Biomedical subjects

S Saarikoski

Publications and source records attributed to S Saarikoski.

At least 37 records · Page 2Linked to original sources

PubMed2000

Does apolipoprotein E genotype relate to BMD and bone markers in postmenopausal women?

OBJECTIVES: Bone mineral density (BMD) and development of osteoporosis are partly determined by genetic factors. The associations between one of suggested candidate, apolipoprotein E (apo E) genotype to bone mineral density (BMD) and bone biochemical markers was studied in 464 subjects recruited from a population-based group of early postmenopausal women (n = 13100). Additionally, the influence of apo E genotype on BMD changes during a 5-year follow-up with or without hormone replacement therapy (HRT) was investigated. METHODS: Participants were randomized into two treatment groups: HRT group: Sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate with or without vitamin D3, 100-300 IU/day + calcium lactate, 500 mg/day (n = 232), and the non-HRT group: Calcium lactate, 500 mg/day alone or in combination with vitamin D3, 100-300 IU/day (n = 232). BMD was measured from the lumbar spine and proximal femur at baseline and after 5 years of treatment (n = 352). In a subgroup (n = 59), the serum concentrations of bone biochemical markers (intact osteocalcin (OC), bone-specific alkaline phosphatase (BAP) and type I collagen carboxy-terminal telopeptide (ICTP)) were measured at baseline and after 1 year of follow-up. RESULTS: At baseline, the BMDs were similar between the five apo E genotype groups (2/3, 2/4, 3/3, 3/4, 4/4). No significant differences in lumbar or femoral neck BMDs of women with the apo E4 allele were found compared with those without it. There was a statistically significant difference in 5-year BMD changes between the HRT and non-HRT groups. After 5 years, the BMD of the femoral neck had remained constant and the mean lumbar spine BMD had increased by 1.5% in the HRT group, whereas both BMDs had decreased by 4-5% in the non-HRT group. However, the apo E genotype did not modify the changes in BMD in either group. Additionally, the baseline concentrations of bone metabolic markers and their 1-year changes showed no genotype-related associations. CONCLUSIONS: The results of our population-based study indicate that apo E genotype does not modify lumbar or femoral neck BMDs or serum bone biochemical markers or their response to HRT in early postmenopausal Caucasian women.

Apolipoproteins E↗

PubMed2000

Accumulation of cadmium, zinc, and copper in maternal blood and developmental placental tissue: differences between Finland, Estonia, and St. Petersburg.

Cadmium, zinc, and copper from placental tissue and blood samples at the first trimester (n = 64) and at term (n = 152) were analyzed; the welfare of newborns and placental 7-ethoxycoumarin O-deethylase (ECOD) activities in vitro were determined. The study material was collected from Finland, Estonia, and Russia. The results demonstrate that Cd starts to accumulate in the placenta during the first trimester and that Zn and Cu contents were significantly higher at the first trimester than at term. Among nonsmokers a negative correlation was found between placental Cu content and birth weight of neonates. Among smokers a positive correlation between placental Zn content and birth weight and ECOD activity was found. The birth weights correlated inversely with the length of time the mothers smoked. The highest Cd concentrations were detected in the samples collected from St. Petersburg. The data demonstrate an inverse accumulation of Zn and Cd throughout the pregnancy in the placenta and maternal blood samples. Zn may act as a positive marker or even an enzymatic enhancement for the human placental vital functions. Smoking, parity, age, and especially the place of residence affect the Cd, Zn, and Cu contents and ratios in placenta and mother's blood.

7-Alkoxycoumarin O-Dealkylase↗

PubMed2000

Identification of early postmenopausal women with no bone response to HRT: results of a five-year clinical trial.

