title: Treatment with high-dose estrogen (diethylstilbestrol) significantly decreases plasma estrogen and androgen levels but does not influence in vivo aromatization in postmenopausal breast cancer patients.
abstract: While growth factors and hormones are known to influence aromatase expression in experimental systems, little is know about potential factors influencing peripheral aromatization in postmenopausal women. The fact that peripheral aromatase activity is higher in old compared to young women and the finding of relatively high tissue estradiol (E2) concentrations after the menopause suggests peripheral aromatization could be influenced by estrogen concentration. To test this hypothesis, we determined plasma hormone levels (n=9) and in vivo aromatization (n=3) in postmenopausal women suffering from advanced breast cancer before and during treatment (4 weeks) with diethylstilbestrol (DES) 5mg three times daily. Plasma levels of cortisol (C), corticosteroid-binding globulin (CBG), and sex hormone binding globulin (SHBG) were significantly increased in all patients (P<0.05 for all). While we found no change in total body aromatization and plasma estrone (E(1)) levels, estradiol (E(2)) and estrone sulfate (E(1)S) were suppressed by a mean of 48.8 and 68.2%, respectively (P=0.043 and 0.008). Surprisingly, plasma levels of androstenedione (A), testosterone (T), dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) were also suppressed by a mean in the range of 32.1 to 52.6% (P<0.05 for all androgens). In contrast, no change in plasma progesterone or 17alpha-hydroxyprogesterone was found. Thus, one possible explanation to our findings could be that DES administered in high doses reduces 17,20-lyase activity in the adrenal gland.
authors.affiliation: Department of Medicine, Section of Oncology, Haukeland University Hospital, N-5021 Bergen, Norway.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Geisler
authors.forename: Ben
authors.initials: B
authors.lastname: Haynes
authors.forename: Gun
authors.initials: G
authors.lastname: Anker
authors.forename: Hildegunn
authors.initials: H
authors.lastname: Helle
authors.forename: Dagfinn
authors.initials: D
authors.lastname: Ekse
authors.forename: Mitch
authors.initials: M
authors.lastname: Dowsett
authors.forename: Per Eystein
authors.initials: PE
authors.lastname: Lønning
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000097:blood*; D000735:Androstenedione / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy*; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004334:Drug Administration Schedule; D004958:Estradiol / Q000097:blood; D004967:Estrogens / Q000008:administration & dosage* / Q000097:blood*; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D004970:Estrone / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D008875:Middle Aged; D017698:Postmenopause / Q000502:physiology*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism
chemical_list: D000728:Androgens; D004967:Estrogens; D004968:Estrogens, Non-Steroidal; D012738:Sex Hormone-Binding Globulin; D004970:Estrone; D000735:Androstenedione; D004958:Estradiol; D004054:Diethylstilbestrol; C017296:estrone sulfate; D006854:Hydrocortisone