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Biomedical subjects

C Christiansen

Publications and source records attributed to C Christiansen.

At least 307 records · Page 17Linked to original sources

Influence of menopause on serum lipids and lipoproteins.

The influence of the menopause on serum lipids and lipoproteins was examined longitudinally at 6-week intervals for 2-3 years in pre-menopausal women undergoing the menopause. Serum lipid and lipoprotein profiles were also examined cross-sectionally in 4 groups of pre-menopausal, peri-menopausal and post-menopausal women, who were followed up longitudinally at 3-monthly examinations for 1-2 years. The results covering 1360 examinations and 270 woman-years are reported here. Serum concentrations of total cholesterol (P = 0.001), low-density-lipoprotein (LDL) cholesterol (P = 0.001) and triglycerides (P less than 0.05) increased significantly as a consequence of the menopause and all increases occurred within 6 months of cessation of menstrual periods. High-density-lipoprotein (HDL) cholesterol decreased significantly (P less than 0.05) as a consequence of the menopause, but the decline occurred gradually over the 2 years preceding cessation of menses. In addition to the menopausal changes, serum concentrations of total cholesterol and LDL-cholesterol increased gradually in the pre-menopausal and post-menopausal years, but were significantly related to biological age only in the pre-menopausal groups (P less than 0.05). Serum triglycerides and HDL-cholesterol levels remained virtually unchanged in the pre-menopausal as well as the post-menopausal groups and were only influenced by the actual menopause. Serum lipids and lipoproteins are thus significantly altered as a consequence of the menopause. The result is a more atherogenic lipid profile which may partly explain the increased risk of cardiovascular disease observed in post-menopausal women.

Adult↗

Serum placental protein 14 in pre-menopausal and post-menopausal women--dependency on oestrogen/progestogen status.

In view of the increasing use of oestrogen-progestogen therapy in post-menopausal women the availability of possible biochemical marker of endometrial response to progestogen would be highly desirable. Placental protein 14 (PP14) has recently been shown to be excreted from the endometrium during the secretory phase of the menstrual cycle. In the present study we examined the concentration of serum PP14 (S-PP14) in 15 pre-menopausal women during the menstrual cycle and in 30 early post-menopausal women receiving three different doses of 17 beta-oestradiol (E2), cyclically combined with norethisterone acetate (NETA). S-PP14 levels peaked on day 1 following the onset of menstrual bleeding and on day 7 during NETA administration. It was possible to estimate the area under the S-PP14 curve reliably from one or two blood samples taken at optimal times. In the post-menopausal women, S-PP14 varied in a highly significant dose-dependent manner, i.e., the higher the E2 dose (in relation to the fixed NETA dose) the higher the S-PP14 response was found to be. We suggest that S-PP14 measurements might reflect the quantitative development of the endometrium in the secretory phase in both pre-menopausal and post-menopausal women.

Adult↗

Smoking induces increased androgen levels in early post-menopausal women.

In order to clarify the effect of smoking on androgen status in the early post-menopause we examined 267 women aged 45-54 years, of whom 146 (55%) were smokers. The cigarette smokers had a significantly higher serum concentration of androstenedione (P less than 0.001) and a raised serum concentration of luteinizing hormone (P = 0.06) in comparison with the non-smokers. The number of cigarettes consumed was apparently immaterial. The concentrations of oestrone, oestradiol and follicle-stimulating hormone were similar in the two groups. This study lends support to the hypothesis that the observed decreased risk of endometrial and breast cancer associated with cigarette smoking may be mediated by androgenic protection.

Androstenedione↗

Bone mass measured by photon absorptiometry: comparison of forearm, heel, and spine.

We assessed bone mass quantification at different skeletal sites by single and dual photon absorptiometric (SPA and DPA) methods. Improved DPA measurement of spinal bone mineral density in young healthy subjects showed a short- and long-term precision of 1.2% and 1.6%. Compared to the conventional DPA method the imprecision was reduced by more than 50%. The appendicular measurements were more precise (0.5-1.2%). We present the intercorrelations and predictive errors between peripheral measurements and improved spinal and total body bone measurements in early postmenopausal women (n = 144) recruited in 1988. To compare the improved system with the conventional methods, we retrieved data on age-matched early postmenopausal women (n = 151) recruited in 1983. In the 1988 population all peripheral methods had similar predictive errors in estimation of spinal bone mineral density (SEE = 11-13%) and total body bone mineral density (SEE = 4-5%). Measurement of trabecular bone in the heel and distal forearm did not improve the validity of predicting spinal bone mass. In a cadaver study (n = 11) the predictive error in estimation of the spinal ash weight from forearm measurements was of the same magnitude (15%) as that in estimation of the spinal BMC from the forearm (16%). We conclude that the predictive error in estimation of spinal bone mass from peripheral bone measurements is more likely to be caused by intra-skeletal variation in bone mass than by precision errors. However, this does not reflect the inability of peripheral bone mass measurements to predict fracture risk.