Hormone replacement therapy (HRT) prevents postmenopausal bone loss and fractures. However, the occurrence of women with no bone response to HRT has not been widely examined. We identified the densitometric nonresponders to long-term HRT and investigated some characteristics and biochemical variables as possible predictors of densitometric nonresponse in postmenopausal women. The study population was a subsample of the Kuopio Osteoporosis Study (n = 14,220). A total of 464 early postmenopausal women were randomized into four treatment groups: (1) HRT (sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate); (2) vitamin D3; (3) HRT + Vitamin D3 combined; and (4) placebo. In this study, the data from HRT and placebo groups were analyzed. Lumbar (L2-4) and femoral neck bone mineral density (BMD) were determined by dual-energy X-ray absorptiometry (DXA) at baseline and after 5 years of treatment. A densitometric nonresponder was defined as a woman whose 5-year BMD change was similar to the mean BMD change (+95% CI) of the placebo group or worse. Altogether, 74 women in the HRT group and 104 women in the placebo group complied with the treatment. According to spinal BMD analysis, 11% of the women were classified as densitometric nonresponders; the corresponding proportion for femoral BMD analysis was 26%. Both smoking (p = 0.003) and low body weight (p = 0.028) were significant risk factors for densitometric nonresponse to HRT. After 6 months of treatment the densitometric nonresponders (hip) had a significantly higher mean serum follicle stimulating hormone (FSH) level (p = 0.038) and lower increases in serum estradiol levels (p = 0.006) than the densitometric responders. The mean changes in serum FSH and alkaline phosphatase levels were significantly lower among the densitometric nonresponders (spine) than responders (p = 0.043 and 0.017, respectively). In conclusion, this prospective study shows that especially current smokers and women with low body weight are at increased risk of poor bone response to HRT. Repeated serum FSH, estradiol and alkaline phosphatase measurements during the first months of long-term HRT may be helpful in identifying the women with no bone response to HRT.

Alkaline Phosphatase↗

PubMed2000

Risk factors for perimenopausal fractures: a prospective study.

This prospective study was aimed at determining the risk factors for the development of fractures in perimenopausal women. The study group (n = 3068) was comprised of a stratified population sample of women aged between 47 and 56 years. During the follow-up period of 3.6 years, 257 (8.4%) of the women sustained a total of 295 fractures. After adjustment for covariates, the relative risk (RR) of sustaining a fracture was found to be 1.4 [95% confidence interval (CI) 1.2-1.6] for a 1 standard deviation (SD) decrease in the spinal and femoral neck bone mineral density (BMD). Women with a previous fracture history were found to have an increased risk of fracture [RR 1.7 (95% CI 1.3-2.2)] and those reporting three or more chronic illnesses exhibited a RR of 1.4 (95% CI 1.0-1.9). Women not using hormone replacement therapy (HRT) had a RR of 1.5 (95% CI 1.1-2.2) for all fracture types. When osteoporotic fractures (vertebral, hip, proximal humerus and wrist fractures; n = 98) were used as an endpoint, the independent risk factors were found to be a low BMD (RR for a 1 SD decrease in both spinal and femoral neck BMD was 1.6, 95% CI 1.3-2.0), a previous fracture history (RR 1.9, 95% CI 1.3-2.9) and nonuse of HRT (RR 2.2, 95% CI 1.3-4.0). The independent risk factors for all other fractures (n = 158) were a low BMD (RR for a 1 SD decrease in the spinal BMD was 1.4, 95% CI 1.2-1.6 and in the femoral neck BMD was 1.3, 95% CI 1.1-1.5), a previous fracture history (RR 1.6, 95% CI 1.1-2.2), smoking (RR 1.8, 95% CI 1.1-2.7) and having had three or more chronic illnesses (RR 1.6, 95% CI 1.1-2.2). Weight, height, age, menopausal status, maternal hip fracture, use of alcohol, coffee consumption or dietary calcium intake were not independently associated with the development of any particular type of fracture. We conclude that the independent risk factors for perimenopausal fractures are a low bone density, previous fracture history, nonuse of HRT, having had three or more chronic illnesses and smoking, the gradient of risk being similar for spinal and femoral neck BMD measurements in the perimenopausal population. The risk factors are slightly different for perimenopausal osteoporotic than for other types of fractures.

Analysis of Variance↗

PubMed2000

Risk factors for perimenopausal distal forearm fracture.

