Oestrogen effects on calcitriol levels in post-menopausal women: a comparison of oral versus transdermal administration.
OBJECTIVE
In some studies oral oestrogen therapy in post-menopausal women has been shown to increase both total and free 1,25-dihydroxyvitamin D (calcitriol) levels, suggesting that oestrogen therapy may prevent post-menopausal bone loss, in part, by increasing calcium absorption as a result of raised calcitriol levels. Transdermal oestrogen, however, has not been shown to increase calcitriol levels although it prevents bone loss. These two routes of administration have not previously been directly compared in the same subjects at bioequivalent doses as assessed by FSH and LH suppression.


METHODS
In a randomized cross-over study, 15 women at least 12 months post-menopausal (mean age 56 years (range 50-66)) were randomized to either oral conjugated equine oestrogen (1.25 mg daily) or transdermal 17 beta-oestradiol (100 micrograms daily) for 12 weeks after which each subject changed 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 at the end of each treatment period prior to administration of the MPA.


METHODS
Serum calcium, phosphorus, albumin, bicarbonate, intact parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (calcitriol), 25-hydroxyvitamin D (25OHD), vitamin D-binding protein (DBP) were measured. The free calcitriol index was calculated as the molar ratio of calcitriol to DBP. Free calcitriol was measured by centrifugal ultrafiltration.


RESULTS
The degree of suppression of FSH and LH was similar with the two routes of oestrogen administration. Total calcitriol was significantly higher with oral oestrogen treatment compared to transdermal oestrogen and compared to baseline (mean +/- SEM, baseline 80 +/- 5; oral oestrogen 102 +/- 8; transdermal oestrogen 82 +/- 4) as was DBP (mean +/- SEM, baseline 5.2 +/- 0.2; oral oestrogen 6.9 +/- 0.4; transdermal 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 treatment 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). Calcium was not different between treatment groups and was not different from baseline.


CONCLUSIONS
These results show that in this study the total calcitriol rose after oral but not transdermal oestrogen due to a rise in vitamin D-binding protein. Free calcitriol was not affected by oral or transdermal oestrogen treatment despite a fall in plasma phosphorus and a rise in PTH, both of which are considered agonists for calcitriol production. We may therefore conclude that neither oral nor transdermal oestrogen replacement routinely stimulates free calcitriol levels. In the studies where a rise in free calcitriol was noted, the degree of suppression of bone resorption by oestrogen may have been greater, thus producing a larger demand for calcium due to filling of a larger bone remodelling space with consequent stimulation of calcitriol levels.
Dick
I M
IM
Department of Medicine, University of WA, Nedlands, Australia.
Prince
R L
RL
Kelly
J J
JJ
Ho
K K
KK
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000368:Aged; D002117:Calcitriol / Q000097:blood*; D018592:Cross-Over Studies; D004958:Estradiol / Q000008:administration & dosage*; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood*; D014809:Vitamin D-Binding Protein / Q000097:blood
D004966:Estrogens, Conjugated (USP); D014809:Vitamin D-Binding Protein; D004958:Estradiol; D002117:Calcitriol