Transdermal estrogen replacement does not increase calcitonin secretory reserve in postmenopausal women

Abstract

The effect of transdermal estrogen replacement on ionized calcium and calcitonin levels was examined in 15 postmenopausal women. Following baseline measurement of calcitonin and ionized calcium in the fasting state, the effect of calcium infusion on calcitonin levels was studied. Estrogen replacement resulted in a fall in baseline ionized calcium, however, the rate of rise of calcium was the same before and after estrogen administration. Thus the time at which a particular calcium concentration was attained was later after the commencement of the calcium infusion following estrogen replacement. Although there was no detectable difference in baseline calcitonin concentrations (pre-estrogen, 2.4\m=+-\0.4; post-estrogen, 2.1\m=+-\0.4 pmol/l), following estrogen replacement the time at which a particular calcitonin concentration was attained was later after the commencement of the calcium infusion, reflecting the slower attainment of a particular calcium concentration (p=0.014 by ANOVA). Analysis of total calcitonin production by area under the curve, however, did not show a significant difference before and after estrogen replacement (643 \ m=+-\ 184 and 407\m=+-\115 pmol \ m=. \ l \ m=-\ 1\ m=. \ 100mi n\m=-\1, respectively). When the calcitonin response to calcium infusion was compared at the same calcium concentration, estrogen status had no effect on the relationship. We conclude that transdermal estrogen replacement has no effect on calcitonin secretory reserve in postmenopausal women and does not alter the relationship between elevated calcium and calcitonin levels. We cannot exclude an effect of estrogen on baseline calcitonin levels as the calcium concentration was lower but the calcitonin levels not different.The mechanism by which estrogen therapy reduces bone résorption in postmenopausal women re¬ mains unclear. One potential mechanism which has been proposed is the stimulatory effect of estrogen on calcitonin secretion (1), a hormone which has been shown to act on bone to inhibit osteoclast function and bone résorption (2). Consistent with the hypothesis that the bone loss is associated with estrogen deficiency and mediated by calcitonin de¬ ficiency, calcitonin levels are reported to be lower in women than men (3-5) and to rise less after a calcium stimulus than in men (4,5). In some studies calcitonin secretion in response to a calcium stim¬ ulus has been shown to decrease with age in men and women (5,6) and after the menopause in women (7). There have been reports of lower cal¬ citonin levels in osteoporotic women compared to normal postmenopausal women suggesting a role for calcitonin deficiency in the pathogenesis of osteoporosis (8,9), but this remains controversial with other studies showing no difference (10) or higher calcitonin levels in osteoporosis (11,12).The effect of oral estrogen replacement on cal¬ citonin secretion is controversial with three similar studies from the same group showing a rise in cal¬ citonin levels (1,13,14) despite a fall in plasma cal¬ cium while other studies show lo...