PubMed Health⌕ Search

Biomedical subjects

A P Hermann

Publications and source records attributed to A P Hermann.

At least 19 recordsLinked to original sources
PubMed2006

No effect of vitamin K1 intake on bone mineral density and fracture risk in perimenopausal women.

INTRODUCTION: Vitamin K functions as a co-factor in the post-translational carboxylation of several bone proteins, including osteocalcin. AIM: The aim of this study was to investigate the relationship between vitamin K(1) intake and bone mineral density (BMD) and fracture risk in a perimenopausal Danish population. DESIGN: The study was performed within the Danish Osteoporosis Prevention Study (DOPS), including a population-based cohort of 2,016 perimenopausal women. During the study approximately 50% of the women received hormone replacement therapy (HRT). Associations between vitamin K(1) intake and BMD were assessed at baseline and after 5-years of follow-up (cross-sectional design). Moreover, associations between vitamin K(1) intake and 5-year and 10-year changes in BMD were studied (follow-up design). Finally, fracture risk was assessed in relation to vitamin K(1) intake (nested case-control design). RESULTS: In our cohort, dietary vitamin K(1) intake (60 mug/day) was close to the daily intake recommended by the Food and Agriculture Organization (FAO). Cross-sectional and longitudinal analyses showed no associations between intake of vitamin K(1) and BMD of the femoral neck or lumbar spine. Neither did BMD differ between those 5% that had the highest vitamin K(1) intake and those 5% that had the lowest. During the 10-years of follow-up, 360 subjects sustained a fracture (cases). In a comparison between the cases and 1,440 controls, logistic regression analyses revealed no difference in vitamin K(1) intake between cases and controls. CONCLUSION: In a group of perimenopausal and early postmenopausal women, vitamin K(1) intake was not associated with effects on BMD or fracture risk.

Adult↗
PubMed2006

Prevalence of overweight, obesity and physical inactivity in 20- to 29-year-old, Danish men. Relation to sociodemography, physical dysfunction and low socioeconomic status: the Odense Androgen Study.

OBJECTIVE: To assess the prevalence of overweight, obesity and physical inactivity in 20- to 29-year-old men and to analyze whether sociodemography, physical dysfunction and low socioeconomic status are independent correlates of obesity and physical inactivity. DESIGN: Population-based, cross-sectional study. SUBJECTS: Seven hundred and eighty-three Caucasian, Danish men, aged 20-29 years recruited from 2042 respondents in a questionnaire survey of 3000 men, randomly drawn from the Danish Civil Registration System. METHODS: Questionnaire, interview and physical examination. RESULTS: The 783 included men and the 2042 questionnaire respondents matched the background population demographically. The 783 men matched the questionnaire respondents as regards BMI, physical activity, chronic disease, medication, smoking, sociodemography and socioeconomic status. The prevalence of overweight and obesity was 31.7 and 7.9%, respectively (World Health Organization criteria). Using waist circumference (WC) cutoffs of 94 and 102 cm, the prevalence was 16.2 and 10.6%, respectively; 24.4% were physically inactive. BMI and WC increased significantly from age 20 to 29 years. Physical activity decreased significantly with age and correlated inversely with WC, but not with BMI. Occupation, geography, partner status, fatherhood and tobacco exposure were independently related with obesity and physical inactivity. Obesity was also related to musculoskeletal complaints, whereas chronic diseases and low educational level were associated with physical inactivity. Age was not independently related with either outcome. CONCLUSION: In affluent societies, sociodemographic changes may partly explain the age-related decrease in physical activity and the parallel increase in WC and BMI.

Adiposity↗
PubMed2005

Plasma concentrations of 25-hydroxy-vitamin D and 1,25-dihydroxy-vitamin D are related to the phenotype of Gc (vitamin D-binding protein): a cross-sectional study on 595 early postmenopausal women.

