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Biomedical subjects

J Heikkinen

Publications and source records attributed to J Heikkinen.

At least 19 recordsLinked to original sources

Ultrasonic depolymerization of aqueous polyvinyl alcohol.

Ultrasonication has proved to be a highly advantageous method for depolymerizing macromolecules because it reduces their molecular weight simply by splitting the most susceptible chemical bond without causing any changes in the chemical nature of the polymer. Most of the effects involved in controlling molecular weight can be attributed to the large shear gradients and shock waves generated around collapsing cavitation bubbles. In general, for any polymer degradation process to become acceptable to industry, it is necessary to be able to specify the sonication conditions which lead to a particular relative molar mass distribution. This necessitates the identification of the appropriate irradiation power, temperature, concentration and irradiation time. According to the results of this study the reactors constructed worked well in depolymerization and it was possible to degrade aqueous polyvinyl alcohol (PVA) polymer with ultrasound. The most extensive degradation took place at the lowest frequency used in this study, i.e. 23 kHz, when the input power was above the cavitation threshold and at the lowest test concentration of PVA, i.e. 1% (w/w). Thus this study confirms the general assumption that the shear forces generated by the rapid motion of the solvent following cavitational collapse are responsible for the breakage of the chemical bonds within the polymer. The effect of polymer concentration can be interpreted in terms of the increase in viscosity with concentration, causing the molecules to become less mobile in solution and the velocity gradients around the collapsing bubbles to therefore become smaller.

Journal Article↗

Effects of peroral and transdermal oestrogen replacement therapy on glucose and insulin metabolism.

OBJECTIVE: Conflicting data have been reported previously on the effects of oestrogen replacement therapy on glucose tolerance, and the effects on glycosylated haemoglobin GHbA(1c) have been studied only among diabetics. The objective of this study was to evaluate the effects on glucose and insulin metabolism among nondiabetic women and to compare the outcomes of peroral and transdermal modes of administration. DESIGN: The effects of peroral oestradiol valerate 2 mg/day with placebo gel were compared to those of transdermal 17 beta-oestradiol gel (1 mg oestradiol/day) and placebo tablets in a randomised, double-blind, double-dummy study for six months. PATIENTS: Seventy-nine hysterectomised, nondiabetic postmenopausal women, 39 women in the peroral oestrogen group and 40 in the gel group. MEASUREMENTS: Oral glucose tolerance tests (OGTT) with blood glucose, serum C-peptide and insulin determinations were performed. GHbA(1c), IGF-I and IGFBP-1 were measured at baseline and after six months of therapy. In addition, insulin sensitivity and insulin secretion indices were obtained from OGTT. RESULTS: A small significant reduction in the GHbA(1c) concentration was observed during both peroral (P < 0.05) and transdermal oestrogen therapy (P < 0.05). However, no effect on insulin sensitivity was observed. The response to a standard 75 g oral glucose load was similar in the study groups. Compared with the baseline values, the area under the curve for C-peptide decreased by 8% both in the peroral group (P < 0.05) and in the gel group (P < 0.01). The fasting and postchallenge glucose and insulin levels or insulin release indices were not significantly altered. Peroral oestrogen decreased IGF-I and increased IGFBP-1, but these findings were not associated with the changes in glucose metabolism. CONCLUSIONS: Neither peroral nor transdermal oestradiol replacement therapy seemed to induce any negative effects on glucose metabolism over a time period of 6 months.

Administration, Cutaneous↗

Cytokine levels in midtrimester amniotic fluid in normal pregnancy and in the prediction of pre-eclampsia.

Midtrimester amniotic fluid cytokines may reflect the function of the maternal immune system in the maternal-fetal interface and thus be predictive of pre-eclampsia. We determined the concentrations of interleukin (IL)-6, IL-8, IL-10, IL-11, IL-12, IL-15, tumour necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta in amniotic fluid at 14-16 weeks of gestation from women with normal pregnancies and from those who subsequently developed severe pre-eclampsia. The concentrations of the cytokines in amniotic fluid did not significantly differ between patients and normal controls. The median concentration of IL-6 was 950 pg/ml in normal pregnant women and 578 pg/ml in the patient group. The median concentration of IL-8 was 606 pg/ml in normal controls and 294 pg/ml in the patient group. The levels of IL-6, IL-8 and TGF-beta correlated positively with each other. TNF-alpha concentrations were low and similar in both groups. IL-10 and IL-12 were detected at very low levels in 37 and 7% of the samples, respectively. No difference was found in IL-15 concentrations between the groups. IL-11 was found only at low levels in both groups. Although none of the cytokines measured was predictive of pre-eclampsia, this study provides information of cytokines in amniotic fluid during the period when the spiral arteries are remodelled.