This prospective population-based cohort study investigated factors predicting distal forearm fracture (DFF) in perimenopausal women. The study population consisted of 11,798 women from the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) Study in Finland. Mean baseline age of these women was 52.3 (SD 2.9) years (range 47-56 years) and 68% were postmenopausal. Three hundred and sixty-eight women (3.1%) had a validated DFF during the 5-year follow-up. Previous wrist fracture, postmenopausal state, age and nulliparity were independent predictors of DFF, while hormone replacement therapy (HRT), dairy calcium and overweight protected against it in multivariate Cox regression analysis: previous wrist fracture increased the DFF risk by 158% (p < 0.0001), menopause by 69% (p = 0.002) and age by 6% per year (p = 0.010), whereas the continuous use of HRT decreased the risk by 63% (p = 0.0001), the use of dairy calcium at 1000-1499 mg/day (vs < 500 mg/day) by 39% (p = 0.004), overweight (BMI > 25 kg/m2) by 36% (p = 0.0002) and parity by 29% (p = 0.031). Combining dichotomous low weight, low use of calcium, non-use of HRT and previous wrist fracture into a risk score gave a dose-response effect by score level: the presence (vs absence) of all four risk factors resulted in a 12-fold DFF risk. Nevertheless, the sensitivity and specificity of the score for detecting DFF remained low. It was concluded that HRT, high nutritional calcium intake and overweight protect against but a history of wrist fracture predisposes to perimenopausal distal forearm fracture. A simple risk factor inquiry would help to identify perimenopausal women at high risk of distal forearm fracture.

Cohort Studies↗

PubMed2000

Variants of the long control region of human papillomavirus type 16.

Expression of the human papillomavirus (HPV) E6 and E7 oncogenes is regulated on the transcriptional level by specific protein-binding sites contained in the viral long control region (LCR). Sequence changes within the LCR region may have an impact on the transcription of viral oncogenes, possibly resulting in differences in the oncogenic potential of the virus. The present study was designed to determine the sequence variability of the LCR of HPV 16 and to assess whether certain LCR variants do correlate with the clinical outcome of the disease of the uterine cervix. The entire LCR segment of HPV 16 was analysed from 37 cervical biopsy specimens derived from 28 women included in the Kuopio long-term prospective follow-up study. The LCR sequence was identical with the reference sequence in six HPV 16 isolates. Overall, 14 different HPV 16 LCR variants were identified. One of the variants showed sequence variation typical of the Asian-American variant lineage of HPV 16, and all the other variants appeared to belong to the European variant group. The European variants exhibited low genetic diversity, and only five of these LCR variants contained nucleotide changes involving known or proposed binding sites for transcription factors. The variants with changes at nucleotide positions 7193 and 7521 was the most prevalent, accounting for almost 37% of infections. This variant (7193; 7521) has been previously demonstrated to have similar transcriptional activity compared with the reference isolate by Veress and colleagues J Gen Virol 1999, 80, 1035-1043. The reference isolate, variant (7193; 7521) and variants with changes within transcription factor binding sites accounted for most of the infections, and no significant differences were found in the comparison of the distribution of these different LCR isolates in cases where the disease showed progression to severe cervical intraepithelial neoplasia (CIN) or carcinoma in situ (CIS). Notably, both the reference isolate and variant (7193; 7521) were also closely associated with infections showing more aggressive behaviour. According to the present findings, in European HPV 16 isolates, intratype genetic variation of the LCR region does not seem to be commonly responsible for differences in the pathogenicity of the virus and thereby for a risk of progressive infections.

DNA, Viral↗

PubMed2000

Expression of transcription factor AP-2alpha predicts survival in epithelial ovarian cancer.

