Progestin Resistance and Corresponding Management of Abnormal Endometrial Hyperplasia and Endometrial Carcinoma

Abstract

With a younger tendency in morbidity age, endometrial cancer (EC) incidence has grown year after year. Worse, even more commonly occurring is endometrial hyperplasia (EH), which is a precancerous endometrial proliferation. For young women with early EC and EH who want to preserve fertility, progestin therapy has been utilized as a routine fertility-preserving treatment approach. Nevertheless, progestin medication failure in some patients is mostly due to progestin resistance and side effects. In order to further analyze the potential mechanisms of progestin resistance in EH and EC, to provide theoretical support for effective therapeutic strategies, and to lay the groundwork for searching novel treatment approaches, this article reviews the current therapeutic effects of progestin in EH and EC, as well as the mechanisms and molecular biomarkers of progestin resistance, and systematically expounds on the potential therapeutic methods to overcome progestin resistance.

Possible Participation of Adenine Nucleotide Translocase ANT1 in the Cytotoxic Action of Progestins, Glucocorticoids, and Diclofenac on Tumor Cells

“…Such a concentration should not cause dramatic side effects. DCF has recently been shown to have a cytotoxic effect by increasing ROS production and causing microtubule destabilization in HeLa tumor cells [ 30 ]. The IC 50 for DCF on the HeLa cells obtained in our study is 384 µM, which is in the same range as the values obtained earlier, 200 and 548 µM [ 22 , 41 ].)…”

“…The importance of studying new pharmacological properties of progestins is due to the possibility of their usage as monotherapy drugs in the treatment of hormone-dependent tumors [ 3 , 8 , 30 ], as well as due to their anti-inflammatory and immunomodulatory action in the treatment of cancer-associated inflammation [ 7 , 31 , 32 ].…”

Fertility-sparing re-treatment for endometrial cancer and atypical endometrial hyperplasia patients with progestin-resistance: a retrospective analysis of 61 cases

“…Adverse effects were minor and there were no recorded deaths due to the disease during the follow-up period. Progestin carries out its anticancer function by antagonizing estrogen stimulation, inhibiting cell proliferation, promoting differentiation, reversing malignant phenotype [15]. Conservative treatment with high-dose progestin can achieve a good remission rate for young EC patients.…”