The major transporter of vitamin D metabolites in the circulation is the multifunctional plasma protein Gc, also known as group-specific component, Gc globulin, vitamin D-binding protein, or DBP. There are several phenotypes of Gc, and we examined the influence of Gc phenotype and Gc concentration on vitamin D status. By using isoelectric focusing we identified the Gc phenotype of 595 caucasian recent postmenopausal women enrolled into the Danish Osteoporosis Prevention Study (DOPS). We measured plasma concentration of Gc by immunonephelometry (coefficient of variation [CV] < 5%), 25-hydroxy vitamin D (25OHD) by a competitive protein-binding assay (CV 10%), and 1,25-dihydroxy-vitamin D (1,25(OH)(2)D) by a radioimmunoassay (CV 6--14%), and calculated index as the molar ratio of vitamin concentration divided by Gc concentration. Plasma levels of Gc, 25OHD, 25OHD index, and 1,25(OH)(2)D, but not 1,25(OH)(2)D index, differed significantly between women with different Gc phenotype, being highest in Gc1-1, intermediate in Gc1-2, and lowest in Gc2-2. In multiple regression analysis, Gc concentration was an independent predictor of 1,25(OH)(2)D, whereas Gc phenotype was a significant predictor of 25OHD concentration, even after adjustment for the effects of season, sunbathing habits, skin thickness, use of vitamin supplements, smoking, and body mass index (BMI). Plasma parathyroid hormone (PTH) level did not differ between Gc phenotypes. Despite the fact that more than 60% of the women with Gc phenotype Gc2-2 had plasma 25OHD levels of less than 50 nmol/L none of them had plasma PTH higher than reference limits. Bone mineral content (BMC), Bone mineral density (BMD), and bone markers did not differ between Gc phenotypes. In conclusion, plasma 1,25(OH)(2)D, 25OHD, and 25OHD index are related to Gc phenotype, and we speculate that the thresholds for vitamin D sufficiency differ between Gc phenotypes.

Cross-Sectional Studies↗
PubMed2004

Significantly higher adrenocorticotropin-stimulated cortisol and 17-hydroxyprogesterone levels in 337 consecutive, premenopausal, caucasian, hirsute patients compared with healthy controls.

OBJECTIVE: To investigate whether elevated ACTH-stimulated 17-hydroxyprogesterone (17OHP) levels are caused by CYP21 genetic defects or by a general adrenal hyperresponsiveness in hirsute patients. METHODS: A total of 337 hirsute patients were evaluated by Ferriman-Gallwey score, serum testosterone, ACTH-stimulated 17OHP, and cortisol during the follicular phase. A cutoff value of 16 nmol/liter for maximum ACTH-stimulated 17OHP (M17OHP) responses was defined as the upper limit of the 95% confidence interval (CI) for the 97.5 percentile in 42 female controls. All patients were offered total screening of the CYP21 gene, and 252 healthy, premenopausal women with regular menses underwent genetic screening. RESULTS: Patients were divided into idiopathic hirsutism (IH) (n = 180) and polycystic ovary syndrome (PCOS) (n = 157) groups. M17OHP levels were significantly higher in IH [geometric mean value (nmol/liter +/- 2 sd) 12.2 (4.6-32.3)] and PCOS [11.9 (5.3-27.2)] compared with controls [8.5 (5.1-14.2)] (P < 0.001). A similar percentage of IH and PCOS patients had elevated M17OHP (20.5 vs. 20.8%, not significant), and these also had significantly higher 30-min cortisol levels compared with controls (P < 0.05). The prevalence of CYP21 mutations in patients was 8.6% compared with 6.3% in controls (P = 0.38). Ten of 19 carriers had M17OHP levels below the cutoff limit. CONCLUSION: The significantly higher ACTH-stimulated levels of cortisol and 17OHP in hirsute patients indicated adrenal hyperresponsiveness in IH and PCOS. CYP21-carrier status could not explain the observed high prevalence of abnormal ACTH-stimulated 17OHP levels in the hirsute population.

17-alpha-Hydroxyprogesterone↗
PubMed2004

No effect of vitamin A intake on bone mineral density and fracture risk in perimenopausal women.