Adult↗

Lysyl hydroxylase 3 is a multifunctional protein possessing collagen glucosyltransferase activity.

Lysyl hydroxylase (EC ) and glucosyltransferase (EC ) are enzymes involved in post-translational modifications during collagen biosynthesis. We reveal in this paper that the protein produced by the cDNA for human lysyl hydroxylase isoform 3 (LH3) has both lysyl hydroxylase and glucosyltransferase (GGT) activities. The other known lysyl hydroxylase isoforms, LH1, LH2a, and LH2b, have no GGT activity. Furthermore, antibodies recognizing the amino acid sequence of human LH3 and those against a highly purified chicken GGT partially inhibited the GGT activity. Similarly, a partial inhibition was observed when these antibodies were tested against GGT extracted from human skin fibroblasts. In vitro mutagenesis experiments demonstrate that the amino acids involved in the GGT active site differ from those required for LH3 activity.

Alternative Splicing↗

Mutational analysis of the lysyl hydroxylase 1 gene (PLOD) in six unrelated patients with Ehlers-Danlos syndrome type VI: prenatal exclusion of this disorder in one family.

Screening of full length cDNAs for lysyl hydroxylase 1 (LH1; also PLOD) amplified from dermal fibroblasts from six unrelated patients with the autosomal recessive disorder Ehlers-Danlos syndrome type VI (EDS VI) has shown them to be both homozygous and compound heterozygous for mutations in the gene. These mutations, which were verified in genomic DNA, result in a deficiency of LH activity (<25% of normal) in the probands, who are clinically characterized by kyphoscoliosis and extensibility of skin and joints. Four novel mutations identified in these patients include a mutation of an inserted C in one homozygous patient (1702insC) and three point mutations resulting in premature termination codons (PTCs): Y142X, Q327X (in two patients), and R670X. In the family with the R670X mutation we have prenatally excluded EDS VI by the characterization of mutations and their allelic inheritance. We have identified two previously reported mutations in the new patients: a seven exon duplication (in two patients) and a point mutation that codes for a PTC, Y511X, (in two patients). Genotype analysis indicated that the Y511X mutation may originate from a common ancestral gene. Several alternative splicing pathways have been identified which bypass the PTCs and can also restore the open reading frame.

Adult↗

Determinants of bone mass and bone geometry in adolescent and young adult women.

Bone mass and bone geometry are considered to have independent effects on bone strength. The purpose of this study was to obtain data on bone mass and geometry in young female populations and how they are influenced by body size and lifestyle factors. In a cross-sectional, observational study in six European countries, 1116 healthy Caucasian girls aged 11-15 and 526 women aged 20-23 participated. Their radius was scanned at the ultradistal site and at a site approximately 30% of the radius length from the distal end with dual energy X-ray absorptiometry (DXA). The following parameters were assessed from the scans: bone mineral content (BMC), bone mineral density (BMD), cortical wall thickness (CWT), middistal diameter (D), cortical index (CI = 2CWT/D), and the Breaking Bending Resistance Index (BBRI = (D4 - [D-CWT]4)/D). Calcium intake was assessed by 3-day food records and physical activity by questionnaire. Body size parameters were measured by anthropometry. All parameters showed an increasing trend with pubertal stage and age, except for physical activity and calcium intake. BMC and BMD were relatively more dependent on body weight and age at menarche, whereas variation in D and the mechanical index BBRI was better explained by differences in height and grip strength. CI and CWT were relatively independent of variation in body size, whereas BMC and BBRI especially were explained for a substantial proportion (25-33% in the young adults) by body size parameters. Dietary intake of calcium and level of physical activity seem to contribute little to variation in bone parameters.

Adolescent↗

Long-term continuous combined hormone replacement therapy in the prevention of postmenopausal bone loss: a comparison of high- and low-dose estrogen-progestin regimens.