Absorptiometry, Photon↗

Five years with continuous combined oestrogen/progestogen therapy. Effects on calcium metabolism, lipoproteins, and bleeding pattern.

OBJECTIVE: To study the effect of long-term continuous combined oestrogen/progestogen therapy on calcium metabolism, lipoproteins, and bleeding pattern in early postmenopausal women. DESIGN: A prospective, open, controlled study. After initial examinations, control examinations were performed every three months for the first two years and every year for the following three (two) years, with determinations of bone mass, serum lipoproteins, and bleeding pattern. SETTING: Out-patient research clinic at The Department of Clinical Chemistry, Glostrup Hospital, Denmark. PARTICIPANTS: Eighteen healthy women between 6 months and 3 years after a natural menopause, entered in a trial of continuous long-term hormone replacement therapy and a comparison group of 19 age-matched untreated women. INTERVENTION: The treated group received 2 mg of 17 beta-oestradiol combined with 1 mg of norethisterone acetate orally each day continuously for 5 years with a 3 month therapy-free interval after the first 2 years. The women were investigated before treatment, then every 3 months for the first 2 years and every year for the next 3 years for determinations of bone mass, serum lipoproteins and bleeding patterns. The comparison group was followed-up in parallel for the first 4 years. Forearm bone mass was measured with single photon absorptiometry. Blood and urine samples were taken in the morning after an overnight fast and tobacco abstinence. MAIN OUTCOME MEASURES: The effects of hormone therapy on bone mineral content in the forearm, on serum and urine indices of calcium metabolism, on serum levels of total, high (HDL-C) and low (LDL-C) density lipoprotein cholesterol, and bleeding pattern. RESULTS: Bone mineral content in the forearm was stable during the 5 years of treatment, whereas it declined significantly averaging 10% after 4 years in the comparison group. The biochemical estimates of bone turnover decreased to premenopausal level in the hormone group, whereas they remained at a high level in the comparison group. In the hormone group total cholesterol and LDL-C decreased by 20% whereas HDL-C was virtually unchanged. The treatment was associated with minor irregular bleeding in nine women during the first 6 months of treatment, after which no bleeding was experienced. CONCLUSION: Continuous combined oestrogen/progestogen therapy can keep early postmenopausal women free of bleeding episodes for a period of 5 years, after the first 6 months in which spotting occurs in 25%. The therapy prevented bone loss completely. The changes in serum lipoproteins were concordant with a lipid profile associated with a decreased risk of coronary heart disease.

Bone Density↗

Effects of growth hormone (GH) on plasma bone Gla protein in GH-deficient adults.

Both deficiency and excess of GH are related to disturbances in calcium metabolism. Bone Gla protein (BGP) is the only specific marker of bone turnover identified in peripheral blood. We, therefore, determined plasma BGP in 21 adult GH-deficient patients treated with biosynthetic human GH in a double blind cross-over study. We also examined 9 patients with acromegaly before and after surgery. The GH-deficient patients had normal initial plasma BGP concentrations, whereas the acromegalic patients had highly significantly increased concentrations (P less than 0.001). During treatment with human GH, plasma BGP (and other nonspecific biochemical markers of bone turnover) increased significantly (P less than 0.001). During placebo treatment plasma BGP showed baseline values. In the acromegalic patients a significant decrease in plasma BGP concentrations was seen 1 week after surgery. The present study suggests that plasma BGP is a useful biochemical marker of the effect of treatment of both GH deficiency and GH excess/disorders.

Acromegaly↗

Is it possible to prevent bone loss in young women treated with luteinizing hormone-releasing hormone agonists?

Recent studies have shown that treatment with the LHRH agonist nafarelin gives symptomatic and objective relief to women with endometriosis. Such a treatment, however, results in increased bone turnover and loss of bone mass. In the present study 17 women with endometriosis were treated with 400 mg nafarelin combined with 1.2 mg norethisterone (NET) for 6 months, followed by 6 months with only 1.2 mg NET. The data were compared to data from a previously published study of 9 women treated for 6 months with 400 mg nafarelin alone, followed by 6 months without treatment. In the group treated with nafarelin plus NET the biochemical parameter of bone resorption (fasting urinary hydroxyproline) remained virtually unchanged, compared to a highly significant increase in the nafarelin-treated group. Estimates of bone formation (serum alkaline phosphatase and plasma bone Gla protein) increased in the nafarelin plus NET group, but to only a minor extent compared to those in the nafarelin group. In addition, bone mineral in the forearm, the spine, and the total skeleton remained virtually unchanged in the group treated with nafarelin plus NET, compared to the bone loss of 2-6%/6 months in the nafarelin group. We conclude that addition of NET to nafarelin treatment of endometriosis seems to have a bone-sparing effect.