In recent studies from Sweden and the United States, a high vitamin A intake has been associated with low bone mineral density (BMD) and increased fracture risk. In Sweden and the United States, food items such as milk and breakfast cereals are fortified with vitamin A, whereas in Denmark there is no mandatory fortification with vitamin A. In the present study, we investigated relations between vitamin A intake and BMD and fracture risk in a Danish population consuming mostly unfortified food items. Within a population-based cohort study in 2,016 perimenopausal women, associations between BMD and vitamin A intake were assessed at baseline and after 5-year follow-up. Moreover, associations between baseline vitamin A intake and 5-year changes in BMD were studied. Finally, fracture risk was assessed in relation to vitamin A intake. In our cohort, dietary retinol intake (0.53 mg/day) was lower than the intake reported in recent studies form Sweden (0.78 mg/day) and the United States (1.66 mg/day). Cross-sectional and longitudinal analyses showed no associations between intake of vitamin A and BMD of the femoral neck or lumbar spine. Neither did BMD differ between those 5% who had the highest, and those 5% who had the lowest, vitamin A intake. During the 5-year study period, 163 subjects sustained a fracture (cases). Compared to 978 controls, logistic regression analyses revealed no difference in vitamin A intake. Thus, in a Danish population, average vitamin A intake is lower than in Sweden and the United States and not associated with detrimental effects on bone.

Bone Density↗
PubMed2003

Hormone replacement therapy dissociates fat mass and bone mass, and tends to reduce weight gain in early postmenopausal women: a randomized controlled 5-year clinical trial of the Danish Osteoporosis Prevention Study.

The aim of this study was to study the influence of hormone replacement therapy (HRT) on weight changes, body composition, and bone mass in early postmenopausal women in a partly randomized comprehensive cohort study design. A total of 2016 women ages 45-58 years from 3 months to 2 years past last menstrual bleeding were included. One thousand were randomly assigned to HRT or no HRT in an open trial, whereas the others were allocated according to their preferences. All were followed for 5 years for body weight, bone mass, and body composition measurements. Body weight increased less over the 5 years in women randomized to HRT (1.94 +/- 4.86 kg) than in women randomized to no HRT (2.57 +/- 4.63, p = 0.046). A similar pattern was seen in the group receiving HRT or not by their own choice. The smaller weight gain in women on HRT was almost entirely caused by a lesser gain in fat. The main determinant of the weight gain was a decline in physical fitness. Women opting for HRT had a significantly lower body weight at inclusion than the other participants, but the results in the self-selected part of the study followed the pattern found in the randomized part. The change in fat mass was the strongest predictor of bone changes in untreated women, whereas the change in lean body mass was the strongest predictor when HRT was given. Body weight increases after the menopause. The gain in weight is related to a decrease in working capacity. HRT is associated with a smaller increase in fat mass after menopause. Fat gain protects against bone loss in untreated women but not in HRT-treated women. The data suggest that women's attitudes to HRT are more positive if they have low body weight, but there is no evidence that the conclusions in this study are skewed by selection bias.

Age Factors↗
PubMed2002

When should densitometry be repeated in healthy peri- and postmenopausal women: the Danish osteoporosis prevention study.

Intervention should be considered in postmenopausal women with bone mineral density (BMD) > or = 1 SD below the reference (T or Z score < -1). However, it is unclear when densitometry should be repeated. This study aimed at determining the need for repeat DXA within 5 years in untreated peri-/postmenopausal women to detect declines of T or Z score to below -1 with 85% confidence. A cohort of 925 healthy women (aged 51.2 +/- 2.9 years) were followed within the Danish Osteoporosis Prevention Study (DOPS) for 5 years without hormone-replacement therapy (HRT). DXA of spine, hip, and forearm was done at 0,1, 2, 3, and 5 years (Hologic QDR-1000/2000). The annual loss in SD units was 0.12 +/- 0.10 at the spine (1.3%), 0.10 +/- 0.09 at the femoral neck (1.2%), and 0.07 +/- 0.09 at the ultradistal (UD) forearm (1.0%). Accordingly, T scores below -1 developed earlier at the spine. The need for a future DXA scan to predict declines of T and Z scores below -1 depended strongly on baseline BMD. In subjects with a positive T score, the risk of developing T < -1 remained at <15% for 5 years at all measured sites. A new scan was needed after 1 year if the T score was below -0.5, and after 3 years if the T score was between 0 and -0.5. Slightly longer intervals apply if Z scores are used. Follow-up densitometry in untreated women should be individually targeted from baseline BMD rather than scheduled at fixed time intervals. An algorithm for planning repeat densitometry in perimenopausal women is provided.

Absorptiometry, Photon↗
PubMed2001

Evaluation of methods for prediction of bone mineral density by clinical and biochemical variables in perimenopausal women.