We studied the effect of four continuous combined estradiol valerate (E2V) and medroxyprogesterone acetate (MPA) dose combinations in six treatment groups (n = 70 per group) receiving regimens containing 1 mg or 2 mg E2V combined to 2.5 mg or 5 mg MPA, on bone mineral density (BMD) and endometrium in 419 healthy postmenopausal women over 4 treatment years. In two groups the 1 mg dose of E2V was increased to 2 mg after the first 6 months, while the MPA doses remained constant (2.5 mg or 5 mg). The remaining four groups received 1 E2V + 2.5 mg MPA, 1 mg E2V + 5 mg MPA, 2 mg E2V + 2.5 mg MPA, or 2 mg E2V + 5 mg MPA throughout the study. BMD at the spine and hip was measured by dual-energy X-ray absorptiometry and endometrial biopsy samples were taken at 6, 12, 24, 36 and 48 month follow-ups. Combinations containing the low dose of 1 mg of E2V (with 2.5 mg or 5 mg MPA) resulted in a mean BMD increase of 6.2% at the spine and 2.9% at the femoral neck after 4 years of treatment. With 2 mg E2V the corresponding increases were 7.4% and 2.9%, respectively. The largest increases in BMD were seen in women for whom the E2V dose was doubled after the initial 6 months of treatment: 8.9% at the spine and 4.2% in the femoral neck. Both MPA doses (2.5 mg and 5 mg) effectively prevented estrogen-induced stimulation of the endometrium. No endometrial hyperplasia was observed in any of the treatment groups. Lower-dose combinations of continuous combined estrogen-progestin regimens are effective in increasing and maintaining BMD and provide a good endometrial safety profile for the long-term prevention of osteoporosis in postmenopausal women.

Aged↗

Insulin-like growth factor binding protein-1 (IGFBP-1) and IGF-I during oral and transdermal estrogen replacement therapy: relation to lipoprotein(a) levels.

Low levels of insulin-like growth factor binding protein-1 (IGFBP-1) have recently been associated with several risk factors for cardiovascular disease. The effects of estrogen replacement therapy (ERT) on plasma IGFBP-1 levels are, however, unclear. A double-blind, placebo-controlled study for 6 months was conducted in 73 hysterectomized postmenopausal women randomized into two groups: oral estradiol (E2) valerate, 2 mg/day (n = 35) and transdermal E2 gel, 1 mg/day (n=38). Plasma IGFBP-1, insulin-like growth factor-I (IGF-I) and lipoprotein(a) (Lp(a)) were determined at baseline, 3 and 6 months. The groups were similar for age and BMI. The baseline levels of estrone (E1), E2, IGFBP-1, IGF-I and Lp(a) did not differ between the groups. During treatment, serum estradiol concentrations increased in both groups. During oral ERT, IGFBP-1 levels increased by 104% (P<0.001), whereas IGF-I levels decreased by 13% (mean, P<0.05). IGF-I and IGFBP-1 levels remained unchanged in the transdermal group. Lp(a) levels decreased by 23% (median, P<0.001) in the oral group, but were unaffected by transdermal therapy. The change in IGFBP-1 concentrations during oral ERT showed an inverse correlation to that in Lp(a) (r = -0.40, P<0.05, Spearman correlation). In conclusion, oral ERT seems to enhance plasma levels of IGFBP-1, which may be one reason for the reduced Lp(a) levels.

Administration, Cutaneous↗

Regulation of plasma low density lipoprotein levels in postmenopausal women.

To study the regulation of plasma low density lipoprotein (LDL) cholesterol in postmenopausal women (n = 79), fasting plasma lipids and lipoproteins, the fractional catabolic rate (FCR) and production rate for LDL apolipoprotein B (apo B), cholesterol absorption, apolipoprotein E phenotype and polymorphisms of the apo B and 7alpha-hydroxylase genes were determined. The level of LDL cholesterol was related to FCR (r= -0.757, P < 0.001) and the production (r= 0.531, P < 0.001) of LDL apo B and body mass index (r = 0.265, P <0.05). In contrast, cholesterol absorption efficiency, apolipoprotein E phenotype, EcoRI and XbaI polymorphisms of the apo B gene and the polymorphism of 7alpha-hydroxylase gene were found to have no significance for the regulation of LDL cholesterol concentration in these postmenopausal women.

Apolipoproteins E↗

A nonsense codon of exon 14 reduces lysyl hydroxylase mRNA and leads to aberrant RNA splicing in a patient with Ehlers-Danlos syndrome type VI.