The 52-kDa activator protein (AP)-2 is a DNA-binding transcription factor which has been reported to have growth inhibitory effects in cancer cell lines and in human tumours. In this study the expression of AP-2alpha was analysed in 303 epithelial ovarian carcinomas by immunohistochemistry (IHC) with a polyclonal AP-2alpha antibody and its mRNA status was determined by in situ hybridization (ISH) and reverse transcriptase-polymerase chain reaction (RT-PCR). The immunohistochemical expression of AP-2alpha was correlated with clinicopathological variables, p21/WAF1 protein expression and survival. In normal ovaries, epithelial cells expressed AP-2alpha protein only in the cytoplasm. In carcinomas nuclear AP-2alpha expression was observed in 28% of the cases although cytoplasmic expression was more common (51%). The expression of AP-2alpha varied according to the histological subtype and differentiation. AP-2alpha and p21/WAF1 expressions did not correlate with each other. Both in univariate (P = 0.002) and multivariate analyses (relative risks (RR) 1.6, 95% confidence interval (CI) 1.13-2.18, P= 0.007) the high cytoplasmic AP-2alpha expression favoured the overall survival. In contrast, the nuclear AP-2alpha expression combined with low cytoplasmic expression increased the risk of dying of ovarian cancer (RR = 2.10, 95% CI 1.13-3.83, P= 0.018). The shift in the expression pattern of AP-2alpha (nuclear vs cytoplasmic) in carcinomas points out to the possibility that this transcription factor may be used by oncogenes in certain histological subtypes. Based on the mRNA analyses, the incomplete expression and translation of AP-2alpha in ovarian cancer may be due to post-transcriptional regulation.

Aged↗

PubMed2000

The protective effect of hormone-replacement therapy on fracture risk is modulated by estrogen receptor alpha genotype in early postmenopausal women.

Genetic factors regulate bone mineral density (BMD) and possibly development of osteoporosis. It has been suggested that estrogen receptor alpha (ERalpha) genotype is associated with BMD, but the association between ERalpha genotype, fracture risk, and postmenopausal hormone replacement therapy (HRT) has not been studied. Therefore, we evaluated whether ERalpha polymorphism is associated with fracture risk in a 5-year trial with HRT in a population-based, randomized group of 331 early postmenopausal women. The participants consisted of two treatment groups: the HRT group (n = 151) received a sequential combination of 2 mg of estradiol valerate (E2Val) and 1 mg of cyproterone acetate with or without vitamin D3, 100-300 IU + 93 mg calcium as lactate per day; and the non-HRT group (n = 180) received 93 mg of calcium alone or in combination with vitamin D3, 100-300 IU/day. All new symptomatic, radiographically defined fractures were recorded. Pvu II restriction fragment length polymorphism of the ERalpha was determined using polymerase chain reaction (PCR). In all, 28 women sustained 33 fractures during the approximately 5.1-year follow-up. In the HRT group, the ERalpha genotype (PP, Pp, and pp) was not significantly associated with fracture risk (p = 0.138; Cox proportional hazards model). When the genotype was dichotomized (PP + Pp vs. pp), the incidence of new fractures in the HRT group was significantly reduced in women with the P allele (p = 0.046) with the relative risk (HR) of 0.25 (95% CI, 0.07-0.98), in comparison with the non-P allele group. After adjustment for time since menopause and previous fracture, the association between the dichotomous genotype and fracture risk persisted with HR of 0.24 (95% CI, 0.06-0.95;p = 0.042). In the non-HRT group, the ERalpha genotype was not significantly associated with fracture risk. During HRT, women with the pp genotype have a greater fracture risk than those with the P allele. The results suggest that the pp genotype is a relatively hormone-insensitive genotype, and it appears that women with the P allele may benefit more from the protective effect of HRT on fracture risk than women with the pp genotype.

Androgen Antagonists↗

PubMed2000

Early postmenopausal bone loss is associated with PvuII estrogen receptor gene polymorphism in Finnish women: effect of hormone replacement therapy.

