Archives of Gynecology and Obstetrics

, Volume 291, Issue 3, pp 591–598 | Cite as

The effects of different doses of melatonin treatment on endometrial implants in an oophorectomized rat endometriosis model

  • Nilufer CetinkayaEmail author
  • Rukset Attar
  • Gazi Yildirim
  • Cem Ficicioglu
  • Ferda Ozkan
  • Bayram Yilmaz
  • Narter Yesildaglar
General Gynecology



To determine the effects of different doses of melatonin treatment on endometrial implants, the activity of antioxidant enzyme superoxide dismutase (SOD), the angiogenesis factor, the vascular endothelial growth factor (VEGF) and the waste metabolite product of lipid peroxidation malondialdehyde (MDA) in an oophorectomized rat endometriosis model.


Thirty-two, female, non-pregnant, nulligravid Sprague–Dawley, albino rats were used in this prospective, randomized, controlled and experimental study. Endometriosis was surgically induced in oophorectomized rats, and estradiol treatment was started after the first operation and continued till the end of the study. Second look, third look and necropsy operations were performed in the 2nd, 4th and 6th weeks. Mean volumes, histological scores and biochemical parameters were evaluated throughout the study.


The mean volumes of endometriotic foci were 98.8 mm3 ± 17.2 vs. 108.2 mm3 ± 17.5, 54.1 mm3 ± 15.6 vs. 25.8 mm3 ± 3.6, 42.8 mm3 ± 10.5 vs. 32.7 mm3 ± 6.0 and histopathological scores were 2.2 ± 0.2 vs. 1.7 ± 0.1, 2.6 ± 0.2 vs. 2.2 ± 0.2, 2.6 ± 0.1 vs. 2.7 ± 0.2 in the 10 vs. 20-mg/kg/day melatonin group at the end of the second, fourth and sixth weeks, respectively. When the groups were compared, no significant differences were seen in the histopathologic scores, SOD and VEGF levels between the groups. However, the endometriotic foci volumes were significantly decreased in both melatonin treatment groups with respect to the control group at the end of the fourth and sixth weeks. Moreover, the mean MDA levels were significantly lower in the control group than in the 10-mg/kg/day melatonin group at the end of the fourth and sixth weeks.


Melatonin treatment resulted in the regression of endometriotic lesions in oophorectomized rats. Higher doses of melatonin treatment might be more effective in the regression of implants and improvement of histologic scores as well as in the precise evaluation of SOD, MDA and VEGF distributions in the rat experimental models.


Endometriosis Rats Experimental endometriosis model Melatonin 


Conflict of interest

We declare that we have no conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Nilufer Cetinkaya
    • 1
    Email author
  • Rukset Attar
    • 2
  • Gazi Yildirim
    • 2
  • Cem Ficicioglu
    • 2
  • Ferda Ozkan
    • 3
  • Bayram Yilmaz
    • 4
  • Narter Yesildaglar
    • 5
  1. 1.Department of Gynecologic OncologyZekai Tahir Burak Women’s Health Education and Research HospitalAnkaraTurkey
  2. 2.Department of Obstetrics and Gynecology, Center for Reproductive MedicineYeditepe University HospitalIstanbulTurkey
  3. 3.Department of PathologyYeditepe University HospitalIstanbulTurkey
  4. 4.Department of PhysiologyYeditepe University HospitalIstanbulTurkey
  5. 5.Department of Obstetrics and GynecologySevket Yilmaz Training and Research HospitalBursaTurkey

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