Ehlers-Danlos syndrome type VI (EDSVI) is an autosomal recessively inherited connective tissue disease, characterized by kyphoscoliosis, muscular hypotonia and ocular manifestations. The cause of the syndrome is a deficiency in the activity of lysyl hydroxylase (LH), one of the enzymes involved in the post-translational modification of collagens. We describe here an unusual compound heterozygote British patient with EDSVI. Our investigations indicate that a maternally inherited nonsense mutation (Y511X) in exon 14 of the LH gene (PLOD1) results in a reduction of the mRNA level as well as a skipping of exon 14 sequences in the mRNA that produces a protein shortened by 38 amino acids. The transcription of the other allele of the LH gene is considerably reduced from the normal for reasons that are not yet known. As a consequence, the LH activity of the skin fibroblasts of the patient is markedly reduced.

Blotting, Southern↗

Mechanisms regulating LDL metabolism in subjects on peroral and transdermal estrogen replacement therapy.

To study the mechanisms of low density lipoprotein (LDL) cholesterol lowering by peroral and transdermal estrogen replacement therapy (ERT), 79 hysterectomized postmenopausal women aged 48 to 62 years were randomized in a double-blind double-dummy trial to receive either peroral estradiol valerate (2 mg/d) or transdermal estradiol gel (1 mg/d) for 6 months. Plasma LDL cholesterol decreased from 4. 19+/-0.83 (mean+/-SD) to 3.39+/-0.78 mmol/L (P<0.001) in the peroral group and from 4.11+/-0.86 to 3.72+/-0.78 mmol/L (P<0.001) in the transdermal estrogen group. Peroral estrogen did, but transdermal treatment did not, enhance the fractional catabolic rate (FCR) and production of LDL apolipoprotein B (apoB). However, the decrease of LDL cholesterol was related to an increase in FCR for LDL apoB on both peroral and transdermal ERT (r=-0.645, P<0.001 and r=-0.627, P<0.001, respectively). These changes were associated with changes in the serum estrogen level. Both therapies reduced absorption of dietary cholesterol by 6% to 10% (P<0.05). The effects of estrogen were not modified by the polymorphisms of apoE and apoB or cholesterol 7alpha-hydroxylase. In conclusion, the ERT-induced LDL cholesterol-lowering effect is related to changes in estrogen level, which presumably enhance LDL receptor activity, which is manifested as an increase in FCR for LDL apoB. The small decrease in the absorption efficiency of dietary cholesterol does not seem to contribute largely to the cholesterol lowering on either transdermal or peroral ERT.

Administration, Cutaneous↗

A null-mutated lysyl hydroxylase gene in a compound heterozygote British patient with Ehlers-Danlos syndrome type VI.

A British patient with EDS VI had two novel null mutations in the lysyl hydroxylase gene, one nucleotide deletion in the acceptor splice site of intron 4 in one allele, and an insertion of a C nucleotide in exon 2 of the other allele. The abnormal alleles lead to a markedly decreased lysyl hydroxylase mRNA levels, the finding making the affected cells different from the normal cells. In addition to the mutation analysis, we have revealed many exon-deleted splicing variants for lysyl hydroxylase mRNA which were first discovered in the affected cells, but tracks of similarly spliced mRNA species are also found in the cytoplasm of normal human skin fibroblasts. The data suggest that the splicing machinery of the cell is leaky generating differently spliced transcripts in the cell but only in a small amounts.

Alternative Splicing↗

Quality of myocardial perfusion single-photon emission tomography imaging: multicentre evaluation with a cardiac phantom.

The aim of the study was to evaluate quality of myocardial perfusion single-photon emission tomography (SPET) imaging in Finnish hospitals. Nineteen nuclear medicine departments participated in the study. A myocardial phantom simulating clinical stress and rest conditions was filled with routinely used isotope solution (technetium-99m or thallium-201). The cardiac insert included three reversible defects (simulating ischaemia): 30x30x14 mm(3) septal (90% recovery at rest), 30x20x14 mm(3) posterobasal (full recovery) and 20x20x14 mm(3) lateral (full recovery). There were two fixed defects (simulating infarct): 30x20x14 mm(3) postero-apical and 10x10x6 mm(3) apical. The phantom was imaged and interpreted as a myocardial perfusion patient. Reconstruction, printout and reporting were performed according to the clinical routine of each centre. Three nuclear medicine specialists anonymously evaluated the quality of the image sets. The visual scores of the experts were ranked from 1 to 5. Additionally, points from 0 to 8 were given to research reports according to how well perfusion defects were detected. Quantitative points were calculated by comparing background-subtracted and -normalized counts from 12 regions of interest between stress and rest images. Results for technetium studies (12 departments) were better than those for thallium (7 departments). The average visual scores of the experts were 3.7+/-0. 9 for all image sets, 3.2+/-0.5 for thallium users and 3.9+/-0.6 for technetium users (P=0.003). Five laboratories received a low score which, according to the specialists, is barely sufficient for limited clinical use. Average points for the reports were 5.6+/-2.1, 4.9+/-1.5 and 6.5+/-1.7 (P=0.051), and for the quantitation 8.2+/-1. 0, 7.9+/-0.4 and 8.4+/-1.1 (P=0.185), respectively. Seven out of 22 interpreters did not detect the lateral 20x20x14 mm(3) defect; five of them used thallium. This study demonstrated the heterogeneity of myocardial perfusion SPET in Finland. The participating laboratories used a wide scale of methods and, sometimes, inappropriate imaging protocols. The need for quality assurance in nuclear cardiology, correct use of SPET instrumentation and objective comparison of clinical studies is evident. The method described is suitable for external quality assurance and quality improvement of myocardial SPET imaging, and is recommended for regular use in nuclear medicine.