OBJECTIVES: to predict spinal and femoral bone mineral density (BMD) in perimenopausal women from simple clinical and biochemical variables. METHODS: 2016 women 3-24 months past last menstrual bleeding. Mean age 50.1+/-2.8 years. Age, height, weight, number of full term pregnancies, weekly hours of physical activity, sunbathing habits, use of sun bed, daily intake of calcium and vitamin D, smoking habits, consumption of alcohol, coffee, and tea, history of forearm or femoral neck fractures among the parents, serum osteocalcin (S-OC), serum bone specific isoenzyme of alkaline phosphatase (BSAP), and urine hydroxyproline/creatinine ratio (U-OHP) were used as predictors in three different mathematical models. Lumbar spine (L2-L4) and femoral neck BMD were measured by DEXA. Three mathematical models (multiple regression, logistic regression, and discriminant analysis) were applied. RESULTS: the multiple regression explained 19-21% of the total variation, and the logistic regression and discriminant function had a sensitivity between 53 and 67% with specificity ranging from 67 to 80%. Age, S-OC, serum bone specific alkaline phosphatase, and a maternal history of forearm or femoral neck fractures seemed to be reproducible risk factors for low bone mineral density irrespective of the mathematical model applied. When applied to a separate population, the models performed poorly. CONCLUSIONS: Simple clinical and biochemical variables are not useful to predict spinal and femoral BMD in the individual perimenopausal woman.

Alkaline Phosphatase↗
PubMed2001

[Hormone replacement therapy reduces the risk of forearm fracture in postmenopausal women. Results of the Danish Osteoporosis Prevention Study].

In a prospective, controlled, comprehensive cohort trial of 2,016 healthy early postmenopausal women aged 45-58 years we studied fracture prevention through the use of oestrogen. There were two main study arms: a randomised arm (randomised to HRT [n = 502] or not [n = 504]) and a non-randomised arm (on HRT [n = 221] or not [n = 789] by own choice). After five years, an intention-to-treat analysis (n = 2,016) showed a reduction in the overall fracture risk (RR = 0.73, 95% CI: 0.50-1.05) and in the forearm fracture risk (RR = 0.45, 95% CI: 0.22-0.90) with oestrogen. Restriction of the analysis to women who had adhered to their initial allocation of either oestrogen (n = 395) or no oestrogen (n = 977) showed a significant reduction in both the overall fracture risk (RR = 0.61, 95% CI: 0.39-0.97) and the risk of forearm fractures (RR = 0.24, 95% CI: 0.09-0.69). We conclude that it is possible to reduce the number of forearm fractures in early postmenopausal women by the use of oestrogen as primary prevention.

Aged↗
PubMed2001

Vitamin D status and its adequacy in healthy Danish perimenopausal women: relationships to dietary intake, sun exposure and serum parathyroid hormone.

We conducted this study to assess the prevalence of vitamin D insufficiency in a population of normal perimenopausal women, to examine the influence of sun exposure and vitamin D intake on the concentration of 25-hydroxyvitamin D (25OHD) and to examine the association between parathyroid hormone (PTH) and 25OHD. A total of 2016 healthy women aged 45-58, who had recently undergone a natural menopause, were enrolled over a 2.5-year period in the Danish Osteoporosis Prevention Study. A marked seasonal fluctuation of 25OHD was seen, with an abrupt rise in June and high values until October. The fluctuation could be related to number of hours of sunshine per month with a two months time lag. Dietary vitamin D intake, vitamin supplementation, sunlight exposure, and use of sun-bed were all significantly related to 25OHD concentrations. Sun exposure seemed to contribute the most. The overall prevalence of vitamin D deficiency (defined as serum ) was 7 %. However, in the subgroup avoiding direct sunshine and abstaining from vitamin D supplementation 32.8 % were vitamin D deficient in the winter-spring period. Although mean PTH was increased in the group with low serum 25OHD, PTH was not a sensitive marker of hypovitaminosis D in the individual, as only 16 % of those with vitamin D deficiency had PTH levels above normal range. Thus, we have shown, that healthy middle-aged Danish women are prone to vitamin D insufficiency in the winter-spring period, if they avoid sun exposure in the summer period and abstain from vitamin D supplementation.

Biomarkers↗
PubMed2001

Regional and hormone-dependent effects of apolipoprotein E genotype on changes in bone mineral in perimenopausal women.

