title: The effect of letrozole with misoprostol for medical termination of pregnancy on the expression of steroid receptors in the placenta.
abstract: OBJECTIVE
  What is the effect of letrozole on the expression of steroid receptors in the placentae in cases of termination of pregnancies?
  
  
  CONCLUSIONS
  The expression of estrogen receptor-α (ERα) and progesterone receptor (PR) transcripts, as well as ERα protein, in placentae was suppressed by letrozole pretreatment in second trimester termination of pregnancy.
  
  
  BACKGROUND
  There have been no data in the literature on the effect of letrozole in termination of human pregnancies.
  
  
  METHODS
  This study is part of a clinical randomized trial in which 50 subjects were recruited and 44 placentae were collected.
  
  
  METHODS
  Women (n = 50) requesting second trimester abortion between 12 and 20 gestational weeks were randomized to receive either letrozole or placebo pretreatment for 3 days before administration of vaginal misoprostol. Placentae were collected from both groups of women after the abortion. Total RNA from the frozen placenta samples was extracted and subjected to real-time RT-PCR analysis of ERα and estrogen receptor-β (ERβ), PR and glucocorticoid receptor (GR) transcripts. Immunohistochemical studies of ERα, ERβ, PR and GR expression, as well as Ki67 and PCNA staining for proliferation, were performed. TUNEL assays were performed to determine the extent of apoptosis.
  
  
  RESULTS
  Real-time RT-PCR demonstrated that the median ERα {3.900 [95% confidence interval (CI): -0.643-8.443] in the letrozole group versus 4.714 (95% CI: 1.776-7.652) in the control group; P = 0.005} and the median PR [0.701 (95% CI: 0.333-1.069) in the letrozole group versus 1.774 (95% CI: 1.07-2.478) in the control group; P = 0.003] were significantly lower in the letrozole group compared with the control group. Furthermore, ERα protein levels, in both syncytiotrophoblasts and cytotrophoblasts but not in villous stromal cells, were significantly reduced [H-score of 113 (95% CI: 103-119) in the letrozole group versus 217 (95% CI: 214-290) in the control group, in syncytiotrophoblasts; 100 (95% CI: 98-105) in the letrozole group versus 210 (95% CI: 200-286) in the control group, in cytotrophoblasts; P = 0.004], while the expression levels of ERβ, PR, GR, PCNA, Ki67 and TUNEL were not significantly different between the two groups.
  
  
  CONCLUSIONS
  Only the placentae from the second trimester termination of pregnancy were collected in this study. Information from first trimester terminations is still lacking.
  
  
  CONCLUSIONS
  The results shed some light on the mechanism of action of letrozole pretreatment in termination of pregnancies.
  
  
  BACKGROUND
  This study was funded by the GRF/RGC and CRCG grants of the University of Hong Kong.
  
  
  BACKGROUND
  HKClinicalTrials.com with trial number HKCTR-695.
authors: Department of Obstetrics and Gynaecology, The University of Hong Kong, Hong Kong Special Administrative Region, Queen Mary Hospital, Pokfulam Road, Hong Kong, People's Republic of China.
authors: Vivian Chi-Yan
authors: VC
authors: Lee
authors: Jing
authors: J
authors: Gao
authors: Kai-Fai
authors: KF
authors: Lee
authors: Ernest Hung-Yu
authors: EH
authors: Ng
authors: William Shu-Biu
authors: WS
authors: Yeung
authors: Pak-Chung
authors: PC
authors: Ho
mesh_terms: D000019:Abortifacient Agents / Q000494:pharmacology*; D000028:Abortion, Induced; D017209:Apoptosis / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D000077289:Letrozole; D009570:Nitriles / Q000494:pharmacology*; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics* / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology*
chemical_list: D000019:Abortifacient Agents; D047628:Estrogen Receptor alpha; D009570:Nitriles; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D014230:Triazoles; D000077289:Letrozole
keywords: letrozole pretreatment; misoprostol; second trimester; steroid receptors; termination of pregnancy