The effect of micronized estradiol on bone turnover and calciotropic hormones in older men receiving hormonal suppression therapy for prostate cancer

J Clin Endocrinol Metab. 2002 Nov;87(11):4907-13. doi: 10.1210/jc.2002-020539.

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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkaline Phosphatase / blood
  • Amino Acids / urine
  • Bone Remodeling / drug effects*
  • Calcifediol / blood
  • Calcitriol / blood
  • Calcium / blood
  • Calcium / urine
  • Collagen / urine
  • Collagen Type I
  • Double-Blind Method
  • Estradiol / administration & dosage
  • Estradiol / blood
  • Estradiol / therapeutic use*
  • Estrone / blood
  • Gonadotropin-Releasing Hormone / analogs & derivatives
  • Humans
  • Osteocalcin / blood
  • Parathyroid Hormone / blood
  • Peptide Fragments / blood
  • Peptides / urine
  • Placebos
  • Procollagen / blood
  • Sex Hormone-Binding Globulin / analysis
  • Testosterone / blood

Substances

  • Amino Acids
  • Collagen Type I
  • Parathyroid Hormone
  • Peptide Fragments
  • Peptides
  • Placebos
  • Procollagen
  • Sex Hormone-Binding Globulin
  • collagen type I trimeric cross-linked peptide
  • procollagen Type I N-terminal peptide
  • Osteocalcin
  • Estrone
  • Gonadotropin-Releasing Hormone
  • Testosterone
  • Estradiol
  • deoxypyridinoline
  • Collagen
  • Alkaline Phosphatase
  • Calcitriol
  • Calcifediol
  • Calcium