The review presents the latest data on the safety and efficiency of hormone therapy with estrogens. The authors separate the concepts of " hormone replacement therapy" and "menopausal hormone therapy", focusing on the fundamental differences in approaches to treating reproductive-aged and postmenopausal women with estrogen deficiency. The article discusses the features of therapy selection in women with gynecologic pathology and some chronic diseases. The article contains information about the basic principles of prescribing menopausal hormone therapy to minimize the risks of cancer and adverse cardiovascular events during estrogen treatment that includes the use of transdermal estrogens, 17β-estradiol gel 0.1% in particular, in minimum effective doses and natural progesterone, at the beginning of treatment within the therapeutic time window, a therapy duration of up to five years, by reviewing the benefits/risks of an intervention during treatment over time. The article describes some clinical situations, in which it is recommended to avoid prescribing oral estrogens due to the pharmacokinetic features: hypertriglyceridemia, high basic risks of venous thromboembolic events and strokes, gallbladder diseases, intake of anticonvulsants and thyroxine, female alcoholism, and also probably coronavirus infection. In addition, the review analyzes updated recommendations for hormone replacement therapy in women with premature ovarian failure, by relying on data from international clinical protocols. Conclusion. Hormone therapy is generally a safe pharmacological intervention, since it is prescribed either to reproductive-aged women with ovarian failure/loss of ovarian function or to healthy women with menopausal symptoms aged 40 to 50 years.