Genetic factors regulate bone mineral density (BMD) and possibly the development of osteoporosis. An association between estrogen receptor (ER) polymorphism, BMD, and postmenopausal hormone replacement therapy (HRT) has not been established. Therefore, we studied the influence of the ER genotype on BMD before and after a 5-year HRT in a placebo-controlled, population-based, randomized group of 322 early postmenopausal women. The participants were randomized into two treatment groups: the HRT group (n = 145) received a sequential combination of 2 mg estradiol valerate and 1 mg CPA with or without vitamin D3, 100-300 IU + 500 mg calcium lactate/day (equal to 93 mg Ca2+), and the non-HRT group (n = 177) received calcium lactate, 500 mg alone or in combination with vitamin D3, 100-300 IU/day. PvuII restriction fragment length polymorphism (RFLP) of the ERalpha was determined using polymerase chain reaction (PCR). BMDs of the lumbar spine (L2-4) and proximal femur were measured by using dual-energy X-ray absorptiometry (DXA). At the baseline, there were no significant differences in the lumbar or femoral neck BMDs between the three ER PvuII genotype groups (PP, Pp, pp). After 5 years, the BMD of the femoral neck remained unaltered and that of the lumbar spine increased by 1.7% in the HRT group, whereas both BMDs were decreased by 4-5% in the non-HRT group. The ER genotype did not modulate the femoral neck BMD change during the follow-up. In contrast, in the non-HRT-group the lumbar spine BMD decreased more in subjects with the ER genotypes PP (6.4%) and Pp (5.2%) than in subjects with the pp genotype (2.9%) (p = 0.002). In the HRT group, the relative changes of the lumbar spine BMD were similar in all three ER genotype groups. Thus without HRT, the pp genotype was associated with a smaller decrease in the lumbar spine BMD than the Pp and PP genotypes. Long-term HRT seemed to eliminate the ER genotype-related differences in the BMD. We conclude that subjects with the ER PvuII genotypes PP and Pp may have a greater risk of relatively fast bone loss after menopause than those with the pp genotype and that they may preferentially derive benefit from HRT.

Deoxyribonucleases, Type II Site-Specific↗

PubMed2000

Semen quality among Danish and Finnish men attempting to conceive. The Danish First Pregnancy Planner Study Team.

OBJECTIVE: To assess differences in semen quality between similar populations from Denmark and Finland. DESIGN: Comparison of semen quality between 221 Finnish men (of whom 115 had no proven fertility) and 411 Danish men with no proven fertility in two follow-up studies among normal couples trying to conceive. METHODS: In Finland male partners of couples without experienced infertility attempting to conceive were recruited through advertisements in local newspapers from 1984 to 1986. From 1992 to 1995 Danish men who lived with a partner and who had not attempted to achieve a pregnancy previously were recruited through their union when they discontinued birth control. All semen analyses were performed in accordance with the World Health Organization guidelines. RESULTS: Median sperm concentration, total sperm count and the percentage of morphologically normal spermatozoa were significantly higher among the Finnish men without proven fertility (104.0 million/ml, 304.0 million and 58% respectively) compared with the Danish men (53.0 million/ml, 140.8 million, and 41% respectively). Sperm concentration was 105.7% (95% confidence interval (CI) 58.1%-167.6%) and total sperm count was 127.4% (95% CI 71.4%-201.6%) higher among Finnish men without proven fertility than among Danish men after control for confounders. CONCLUSIONS: Some, but hardly all, of the observed difference in semen quality may be explained by differences in recruitment procedures, selection of the men and by methodological differences in semen analysis between the two countries. Also a birth cohort effect may explain some of the differences between countries as the Finnish men were recruited 11 years before the Danish men. Therefore, follow-up studies with identical recruitment and selection of men from the two countries are needed.

Adult↗

PubMed1999

Validity of self-reports of fractures in perimenopausal women.

The validity of self-report of fractures in postal inquiry among perimenopausal women was evaluated. Self-reports of fractures in the 1989 baseline postal inquiry data of the Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) were compared with information in patient records. The study population consisted of 373 women who reported fractures sustained during the last 10 years and 200 randomly selected women who did not report fractures from a population base of 2,007 women aged 47-56 years. Self-report as a screening test for fracture was evaluated in the total sample of 2,007 women by estimating the number of false negative reports in all the women who did not report a fracture with the information on these 200 women. Of the self-reports of fractures, 84% proved to be true fractures, 12% soft tissue injuries, and the rest either self-diagnoses or misnomers. Self-report of wrist fracture was more accurate (95%). The sensitivity of self-report to detect fracture was 78% for all fractures and 95% for wrist fracture, while the respective specificities were 96 and 99%. Self-report is a relatively accurate way to obtain information about past major fractures in perimenopausal women. However, it is rather insensitive in the detection of minor fractures, if the reporting period is several years.

Female↗

PubMed1999

Failure to demonstrate human papillomavirus DNA in epithelial ovarian cancer by general primer PCR.

