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Growth stabilization and regression of meningiomas after discontinuation of cyproterone acetate: a case series of 12 patients

Acta Neurochirurgica volume 157, pages 1741–1746 (2015)Cite this article

Abstract

Background

The relationship between meningiomas and exogenous sex hormones is well known, but cyproterone acetate (CA), a progesterone agonist, seems to have a stronger influence on tumor growth.

Objective

To show the close relationship between CA treatment and meningioma growth.

Methods

Since 2010, all patients referred to our clinic for a suspicion of meningioma were questioned specifically about exogenous sex hormone intake and more specifically about CA intake. Twelve patients harboring one or multiple meningiomas and treated with CA were identified. CA was stopped in all cases. Tumor volumes and diameters were measured on serial MRIs and compared to the last MRI before CA withdrawal.

Results

Ten patients with multiple tumors had been taking the drug for a longer period of time (mean of 20.4 years) than the two patients with one tumor (10 years). Two patients with multiple tumors underwent surgery because of rapidly decreased visual acuity at the time of diagnosis. Discontinuation of CA led to tumor shrinkage in 11 patients and a stop in tumor growth in one [mean tumor volume reduction was around 10 cm3/year; range (0.00; 76)]. There was no regrowth during a mean follow-up period of 12 months (range: 5–35).

Conclusion

For patients diagnosed with a meningioma and treated with CA, medication withdrawal followed by observation should be the first line of treatment. Care should be taken with long-term use of high doses of CA, and serial brain MRIs should be considered after several years of CA.

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References

  1. Adams EF, Schrell UM, Fahlbusch R, Thierauf P (1990) Hormonal dependency of cerebral meningiomas. Part 2: In vitro effect of steroids, bromocriptine, and epidermal growth factor on growth of meningiomas. J Neurosurg 73(5):750–755

    CAS  Article  PubMed  Google Scholar 

  2. Cebula H, Pham TQ, Boyer P, Froelich S (2010) Regression of meningiomas after discontinuation of cyproterone acetate in a transsexual patient. Acta Neurochir (Wien) 152(11):1955–1956

    Article  Google Scholar 

  3. Clark VE, Erson-Omay EZ, Serin A et al (2013) Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO. Science 339(6123):1077–1080

    CAS  Article  PubMed  Google Scholar 

  4. Claus EB, Calvocoressi L, Bondy ML, Wrensch M, Wiemels JL, Schildkraut JM (2013) Exogenous hormone use, reproductive factors, and risk of intracranial meningioma in females. J Neurosurg 118(3):649–656

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  5. Fan Z-X, Shen J, Wu Y-Y, Yu H, Zhu Y, Zhan R-Y (2013) Hormone replacement therapy and risk of meningioma in women: a meta-analysis. Cancer Causes Control 24(8):1517–1525

    Article  PubMed  Google Scholar 

  6. Gazzeri R, Galarza M, Gazzeri G (2007) Growth of a meningioma in a transsexual patient after estrogen-progestin therapy. N Engl J Med 357(23):2411–2412

    CAS  Article  PubMed  Google Scholar 

  7. Gil M, Oliva B, Timoner J, Maciá MA, Bryant V, de Abajo FJ (2011) Risk of meningioma among users of high doses of cyproterone acetate as compared with the general population: evidence from a population-based cohort study. Br J Clin Pharmacol 72(6):965–968

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  8. Gonçalves AMG, Page P, Domigo V, Méder J-F, Oppenheim C (2010) Abrupt regression of a meningioma after discontinuation of cyproterone treatment. AJNR Am J Neuroradiol 31(8):1504–1505

    Article  PubMed  Google Scholar 

  9. Gruber T, Dare AO, Balos LL, Lele S, Fenstermaker RA (2004) Multiple meningiomas arising during long-term therapy with the progesterone agonist megestrol acetate. Case report. J Neurosurg 100(2):328–331

    Article  PubMed  Google Scholar 

  10. Gruber TJ, Fabiano AJ, Deeb G, Lele SB, Fenstermaker RA (2011) Intracranial meningiomas in patients with uterine sarcoma treated with long-term megestrol acetate therapy. World Neurosurg 76(5):477.e16–20

    Article  PubMed  Google Scholar 

  11. Grunberg SM, Weiss MH, Spitz IM, Ahmadi J, Sadun A, Russell CA, Lucci L, Stevenson LL (1991) Treatment of unresectable meningiomas with the antiprogesterone agent mifepristone. J Neurosurg 74(6):861–866

    CAS  Article  PubMed  Google Scholar 

  12. Hsu DW, Efird JT, Hedley-Whyte ET (1997) Progesterone and estrogen receptors in meningiomas: prognostic considerations. J Neurosurg 86(1):113–120

    CAS  Article  PubMed  Google Scholar 

  13. Klaeboe L, Lonn S, Scheie D, Auvinen A, Christensen HC, Feychting M, Johansen C, Salminen T, Tynes T (2005) Incidence of intracranial meningiomas in Denmark, Finland, Norway and Sweden, 1968–1997. Int J Cancer 117(6):996–1001