Algorithms↗

Calcium intake is weakly but consistently negatively associated with iron status in girls and women in six European countries.

Several studies indicate that intake of calcium can inhibit iron absorption especially when taken simultaneously. In the CALEUR study, a cross-sectional study among girls (mean 13.5 y) and young women (mean 22.0 y) in six European countries, the association between calcium intake and iron status was studied. In 1,080 girls and 524 women, detailed information on calcium intake was collected by means of a 3-d food record, and serum ferritin, serum iron, serum transferrin and transferrin saturation were measured as indicators of iron status. The mean levels of serum iron, ferritin and transferrin were 15.8 +/- 6.1 mmol/L, 34.5 +/- 19.1 microg/L and 3. 47 +/- 0.47 g/L, respectively, in girls and 16.9 +/- 7.5 mmol/L, 40. 2 +/- 30.5 and microg/L, 3.59 +/- 0.60 g/L, respectively, in women. A consistent inverse association between calcium intake and serum ferritin was found, after adjusting the linear regression model for iron intake, age, menarche, protein, tea and vitamin C intake and country, irrespective of whether calcium was ingested simultaneously with iron. The adjusted overall regression coefficients for girls and women were -0.57 +/- 0.20 and -1.36 +/- 0.46 per 100 mg/d increase in calcium intake, respectively. Only in girls, transferrin saturation as a measure for short-term iron status was inversely associated with calcium intake (adjusted overall coefficient -0.18 +/- 0.08). However, analysis per country separately showed no consistency. We conclude that dietary calcium intake is weakly inversely associated with blood iron status, irrespective of whether calcium was ingested simultaneously with iron.

Adolescent↗

Modeling a Poisson forest in variable elevations: a nonparametric Bayesian approach.

A nonparametric Bayesian formulation is given to the problem of modeling nonhomogeneous spatial point patterns influenced by concomitant variables. Only incomplete information on the concomitant variables is assumed, consisting of a relatively small number of point measurements. Residual variation, caused by other unmeasured influential factors, is modeled in terms of a spatially varying baseline intensity function. A Markov chain Monte Carlo scheme is proposed for the simultaneous nonparametric estimation of each unknown function in the model. The suggested method is illustrated by reanalysing a data set in Rathbun (1996, Biometrics 52, 226-242), and the estimated models are compared with those obtained by Rathbun.

Altitude↗

Dietary calcium and bone density in adolescent girls and young women in Europe.

