Preview

Problems of Endocrinology

Advanced search

Tamoxifen in patients with dopamine agonist-resistant prolactinomas

Abstract

Aim — to assess the efficacy and safety of tamoxifen in patients with prolactin-secreting pituitary tumors resistant to treatment with dopamine agonists.


Material and methods. The study included 6 females aged 23—38 years. All patients received cabergoline for a prolonged time without normalization of prolactin levels and reversal of secondary hypogonadism. The cabergoline dose was 1—7 mg/week. Cabergoline administration was combined with tamoxifen at a dose of 20 mg per day, with a subsequent increase to 40 mg per day after 4 weeks of treatment. Patients received this combination therapy for 3 months.


Results. Combined cabergoline and tamoxifen therapy resulted in a significant reduction in prolactin levels in all treated patients, which amounted to 22—66% of the baseline value. However, none of the patients achieved complete normalization of prolactin levels. Despite this fact, 2 patients developed normalization of the menstrual cycle. One of these got pregnant 1.5 months after discontinuation of tamoxifen and gave birth to a child. The second patient had amenorrhea recurrence after tamoxifen discontinuation. After tamoxifen discontinuation, two patients with amenorrhea were treated with dydrogesterone to prevent endometrial hyperplasia. One patient who had a normal menstrual function before tamoxifen developed endometrial hyperplasia, which was the cause for separate diagnostic curettage and a reduction in the tamoxifen dose to 20 mg per day. One month after tamoxifen discontinuation, the patient naturally conceived and subsequently gave birth to twins. One patient underwent placement of an intrauterine system containing levonorgestrel 2 months before the start of tamoxifen.


Conclusion. Tamoxifen in combination with cabergoline provides an additional decrease in prolactin levels in patients with initial resistance to dopamine agonists. In patients with dopamine agonist-resistant prolactinomas and hypoestrogenemia, tamoxifen leads to normalization of the menstrual cycle.

About the Authors

Natalia S. Fedorova

Endocrinology Research Centre


Russian Federation

MD



Larisa K. Dzeranova

Endocrinology Research Centre


Russian Federation

MD, PhD



Ekaterina A. Pigarova

Endocrinology Research Centre


Russian Federation

MD, PhD



Svetlana U. Vorotnikova

Endocrinology Research Centre


Russian Federation

MD



Galina A. Melnichenko

Endocrinology Research Centre


Russian Federation

MD, PhD, Professor



References

1. Colao A. Pituitary tumours: the prolactinoma. Best Pract Res Clin Endocrinol Metab.2009;23(5):575-596. doi: 10.1016/j.beem.2009.05.003

2. Gillam MP, Molitch ME, Lombardi G, Colao A. Advances in the treatment of prolactinomas. Endocr Rev. 2006;27(5):485-534. doi: 10.1210/er.2005-9998

3. Fainstein Day P, Glerean M, Lovazzano S, et al. Gender differences in macroprolactinomas: study of clinical features, outcome of patients and Ki-67 expression in tumor tissue. Front Horm Res.2010;38:50-58. doi: 10.1159/000318494

4. Ciccarelli A, Daly AF, Beckers A. The Epidemiology of prolactinomas. Pituitary. 2005;8(1):3-6. doi: 10.1007/s11102-005-5079-0

5. Berinder K, Stackenas I, Akre O, et al. Hyperprolactinaemia in 271 women: up to three decades of clinical follow-up. Clin Endocrinol (Oxf). 2005;63(4):450-455. doi: 10.1111/j.1365-2265.2005.02364.x

6. Molitch ME. Pharmacologic resistance in prolactinoma patients. Pituitary. 2005;8(1):43-52. doi: 10.1007/s11102-005-5085-2

7. Babey M, Sahli R, Vajtai I, et al. Pituitary surgery for small prolactinomas as an alternative to treatment with dopamine agonists. Pituitary. 2011;14(3):222-230. doi: 10.1007/s11102-010-0283-y

8. Laws ER, Jane JA, Jr. Neurosurgical approach to treating pituitary adenomas. Growth Horm IGF Res. 2005;15 Suppl A:S36-S41. doi: 10.1016/j.ghir.2005.06.008

9. Mortini P, Losa M, Barzaghi R, et al. Results of transsphenoidal surgery in a large Series of patients with pituitary adenoma. Neurosurgery. 2005;56(6):1222-1233. doi: 10.1227/01.neu.0000159647.64275.9d

10. Faupel-Badger JM. Effects of raloxifene on circulating prolactin and estradiol levels in premenopausal women at high risk for developing breast cancer. Cancer Epidemiology Biomarkers & Prevention. 2006;15(6):1153-1158. doi: 10.1158/1055-9965.epi-05-0898

11. Jones ME, van Leeuwen FE, Hoogendoorn WE, et al. Endometrial cancer survival after breast cancer in relation to tamoxifen treatment: Pooled results from three countries. Breast Cancer Res. 2012;14(3):R91. doi: 10.1186/bcr3206

12. Shi Q, Li J, Li M, et al. The role of levonorgestrel-releasing intrauterine system for endometrial protection in women with breast cancer taking tamoxifen. Eur J Gynaecol Oncol. 2014;35(5):492-498.