One of the recent controversies with substantial clinical interest is the role of HPV in pathogenesis of ovarian cancer. The available highly conflicting data are based on analysis of 175 ovarian carcinomas so far. As an attempt to further elucidate this issue, the first systematic study of HPV detection in ovarian cancer was carried out using a highly sensitive general primer PCR (confirmed by hybridization for low- and high-risk HPV types separately) in a series of 98 histologically and clinically well-characterized epithelial ovarian malignancies. Despite the high (fg) sensitivity and a wide HPV type coverage of the technique used, all 98 ovarian carcinomas failed to demonstrate any signs of HPV DNA whatsoever. The preexisting 12 reports comprising a total of 175 ovarian tumors analyzed for HPV were summarized, giving highly discrepant results (i.e., detection rates from 0 to 100%) with the overall HPV DNA detection rate of 25.7%. The reasons for these discrepant findings are most probably technical. Our data are consistent with those of the majority of the most recent reports failing to disclose HPV DNA in ovarian neoplasia. The present completely negative results make the authors inclined to conclude that HPV is highly unlikely to play any causal role in the pathogenesis of epithelial ovarian neoplasia.

Adenocarcinoma↗

PubMed1999

p21/WAF1 expression as related to p53, cell proliferation and prognosis in epithelial ovarian cancer.

The role and prognostic value of the tumour suppressor p21/WAF1 expression in epithelial ovarian cancer has not yet been defined. Therefore, the expression of p21/WAF1 was assessed immunohistochemically (IHC) in 316 epithelial ovarian malignancies in relation to p53, cell proliferation and patient survival. p21/WAF1 expression was inversely correlated with p53 and cell proliferation. Low p21/WAF1 expression was significantly associated with high grade of the tumour (P = 0.0005), advanced FIGO stage (P = 0.001) and primary residual tumour (P = 0.0001). Low p21/WAF1 expression was a marker of poor overall survival (P = 0.012). Similarly, p53-positivity and high cell proliferative activity were significant predictors of poor survival in univariate analyses. Moreover, the patients with p21-/p53+ tumours had a poorer overall (P < 0.00005) and recurrence-free (P = 0.0005) survival in univariate analyses, and the p21/p53 expression independently predicted tumour recurrence in Cox's multivariate analysis. Our results suggest that p21/WAF1 expression is mostly p53-dependent in epithelial ovarian cancer. High p21/WAF1 expression seems to function as a negative cell cycle regulator and as a marker of favourable disease outcome in epithelial ovarian cancer. In addition, the patients with their tumour expressing no or low p21/WAF1 protein but positive for p53 had a notably higher risk of recurrent disease, implicating that these patients might be more prone to treatment failures.

Carcinoma↗

PubMed1999

Is the response of serum lipids and lipoproteins to postmenopausal hormone replacement therapy modified by ApoE genotype?

Postmenopausal hormone replacement therapy (HRT) has favorable effects on the serum lipid profile, and it also decreases the risk of cardiovascular diseases. The apolipoprotein E genotype has influence on serum levels of lipids and lipoproteins; apoE allele epsilon4 (apoE4) is associated with high total and LDL cholesterol levels. Genotype also influences the lipid responses to treatment with diet and statins, but the effect of HRT in different apoE genotypes is unknown. We studied the effects of HRT on the concentrations of serum lipids in apoE4-positive early postmenopausal women (genotypes 3/4 and 4/4) compared with apoE4-negative women (genotypes 2/3 and 3/3) in a population-based, prospective 5-year study. In all, 232 early postmenopausal women were randomized into 2 treatment groups: an HRT group (n=116), which received a sequential combination of 2 mg estradiol valerate (E2Val) from day 1 to 21 and 1 mg cyproterone acetate (CPA) from day 12 to 21 (Climen), and a placebo group (n=116), which received 500 mg/d calcium lactate. Serum concentrations of total, LDL, and HDL cholesterol and triglycerides were measured at baseline and after 2 and 5 years of treatment. A total of 154 women completed the final analysis. During the follow-up period, serum total cholesterol and LDL cholesterol concentrations decreased in the HRT group in apoE4-negative women (8.1% and 17.1%, respectively; P<0.001) but did not change in the HRT group in apoE4-positive women or in the placebo group. Serum HDL cholesterol concentrations decreased in the placebo group (apoE4-negative, 3.9%, P=0.015; apoE4-positive, 8.1%, P=0.004) but did not change significantly in the HRT group. Serum triglyceride levels tended to increase in both study groups and genotypes (15.1% to 36.2%, P<0.038 to 0.001), but no differences were observed between the study groups or genotypes, respectively. Our finding was that in postmenopausal Finnish women LDL cholesterol levels in apoE4-negative subjects respond more favorably to HRT than those in apoE4-positive subjects. This finding has potential importance in postmenopausal women with hypercholesterolemia, if confirmed in other studies.

