**4. Conclusions: future perspectives for middle aged women treated for perimenopausal symptoms**

The discussed non-oral routes of MHT, meaning the transdermal/percutaneous route for estrogens, the vaginal route for micronized progesterone, and intrauterine system for proges-terone/progestogen are an update safe option for women with intact uterus, when the recommendation for MHT is during the "window of opportunity". The technology of obtaining these drugs/system will help medical staff and middle aged women to have a better quality of life, and less morbidity and mortality. The risk of endometrial proliferative lesions as hyperplasia and carcinoma is reduced in comparison to non-user women, and their prognosis is better comparative to non-users regarding tumor aggression and women's survival. Endometrial transcriptome and new biomarkers highlight priority areas for future research, such as increasing the diagnostic reproductibility of endometrial hyperplasia-benign, and EIN and to improve the discrimination between EIN and carcinoma, and identifying new biomarkers to stratify risks or serve as indicators of response to clinical treatment.
