PMID- 23980056
OWN - NLM
STAT- MEDLINE
DCOM- 20140616
LR  - 20220311
IS  - 1460-2350 (Electronic)
IS  - 0268-1161 (Linking)
VI  - 28
IP  - 11
DP  - 2013 Nov
TI  - The effect of letrozole with misoprostol for medical termination of pregnancy on 
      the expression of steroid receptors in the placenta.
PG  - 2912-9
LID - 10.1093/humrep/det345 [doi]
AB  - STUDY QUESTION: What is the effect of letrozole on the expression of steroid 
      receptors in the placentae in cases of termination of pregnancies? SUMMARY 
      ANSWER: The expression of estrogen receptor-alpha (ERalpha) and progesterone receptor 
      (PR) transcripts, as well as ERalpha protein, in placentae was suppressed by 
      letrozole pretreatment in second trimester termination of pregnancy. WHAT IS 
      KNOWN ALREADY: There have been no data in the literature on the effect of 
      letrozole in termination of human pregnancies. STUDY DESIGN, SIZE, DURATION: This 
      study is part of a clinical randomized trial in which 50 subjects were recruited 
      and 44 placentae were collected. PARTICIPANTS/MATERIALS, SETTING, 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 ERalpha and estrogen 
      receptor-beta (ERbeta), PR and glucocorticoid receptor (GR) transcripts. 
      Immunohistochemical studies of ERalpha, ERbeta, 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. MAIN RESULTS AND THE ROLE OF CHANCE: 
      Real-time RT-PCR demonstrated that the median ERalpha 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, ERalpha 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 ERbeta, PR, GR, PCNA, 
      Ki67 and TUNEL were not significantly different between the two groups. 
      LIMITATIONS, REASONS FOR CAUTION: Only the placentae from the second trimester 
      termination of pregnancy were collected in this study. Information from first 
      trimester terminations is still lacking. WIDER IMPLICATIONS OF THE FINDINGS: The 
      results shed some light on the mechanism of action of letrozole pretreatment in 
      termination of pregnancies. STUDY FUNDING/COMPETING INTEREST(S): This study was 
      funded by the GRF/RGC and CRCG grants of the University of Hong Kong. TRIAL 
      REGISTRATION NUMBER: HKClinicalTrials.com with trial number HKCTR-695.
FAU - Lee, Vivian Chi-Yan
AU  - Lee VC
AD  - 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.
FAU - Gao, Jing
AU  - Gao J
FAU - Lee, Kai-Fai
AU  - Lee KF
FAU - Ng, Ernest Hung-Yu
AU  - Ng EH
FAU - Yeung, William Shu-Biu
AU  - Yeung WS
FAU - Ho, Pak-Chung
AU  - Ho PC
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20130826
PL  - England
TA  - Hum Reprod
JT  - Human reproduction (Oxford, England)
JID - 8701199
RN  - 0 (Abortifacient Agents)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Nitriles)
RN  - 0 (Proliferating Cell Nuclear Antigen)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Progesterone)
RN  - 0 (Triazoles)
RN  - 7LKK855W8I (Letrozole)
SB  - IM
MH  - Abortifacient Agents/*pharmacology
MH  - *Abortion, Induced
MH  - Apoptosis/drug effects
MH  - Estrogen Receptor alpha/*genetics/metabolism
MH  - Female
MH  - Gene Expression/*drug effects
MH  - Humans
MH  - Letrozole
MH  - Nitriles/*pharmacology
MH  - Placenta/*drug effects/metabolism
MH  - Pregnancy
MH  - Pregnancy Trimester, Second
MH  - Proliferating Cell Nuclear Antigen/metabolism
MH  - RNA, Messenger/metabolism
MH  - Receptors, Progesterone/*genetics/metabolism
MH  - Triazoles/*pharmacology
OTO - NOTNLM
OT  - letrozole pretreatment
OT  - misoprostol
OT  - second trimester
OT  - steroid receptors
OT  - termination of pregnancy
EDAT- 2013/08/28 06:00
MHDA- 2014/06/17 06:00
CRDT- 2013/08/28 06:00
PHST- 2013/08/28 06:00 [entrez]
PHST- 2013/08/28 06:00 [pubmed]
PHST- 2014/06/17 06:00 [medline]
AID - det345 [pii]
AID - 10.1093/humrep/det345 [doi]
PST - ppublish
SO  - Hum Reprod. 2013 Nov;28(11):2912-9. doi: 10.1093/humrep/det345. Epub 2013 Aug 26.