ABSTRACT
This study compared the antiproliferative effects of metformin and progesterone, via examination of the Bcl-2/Bax-caspase apoptotic pathway in estrogen-induced endometrial hyperplasia (EH) in 40 rats. Two rats died after bilateral oophorectomy, and 1 week after surgery, the remaining 38 were randomly divided into three groups: the first (control, n = 12) received 4 mg/kg 17ß estradiol hemihydrate (E); the second (n = 13) received 4 mg/kg 17ß estradiol hemihydrate and 50 mg/kg metformin (E + M); and the third (n = 13) received 4 mg/kg 17ß estradiol hemihydrate and 1 mg/day medroxiprogesterone acetate (E + MPA). Histological markers and Bcl-2, Bax and caspase 9 expression were analyzed. Luminal epithelial thickness, density of gland and epithelial height was significantly higher in group E than in groups E + M and E + MPA. Histopathologic parameters were similar between the E + M and E + MPA groups. Bcl-2/Bax ratio was significantly decreased in the E + M and E + MPA groups and caspase 9 expression levels were significantly increased in the E + M and E + MPA groups, compared with the control group. In addition, Bcl-2/Bax ratio and caspase 9 expression were similar between the E + M and E + MPA groups. The data indicate that metformin reduces estrogen-induced EH in rats, via activation of the caspase-dependent mitochondrial apoptotic pathway, to the same degree as progesterone.
Subject(s)
Apoptosis/drug effects , Endometrial Hyperplasia/metabolism , Metformin/pharmacology , Progesterone/pharmacology , Proto-Oncogene Proteins c-bcl-2/metabolism , Animals , Disease Models, Animal , Endometrial Hyperplasia/chemically induced , Estradiol , Female , RatsSubject(s)
Carcinoma, Endometrioid/surgery , Carcinoma, Transitional Cell/pathology , Neoplasms, Multiple Primary/surgery , Ovarian Neoplasms/pathology , Uterine Neoplasms/surgery , Carcinoma, Endometrioid/pathology , Carcinoma, Transitional Cell/surgery , Female , Humans , Hysterectomy , Incidental Findings , Middle Aged , Neoplasms, Multiple Primary/diagnosis , Neoplasms, Multiple Primary/pathology , Ovarian Neoplasms/surgery , Ovariectomy , SalpingectomyABSTRACT
The aim of this study was to analyse low molecular weight heparin (LMWH) use during pregnancy in terms of patient evaluation, treatment indication and social and financial costs. This was a retrospective analysis of patients using LMWH in their pregnancies. A total of 147 women were included in the study. The most common indications were thrombophilia (55/147, 37.4%); recurrent pregnancy loss (RPL); (47/147, 32.0%) and previous single pregnancy loss (18/147, 12.2%). In the RPL group, 53.1% of patients were not evaluated with standard tests; 31.9% of women were incompletely evaluated and 15% were properly evaluated. Out of 104 women screened for thrombophilia, 32 (32/104, 30.8%) were tested during pregnancy. Despite published guidelines and increasing scientific evidence against their use in some indications, LMWHs are prescribed widely during pregnancy for a variety of indications. Public and healthcare providers' education to change this attitude should be implemented.