scholar 

  22. A. de Vet, J.S. Laven, F.H. de Jong, A.P. Themmen, B.C. Fauser, Anti-Müllerian hormone serum levels: Aputative marker for ovarian aging. Fertil. Steril. 77, 357–362 (2002)

    Article  PubMed  Google Scholar 

  23. M. Karamouti, P. Kollia, A. Kallitsaris, N. Vamvakopoulos, G. Kollios, I.E. Messinis, Growth hormone, insulin-like growth factor I, and leptin interaction in human cultured lutein granulosa cells steroidogenesis. Fertil. Steril. 90, 1444–1450 (2008)

    Article  CAS  PubMed  Google Scholar 

  24. J.R. Silva, J.R. Figueiredo, R. van den Hurk, Involvement of growth hormone (GH) and insulin-like growth factor (IGF) system in ovarian folliculogenesis. Theriogenology 71(8), 1193–1208 (2009)

    Article  CAS  PubMed  Google Scholar 

  25. L. Poretsky, N.A. Cataldo, Z. Resenwaks, I.C. Giudice, The insulin-related ovarian regulatory system in health and disease. Endocrinol. Rev. 20, 535–582 (1999)

    Article  CAS  Google Scholar 

  26. K. Kucuk, H. Kozinoglu, K. Ayten, Growth hormone co-treatment within a GnRH agonist long protocol in patients with poor ovarian response: a prospective, randomized, clinical trial. J. Assist. Reprod. Genet. 25, 123–127 (2008)

    Article  PubMed  PubMed Central  Google Scholar 

  27. J. Zhao, H.T.A. van Tol, M.A. Taverne, G.C. van deWeijden, M.M. Bevers, R. van den Hurk, The effect of growth hormone on rat preantral follicles in vitro. Zygote 3, 275–283 (2000)

    Article  Google Scholar 

  28. A. Colao, B. Merola, D. Ferone, G. Lombardi, Acromegaly. J. Clin. Endocrinol. Metab. 82, 2777–2781 (1997)

    Article  CAS  PubMed  Google Scholar 

  29. R. Cozzi, R. Attanasio, M. Barausse, Pregnancy in acromegaly: a one-center experience. Eur. J. Endocrinol. 155, 279–284 (2006)

    Article  CAS  PubMed  Google Scholar 

  30. M. Dias, C. Boguszewski, M. Gadelha, L. Kasuki, N. Musolino, J. Vieira, J. Abucham, Acromegaly and pregnancy: a prospective study. Eur. J. Endocrinol. 170, 301–310 (2014)

    Article  CAS  PubMed  Google Scholar 

  31. A. Atmaca, S. Dagdelen, T. Erbas, Follow-up of pregnancy in acromegalic women: different presentations and outcomes. Exp. Clin. Endocrinol. Diabetes 114, 135–139 (2006)

    Article  CAS  PubMed  Google Scholar 

  32. V. Herman-Bonert, M. Seliverstov, S. Melmed, Pregnancy in acromegaly: successful therapeutic outcome. J. Clin. Endocrinol. Metab. 83, 727–731 (1998)

    CAS  PubMed  Google Scholar 

  33. S. Cheng, L. Grasso, J. Martinez-Orozco, R. Al-Agha, R. Pivonello, A. Colao, S. Ezzat, Pregnancy in acromegaly: experience from two referral centers and systematic review of the literature. Clin. Endocrinol. (Oxf.). 76, 264–271 (2012)

    Article  PubMed  Google Scholar 

  34. A. Giustina, P. Chanson, D. Kleinberg, M.D. Bronstein, D.R. Clemmons, A. Klibanski, A.J. van der Lely, C.J. Strasburger, S.W. Lamberts, K.K. Ho, F.F. Casanueva, S. Melmed; Acromegaly Consensus Group, Expert consensus document: A consensus on the medical treatment of acromegaly. Nat. Rev. Endocrinol. 10(4), 243–248 (2014)

