Transdermal estradiol in the treatment of postmenopausal bone loss

The effects on calcium metabolism and forearm bone mineral density of sequential transdermal estradiol (ESTRADERM TTS-50), 50 micrograms/day and medroxyprogesterone (10 mg/day for 12 days) was studied in a randomised controlled trial in 34 healthy females 2-4 years after the menopause. At the end of the 18 months' treatment course with transdermal estradiol, bone density was increased by 4.31% (P less than 0.01) but was decreased by 3.5% (P less than 0.01) in the control group. In the treated group, serum calcium, calcium excretion and hydroxyproline excretion significantly fell during the first 2 months with no significant changes thereafter. Serum alkaline phosphatase significantly decreased only after 4 months, it continued to fall until the fourteenth month when a plateau became apparent. Serum phosphate and tubular maximum for urinary phosphate progressively fell until the tenth month of therapy but thereafter they rose up to initial values. Serum intact parathyroid hormone did not show any significant change. In conclusion, small doses of transdermal estradiol are as effective as oral estrogens. This suggests that the bone sparing effects of estrogens may be due only to low circulating estradiol concentrations, but not to supraphysiological estrone levels. It seems also that estrogens exert both a straight inhibition of bone resorption and a partial inhibition of parathyroid responsiveness.