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

被引:32
作者
DICK, IM
PRINCE, RL
KELLY, JJ
HO, KKY
机构
[1] UNIV WESTERN AUSTRALIA,DEPT MED,NEDLANDS,WA 6009,AUSTRALIA
[2] SIR CHARLES GAIRDNER HOSP,DEPT ENDOCRINOL,NEDLANDS,WA 6009,AUSTRALIA
[3] ST VINCENTS HOSP,GARVAN INST MED RES,DARLINGHURST,NSW 2010,AUSTRALIA
关键词
D O I
10.1111/j.1365-2265.1995.tb01918.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BACKGROUND AND OBJECTIVES 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. DESIGN AND PATIENTS 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 mu g 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. MEASUREMENTS Serum calcium, phosphorus, albumin, bicarbonate, intact parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (calcitriol), 25-hydroxyvltamin D (250HD), 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.
引用
收藏
页码:219 / 224
页数:6
相关论文
共 24 条
[1]   PROGESTIN ANTAGONISM OF ESTROGEN STIMULATED 1,25-DIHYDROXYVITAMIN-D LEVELS [J].
BIKLE, DD ;
HALLORAN, BP ;
HARRIS, ST ;
PORTALE, AA .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1992, 75 (02) :519-523
[2]   INFLUENCE OF THE VITAMIN-D-BINDING PROTEIN ON THE SERUM CONCENTRATION OF 1,25-DIHYDROXYVITAMIN-D3 - SIGNIFICANCE OF THE FREE 1,25-DIHYDROXYVITAMIN-D3 CONCENTRATION [J].
BOUILLON, R ;
VANASSCHE, FA ;
VANBAELEN, H ;
HEYNS, W ;
DEMOOR, P .
JOURNAL OF CLINICAL INVESTIGATION, 1981, 67 (03) :589-596
[3]   EFFECTS OF ESTROGEN ON CIRCULATING FREE AND TOTAL 1,25-DIHYDROXYVITAMIN-D AND ON THE PARATHYROID-VITAMIN-D AXIS IN POSTMENOPAUSAL WOMEN [J].
CHEEMA, C ;
GRANT, BF ;
MARCUS, R .
JOURNAL OF CLINICAL INVESTIGATION, 1989, 83 (02) :537-542
[4]   BIOLOGIC EFFECTS OF TRANSDERMAL ESTRADIOL [J].
CHETKOWSKI, RJ ;
MELDRUM, DR ;
STEINGOLD, KA ;
RANDLE, D ;
LU, JK ;
EGGENA, P ;
HERSHMAN, JM ;
ALKJAERSIG, NK ;
FLETCHER, AP ;
JUDD, HL .
NEW ENGLAND JOURNAL OF MEDICINE, 1986, 314 (25) :1615-1620
[5]   CHROMATOGRAPHY OF SERUM ON SEP-PAK-C18 CORRECTS FALSELY ELEVATED VITAMIN-D METABOLITE LEVELS MEASURED BY PROTEIN-BINDING ASSAY [J].
DEAN, B ;
KOLAVCIC, MS ;
WARK, JD ;
HARRISON, LC .
CLINICA CHIMICA ACTA, 1988, 176 (02) :169-178
[6]   EARLY POSTMENOPAUSAL BONE LOSS IS NOT ASSOCIATED WITH A DECREASE IN CIRCULATING LEVELS OF 25-HYDROXYVITAMIN D, 1,25-DIHYDROXYVITAMIN-D, OR VITAMIN-D-BINDING PROTEIN [J].
FALCH, JA ;
OFTEBRO, H ;
HAUG, E .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1987, 64 (04) :836-841
[7]   EFFECT OF ESTROGEN ON CALCIUM-ABSORPTION AND SERUM VITAMIN-D METABOLITES IN POST-MENOPAUSAL OSTEOPOROSIS [J].
GALLAGHER, JC ;
RIGGS, BL ;
DELUCA, HF .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1980, 51 (06) :1359-1364
[8]   BIOLOGICAL EFFECTS OF VARIOUS DOSES OF CONJUGATED EQUINE ESTROGENS IN POST-MENOPAUSAL WOMEN [J].
GEOLA, FL ;
FRUMAR, AM ;
TATARYN, IV ;
LU, KH ;
HERSHMAN, JM ;
EGGENA, P ;
SAMBHI, MP ;
JUDD, HL .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1980, 51 (03) :620-625
[9]   25(OH)D3 METABOLISM IN KIDNEY-CELL-CULTURES - LACK OF A DIRECT EFFECT OF ESTRADIOL [J].
HENRY, HL .
AMERICAN JOURNAL OF PHYSIOLOGY, 1981, 240 (02) :E119-E124
[10]  
HOLLIS BW, 1986, CLIN CHEM, V32, P2060