Tobacco smoking and chewing as risk factors for multiple human papillomavirus infections and cervical squamous intraepithelial lesions in two countries (Côte d'Ivoire and Finland) with different tobacco exposure.

Our objective was to compare the association between tobacco smoking and chewing and the risk of multiple human papillomavirus (HPV) infections and cervical squamous intraepithelial lesions (SILs) in two populations with different tobacco exposure. We studied 2,162 women from Côte d'Ivoire, West Africa, and 419 women from Finland, Northern Europe, with baseline data on cervical screening, HPV DNA status and smoking and chewing habits. The proportion of women who smoked and/or chewed tobacco was higher in Finland (36.8%) than in Côte d'Ivoire (3.7%), where tobacco chewing (2.6%) was more common than tobacco smoking (1.4%). Having multiple HPV infections was common in HPV16 and/or 18-infected women (60.4% in Finland and 47.2% in Côte d'Ivoire). There was no increased risk of multiple HPV infections among tobacco consumers. We found that women >or=30 years of age exposed to tobacco through smoking in Finland (OR: 2.2, 95% CI: 0.5-8.7) and chewing in Côte d'Ivoire (OR: 5.5, 95% CI: 2.1-14) had a moderately or highly increased risk of high-grade SIL, respectively. In the latter, the risk was statistically significant. Our findings emphasize the need for health initiatives targeted to prevent tobacco smoking or chewing among women especially in less industrialized countries.

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 = 13100) 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 year); (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-verterbral 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.

Quantification of angiogenesis by the Chalkley method and its prognostic significance in epithelial ovarian cancer.

AIM: The aim of the present study was to clarify prognostic role of angiogenesis in epithelial ovarian cancer. METHODS: Quantification of angiogenesis was performed by the Chalkley method after immunostaining of 175 epithelial ovarian cancer specimens with an antibody against CD34. RESULTS: The Chalkley count was categorised into two groups according to the median value: low <8 or high > or =8. The low Chalkley count correlated significantly with serous and clear cell histological subtype of the tumour (p<0.0005), whereas there existed no association with FIGO (International Federation of Gynecology and Obstetrics) stage, histological grade, presence of primary residual tumour, age at diagnosis, or chemotherapy response. In univariate analysis, the high Chalkley count predicted poor overall survival in the subgroup of patients with FIGO stages III-IV tumours (p=0.007) but not in the entire study cohort. However, in multivariate analysis, the Chalkley count was found to be an independent predictor of death from ovarian cancer in the entire study cohort (p=0.044, RR=1.50, 95% CI 1.01-2.21) as well as in the subgroup of FIGO stages III-IV tumours (p=0.046, RR=1.58, 95% CI 1.01-2.46) together with the presence of primary residual tumour (p<0.0005, RR=5.10, 95% CI 3.02-8.62, and p=0.002, RR=4.28, 95% CI 1.34-13.73, respectively). CONCLUSIONS: The Chalkley count seems to be suitable for evaluation of angiogenesis and to have prognostic significance in ovarian cancer.

Hormone replacement therapy and mortality in 52- to 70-year-old women: the Kuopio Osteoporosis Risk Factor and Prevention Study.

