An open, randomized, controlled study of transdermal hormone replacement therapy on the rate of bone loss in primary biliary cirrhosis

J Intern Med. 2004 Jul;256(1):63-9. doi: 10.1111/j.1365-2796.2004.01342.x.


Objectives: The prevalence of osteoporosis amongst patients with primary biliary cirrhosis (PBC) is high and may be a serious clinical problem. Hormone replacement therapy (HRT) is effective in preventing bone loss but has not been evaluated in randomized trials in PBC. The primary aim was to study the effect of transdermal HRT in combination with daily vitamin D and calcium supplementation on bone loss compared with vitamin D and calcium supplementation only in postmenopausal women with PBC. The secondary aim was to study the safety of transdermal HRT.

Subjects/interventions: Eighteen females with PBC were randomized to receive 2 years therapy with either (i) transdermal oestradiol 50 microg 24 h(-1) two times per week + medroxyprogesterone 2.5 mg day(-1) + alfacalcidol 0.25 microg day(-1) and calcium 1 g day(-1) or (ii) alfacalcidol 0.25 microg day(-1) and calcium 1 g day(-1). Dual-energy X-ray absorptiometry for measurement of bone mineral density (BMD) and sampling of blood and serum for measurements of biochemical markers of liver function was performed before, during and at the end of treatment.

Results: BMD increased significantly at the lumbar spine (P < 0.05) and the femoral neck (P < 0.05) in the HRT group whereas no significant change was found in the control group. One oestrogen-treated patient was excluded after 1 year because of deteriorating, but reversible, aminotransferases. Dropout frequency because of nonliver-related causes was higher in the HRT group. Otherwise, no difference with respect to adverse liver reactions was found between the groups.

Conclusion: Transdermal HRT increases BMD in PBC patients with few severe side effects related to the liver.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alkaline Phosphatase / blood
  • Bilirubin / blood
  • Biomarkers / blood
  • Bone Density / drug effects
  • Calcium / administration & dosage
  • Drug Therapy, Combination
  • Estradiol / administration & dosage
  • Estrogen Replacement Therapy
  • Female
  • Femur Neck / physiopathology
  • Hormone Replacement Therapy*
  • Humans
  • Hydroxycholecalciferols / administration & dosage
  • Liver / metabolism
  • Liver Cirrhosis, Biliary / complications*
  • Liver Cirrhosis, Biliary / drug therapy
  • Liver Cirrhosis, Biliary / metabolism
  • Lumbar Vertebrae / physiopathology
  • Medroxyprogesterone / administration & dosage
  • Middle Aged
  • Osteoporosis / etiology*
  • Osteoporosis / metabolism
  • Osteoporosis / prevention & control*
  • Statistics, Nonparametric
  • Transaminases / blood


  • Biomarkers
  • Hydroxycholecalciferols
  • Estradiol
  • Transaminases
  • Alkaline Phosphatase
  • Medroxyprogesterone
  • Bilirubin
  • Calcium
  • alfacalcidol