We studied 479 perimenopausal Danish women aged 45-58 years to examine differences between APOE genotypes with respect to (1) baseline total body bone mineral density (BMD) and densities measured in five different regions (ultradistal forearm, proximal forearm, lumbar spine, femoral neck, and total hip region); (2) serum levels of alkaline phosphatase, bone isoenzyme alkaline phosphatase, osteocalcin, parathyroid hormone (PTH), 25-hydroxyvitamin D, and urine hydroxyproline/creatinine excretion ratio; and (3) changes in bone mineral during 5 years of follow-up. Baseline BMDs were identical, whereas serum levels of alkaline phosphatase and its bone isoenzyme were higher in women with APOE 2-2 and APOE 2-3 than in women with APOE 3-3 and APOE 3-4 and lower in women with APOE 4-4. Among women not receiving hormonal-replacement therapy (HRT; n = 262), those with APOE 2-2 and APOE 2-3 had 30-40% lower rates of femoral neck and total hip bone mineral loss than women with APOE 3-3 and APOE 3-4, whereas the rates of mineral loss in other skeletal regions did not differ between these APOE genotypes. Women with APOE 4-4 appeared to have lower rates of bone mineral loss in all regions. Women treated with hormones throughout the follow-up period (n = 113) gained bone mineral, and women with APOE 3-4 and APOE 4-4 gained relatively more mineral than other women. A comparison of untreated and treated women with APOE 2-3, APOE 3-3, and APOE 3-4 suggests a possible modification of the effect of APOE genotype by HRT. In conclusion, the common APOE polymorphism has a complex effect on bone metabolism in perimenopausal Danish women including possible modification by hormone use: (1) among women not receiving HRT, those with APOE*2 have lower bone mineral losses in the femoral neck and hip region than other women, and (2) among women receiving HRT, those with APOE*4 gain more bone mineral than other women.

Alkaline Phosphatase↗
PubMed2001

Discordance between changes in bone mineral density measured at different skeletal sites in perimenopausal women--implications for assessment of bone loss and response to therapy: The Danish Osteoporosis Prevention Study.

Assessing bone loss and gain is important in clinical decision-making, both in evaluating treatment and in following untreated patients. The aim of this study was to correlate changes in bone mineral density (BMD) at different skeletal sites during the first 5 years after menopause and determine if forearm measurements can substitute for dual-energy X-ray absorptiometry (DXA) of the spine and hip. BMD was measured at 0, 1, 2, 3, and 5 years using Hologic 1000/W and 2000 densitometers in 2,016 perimenopausal women participating in a national cohort study. This analysis comprises 1,422 women remaining in the study after 5 years without changes to their initial treatment (hormone-replacement therapy [HRT], n = 497, or none, n = 925). Despite correlated rates of change between forearm and spine (r2 = 0.11; p < 0.01), one-half of those who experienced a significant decrease in spine BMD at 5 years showed no significant fall in forearm BMD (sensitivity, 50%; specificity, 85%; kappa = 0.25). The total hip had significant better agreement with spine (sensitivity, 63%; specificity, 85%; kappa = 0.37; p < 0.01). Analysis of quartiles of change also showed significant better agreement with spine and whole body for the total hip than for the femoral neck or ultradistal (UD) forearm. In a logistic regression analysis for identification of group (HRT or control), the prediction was best for whole body (82.6%) and spine (80.9%), followed by total hip (78.5%) and forearm (74.7%). In conclusion, changes at the commonly measured sites are discordant, and DXA of the forearm is less useful than DXA of the hip or spine in determining the overall skeletal response to therapy or assessing bone loss in untreated women.

Absorptiometry, Photon↗
PubMed2000

Hormonal replacement therapy reduces forearm fracture incidence in recent postmenopausal women - results of the Danish Osteoporosis Prevention Study.