    CAS  Article  PubMed  Google Scholar 

  14. Korhonen K, Raitanen J, Isola J, Haapasalo H, Salminen T, Auvinen A (2010) Exogenous sex hormone use and risk of meningioma: a population-based case–control study in Finland. Cancer Causes Control 21(12):2149–2156

    CAS  Article  PubMed  Google Scholar 

  15. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114(2):97–109

    PubMed Central  Article  PubMed  Google Scholar 

  16. Lusis EA, Scheithauer BW, Yachnis AT, Fischer BR, Chicoine MR, Paulus W, Perry A (2012) Meningiomas in pregnancy: a clinicopathologic study of 17 cases. Neurosurgery 71(5):951–961

    Article  PubMed  Google Scholar 

  17. Ostrom QT, Gittleman H, Farah P, Ondracek A, Chen Y, Wolinsky Y, Stroup NE, Kruchko C, Barnholtz-Sloan JS (2013) CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2006–2010. Neuro-Oncology 15(Suppl 2):ii1–ii56

    PubMed Central  Article  PubMed  Google Scholar 

  18. Piper JG, Follett KA, Fantin A (1994) Sphenoid wing meningioma progression after placement of a subcutaneous progesterone agonist contraceptive implant. Neurosurgery 34(4):723–725, discussion 725

    CAS  Article  PubMed  Google Scholar 

  19. Pozzati E, Zucchelli M, Schiavina M, Contini P, Foschini MP (2007) Rapid growth and regression of intracranial meningiomas in lymphangioleiomyomatosis: case report. Surg Neurol 68(6):671–674, discussion 674–675

    Article  PubMed  Google Scholar 

  20. Pravdenkova S, Al-Mefty O, Sawyer J, Husain M (2006) Progesterone and estrogen receptors: opposing prognostic indicators in meningiomas. J Neurosurg 105(2):163–173

    CAS  Article  PubMed  Google Scholar 

  21. Qi Z-Y, Shao C, Huang Y-L, Hui G-Z, Zhou Y-X, Wang Z (2013) Reproductive and exogenous hormone factors in relation to risk of meningioma in women: a meta-analysis. PLoS ONE 8(12):e83261

    PubMed Central  Article  PubMed  Google Scholar 

  22. Roelvink NC, Kamphorst W, van Alphen HA, Rao BR (1987) Pregnancy-related primary brain and spinal tumors. Arch Neurol 44(2):209–215

    CAS  Article  PubMed  Google Scholar 

  23. Schrell UM, Koch HU, Marschalek R, Schrauzer T, Anders M, Adams E, Fahlbusch R (1998) Formation of autocrine loops in human cerebral meningioma tissue by leukemia inhibitor factinterleukin-6, and oncostatin M: inhibition of meningioma cell growth in vitro by recombinant oncostatin M. J Neurosurg 88(3):541–548

  24. Shimizu J, Matsumoto M, Yamazaki E, Yasue M (2008) Spontaneous regression of an asymptomatic meningioma associated with discontinuation of progesterone agonist administration. Neurol Med Chir (Tokyo) 48(5):227–230

    Article  Google Scholar 

  25. Vadivelu S, Sharer L, Schulder M (2010) Regression of multiple intracranial meningiomas after cessation of long-term progesterone agonist therapy. J Neurosurg 112(5):920–924

    CAS  Article  PubMed  Google Scholar 

Download references

Conflicts of interest

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

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    Affiliations

    1. Department of Neurosurgery, Hôpital Lariboisière, Paris VII-Diderot University, 2 rue Ambroise Pare, Paris, 75475, France

      Anne Laure Bernat, Kenichi Oyama, Selma Hamdi, Emmanuel Mandonnet, Bernard George & Sebastien Froelich

    2. Department of Gynecology, Hôpital Lariboisière, Paris, France

      Dominique Vexiau

    3. Paris VII-Diderot University, 2 rue Ambroise Pare, Paris, 75475, France

      Emmanuel Mandonnet

    4. Department of Visceral Surgery, Hôpital Lariboisière, Paris, France

      Marc Pocard

    Authors
    1. Anne Laure Bernat
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    2. Kenichi Oyama
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    Correspondence to Anne Laure Bernat.

    Additional information

    Anne Laure Bernat and Kenichi Oyama contributed equally to this work.

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    Cite this article

    Bernat, A.L., Oyama, K., Hamdi, S. et al. Growth stabilization and regression of meningiomas after discontinuation of cyproterone acetate: a case series of 12 patients. Acta Neurochir 157, 1741–1746 (2015). https://doi.org/10.1007/s00701-015-2532-3

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    • DOI: https://doi.org/10.1007/s00701-015-2532-3

    Keywords

    • Cyproterone acetate
    • Meningioma
    • Meningiomatosis
    • Progesterone agonist