Nuclear morphometric changes and therapy monitoring in patients with endometrial hyperplasia: a study comparing effects of intrauterine levonorgestrel and systemic medroxyprogesterone

• Published in: Gynecologic oncology 2003-12, Vol.91 (3), p.526-533
• Main Authors: Vereide, A.B, Arnes, M, Straume, B, Maltau, J.M, Ørbo, A
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Cell Nucleus - drug effects; Cell Nucleus - pathology; Endometrial Hyperplasia - drug therapy; Endometrial Hyperplasia - pathology; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; Hormones. Endocrine system; Humans; Intrauterine Devices; Levonorgestrel - administration & dosage; Medical sciences; Medroxyprogesterone - therapeutic use; Middle Aged; Non tumoral diseases; Pharmacology. Drug treatments
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2003.07.002

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. 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. 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. 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.