OBJECTIVES: To study the fracture reducing potential of hormonal replacement therapy (HRT) in recent postmenopausal women in a primary preventive scenario. METHODS: Prospective controlled comprehensive cohort trial: 2016 healthy women aged 45-58 years, from three to 24 months past last menstrual bleeding were recruited from a random sample of the background population. Mean age was 50. 8+/-2.8 years, and the number of person years followed was 9335.3. There were two main study arms: a randomised arm (randomised to HRT; n=502, or not; n=504) and a non-randomised arm (on HRT; n=221, or not; n=789 by own choice). First line HRT was oral sequential oestradiol/norethisterone in women with intact uterus and oral continuous oestradiol in hysterectomised women. RESULTS: After five years, a total of 156 fractures were sustained by 140 women. There were 51 forearm fractures in 51 women. By intention-to-treat analysis (n=2016), overall fracture risk was borderline statistically significantly reduced (RR=0.73, 95% CI: 0.50-1.05), and forearm fracture risk was significantly reduced (RR=0.45, 95% CI: 0.22-0.90) with HRT. Restricting the analysis to women who had adhered to their initial allocation of either HRT (n=395) or no HRT (n=977) showed a significant reduction in both the overall fracture risk (RR=0.61, 95% CI: 0.39-0.97) and the risk of forearm fractures (RR=0.24, 95% CI: 0.09-0.69). Compliance with HRT was 65% after five years. CONCLUSIONS: It is possible to reduce the number of forearm fractures and possibly the total number of fractures in recent postmenopausal women by use of HRT as primary prevention.

Age Factors↗
PubMed2000

Premenopausal smoking and bone density in 2015 perimenopausal women.

The importance of cigarette smoking in relation to bone mass remains uncertain, especially in younger women. In a recent meta-analysis including 10 studies in premenopausal women no effect was seen in this age group. We used baseline data from a large national cohort study (Danish Osteoporosis Prevention Study [DOPS]) to study the cumulated effect of pre- and perimenopausal smoking on bone mineral density (BMD) measured shortly after the cessation of cyclic bleedings. Baseline observations on 2015 recently menopausal women were available. Eight hundred thirty-two women were current smokers and 285 were exsmokers. Significant negative associations of cigarette smoking coded as current, ex-, or never smoking were seen on bone mass in the lumbar spine (P = 0.012), femoral neck (P<0.001), and total body (P<0.001). Quantitatively, the differences between current smokers and never smokers were limited to 1.6, 2.9, and 1.9%, respectively. A statistical interaction was found between smoking and fat mass, indicating that women in the highest tertile of fat mass were unaffected by cigarette smoking. Serum vitamin D levels and osteocalcin were inversely related to the number of cigarettes smoked per day (r = 0.11 and P<0.001; r = 0.17 and P = 0.04), respectively. Bone alkaline phosphatase (BALP) and urinary hydroxyproline (U-OHP) were unaffected by current smoking. The average cumulated effect of premenopausal smoking on bone is small but biologically significant. Reduced body mass in smokers explains part of the negative effect on the skeleton and a complex interaction between smoking and fat mass on the skeleton is indicated. Serum levels of 25-hydroxyvitamin D (25-OHD) and osteocalcin are lower in smokers, which may effect rate of bone loss.

Alkaline Phosphatase↗
PubMed1999

The Danish Osteoporosis Prevention Study (DOPS): project design and inclusion of 2000 normal perimenopausal women.

OBJECTIVE: In 1990 we initiated a 20 year, partly randomised study (Danish Osteoporosis Prevention Study, DOPS) in order to (a) evaluate clinical, biochemical and osteodensitometric variables as predictors of low bone mass and future osteoporotic fractures, and (b) test the hypothesis, that hormone replacement therapy (HRT) initiated shortly after menopause reduces the risk of later osteoporotic fractures. This report describes study design and baseline characteristics of the DOPS-cohort. METHODS: The study design is pragmatic, attempting to mimic the normal clinical situation. Several HRT alternatives are available according to clinical need. It was considered futile, impractical and unethical to use placebo for 20 years. Instead the study focus on hard endpoints (fractures) confirmed by independent persons (peripheral fractures) or by methods which allow investigator blinding (spinal X-rays). Statistical evaluation will focus on intention to treat analyses evaluating the decision of HRT and it's feasibility. With a compliance of 60% we will have sufficient statistical power (88%) to detect a fracture reduction of 40% in the treatments group. Clinical risk factors, current daily intakes of macronutrients, vitamins and minerals, anthropometric variables, biochemical variables (including bone markers and 25-hydroxyvitamin D), regional bone mineral density (BMD) and total body composition were assessed in all participants at entry and at various follow up intervals. RESULTS: 2016 study participants were recruited by direct mailing to a random sample of 45-58 years old women. In the randomised arm 501 were allocated to HRT and 505 to no treatment. In the non-randomised arm 219 preferred HRT and 791 preferred no treatment. Post-randomisation analysis revealed a slight but significant difference in age (50.01 versus 50.44 years) but no difference in menopausal age, prevalence of hysterectomy, educational level, BMI, serum bone alkaline phosphatase, serum osteocalcin, urine hydroxyproline or serum 25-hydroxyvitamin D. In the non-randomised arm women preferring HRT were closer to menopause, had a higher prevalence of hysterectomy, were better educated, were leaner, and had lower bone turnover than the women, who refused HRT. CONCLUSION: It is possible to include a sufficient number of perimenopausal women in a randomised 20 year study on the antifracture effect of HRT.

