ESTROGEN EFFECTS ON CALCITRIOL LEVELS IN POSTMENOPAUSAL WOMEN - A COMPARISON OF ORAL VERSUS TRANSDERMAL ADMINISTRATION

BACKGROUND AND OBJECTIVES In some studies oral oestrogen therapy in po st-menopausal women has been shown to increase both total and free 1,2 5-dihydroxyvitamin D (calcitriol) levels, suggesting that oestrogen th erapy may prevent post-menopausal bone loss, in part, by increasing ca lcium absorption as a result of raised calcitriol levels. Transdermal oestrogen, however, has not been shown to increase calcitriol levels a lthough it prevents bone loss. These two routes of administration have not previously been directly compared in the same subjects at bioequi valent doses as assessed by FSH and LH suppression. DESIGN AND PATIENT S In a randomized cross-over study, 15 women at least 12 months post-m enopausal (mean age 56 years (range 50-66)) were randomized to either oral conjugated equine oestrogen (1.25 mg daily) or transdermal 17 bet a-oestradiol (100 mu g daily) for 12 weeks after which each subject ch anged over to the alternative medication. For the last 12 days of each medication, 10 mg medroxyprogesterone acetate (MPA) was added to the treatment protocol. A fasting blood sample was taken at baseline and a t the end of each treatment period prior to administration of the MPA. MEASUREMENTS Serum calcium, phosphorus, albumin, bicarbonate, intact parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (calcitriol), 25-hy droxyvltamin D (250HD), vitamin D-binding protein (DBP) were measured. The free calcitriol index was calculated as the molar ratio of calcit riol to DBP. Free calcitriol was measured by centrifugal ultrafiltrati on. RESULTS The degree of suppression of FSH and LH was similar with t he two routes of oestrogen administration. Total calcitriol was signif icantly higher with oral oestrogen treatment compared to transdermal o estrogen and compared to baseline (mean +/- SEM, baseline 80 +/- 5; or al oestrogen 102 +/- 8; transdermal oestrogen 82 +/- 4) as was DBP (me an +/- SEM, baseline 5.2 +/- 0.2; oral oestrogen 6.9 +/- 0.4; transder mal oestrogen 5.8 +/- 0.2) which accounted for the rise in calcitriol. Free calcitriol measured by equilibrium dialysis showed no rise with either oestrogen preparation. Phosphorus was not different between tre atment groups and fell with both oestrogen treatments (baseline 1.32 /- 0.15, oral oestrogen 1.23 +/- 0.10, transdermal oestrogen 1.17 +/- 0.16) and PTH rose with both treatments (baseline 1.33 +/- 0.21, oral oestrogen 1.52 +/- 0.27, transdermal oestrogen, 1.99 +/- 0.32). Calciu m was not different between treatment groups and was not different fro m baseline. CONCLUSIONS These results show that in this study the tota l calcitriol rose after oral but not transdermal oestrogen due to a ri se in vitamin D-binding protein. Free calcitriol was not affected by o ral or transdermal oestrogen treatment despite a fall in plasma phosph orus and a rise in PTH, both of which are considered agonists for calc itriol production. We may therefore conclude that neither oral nor tra nsdermal oestrogen replacement routinely stimulates free calcitriol le vels. In the studies where a rise in free calcitriol was noted, the de gree of suppression of bone resorption by oestrogen may have been grea ter, thus producing a larger demand for calcium due to filling of a la rger bone remodelling space with consequent stimulation of calcitriol levels.