PMID- 20851230
OWN - NLM
STAT- MEDLINE
DCOM- 20110207
LR  - 20131121
IS  - 1879-0518 (Electronic)
IS  - 0010-7824 (Linking)
VI  - 82
IP  - 4
DP  - 2010 Oct
TI  - Endometrial safety of a novel monophasic combined oral contraceptive containing 
      0.02 mg ethinylestradiol and 2 mg chlormadinone acetate administered in a 
      24/4-day regimen over six cycles.
PG  - 358-65
LID - 10.1016/j.contraception.2010.04.013 [doi]
AB  - BACKGROUND: This study was conducted to examine whether small doses of 
      ethinylestradiol (EE, 0.02 mg) and chlormadinone acetate (CMA, 2 mg) administered 
      in a novel 24/4-day regimen during six cycles would suffice to suppress 
      proliferation and to cause secretory changes in the endometrium. STUDY DESIGN: 
      This Phase II, randomized (two assessment groups), single-center, open, 
      uncontrolled, multiple-dosing study treated 59 female subjects. The subjects 
      underwent three endometrial biopsies: one pretreatment, one during medication 
      (either at Cycle 3 or Cycle 6) and one during the first post-treatment cycle. 
      RESULTS: The study revealed that 0.02 mg EE/2 mg CMA effectively transformed the 
      endometrium from a proliferative state into a secretory or inactive state after 
      three (90% of subjects) and six (76% of subjects) medication cycles. The mean 
      endometrial thickness decreased markedly from 10.2 (SD+/-3.0) mm (pretreatment) to 
      an unfavorable level for the nidation of a blastocyst [5.3 (SD+/-2.1) and 4.1 
      (SD+/-2.2) mm in Medication Cycles 3 and 6, respectively]. Correspondingly, 
      estradiol and progesterone levels decreased during treatment. In the 
      post-treatment cycle, endometrial biopsy and ultrasound evaluation as well as sex 
      hormone levels suggested a quick return to fertility. There were no signs of 
      hyperplasia, endometrial polyps, neoplasia or other detrimental histopathological 
      changes at any time during the trial. Treatment-related adverse events (AEs) were 
      reported by 22 (37%) of 59 subjects and were reported most commonly in Cycle 1, 
      decreasing continuously thereafter. No AEs led to discontinuation of the trial 
      medication and there were no serious AEs. CONCLUSIONS: The 24/4-day regimen of 
      0.02 mg EE/2 mg CMA provided effective and reversible endometrial effects with 
      secretory transformation or suppression without inducing pathological changes.
CI  - Copyright (c) 2010 Elsevier Inc. All rights reserved.
FAU - Rabe, Thomas
AU  - Rabe T
AD  - University Women's Hospital, Heidelberg, Germany. 
      thomas.rabe@med.uni-heidelberg.de
FAU - Hartschuh, Elena
AU  - Hartschuh E
FAU - Wahlstrom, Torsten
AU  - Wahlstrom T
FAU - Hoschen, Kornelia
AU  - Hoschen K
FAU - Konig, Simone
AU  - Konig S
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - United States
TA  - Contraception
JT  - Contraception
JID - 0234361
RN  - 0 (Contraceptives, Oral, Combined)
RN  - 0 (Contraceptives, Oral, Synthetic)
RN  - 0 (Estrogens)
RN  - 0SY050L61N (Chlormadinone Acetate)
RN  - 423D2T571U (Ethinyl Estradiol)
SB  - IM
MH  - Adult
MH  - Chlormadinone Acetate/administration & dosage/adverse effects/*pharmacology
MH  - Contraceptives, Oral, Combined/administration & dosage/adverse 
      effects/*pharmacology
MH  - Contraceptives, Oral, Synthetic/adverse effects/*pharmacology
MH  - Endometrium/*drug effects/pathology
MH  - Estrogens/adverse effects/*pharmacology
MH  - Ethinyl Estradiol/administration & dosage/adverse effects/*pharmacology
MH  - Female
MH  - Humans
MH  - Young Adult
EDAT- 2010/09/21 06:00
MHDA- 2011/02/08 06:00
CRDT- 2010/09/21 06:00
PHST- 2009/09/18 00:00 [received]
PHST- 2010/04/13 00:00 [revised]
PHST- 2010/04/14 00:00 [accepted]
PHST- 2010/09/21 06:00 [entrez]
PHST- 2010/09/21 06:00 [pubmed]
PHST- 2011/02/08 06:00 [medline]
AID - S0010-7824(10)00150-2 [pii]
AID - 10.1016/j.contraception.2010.04.013 [doi]
PST - ppublish
SO  - Contraception. 2010 Oct;82(4):358-65. doi: 10.1016/j.contraception.2010.04.013.