OBJECTIVES: To analyze prospectively the association between hormone replacement therapy (HRT) and mortality in women before old age. DESIGN AND METHODS: A group of 11,667 women (91% of the age cohort of the area) aged 52-62 years from the population-based Kuopio Osteoporosis Risk Factor and Prevention Study were followed for 7 years in 1994-2001. Information about HRT use and health events was obtained from two repeated questionnaires in 1989 and 1994. Information about deaths and causes of death from the follow-up period was obtained from the Statistics Finland. Cox's proportional-hazards models were used to calculate risk of death related to the use of HRT. RESULTS: At the start of follow-up, 2203 women had used HRT > 5 years, 3945 women < or = 5 years and 5519 women had never used it. During the follow-up, 361 deaths occurred. Compared with non-users of HRT, the adjusted hazard ratio (HR) of death from any cause was 1.05 (95% confidence interval (CI) 0.80-1.36) in women who used HRT < or = 5 years and 1.06 (95% CI 0.78-1.46) in women who used HRT > 5 years. The adjusted HR for coronary heart disease (CHD) mortality in women who used HRT < or = 5 years was 0.79 (95% CI 0.36-1.73), and in women who used HRT > 5 years, 2.16 (95% CI 0.93-4.98). For breast cancer mortality the adjusted HR for < or = 5 years of HRT use was 0.96 (95% CI 0.32-2.82) and 2.62 (95% CI 0.98-7.00) for > 5 years of HRT use. CONCLUSIONS: History of HRT use does not affect overall or CHD mortality in women. More than 5 years of HRT use may increase the risk of breast cancer mortality.

Fracture risk and bone density of peri- and early postmenopausal women with uterine leiomyomas.

OBJECTIVES: Fracture risk and bone mineral density (BMD) among peri- and early postmenopausal women with leiomyomas requiring hysterectomy was evaluated. METHODS: We counted fractures among women with or without leiomyomas using data from the Kuopio Osteoporosis Study. The study population consisted of 6086 women aged 47-56 years with never-use of hormone replacement therapy (HRT) responding to the baseline and 5-year follow-up inquiries. Part of the sample (n=1271) underwent bone densitometry. RESULTS: Hysterectomy was carried out in 927 women, and 59% reported that this was attributable to leiomyomas. The hazard ratio (HR) was 0.68 (95% CI 0.49-0.94) for any and 0.73 (95% CI 0.43-1.26) for distal forearm fracture among women with leiomyomas compared to those without any. Among women postmenopausal at baseline, the corresponding HRs were 0.62 (95% CI 0.44-0.87) and 0.54 (95% CI 0.31-0.96); after adjusting for age, time since menopause weight, height and previous fracture 0.69 (95% CI 0.49-0.97) and 0.63 (95% CI 0.35-1.11). The baseline BMDs were 1.15 g/cm2 among hysterectomized leiomyoma and 1.12 g/cm2 (ns) among non-hysterectomized women at lumbar (L2-L4), and 0.94 and 0.93 g/cm2 (ns) at femoral sites. The follow-up lumbar BMDs were 1.13 and 1.09 g/cm2 (p<0.001) and the corresponding femoral values were 0.90 and 0.89 g/cm2 (ns), respectively. Among postmenopausal women, the corresponding baseline lumbar BMDs were 1.15 and 1.08 g/cm2 (p<0.001), femoral 0.93 and 0.90 g/cm2 (p=0.003); the follow-up lumbar BMDs 1.13 g/cm2 versus 1.07 g/cm2 (p<0.001); femoral BMDs 0.89 versus 0.87 (ns). CONCLUSIONS: Peri- and early postmenopausal women with a history of leiomyomas seem to have better BMD and less fractures compared with those without leiomyomas. This may be mediated through higher estrogen levels leading to higher BMD and the growth of leiomyomas.

Online discussions mirroring family life during pregnancy.

OBJECTIVE: The aim of this study was to find out what aspects of their parenthood parents revealed, and how they expressed their thoughts concerning maternity care services on an online communication forum. BACKGROUND: The 'Information Society' offers a growing variety of health services as part of public primary health care via the internet. Little is known about the contents produced online by pregnant families, and how they reflect on both family life and maternity care services. METHODS: The data for this study were obtained from online discussions between families (n=21) in Net Clinic, an internet-based service designed for public maternity care. The data included experiences of family life during pregnancy, childbirth and parenting, and was analysed by inductive content analysis. RESULTS: While maturing into parenthood, both women and men recognised the uniqueness of their new role and wanted to prepare for safe childbirth. Online communication in the home environment nourished new social networks among families who were expecting their first, second or third child. In addition, families reflected on maternity care services on the Net Clinic's communication forum. This provided realistic feedback to maternity care professionals. CONCLUSIONS: Today, the relationship between clients and professionals is inevitably changing. More online services and advocacy are needed if families are to have access to online health services. The role of professionals is diversifying from being authorities to supporting and facilitating clients' individual self-care. Based on direct client feedback, the quality of maternity care can be improved.