Apolipoprotein E4↗

PubMed1999

Prevention of femoral and lumbar bone loss with hormone replacement therapy and vitamin D3 in early postmenopausal women: a population-based 5-year randomized trial.

The long term effects of hormone replacement therapy (HRT) and vitamin D3 (Vit D) on bone mineral density (BMD) were studied. A total of 464 nonosteoporotic early postmenopausal women from the Kuopio Osteoporosis Study (n = 13100) were randomized to four groups: 1) HRT (sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate, 2) Vit D3 (300 and 100 IU/day during the fifth year), 3) HRT and Vit D combined, and 4) placebo. Lumbar (L2-L4) and femoral neck BMD were determined by dual x-ray absorptiometry (DXA) at baseline and after 2.5 and 5 yr of treatment. Intention to treat analysis (n = 464) showed that after 5 yr, lumbar BMD remained unchanged in the HRT and HRT plus Vit D groups [+0.2% (P = 0.658) and +0.9% (P = 0.117), respectively], whereas lumbar BMD decreased by 4.6% in the Vit D group and by 4.5% in the placebo group (P < 0.001 in both). The loss of femoral neck BMD was less in the HRT (-1.4%; P = 0.005) and HRT plus Vit D (-1.3%; P = 0.003) groups than in the Vit D and placebo groups (-4.3%; P < 0.001 in both). Among those 370 women who complied with the 5-yr treatment, the effect was more pronounced: lumbar BMD had increased by 1.5% in the HRT (P = 0.009) and by 1.8% in the HRT plus Vit D group (P = 0.005), with a plateau after 2.5 yr, whereas lumbar BMD had decreased in both the Vit D and placebo groups (4.6% and 4.7%; P < 0.001, respectively). Femoral neck BMD decreased again less in the HRT (-0.4%) and HRT plus Vit D (-0.6%) groups than in the Vit D and placebo groups (-4.4% in both). This study confirms the positive long term effect of HRT on BMD also seen in intention to treat analysis. The data suggest that low dose vitamin D3 supplementation does not prevent bone loss in healthy, nonosteoporotic, early postmenopausal women, and it confers no benefit additional to that of HRT alone.

Cholecalciferol↗

PubMed1998

HRT and Vit D in prevention of non-vertebral fractures in postmenopausal women; a 5 year randomized trial.

OBJECTIVES: We investigated the incidence of new non-vertebral fractures during HRT or low-dose vitamin (Vit) D3 supplementation in a 5-year prospective trial. METHODS: A total of 464 early postmenopausal women, (a subgroup of the Kuopio Osteoporosis Study, n = 13,100) were randomized to four groups: (1) HRT, a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate; (2) Vit D (300 IU/day and 100 IU/day during the fifth years); (3) HRT + Vit D; and (4) placebo. Lumbar (L2-4) and femoral neck bone mineral densities (BMD) were determined by dual X-ray absorptiometry (DXA) at baseline, after 2.5 and 5 years of treatment. All new symptomatic non-vertebral, radiographically defined fractures were recorded. RESULTS: Altogether, 368 women (79%) completed the 5 year treatment. In all, 32 women had 39 non-vertebral fractures during a mean of 4.3 year follow-up (HRT 4, Vit D 10, HRT + Vit D 8 and placebo 17). The reduction in the incidence of new non-vertebral fractures was significant in women with HRT alone (P = 0.032) when adjusted by baseline BMD and previous fractures; observed also with the intention-to-treat principle (P = 0.048). When the HRT groups were pooled, HRT showed a significantly lower incidence of new non-vertebral fractures (P = 0.042) than women receiving placebo and also after adjusting as above (P = 0.016); both in valid-case and in the intention-to-treat analysis. In the Vit D group, the fracture incidence was non-significantly decreased (P = 0.229) in comparison with the placebo group. The estimated risk of new non-vertebral fractures among women treated with HRT alone was 0.29 (95% CI, 0.10-0.90) and with Vit D 0.47 (95% CI, 0.20-1.14) and with HRT + Vit D 0.44 (95% CI, 0.17-1.15), in comparison with the placebo group (adjusted by femoral BMD and previous fractures). CONCLUSIONS: This study is the first prospective trial confirming the beneficial effect of HRT on prevention of peripheral fractures in non-osteoporotic postmenopausal women. The effect of low-dose Vit D remains to be proved.

