title: The effect of micronized estradiol on bone turnover and calciotropic hormones in older men receiving hormonal suppression therapy for prostate cancer.
abstract: To examine the effect of estradiol (E(2)) without the confounding effect of hypothalamic-pituitary feedback, we studied men with prostate cancer in whom gonadotropin secretion was suppressed by LH-releasing hormone agonists (LHRH-A). Fourteen men over 65 yr of age and receiving established LHRH-A treatment (EST group) without bony metastases and 12 men who received LHRH-A as neoadjuvant therapy for locally advanced prostate cancer (NEO group) were randomized (double blind) to receive either 1 mg/d micronized E(2) (n = 12) or placebo (PL; n = 13) for 9 wk. E(2), estrone, testosterone, SHBG, PTH, and 25-hydroxy- and 1,25-dihydroxyvitamin D levels as well as markers of bone resorption [N- and C-telopeptide cross-links (NTX and CTX) and deoxypyridinoline] and bone formation (bone-specific alkaline phosphatase, osteocalcin, and N-terminal type I collagen) were measured before LHRH-A in the NEO group, before [baseline (BL)] and after 9 wk of E(2) or PL in all patients, and 6 wk after E(2) treatment in the EST group. In the NEO group, hormone levels fell 3 wk after the initial LHRH-A injection, and deoxypyridinoline increased significantly (P = 0.006). At BL, the EST group had higher bone turnover due to the longer duration of LHRH-A treatment. With E(2) treatment, E(2) levels rose into the normal male range, and two resorption markers decreased significantly from BL by 33% for NTX (P < 0.001) and 28% for CTX (P = 0.009). Bone formation markers did not change. PTH increased by 43% from BL (P < 0.01) in the E(2) group and decreased 16% from BL in the PL group (P < 0.01). Ionized calcium did not change in the E(2) group, but increased in the PL group by 2.3% (P < 0.01). NTX and CTX increased 6 wk after E(2) withdrawal in the EST group. We conclude that E(2) inhibits bone resorption in hypogonadal men through a direct skeletal effect that is independent of PTH. Low dose estrogen may be an option for the prevention and/or treatment of bone loss in this population.
authors.affiliation: Division of Endocrinology and Metabolism, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-1317, USA. taxel@nso.uchc.edu
authors.forename: Pamela
authors.initials: P
authors.lastname: Taxel
authors.forename: Pamela M
authors.initials: PM
authors.lastname: Fall
authors.forename: Peter C
authors.initials: PC
authors.lastname: Albertsen
authors.forename: Robert D
authors.initials: RD
authors.lastname: Dowsett
authors.forename: Margaret
authors.initials: M
authors.lastname: Trahiotis
authors.forename: Jill
authors.initials: J
authors.lastname: Zimmerman
authors.forename: Christine
authors.initials: C
authors.lastname: Ohannessian
authors.forename: Lawrence G
authors.initials: LG
authors.lastname: Raisz
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood; D000596:Amino Acids / Q000652:urine; D016723:Bone Remodeling / Q000187:drug effects*; D002112:Calcifediol / Q000097:blood; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000097:blood / Q000652:urine; D003094:Collagen / Q000652:urine; D024042:Collagen Type I; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D004970:Estrone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives; D006801:Humans; D015675:Osteocalcin / Q000097:blood; D010281:Parathyroid Hormone / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000652:urine; D010919:Placebos; D011347:Procollagen / Q000097:blood; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013739:Testosterone / Q000097:blood
chemical_list: D000596:Amino Acids; D024042:Collagen Type I; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D010455:Peptides; D010919:Placebos; D011347:Procollagen; D012738:Sex Hormone-Binding Globulin; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D015675:Osteocalcin; D004970:Estrone; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D004958:Estradiol; C036020:deoxypyridinoline; D003094:Collagen; D000469:Alkaline Phosphatase; D002117:Calcitriol; D002112:Calcifediol; D002118:Calcium