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Hormone Replacement Therapy May Reduce the Return of Endogenous Lead from Bone to the Circulation

The following is a series of extracts from an article in Volume 103 Number 12, December 1995. "Environmental Health Perspectives" by: Colin E. Webber David R, Chettle, Robert J Bowins, Lesley F. Beaumont, Christopher L. Gordon, Xinni Song, Jennifer M. Blake, and Robert H. McNutt. full EHP article

The concentration of lead in bone apparently increases steadily throughout life. By the time a woman reaches the age of menopause she can expect to have a bone lead content of about 12 g/g mineral in cortical bone, with somewhat higher levels in trabecular bone (I). Because about 95% of body lead resides in the skeleton, a typical endogenous lead burden for a menopausal woman will be 30 mg.

Materials and Methods

White women who were typically between 1 and 5 years post-menopause were recruited from the local community and placed on calcium supplementation (500mg/day). Six months later each woman chose either to add HRT to the calcium supplementation or to remain on calcium alone. Those given HRT received either a low-doses, continuous or a moderate-dose, cyclical regime. The lead concentrations of bone, blood, serum and urine were measured during the fourth or fifth year of HRT.

Results

Moderate-dose HRT increased bone mineral mass at the spine, while low-dose HRT eliminated a rate of loss of 0.3g mineral/year observed on calcium alone. HRT produced no differences in rates of change of mineral mass at the radius tibia lead content was significantly lower in the group of subjects not taking hormones (p=0.049).

Discussion

These results suggest that postmenopausal women who are on HRT will have a greater skeletal lead burden than women not on hormones. The excess lead is located within cortical bone, rather than trabecular bone, probably because the retention time in cortical bone is at least twice that of trabecular bone. This is consistent with measures of blood lead made during the second National Health and Nutrition Examination Survey (NHANES II). In 849 women between 40 and 60 years of age, blood concentration post menopause was 13.0 g/dL, whereas in pre-menopausal women it averaged 11.9 g/dL. The increased blood lead is thought to be due to the release of lead from bone as a consequence of menopause-related increases in bone turnover.

Hormone replacement prevents the menopause-associated increase in bone turnover, and lead would be expected to remain in the skeleton. The menopause-related increase in the blood lead is greater for white than for black women because the increase in bone turnover is greater for white women. Especially at risk for increased blood lead after menopause are white women who have no children. This is thought to be because skeletal lead burdens would have been reduced by a postpartum increase in bone turnover in lactating women resulting in less lead being available for mobilization after menopause.

The transfer of calcium between bone and the circulation takes place through the processes of mineral exchange and bone turnover. The purpose of exchange and turnover is to release minerals to the circulation, repair damaged bone, replace affected bone and reorganize bone in response to altered mechanical environments. It has been estimated that each day the mass of calcium involved in exchange is about 10 times the mass of calcium involved in turnover. In recently proposed compartmental models of lead metabolism the assumption is made that these same processes are responsible for the movement of lead between the circulation and bone. Lead on bone surfaces is considered to be rapidly exchangeable, whereas lead distributed throughout the bone volume is in exchange with bone surface lead. It is known that elements that are bone-volume seekers such as lead and the alkaline earth elements are retained to a greater extent in older bone than in newly formed bone. Thus about 10mg of lead remains in bone because of a hormone induced reduction in exchange.

All women in this study took calcium supplementation, and it is possible that in subjects with calcium deficiency, the mass of bone involved in exchange and turnover process may be even greater. The woman who is likely to release the most lead from her skeleton is the woman who has accumulated considerable lead from her environment, who suffers a significant pre-menopause increase in bone turnover and mineral exchange, and who may have a poor calcium intake.

This work was supported by a grant from the International Lead and Zinc Research Organization (ILZRO)

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