Impact of different progestins on endometrial vascularisation of postmenopausal women. A retrospective image analysis-morphometric study.
OBJECTIVE
To determine if the vascularisation of the endometrium is dependent on the administered progestin during sequential hormone replacement therapy.


METHODS
Nine women received percutaneous estradiol-17 beta, 1.5 mg/day from days 1 to 24 combined with 200 mg/day micronised progesterone from days 11 to 24 of the treatment cycle. Fifteen women received percutaneous estradiol, 1.5 mg/day from days 1 to 24, combined with 10 mg/day chlormadinone acetate from days 11 to 24. Eleven women received percutaneous estradiol, 50 microg/day from days 1 to 28 combined with percutaneous norethisterone acetate, 0.3mg/day form days 14 to 28. Twelve women received intranasal estradiol, 300 microg/day from days 1 to 25 combined with 0.5 mg of promegestone from days 11 to 24. Eleven spontaneous cycling women had an endometrial biopsy during luteal phase and served as controls. Endometrial biopsies were processed routinely between days 18 and 24 and sections were immunostained using anti-CD34 antibody to identify vascular endothelial cells, which were treated with an automatic image analysis system.


RESULTS
mean (+/-S.D.) vascular density for controls was 147+/-41.5 vessels/mm(2), with mean vessel area of 143+/-60.9 microm(2). In chlormadinone users endometrial microvascular density and mean vessel area did not differ from the control group (150.2+/-58.6 and 152.9+/-70.5). The other three progestins generated a significant increase of mean vessel density, 179.6+/-51.6 with micronised progesterone, 178.5+/-67.6 with norethisterone and 179.6+/-48.4 with promegestone. The mean vessel area was lower in the latter three groups, respectively, 108.4+/-39.0, 97.5+/-46.5 and 141.6+/-66.7 microm(2), promegestone leading to non significant difference with control.


CONCLUSIONS
regarding vascularisation, chlormadinone and control group gave similar patterns. Promegestone was associated with an increase of the number of vessels, as did micronised progesterone or norethisterone; the mean vascular area was the smallest in the norethisterone group.
Cabinet d'Anatomie et de Cytologie Pathologiques, 34 rue Ducouédic, 75014 Paris, France. mjondet@free.fr
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Jondet
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Dehennin
D000279:Administration, Cutaneous; D000281:Administration, Intranasal; D016022:Case-Control Studies; D002715:Chlormadinone Acetate / Q000008:administration & dosage / Q000494:pharmacology*; D004334:Drug Administration Schedule; D004717:Endometrium / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008833:Microcirculation / Q000187:drug effects; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000494:pharmacology*; D017698:Postmenopause; D011374:Progesterone / Q000008:administration & dosage / Q000494:pharmacology*; D011397:Promegestone / Q000008:administration & dosage / Q000494:pharmacology*
D002715:Chlormadinone Acetate; D011374:Progesterone; D004958:Estradiol; D011397:Promegestone; D009640:Norethindrone