Bone Density↗

PubMed1998

Postmenopausal hormone replacement therapy and autoantibodies against oxidized LDL.

OBJECTIVES: Oxidative modification of low-density lipoprotein (oxLDL) has been suggested to play an important role in the pathogenesis of atherosclerosis, and autoantibodies against oxLDL have recently found to reflect this process. The antioxidant effect and inhibition of LDL oxidation may be one of the cardioprotective mechanisms of postmenopausal estrogen therapy. METHODS: The effects of postmenopausal hormone replacement therapy (HRT) on the concentrations of serum lipids and oxLDL autoantibodies were studied in a population-based prospective 1-year study with 64 early postmenopausal women (mean age 52.2 +/- 0.4 (S.E.M.) years). The participants were randomized into two treatment groups: HRT-group: Sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate alone or in combination with vitamin D3, 300 IU/day + calcium lactate, 500 mg/day (n = 31) and the non-HRT-group: Calcium lactate, 500 mg/day alone or in combination with vitamin D3, 300 IU/day (n = 33). The groups were well matched regarding age, body mass index and baseline serum lipid concentrations. RESULTS: The serum concentrations of total cholesterol and LDL-cholesterol decreased in the HRT-group (4.1%, P = 0.05 and 6.4%, P = 0.03, respectively, paired t-test) but did not change in the non-HRT-group. No changes in the serum concentrations of HDL-cholesterol or triglycerides were observed. Additionally, no changes in oxLDL autoantibody concentrations were observed in either group. CONCLUSIONS: Although 1-year HRT lowered serum total- and LDL-cholesterol levels, it did not influence oxLDL antibody titers. On the basis of the present results we cannot question the possibility of there being beneficial effects of HRT on the oxidative modification of LDL. However, this effect is not reflected in the levels of oxLDL autoantibodies.

Autoantibodies↗

PubMed1998

Relationships between risk factors and fractures differ by type of fracture: a population-based study of 12,192 perimenopausal women.

Relationships between selected factors and fractures according to type of fracture were retrospectively examined in 12,192 women aged 47-56 years responding to the baseline postal enquiry of the Kuopio Osteoporosis Study, Finland, in 1989. A total of 1358 women reported fractures sustained during the previous 9.4 years, i.e. at ages 38-57 years. The incidence of fractures per 1000 person-years was 17.2 after menopause and 9.5 before (p < 0.0001). The adjusted fracture risk was elevated in smokers versus non-smokers (OR = 1.5; (95% CI = 1.3-1.9) and in those with chronic health disorders versus the healthy (OR = 1.3; 95% CI 1.1-1.5). Long-term work disability was associated with fractures independently of health disorders (OR = 1.3; 95% CI 1.1-1.6). Anthropometric measures were not associated with the overall fracture risk. Menopause was strongly and linearly related to wrist fracture but not to ankle fracture. A 1 SD increase in body mass index decreased the risk of wrist fracture by 21% (p = 0.0001) but increased that of ankle fracture by 24% (p = 0.002). Smoking was related to ankle fracture (OR = 2.2; 95% CI 1.6-3.2) but not to wrist fracture (OR = 0.9; 95% CI 0.6-1.4). Health disorders were more markedly associated with fractures other than those of the wrist or ankle. Relationships between several risk factors and pre- and perimenopausal fractures vary by type of fracture. This may affect, for example, the comparability of studies with varying fracture profiles.

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