INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-1 - A BIOCHEMICAL MARKER OF ENDOMETRIAL RESPONSE TO PROGESTIN DURING HORMONE REPLACEMENT THERAPY

Objectives: To compare immunohistochemical localization of insulin-lik e growth factor binding protein-1 (IGFBP-1) in endometrial stromal cel ls with endometrial morphology during three regimens of continuous com bined hormone replacement therapy. Methods: Endometrial samples for mo rphological examination and immunohistochemical staining with monoclon al antibody against IGFBP-1 were obtained from 30 menopausal women bef ore treatment and after 12 and 24 months of continuous combined hormon e replacement therapy. All women received percutaneous estradiol-gel r eleasing 1.5 mg estradiol daily. Regarding progestins, patients were d ivided into three groups: one group (n = 15) had a 20 mu g/24 h levono rgestrel-releasing intrauterine device (LNG-IUD); the women in the oth er two groups received micronised natural progesterone either 100 mg o rally (n = 7) or 100-200 mg vaginally (n = 8) daily, 25 days per calen dar month, Results: Before treatment the endometrium of all women was atrophic or subatrophic and no IGFBP-1 could be detected in any of the samples which contained enough stromal cells for evaluation. After 12 and 24 months of treatment, epithelial atrophy with decidual transfor mation in stroma was detected in all specimens in the LNG-IUD group, a nd IGFBP-1 was localized in decidualized stromal cells in all samples. In the other two groups, no signs of progestin effect were detected b y microscopic examination in any of the endometrial samples and IGFBP- 1 staining was completely negative in all of them. Conclusion: A strik ing difference occurred in both morphological and biochemical response in the endometrium of women treated with LNG-IUD compared with those receiving oral or vaginal micronised progesteron during continuous com bined HRT. Micronised progesterone at doses used in this study turned out to be ineffective to prevent the proliferative effect of estrogen. Immunohistochemical localization of IGFBP-1 in endometrial stromal ce lls strongly correlated with decidual reaction in all endometrial spec imens exposed to LNG-IUD, suggesting that the immunostaining of IGFBP- I can be used as a means of assessing the strength of progestin effect in the endometrium during HRT.