    Article  CAS  PubMed  Google Scholar 

  35. P. Maffei, G. Tamagno, G. Battista Nardelli, C. Videau, C. Menegazzo, G. Milan, A. Calcagno, C. Martini, R. Vettor, J. Epelbaum, N. Sicolo, Effects of octreotide exposure during pregnancy in acromegaly. Clin. Endocrinol. (Oxf.). 72, 668–677 (2010)

    Article  CAS  PubMed  Google Scholar 

  36. M. Ragonese, S. Grottoli, P. Maffei, A. Alibrandi, M.R. Ambrosio, G. Arnaldi, A. Bianchi, S. Puglisi, M.C. Zatelli, L. De Marinis, E. Ghigo, A. Giustina, F. Maffezzoni, C. Martini, L. Trementino, S. Cannavo, How to improve effectiveness of pegvisomant treatment in acromegalic patients. J. Endocrinol. Invest. https://doi.org/10.1007/s40618-017-0773-0

  37. A. Giustina, G. Arnaldi, F. Bogazzi, S. Cannavò, A. Colao, L. De Marinis, E. De Menis, E. Degli Uberti, F. Giorgino, S. Grottoli, A.G. Lania, P. Maffei, R. Pivonello, E. Ghigo, Pegvisomant in acromegaly: an update. J. Endocrinol. Invest. 40(6), 577–589 (2017)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. V. Herman-Bonert, S. Melmed. Pregnancy in acromegaly. in Pituitary Tumors in Pregnancy, ed. by M.D. Bronstein (Kluwer Academic Publishers, Norwell, MA, 2001) p. 109–121

    Chapter  Google Scholar 

  39. O. Haliloglu, B. Dogangun, B. Ozcabi, H.U. Kural, F.E. Keskin, H.M. Ozkaya, F.C. Pamukcu, E. Bektas, B.C. Poyraz, H. Buber, O. Evliyaoglu, P. Kadioglu, General health status and intelligence scores of children of mothers with acromegaly do not differ from those of healthy mothers. Pituitary 19(4), 391–398 (2016)

    Article  PubMed  Google Scholar 

  40. S. Neslihan Carda, S.A. Bilge, T.N. Ozturk, G. Oya, O. Ece, B. Hamiyet, The menopausal age, related factors and climacteric symptoms in Turkish women. Maturitas 30, 37–40 (1998)

    Article  CAS  PubMed  Google Scholar 

  41. E.B. Gold, S.L. Crawford, N.E. Avis, C.J. Crandall, K.A. Matthews, L.E. Waetjen, J.S. Lee, R. Thurston, M. Vuga, S.D. Harlow, Factors related to age at natural menopause: longitudinal analyses from SWAN. Am. J. Epidemiol. 178(1), 70–83 (2013)

    Article  PubMed  PubMed Central  Google Scholar 

  42. O. Cohen, B. Schindel, R. Homburg, Uterine leiomyomata-a feature of acromegaly. Hum. Reprod. 13(7), 1945–1946 (1998)

    Article  CAS  PubMed  Google Scholar 

  43. F.I. Sharara, L.K. Neiman, Growth hormone receptor messenger ribonucleotide acid expression in leiomyoma and surrounding myometrium. Am. J. Obstet. Gynecol. 172, 814–819 (1995)

    Article  Google Scholar 

  44. L.C. Guidice, J.C. Irwin, B.A. Dsupin, Insulin like growth factor (IGF), IGF binding proteins (IGFBP) ang IGF receptor gene expression and IGFBP synthesis in human uterine leiomyomata. Hum. Reprod. 8, 1796–1806 (1993)

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine, Division of Endocrinology and Metabolism, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey

    Sema Ciftci Dogansen, Seher Tanrikulu, Gulsah Yenidunya Yalin & Sema Yarman

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  1. Sema Ciftci Dogansen
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  2. Seher Tanrikulu
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Correspondence to Sema Ciftci Dogansen.

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The study was approved by the Ethics Committee of Istanbul University, Istanbul Faculty of Medicine.

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Dogansen, S.C., Tanrikulu, S., Yalin, G.Y. et al. Female gonadal functions and ovarian reserve in patients with acromegaly: experience from a single tertiary center. Endocrine 60, 167–174 (2018). https://doi.org/10.1007/s12020-018-1540-5

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