Nascent body ego: metapsychological and neurophysiological aspects.

For Freud, body ego was the organizing basis of the structural theory. He defined it as a psychic projection of the body surface. Isakower's and Lewin's classical findings suggest that the body surface experiences of nursing provide the infant with sensory-affective stimulation that initiates a projection of sensory processes towards the psychic realm. During nursing, somato-sensory, gustatory and olfactory modalities merge with a primitive somatic affect of satiation, whereas auditory modality is involved more indirectly and visual contact more gradually. Repeated regularly, such nascent experiences are likely to play a part in the organization of the primitive protosymbolic mental experience. In support of this hypothesis, the authors review findings from a neurophysiological study of infants before, during and after nursing. Nursing is associated with a significant amplitude change in the newborn electroencephalogram (EEG), which wanes before the age of 3 months, and is transformed at the age of 6 months into rhythmic 3-5 Hz hedonic theta-activity. Sucking requires active physiological work, which is shown in a regular rise in heart rate. The hypothesis of a sensory-affective organization of the nascent body ego, enhanced by nursing and active sucking, seems concordant with neurophysiological phenomena related to nursing.

Maternal exposure to extremely low frequency magnetic fields: Association with time to pregnancy and foetal growth.

BACKGROUND: Data on reproductive and developmental effects of extremely low frequency magnetic fields (ELF MFs) are inconclusive. This study tested the hypothesis that maternal exposure to ELF MFs is associated with increased time to pregnancy (TTP), reduced birthweight or small for gestational age (SGA). METHODS: The study cohort consisted of 373 mothers who gave birth between 1990 and 1994 in Kuopio University Hospital, Finland. To increase prevalence of high ELF MF exposure, women living in buildings near known ELF MF sources were included. Maternal exposure to ELF MF before and during pregnancy was assessed with short term measurements in residences and questionnaires. Associations between ELF MF exposure and TTP, low birth weight and SGA were analysed by logistic regression (or linear regression for continuous variables), adjusting for factors known to be associated with the selected pregnancy outcomes, such as maternal smoking, alcohol consumption and socioeconomic status. RESULTS: The MF exposure of the mothers was slightly higher than in Finnish residences in general, but very high exposures (>0.4µT) were rare. No consistent association of ELF MF with TTP, birth weight or SGA was found. CONCLUSIONS: ELF MF exposure is not likely to be associated with TTP or prenatal growth at residential exposure levels that were observable in this study.

CD44 expression indicates favorable prognosis in epithelial ovarian cancer.

PURPOSE: The purpose of this study was to investigate the expression and prognostic significance of CD44 in epithelial ovarian cancer. EXPERIMENTAL DESIGN: We analyzed the expression of CD44 by immunohistochemistry in 307 epithelial ovarian cancers and evaluated its relation to hyaluronan, clinicopathological factors, and prognosis. RESULTS: Fifty-one percent of the tumors had a high proportion of CD44-positive cells (i.e., >/==" BORDER="0">10%), and this high CD44 expression was significantly associated with cancer cell-associated hyaluronan, well-differentiated tumor, mucinous histological type, and early stage of the tumor. High CD44 expression predicted better 5-year overall survival (50% versus 22%) and recurrence-free survival (70% versus 34%) in the univariate analyses (P < 0.00005 for both). In the Cox multivariate analyses, the independent predictors of overall survival at 5 years were primary residual tumor (P < 0.0005), International Federation of Gynecologists and Obstetricians (FIGO) stage (P = 0.001), histological grade (P = 0.014), adjuvant chemotherapy (P = 0.004), and stromal hyaluronan level (P < 0.0005), but not CD44. However, the expression of CD44 (P = 0.04) and stromal hyaluronan (P = 0.005) were both independent predictors of recurrence-free survival at 5 years, together with the size of the primary residual tumor (P < 0.0005) and histological type (P = 0.043). CONCLUSIONS: The relatively frequent ectopic expression of CD44 on ovarian cancer cells is thus related to well-differentiated, early-stage tumor and long survival of the patients. Thus, whereas CD44-expressing cancer cells may adhere and implant to the hyaluronan-positive mesothelium, at least in model systems, high expression of CD44 in the tumor does not bring about an unfavorable prognosis.