Adult↗

Serum bone Gla protein: a potential marker of growth hormone (GH) deficiency and the response to GH therapy.

Serum bone Gla protein (BGP), a sensitive and specific biochemical marker of bone formation, was measured in 66 children deficient in GH before and after 3, 6, 9, and 12 months of treatment with biosynthetic human GH. Initial serum BGP levels were significantly lower than those of normal age-matched children. After 3 months of treatment, the mean serum BGP level had increased to normal. There was no relation between baseline serum BGP and the growth response, but the GH-induced increment in serum BGP levels at 3 months was highly significantly related to growth response after 12 months of therapy. The study shows that serum BGP could be a helpful biochemical marker in prediction of the growth response to long term GH therapy.

Adolescent↗

Changes in vitamin D metabolism during natural and medical menopause.

Thirty-nine women were studied longitudinally for 3 yr, during which period 10 women passed a natural menopause. Vitamin D metabolites were determined every 3 months in these 10 women. The same variables were studied in 42 premenopausal women with endometriosis treated for 6 months with nafarelin acetate (a LHRH agonist) given alone in a dose of 200 or 400 micrograms or in a dose of 400 micrograms combined with 1.2 mg norethisterone (NET)/day and followed-up for a further 6 months. No changes were seen in 1,25-dihydroxyvitamin D [1,25-(OH)2D], vitamin D-binding protein, or the free index of 1,25-(OH)2D during the natural menopause. A small increase was found in 25-hydroxyvitamin D [25OHD] and 24,25-(OH)2D3 after correction for seasonal variation. All three nafarelin groups had a significantly decreased free index of 1,25-(OH)2D, which returned to the baseline value on withdrawal of the treatment. Serum 25OHD and 24,25-(OH)2D3 were increased at 6 months and thereafter decreased to baseline values. These changes were still visible after correction for seasonal variation. Vitamin D-binding protein showed a small transient increase in the nafarelin plus NET group, but was unchanged in the other two groups. The 24-h urinary excretion of calcium increased significantly in the groups receiving nafarelin alone, whereas it remained unchanged in the nafarelin plus NET group. We conclude that detectable changes in 1,25-(OH)2D do not occur in natural menopause. Treatment with LHRH agonists produces a significant decrease in serum 1,25-(OH)2D, which does not seem to be dependent on increased bone resorption. This suggests that LHRH agonists may induce a change in other pituitary hormones involved in vitamin D regulation.

24,25-Dihydroxyvitamin D 3↗

17 Beta-estradiol and continuous norethisterone: a unique treatment for established osteoporosis in elderly women.

Forty women aged 64.7 +/- 5.1 yr with established postmenopausal osteoporosis were blindly allocated to 1 yr's treatment with either continuous combined estrogen/progestogen therapy (2 mg estradiol + 1 mg norethisterone acetate + 500 mg calcium daily) or placebo + 500 mg calcium daily. In the group treated with hormones bone mineral density in the spine (dual photon absorptiometry) and bone mineral content in the ultradistal forearm (single photon absorptiometry) increased highly significantly by 8-10% during the 1 yr of treatment. Bone mineral content in the mid-shaft of the forearm (single photon absorptiometry) and the total body bone mineral (dual photon absorptiometry) increased by 3-5% when compared to that in the placebo group, which showed virtually unchanged values at all measurement sites. Seven of the women treated with hormones were examined after a further year of treatment. BMC increased by another 3-6%, reaching a 12% increase in bone mineral density in the spine after 2 yr of treatment. Biochemical estimates of bone resorption (fasting urinary calcium and hydroxyproline) and bone formation (serum alkaline phosphatase and plasma osteocalcin), decreased significantly (P less than 0.001) in the group treated with hormones, but remained unchanged in the placebo group. The reduction in indices of bone resorption was more pronounced than that in bone formation after one year, indicating a positive bone balance. No further changes were seen in these bone turnover parameters during the second year of treatment. In the group treated with hormones, serum levels of triglycerides, total cholesterol, and low density lipoprotein cholesterol decreased by about 12% (P less than 0.05-P less than 0.01), whereas high density lipoprotein cholesterol decreased by about 8% (P less than 0.001). The high density lipoprotein cholesterol/low density lipoprotein cholesterol ratio was unchanged. The hormone treatment did not produce any major side effects, and only minor bleedings were experienced by a few women. The present study demonstrates that treatment with female sex hormones in this particular combination is a realistic approach to the treatment of women with established postmenopausal osteoporosis.