Body Composition↗
PubMed1999

Effect of sex hormone replacement on the insulin-like growth factor system and bone mineral: a cross-sectional and longitudinal study in 595 perimenopausal women participating in the Danish Osteoporosis Prevention Study.

This study used a cross-sectional design to investigate relationships among serum insulin-like growth factor (IGF) parameters (total serum IGF-I, IGF-II, and IGF-binding protein-3), serum estradiol, and bone mineral density (BMD) stratified for potential confounders, and a longitudinal design to investigate the effects of hormonal replacement therapy (HRT) on IGFs and BMD. Five hundred and ninety-five perimenopausal women (median age, 50.0 yr; range, 45-56 yr) participating in the Danish Osteoporosis Prevention Study were investigated in a cross-sectional study, and a randomly selected subgroup of 110 was followed after 5 yr in a longitudinal study for changes in serum IGFs and BMD of lumbar spine, femoral neck, and ultradistal forearm during (n = 46) or without HRT (n = 64). In the cross-sectional study, serum IGF-I correlated positively to distal forearm BMD and spine BMD, but not to femoral neck BMD, after stratification for age, body mass index, and other variables. In the follow-up study, HRT decreased IGF-I and IGF-II, but did not influence the age-related decline in IGF-binding protein-3 significantly. Serum alkaline phosphatase and urinary hydroxyproline/creatinine ratio both decreased during HRT, whereas BMD increased compared to control values. After adjustment for age, body mass index, treatment, and other factors, IGF-I correlated positively to changes in forearm and femoral neck BMD, but not to changes in spine BMD. We conclude that serum IGF-I was positively associated to bone mineral density. Oral HRT decreases IGF-I and IGF-II.

Bone Density↗
PubMed1998

Combined hormone replacement therapy does not protect women against the age-related decline in endothelium-dependent vasomotor function.

BACKGROUND: Improvement in endothelial function may be an important mechanism by which estrogen replacement therapy protects postmenopausal women against coronary artery disease. However, combined hormone replacement therapy is more frequently used owing to the risk of uterine cancer with estrogen-only therapy. Concurrent progesterone treatment may attenuate the beneficial effects of estrogens not only on the lipid profile but also on the endothelium. METHODS AND RESULTS: We studied endothelial vasomotor function in 100 healthy postmenopausal women aged 53.3+/-2.9 years randomized to either combined hormone replacement therapy (n=46) or no substitution (n=54) 2.9+/-0.5 years earlier. In addition, 30 healthy premenopausal women aged 30.3+/-4.2 years were studied. With external ultrasound, brachial artery diameter was measured at rest, during reactive hyperemia (with increased flow causing endothelium-dependent dilation), and after sublingual nitroglycerin (causing endothelium-independent dilation). Compared with premenopausal women, flow-mediated dilation was significantly reduced in both postmenopausal groups. In the postmenopausal women, total cholesterol was lower in the treated women (5.66+/-0.83 versus 6.13+/-0.92 mmol/L; P=.025), whereas HDL cholesterol was similar (1.91+/-0.53 versus 1.85+/-0.46 mmol/L; P=NS). Dilation to flow and to nitroglycerin was similar in the two postmenopausal groups (flow: 2.5+/-2.9% versus 2.2+/-2.2%, P=NS; nitrate: 18.7+/-5.9% versus 17.2+/-6.2%, P=NS). CONCLUSIONS: Long-term combined oral hormone replacement therapy is without beneficial effects on endothelial vasomotor function in healthy postmenopausal women. This supports the view that progesterone may attenuate the beneficial effects of unopposed estrogen replacement.

Adult↗