Nuclear morphometric changes and therapy monitoring in patients with endometrial hyperplasia: a study comparing effects of intrauterine levonorgestrel and systemic medroxyprogesterone.
OBJECTIVE
To show that local application of the levonorgestrel intrauterine device was a better therapy for endometrial hyperplasia (EH) compared to per-oral gestagen treatment based on subjective (WHO criteria) and objective (prognostic data-based morphometric and stereological method/D score, predicting the risk of cancer development for each single patient) evaluation.


METHODS
Women between 30 and 70 years with EH and D score > 0 were treated with levonorgestrel intrauterine device (n = 26) and the results compared to a historic group of women treated with per-oral gestagen (n = 31). In both treatment groups only patients with low risk (D score > 1) and uncertain risk (D score = 0-1) of cancer development were included. Endometrial specimens were investigated prior to treatment and after 3 months of therapy. The endometrial samples from the two groups were examined by light microscopy and objective data-based morphometry to assess tissue characteristics and to evaluate nuclear size variation.


RESULTS
After 3 months all patients treated with levonorgestrel intrauterine device showed regression of hyperplasia, whereas 14 of 31 patients in the per-oral group still had persisting disease. The objective morphometric analysis showed reduction in nuclear size for both treatment groups, including the D score > 1 as well as the D score 0-1 patients. However, the reduction was most obvious for the levonorgestrel intrauterine device-treated patients with initial D score of 0-1.


CONCLUSIONS
The present study indicates that levonorgestrel intrauterine device is a superior alternative to per oral treatment of endometrial hyperplasia. By using objective morphometric treatment monitoring we have shown that the hyperplasia patients with the highest malignant potential (D score = 0-1) were those taking most benefit from local high-dose levonorgestrel therapy.
Vereide
A B
AB
Department of Gynecology and Obstetrics, Institute of Clinical Medicine, Medical Faculty, University of Tromsø, N-9037, Tromsø, Norway.
Arnes
M
M
Straume
B
B
Maltau
J M
JM
Ørbo
A
A
D000328:Adult; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology; D004714:Endometrial Hyperplasia / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D007434:Intrauterine Devices; D016912:Levonorgestrel / Q000008:administration & dosage*; D008525:Medroxyprogesterone / Q000627:therapeutic use*; D008875:Middle Aged
D016912:Levonorgestrel; D008525:Medroxyprogesterone