The objective of this study was to investigate the association between dietary calcium intake and radial bone density among young women, over the whole range of intake and at different levels of calcium intake. The study design was a cross-sectional, observational multicenter investigation in six European countries. One thousand one hundred and sixteen healthy Caucasian girls aged 11-15 years and 526 women aged 20-23 years participated, after having been selected from larger population samples to represent a large range in calcium intake. Bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry at the ultradistal and middistal radius. Calcium intake was assessed with 3-day food records. Other potential determinants of BMD were measured by anthropometry or questionnaires. Mean calcium intake among the girls varied between 609 mg/day in Italy and 1267 mg/day in Finland; intakes for women were in a similar range. After adjustment for height, weight, and age at menarche for the women, and adjustment for age, height, weight, Tanner stage, and bone area for the girls, radial BMD at both sites did not significantly vary among quartiles of calcium intakes for both age groups. In multivariate linear regression, calcium was weakly positively associated with BMD at both sites in the girls (per 100 mg of calcium: beta = 0.57 mg/cm2, p = 0.03 for middistal BMD and beta = 0.56 mg/cm2, p = 0.01 for ultradistal BMD). For middistal BMD, the association was observed predominantly in pre-menarcheal girls. The associations were no longer statistically significant after full adjustment for all determinants of BMD, except again in pre-menarcheal girls. Radial BMD in the women was not associated with calcium intake, except after full adjustment for determinants of BMD, when ultradistal BMD became inversely associated with calcium intake (per 100 mg beta = -1.02, p = 0.03); this finding was due to results in one of the countries and not found in other countries. There was no evidence for a different relation between calcium and BMD at different levels of intake; although there was a positive association at calcium intake levels < 600 mg/day, the interaction was not significant and there was no consistent trend over intake categories. These results do not support the hypothesis that dietary calcium is a determinant of peak BMD in European women, for a wide range of intake. This study does not provide evidence that Recommended Dietary Allowances for calcium should be increased.

Adolescent↗

Quality of brain perfusion single-photon emission tomography images: multicentre evaluation using an anatomically accurate three-dimensional phantom.

The aim of the study was to evaluate the quality of routine brain perfusion single-photon emission tomography (SPET) images in Finnish nuclear medicine laboratories. Twelve laboratories participated in the study. A three-dimensional high resolution brain phantom (Data Spectrum's 3D Hoffman Brain Phantom) was filled with a well-mixed solution of technetium-99m (110 MBq), water and detergent. Acquisition, reconstruction and printing were performed according to the clinical routine in each centre. Three nuclear medicine specialists blindly evaluated all image sets. The results were ranked from 1 to 5 (poor quality-high quality). Also a SPET performance phantom (Nuclear Associates' PET/SPECT Performance Phantom PS 101) was filled with the same radioactivity concentration as the brain phantom. The parameters for the acquisition, the reconstruction and the printing were exactly the same as with the brain phantom. The number of detected "hot" (from 0 to 8) and "cold" lesions (from 0 to 7) was visually evaluated from hard copies. Resolution and contrast were quantified from digital images. Average score for brain phantom images was 2.7 +/- 0.8 (range 1.5-4.5). The average diameter of the "hot" cylinders detected was 16 mm (range 9.2-20.0 mm) and that of the "cold" cylinders detected, 11 mm (5.9-14.3 mm) according to visual evaluation. Quantification of digital images showed that the hard copy was one reason for low-quality images. The quality of the hard copies was good only in four laboratories and was amazingly low in the others when comparing it with the actual structure of the brain phantom. The described quantification method is suitable for optimizing resolution and contrast detectability of hard copies. This study revealed the urgent need for external quality assurance of clinical brain perfusion SPET images.

Brain↗

HRT and exercise: effects on bone density, muscle strength and lipid metabolism. A placebo controlled 2-year prospective trial on two estrogen-progestin regimens in healthy postmenopausal women.

OBJECTIVES: To evaluate the effect of 1- or 3-monthly sequential combinations of estradiol valerate (E2V) and medroxyprogesterone acetate (MPA) on menopausal symptoms, bone density, muscle strength and lipid metabolism in postmenopausal women. METHODS: Changes in bone mineral density (BMD), isometric muscle strength, serum lipids and climacteric symptoms were evaluated in 78 women, 49-55 years of age, with a spontaneous menopause 0.5-3 years earlier. Treatment group I received 2 mg E2V tablets for 11 days, followed by 2 mg E2V + 10 mg MPA for 10 days and placebo for an additional 7 days; treatment group II received 2 mg E2V for 70 days, 2 mg E2V + 20 mg MPA for 14 days, and placebo for 7 days. The placebo group received placebo continuously for 24 months. Each group was further randomised to exercise and non-exercise subgroups. RESULTS: Both hormone regimens significantly reduced menopausal symptoms, and prevented equally well the decrease of BMD both in the lumbar spine and proximal femur. A positive effect of exercise on BMD was observed in the placebo group. No synergistic effect of exercise and estrogen on BMD could be shown. Both hormone regimens increased the isometric strength of back extensor muscles. Serum total and LDL cholesterol decreased during the first year with both estrogen regimens. CONCLUSIONS: Estrogen-progestin regimens were equally effective in the control of menopausal symptoms and preventing bone loss, increasing muscle strength and lowering serum cholesterol.

Bone Density↗