Aged↗

Comparison of two immunoinhibitory methods with agarose gel-electrophoresis for measuring the MB isoenzyme of creatine kinase in serum from cases of suspected myocardial infarction.

Two immunoinhibitory methods for measuring creatine kinase-MB (a dry chemical and a wet chemical method) were compared with the commonly used agarose gel electrophoretic method, using 563 serum samples from 235 patients with suspected acute myocardial infarction. Comparison of the electrophoretic and the dry chemistry methods showed the linear relationship: electrophoretic method = -6.5 U/l + 1.22 x dry chemistry method, r = 0.943. For the wet chemistry method the relationship was: electrophoretic method = -7.2 U/l + 1.19 x wet chemistry method, r = 0.854. Parallel determinations of total creatine kinase were also done and the methods were virtually identical in performance. Compared with the electrophoretic method (which showed a 15% prevalence of acute myocardial infarction), these classifications showed sensitivities of 0.92 and 0.67 and specificities of 0.94 and 0.99 (dry and wet chemistry, respectively; using methods recommended by the manufacturers). After optimization of discriminators the sensitivity was increased to 0.94/0.92 and the specificity to 0.99/0.99.

Adenylate Kinase↗

Vitamin D metabolism in osteoporotic women during treatment with estrogen, an anabolic steroid, or calcitonin.

We assessed the effects of a continuous oral combination of estradiol and norethisterone acetate, nandrolone decanoate, or salmon calcitonin on the vitamin D endocrine system. One hundred and nineteen postmenopausal women, aged 55-75 years, with at least one osteoporotic fracture, were randomly allocated to one year of treatment with estradiol and norethisterone acetate, nandrolone decanoate, or calcitonin, all drugs with a beneficial effect on bone. All three trials were double-blind and placebo-controlled; 104 women (87%) completed the study. We measured the total serum concentration of 1,25-dihydroxyvitamin D (1,25(OH)2D) and vitamin D-binding protein, and estimated the free 1,25(OH)2D index and the "24-hydroxylase activity" initially, and at 6 and 12 months. Furthermore, the 24-h urinary excretions of calcium, phosphate, and adenosine 3'-5'-cyclic monophosphate were assessed initially and at 12 months. The serum concentration of vitamin D-binding protein and 1,25(OH)2D increased transiently during estradiol and norethisterone acetate treatment and vitamin D-binding protein decreased transiently during nandrolone decanoate treatment. None of the other parameters were significantly affected by any of the three treatments. The risk of type II errors was below 10 per cent for all vitamin D measurements. We conclude that the vitamin D metabolites are unlikely to be of major importance for the mechanism by which these drugs exert their positive skeletal effects.

Aged↗

Vitamin D metabolites--relation to age, menopause and endometriosis.

We investigated the influence of menopause, age and sex on vitamin D metabolism in a large group of healthy women (n = 113) and men (n = 108) and in a group of early postmenopausal women (n = 124). Furthermore, we studied the vitamin D metabolism in 42 women with endometriosis. The vitamin D metabolites did not show dependence on age or on duration of menopause. The serum concentrations of vitamin D metabolites did not differ in normal men and women. There were highly significant seasonal oscillations for 25(OH)D and 24,25(OH)2D3 but not for 1,25(OH)2D. Women with endometriosis had significantly elevated serum 1,25(OH)2D compared to the normal women. Our study indicates that ageing is not associated with a significant depletion of 25(OH)D, 24,25(OH)2D or 1,25(OH)2D in normal men and women up to the age of 75 years. Furthermore, changes in vitamin D metabolism seem not to be an important factor in early postmenopausal bone loss. Our results on patients with endometriosis indicate that these patients may have some calcium-metabolic disturbances.

24,25-Dihydroxyvitamin D 3↗

Direct measurement of abdominal fat by dual photon absorptiometry.

