title: Effect of varying doses of tamoxifen on ovarian histopathology, serum VEGF, and endothelin 1 levels in ovarian hyperstimulation syndrome: an experimental study.
abstract: OBJECTIVE
  To examine the effects of low-to-high doses of tamoxifen on ovarian histopathology, serum VEGF, and endothelin 1 levels in ovarian hyperstimulation syndrome (OHSS) in an experimental setting.
  
  
  METHODS
  A total of 20 female Wistar albino rats, 22 days of age, were randomly divided into four groups. Follicle-stimulating hormone 10 IU was administered subcutaneously in 15 rats on 4 consecutive days, with OHSS induction on day 5 by 30 IU of human chorionic gonadotropin. Group 1 (n=5) comprised 35-day-old control rats, group 2 (n=5) 35-day-old OHSS rats, group 3 (n=5) 27-day-old OHSS rats receiving 1 mg/kg of oral tamoxifen for 7 days, group 4 (n=5) 27-day-old OHSS rats receiving 3 mg/kg of oral tamoxifen for 7 days. All rats were decapitated on day 35. Serum VEGF, endothelin 1, and ovarian follicular reserve were assessed in all rats. Kruskal-Wallis variance analysis and the Mann-Whitney U-test were used for statistical comparisons. A Bonferroni correction was performed to control the inflation of significance, with a significance level set at a P-value of less than 0.025.
  
  
  RESULTS
  Despite higher serum VEGF, endothelin 1, follicular reserve, and angiogenesis and fibrosis of the corpus luteum in the OHSS group compared to controls, these differences were not significant (P>0.025, Mann-Whitney U-test). There was a significant reduction in the ovarian follicular reserve in tamoxifen groups compared to controls (P<0.025, Mann-Whitney U-test), while angiogenesis of the corpus luteum, number of atretic follicles, fibrosis, and serum VEGF were significantly higher in rats receiving tamoxifen (P<0.025, Mann-Whitney U-test). Also, significantly lower follicular reserve and fibrosis were observed among rats in the low-dose tamoxifen group in comparison with rats in the high-dose tamoxifen group (P<0.025, Mann-Whitney U-test). No groups had a significant change in endothelin 1 levels (P>0.025, Mann-Whitney U-test).
  
  
  CONCLUSIONS
  Tamoxifen 1 g and 3 g resulted in a dose-dependent increase in VEGF and endothelin 1 levels, and ovarian follicle reserves were significantly reduced in our experimental model.
authors.affiliation: Department of Obstetrics and Gynecology, Fırat University School of Medicine, Elazig, Turkey.
authors.forename: Şehmus
authors.initials: Ş
authors.lastname: Pala
authors.affiliation: Department of Obstetrics and Gynecology, Fırat University School of Medicine, Elazig, Turkey.
authors.forename: Remzi
authors.initials: R
authors.lastname: Atilgan
authors.affiliation: Department of Obstetrics and Gynecology, Fırat University School of Medicine, Elazig, Turkey.
authors.forename: Zehra Sema
authors.initials: ZS
authors.lastname: Ozkan
authors.affiliation: Department of Obstetrics and Gynecology, Fırat University School of Medicine, Elazig, Turkey.
authors.forename: Salih Burçin
authors.initials: SB
authors.lastname: Kavak
authors.affiliation: Department of Biochemistry, Fırat University School of Medicine, Elazig, Turkey.
authors.forename: Nevin
authors.initials: N
authors.lastname: Ilhan
authors.affiliation: Department of Pathology, Fırat University School of Medicine, Elazig, Turkey.
authors.forename: Nusret
authors.initials: N
authors.lastname: Akpolat
authors.affiliation: Department of Obstetrics and Gynecology, Fırat University School of Medicine, Elazig, Turkey.
authors.forename: Ekrem
authors.initials: E
authors.lastname: Sapmaz
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D006062:Gonadotropins / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D016471:Ovarian Hyperstimulation Syndrome / Q000097:blood* / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013629:Tamoxifen / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D019332:Endothelin-1; D006062:Gonadotropins; D042461:Vascular Endothelial Growth Factor A; D013629:Tamoxifen
keywords: OHSS; cystic enlargement of the ovaries; hCG; low-to-high doses of tamoxifen
references.citation: Asian Pac J Cancer Prev. 2013;14(11):6869-74
references.pmid: 24377619
references.citation: Hum Reprod. 2005 Jun;20(6):1511-5
references.pmid: 15845599
references.citation: J Mol Endocrinol. 1998 Jun;20(3):363-74
references.pmid: 9687159
references.citation: Semin Reprod Med. 2010 Nov;28(6):448-57
references.pmid: 21082502
references.citation: Med J Armed Forces India. 2014 Jan;70(1):58-63
references.pmid: 24623949
references.citation: Eur J Obstet Gynecol Reprod Biol. 1999 Jul;85(1):13-20
references.pmid: 10428316
references.citation: BMC Cancer. 2013;13:273
references.pmid: 23731702
references.citation: Fertil Steril. 1999 Apr;71(4):645-51
references.pmid: 10202873
references.citation: Cancer Res. 2002 Apr 1;62(7):1948-51
references.pmid: 11929808
references.citation: Lancet. 1994 Jul 23;344(8917):235-6
references.pmid: 7913160
references.citation: Breast Cancer Res Treat. 2001 May;67(1):51-60
references.pmid: 11518466
references.citation: Mol Reprod Dev. 1998 Nov;51(3):287-94
references.pmid: 9771649
references.citation: Mol Cell Endocrinol. 1999 Mar 25;149(1-2):29-40
references.pmid: 10375015
references.citation: Am J Obstet Gynecol. 2000 Jan;182(1 Pt 1):240-6
references.pmid: 10649185
references.citation: Science. 1988 Mar 11;239(4845):1296-9
references.pmid: 3125611
references.citation: Fertil Steril. 2012 Mar;97(3):517-22
references.pmid: 22265002
references.citation: Mol Cell Endocrinol. 2003 Apr 28;202(1-2):47-52
references.pmid: 12770729
references.citation: Cancer Lett. 1997 Dec 9;120(2):165-71
references.pmid: 9461033
references.citation: Hum Reprod. 1997 Jun;12(6):1129-37
references.pmid: 9221989
references.citation: Am J Physiol Heart Circ Physiol. 2000 Nov;279(5):H2033-42
references.pmid: 11045935
references.citation: Fertil Steril. 1999 May;71(5):808-14
references.pmid: 10231037
references.citation: Reprod Fertil Dev. 2009;21(3):377-92
references.pmid: 19261215
references.citation: Eur J Surg Oncol. 1997 Dec;23(6):570
references.pmid: 9484934
references.citation: Fertil Steril. 2010 Jul;94(2):389-400
references.pmid: 20416867
references.citation: Hum Reprod Update. 2000 May-Jun;6(3):212-24
references.pmid: 10874566
references.citation: Fertil Steril. 2002 Aug;78(2):286-90
references.pmid: 12137864
references.citation: Fertil Steril. 2004 Mar;81 Suppl 1:842-9
references.pmid: 15019818
references.citation: Obstet Gynecol. 1986 Dec;68(6):847-9
references.pmid: 3785798
references.citation: J Clin Endocrinol Metab. 2008 Mar;93(3):935-43
references.pmid: 18171700