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 mon ths and 0.025 mg/day for the following six months and group B, E(2) TT S 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 t wice-weekly application of transdermal patches to the lower abdomen fo r three weeks a month. Serum E(2), alkaline phosphatase (AP), osteocal cin (BGP) and urinary hydroxyproline (OHP) excretion levels were measu red before the operation, at the beginning of ERT and after 6 and 12 m onths of treatment. Bone mineral density (BMD) in the distal regions o f the forearms was measured by single photon absorptiometry at the sta rt of the study and after 6 and 12 months. In Group A, both mean corti cal and trabecular BMD had increased by, respectively, 1.53% and 2.17% after 6 months of therapy; after the second 6 months a significant de crease 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 th e first 6 months of treatment; after the following 6 months, these val ues persisted (+0.15 and -0.03%, respectively). Mean AP, OHP and BGP s erum 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%), f ollowed by an increase at the last evaluation of 22.50% and 35.50%, th at 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 res pect to post-surgical values, but they rose again by 34.50% with the l ower dose (range -45.10% to +65.20%) (P < 0.05). In group B, both AP a nd OHP levels were lower than pre-treatment values after the first 6 m onths (38.60% and 27.60%) (P < 0.03 and P < 0.02, respectively), remai ning unchanged after treatment with 0.05 mg/day (+3.50% and -6.80%, re spectively). 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.