The endometrium: effects of estrogen and estrogen-progestogen replacement therapy.
A large bulk of data link the use of unopposed estrogens to an increased risk of endometrial cancer. Cancers associated with estrogen use are often well differentiated and carry a good prognosis. Concomitant use of progestogens either cyclically or continuously substantially reduces the risk of promoting endometrial cancer. The development of endometrial cancers as a result of prolonged estrogen medication often occurs via hyperplasia (and atypical hyperplasia). The reason for this increase is not known in detail, but estrogens are believed to be promoter substances by increasing miotic activity and possibly also by down-regulating the defense system against abnormal cell clones. Estrogen receptor activity seems to be dependent on the degree of phosphorylation. Receptor interaction with the specific sites upstream of "regulatory genes" may regulate a variety of steps in gene expression from transcription and mRNA half-life to protein processing, permitting a rapid regulation of the nuclear protooncogenes. This may also explain why serum placental protein reflects endometrial status during hormone replacement therapy. Both 17 beta-estradiol and medroxyprogesterone acetate are capable of modulating DNA synthesis in the endometrial glandular epithelium. The endothelin receptor type A seems to be stimulated during the proliferative phase, whereas an increase in the endothelin B type receptor has been noted in secretory and menstrual phases. Furthermore, low doses of oral norethisterone and levonorgestrel induce morphological changes inclusive of breaks in the endothelial lining of veins with and without hemostatic plugs. Endometrial fibrinolytic enzymes seem to be modulated by estrogens and progestogens.(ABSTRACT TRUNCATED AT 250 WORDS)
Samsioe
G
G
Department of Obstetrics and Gynecology, Lund University Hospital, Sweden.
D016889:Endometrial Neoplasms / Q000139:chemically induced / Q000453:epidemiology / Q000473:pathology; D004717:Endometrium / Q000187:drug effects* / Q000473:pathology; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004967:Estrogens / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D011374:Progesterone / Q000009:adverse effects* / Q000627:therapeutic use; D012307:Risk Factors; D014592:Uterine Hemorrhage / Q000517:prevention & control
D004967:Estrogens; D011374:Progesterone