Effects of Estrogens and Calcium on Calcitonin Secretion in Postmenopausal Women*

Abstract

The protective action of estrogens on bone mass may be mediated by an increase in calcitonin (CT) secretion. We reevaluated this hypothesis using a method for measuring CT in extracts of serum that allows sensitive specific measurement of CT monomer. We studied seven healthy postmenopausal women before and on the 7th and 28th days of each of three 4-week treatment periods: estrogen (estradiol valerate; 2 mg/day), calcium supplement (1500 mg/day), and estrogen plus calcium; the three cycles were separated by intervals of 4 weeks. Serum extractable CT (exCT) levels were measured before and after a short calcium stimulation test (2 mg Ca/kg in 5 min) to assess the C-cell secretory response on each day. Estrogen had the expected biological effects, decreasing (P less than 0.05) serum gonadotropin concentrations and fasting or 24-h urinary calcium excretion. The calcium supplement caused a significant increase in 24-h urinary calcium excretion. However, there was no increase in basal or stimulated serum exCT levels during any of the three cycles. On the contrary, basal serum exCT concentrations decreased slightly but significantly during estrogen treatment from 1.9 +/- 0.5 (+/- SE) to 1.5 +/- 0.4 ng/L on day 7 and 1.2 +/- 0.2 ng/L on day 28 (P less than 0.05). This decrease in basal exCT levels did not occur during the combined estrogen and calcium administration period, probably because the slight decrease in serum calcium induced by estrogen did not occur during combined estrogen and calcium administration. In summary, estrogens do not stimulate CT secretion; variations in serum exCT levels appear to be related to the changes in bone metabolism induced by estrogens.

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

“…The lack of a stimulatory effect of estrogen therapy on baseline calcitonin levels in this study of healthy postmenopausal women supports some (15)(16)(17)(18) but not all (1,13,14) previous reports. In one study an increase in basal calcitonin levels occurred only after 6 months of therapy (23) suggesting that es¬ trogen may only have long-term effects on calcito¬ nin secretion.…”

“…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 lower or unchanged calcitonin levels after estrogen therapy (15)(16)(17)(18). Following baseline measurement of calcitonin and ionized calcium in the fasting state, the effect of calcium infusion on calcitonin levels was studied.…”

“…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 lower or unchanged calcitonin levels after estrogen therapy (15)(16)(17)(18). Transdermal estrogen replacement is a more phys¬ iological route of administration than oral estrogen replacement and different hormonal effects be¬ tween the two have been noted.…”

Calcitonin: From the Determination of Circulating Levels in Various Physiological and Pathological Conditions to the Demonstration of Lymphocyte Receptors

“…We indeed demonstrated that es trogen replacement therapy in healthy postmenopausal women did not stimulate CT secretion, as claimed by oth ers [3], but, on the contrary, induced a slight reduction in basal CT levels, consistent with the well-known inhibitory effects of estrogens on bone turnover [16]. Another study in male renal stone formers also supports our hypothesis.…”

The thyroid C cells of ovariectomized rats treated with estradiol

“…Estrogens can act on both synthesis and release of CT. Contrary to these findings, Body et al (1989) concluded that estrogen did not stimulate secretion of CT in postmenopausal women. Eriksen et al (1988) suggested that estrogen has a direct effect on bone cells, as mRNA for estrogen receptor protein was localized within the cytoplasm of normal human osteoblasts.…”