13. Gorski J, Wendell D, Gregg D, Chun TY. Estrogens and the genetic control of tumor growth. Prog Clin Biol Res. 1997;396:233-243.

14. Kovacs K, Stefaneanu L, Ezzat S, Smyth HS. Prolactin-producing pituitary adenoma in a male-to-female transsexual patient with protracted estrogen administration. A morphologic study. Arch Pathol Lab Med. 1994;118(5):562-565.

15. Serri O, Noiseux D, Robert F, Hardy J. Lactotroph hyperplasia in an estrogen treated male-to-female transsexual patient. J Clin Endocrinol Metab. 1996;81(9):3177-3179. doi: 10.1210/jcem.81.9.8784065

16. Kaptain GJ, Simmons NE, Alden TD, et al. Estrogen receptors in prolactinomas: a clinico-pathological study. Pituitary. 1999;1(2):91-98.

17. Shupnik MA, Pitt LK, Soh AY, et al. Selective expression of estrogen receptor alpha and beta isoforms in human pituitary tumors. J Clin Endocrinol Metab. 1998;83(11):3965-3972. doi: 10.1210/jcem.83.11.5236

18. Chaidarun SS. Tumor-specific expression of alternatively spliced estrogen receptor messenger ribonucleic acid variants in human pituitary adenomas. J Clin Endocrinol Metab. 1997;82(4):1058-1065. doi: 10.1210/jc.82.4.1058

19. Friend KE, Chiou YK, Lopes MB, et al. Estrogen receptor expression in human pituitary: correlation with immunohistochemistry in normal tissue, and immunohistochemistry and morphology in macroadenomas. J Clin Endocr Metab. 1994;78(6):1497-1504. doi: 10.1210/jcem.78.6.7515390

20. Pichon M-F, Bression D, Peillon F, Tubiana M. Estrogen receptors in human pituitary adenomas. J Clin Endocr Metab. 1980;51(4):897-902. doi: 10.1210/jcem-51-4-897

21. Zafar M, Ezzat S, Ramyar L, et al. Cell-specific expression of estrogen receptor in the human pituitary and its adenomas. J Clin Endocr Metab. 1995;80(12):3621-3627. doi: 10.1210/jcem.80.12.8530610

22. Manoranjan B, Salehi F, Scheithauer BW, et al. Estrogen receptors alpha and beta immunohistochemical expression: clinicopathological correlations in pituitary adenomas. Anticancer Res. 2010;30(7):2897-2904.

23. Volker W, Gehring WG, von zur Muhlen A, Schneider J. Bromocriptine and tamoxifen — a new therapeutic approach in suppression-resistant prolactin-secreting adenomas. Geburtshilfe Frauenheilkd. 1982;42(11):790-797. doi: 10.1055/s-2008-1037161

24. Pugh DM, Sumano HS. The anti-implantation action of tamoxifen in mice. 1982;5:209-213. doi: 10.1007/978-3-642-68511-8_38

25. El-Gharib MN, Mahfouz AE, Farahat MA. Comparison of letrozole versus tamoxifen effects in clomiphen citrate resistant women with polycystic ovarian syndrome. J Reprod Infertil. 2015;16(1):30-35. PMC4322179

26. Barthelmes L, Gateley CA. Tamoxifen and pregnancy. Breast. 2004;13(6):446-451. doi: 10.1016/j.breast.2004.08.007

27. Everett C. Incidence and outcome of bleeding before the 20th week of pregnancy: prospective study from general practice. BMJ. 1997;315(7099):32-34. doi: 10.1136/bmj.315.7099.32


Supplementary files

1. Рис. 1. Динамика уровня ПРЛ на фоне лечения тамоксифеном.  
Subject
Type Исследовательские инструменты
View (64KB)    
Indexing metadata ▾
2. Рис. 2. Динамика снижения уровня ПРЛ через 3 мес лечения.
Subject
Type Исследовательские инструменты
View (53KB)    
Indexing metadata ▾
3. Рис. 3. Изменение либидо на фоне приема тамоксифена.
Subject
Type Исследовательские инструменты
View (26KB)    
Indexing metadata ▾

Review

For citations:


Fedorova N.S., Dzeranova L.K., Pigarova E.A., Vorotnikova S.U., Melnichenko G.A. Tamoxifen in patients with dopamine agonist-resistant prolactinomas. Problems of Endocrinology. 2017;63(5):291-298.

Views: 7198


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 0375-9660 (Print)
ISSN 2308-1430 (Online)