We have assessed photon absorptiometry as a new technique for direct measurement of the abdominal fat percentage (AF%). The accuracy of the method was assessed in vitro with phantoms consisting of ox muscle, lard, and a mixture of both. The results showed good linearity (r = 0.999). The in vitro reproducibility and the in vivo reproducibility were s.d. = 2.0 and s.d. = 2.8 (AF%), respectively. The AF% was measured in 148 healthy post-menopausal women and found to correlate with other measurements of fatness, such as total body fat per cent (r = 0.82, P less than 0.001), body mass index (r = 0.79, P less than 0.001) and the ratio of waist-to-hip circumference (r = 0.59, P less than 0.001). The waist-to-hip ratio, an important predictor of cardiovascular disease, was more tightly correlated with AF% than with body mass index. We conclude that this method may be a useful new research tool for direct measurements of abdominal fat, a possible cardiovascular risk factor.

Abdomen↗

Dual-energy x-ray absorptiometry: a precise method of measuring bone mineral density in the lumbar spine.

We compared two methods of measuring spinal bone mineral content and density (BMC/BMD): conventional dual-photon absorptiometry (DPA) and a more recent method, dual-energy x-ray absorptiometry (DEXA). The clinical usefulness of both methods was compared in the measurement of BMC in the forearm. DEXA had a long-term in vivo precision of 1% which was significantly better than that of DPA. Changes in the distribution of fatty tissue influenced the accuracy of the two spinal methods in different ways. Forearm BMC discriminated between the bone mass of early and late postmenopausal women to the same degree as DPA and DEXA. The variability in the response to estrogen treatment and placebo was much lower with DEXA and forearm BMC than with DPA. We conclude that DEXA provides a fast and precise measurement of spinal BMC/BMD. The accuracy remains to be evaluated for in vivo studies.

Absorptiometry, Photon↗

Effect of salcatonin given intranasally on early postmenopausal bone loss.

OBJECTIVE: To study the effect of salmon calcitonin (salcatonin) given intranasally on calcium and bone metabolism in early postmenopausal women. DESIGN: Double blind, placebo controlled, randomised group comparison. SETTING: Outpatient clinic for research into osteoporosis. SUBJECTS: 52 Healthy women who had had a natural menopause two and a half to five years previously. INTERVENTIONS: The 52 women were allocated randomly to two years of treatment with either salcatonin 100IU given intranasally (n = 26) or placebo (n = 26). Both groups received a calcium supplement of 500 mg daily. Seven of the women receiving salcatonin and six of those receiving placebo left the study before its end. MAIN OUTCOME MEASURES: Bone mineral content in the spine, the total skeleton, and the forearms after two years of treatment. RESULTS: Bone mineral content in the spine was significantly higher in the women who had received salcatonin than in those who had received placebo both after one year and after two years of treatment. After one year the difference was 3.8% (95% confidence interval 0.0 to 7.6%) and after two years it was 8.2% (3.8 to 12.6%). In contrast, the bone mineral content in the distal and proximal forearms and in the total skeleton declined similarly in both groups by about 2% each year, and after two years of treatment the differences between the groups were not significant. Biochemical estimates of bone turnover were not affected by salcatonin. CONCLUSION: The results suggest that salcatonin given intranasally in the dose used prevents bone loss in the spine of early post menopausal women but does not affect the peripheral skeleton.

Administration, Intranasal↗

New methods for identifying "at risk" patients for osteoporosis.

Bone loss was determined in 178 women in the early postmenopausal period by photon absorptiometry measurement of forearm bone mineral content (BMC) every three months for two years. With a sequential cut-off technique, the results of a single determination of body fat mass, urinary calcium and hydroxyproline, and serum alkaline phosphatase, carried out at the first examination, correctly identified 79% of "fast bone losers" (bone loss greater than 3% annually) and 78% of "slow bone losers". The simple biochemical screening procedure was hereafter tested in a new group of 70 early postmenopausal women, who were followed for two years with measurement of local and total BMC. With this simple approach the majority of women at highest risk of osteoporotic fractures in later life can be identified in the early postmenopausal period and can be started on prophylactic hormone replacement therapy.

Bone and Bones↗

Relation of body fat distribution to serum lipids and lipoproteins in elderly women.

Fat distribution measured by dual photon absorptiometry, serum lipids and lipoproteins were determined in 95 elderly women with mild osteoporosis. Increasing obesity, determined anthropometrically as body mass index (BMI) = body weight/(height)2, was associated with a more central fat distribution (P less than 0.001) Central fat distribution correlated positively and independently of BMI and body weight to serum cholesterol, low density lipoprotein-cholesterol (LDL-C), triglycerides and the ratio LDL-C/HDL-C (P less than 0.05), whereas the correlation between central fat distribution and high density lipoprotein-cholesterol (HDL-C) was negative (P less than 0.05). We conclude that the increased risk of cardiovascular disease observed in subjects with central fat distribution might be partly mediated through changes in the lipoprotein profile.

Absorptiometry, Photon↗