BONE METABOLISM CHANGES AFTER TRANSDERMAL ESTRADIOL DOSE REDUCTION DURING ESTROGEN REPLACEMENT THERAPY - A 1-YEAR PROSPECTIVE-STUDY

Twenty-four surgically menopausal women were randomly allocated to one of two transdermally-administered estrogen replacement therapies (ERT): Group A was administered Estradiol (E(2)) TTS 0.05 mg/day for 6 months and 0.025 mg/day for the following six months and group B, E(2) TTS 0.10 mg/day for the first 6 months and 0.05 mg/day for the following 6 months. For both groups, the treatment regimen was based upon the twice-weekly application of transdermal patches to the lower abdomen for three weeks a month. Serum E(2), alkaline phosphatase (AP), osteocalcin (BGP) and urinary hydroxyproline (OHP) excretion levels were measured before the operation, at the beginning of ERT and after 6 and 12 months of treatment. Bone mineral density (BMD) in the distal regions of the forearms was measured by single photon absorptiometry at the start of the study and after 6 and 12 months. In Group A, both mean cortical and trabecular BMD had increased by, respectively, 1.53% and 2.17% after 6 months of therapy; after the second 6 months a significant decrease was observed in both parameters (2.40% and 3.62%, respectively). In Group B, mean cortical and trabecular BMD increased by 1.50% and 2.10%, respectively (significant increase in trabecular bone) after the first 6 months of treatment; after the following 6 months, these values persisted (+0.15 and -0.03%, respectively). Mean AP, OHP and BGP serum levels rose after the operation. In Group A, AP and OHP showed a significant decrease after the first 6 months (-34.90% and -30.90%), followed by an increase at the last evaluation of 22.50% and 35.50%, that reached statistical significance only for OHP. TTS 0.05 mg/day led to a significant lowering in BGP levels (-30.70%) (P < 0.005) with respect to post-surgical values, but they rose again by 34.50% with the lower dose (range -45.10% to +65.20%) (P < 0.05). In group B, both AP and OHP levels were lower than pre-treatment values after the first 6 months (38.60% and 27.60%) (P < 0.03 and P < 0.02, respectively), remaining unchanged after treatment with 0.05 mg/day (+3.50% and -6.80%, respectively). Osteocalcin levels dropped after 6 months (-16.60%), the same values being recorded at 12 months (+3.80%). Both TTS 0.10 and 0.05 mg/day proved to be effective in counteracting postmenopausal bone loss; the dose reduction from 0.10 to 0.05 mg/day did not lead to the reactivation of bone turnover. However, the lowest E(2) dose of 0.025 mg/day wasn't effective in avoiding bone demineralization.