Does hormone-replacement therapy prevent fractures in early postmenopausal women?

The purpose of this population-based prospective cohort study was to examine the effect of hormone-replacement therapy (HRT) on the risk of fractures. The study population consisted of 7217 postmenopausal women aged 47-56 years (mean, 53.3 years) at baseline from data taken from the Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) in Finland. We compared fracture incidences between HRT users and nonusers. A total of 679 (9.4%) women recorded validated fractures during the 5-year follow-up. Of these, 268 (39%) women had a distal forearm fracture. Two thousand six hundred seventy women (37%) had used HRT >6 months during the follow-up--one-half of them continuously. The relative risk, estimated as hazard ratio with Cox regression, was 0.69 (95% CI, 0.58-0.82) for any fracture and 0.49 (0.36-0.66) for distal forearm fracture among HRT users as compared with never-users. After adjusting for age, body mass index (BMI), number of chronic health disorders, fracture history, and time since menopause (independent risk factors) the corresponding risks were 0.67 (0.55-0.81) and 0.53 (0.37-0.74), respectively. The respective adjusted risks for continuous HRT users were 0.62 (0.48-0.79) and 0.41 (0.26-0.67). The adjusted risk of other than distal forearm fracture was 0.74 (0.55-0.98). The results suggest that HRT has a beneficial effect on prevention of fractures in general and on that of distal forearm fracture in particular in early postmenopausal women.

Smoking may impair the bone protective effects of nutritional calcium: a population-based approach.

Postmenopausal women were randomly selected to investigate the effects of smoking on prevention of bone loss with nutritional calcium. DXA was performed twice, and smoking and calcium intake habits were inquired through the mail in 954 women. Smoking dampened the bone protective effects of nutritional calcium. This may reflect the pathophysiology underlying smoking-induced bone loss postmenopause. This study evaluated the effect of smoking on the bone protective properties of nutritional calcium. Of the random sample of 954 peri- and postmenopausal women selected from the Osteoporosis Risk Factor and Prevention (OSTPRE) study cohort (n = 13,100) in Kuopio, Finland, 182 had smoked at some time (ever smokers) and 772 had never smoked. Women were divided in tertiles according to self-reported dairy nutritional calcium intake (mg/day): < 648 (1st), 648-927 (2nd), > 927 (3rd). Bone mineral density at lumbar spine (LS) and femoral neck (FN) was measured with DXA at baseline in 1989-1991 and at the 5-year follow-up in 1994-1997. In a linear regression model, nutritional calcium intake did not predict annual bone loss in smokers. These results were similar in the subanalysis on 71 current smokers (at both baseline and 5-year measurements) and on 85 past smokers. In never smokers, a statistically significant linear trend was observed between calcium intake and annual bone loss at LS, but at FN only after adjustment for age, weight, hormone replacement therapy (HRT), and other covariates. In analysis of covariance (ANCOVA), no differences in bone loss rate were observed between calcium intake tertiles among smokers. In nonsmokers, the annual bone loss rate was lower in the second (-0.41%) and the third (-0.35%) tertile compared with the first tertile (-0.61%) at LS (p < 0.05) and lower in the third tertile (-0.55%) than in first tertile (-0.72%) at FN after adjustment for age, weight, HRT, and other covariates (p < 0.05). When smokers were added to the nonsmoker group, the differences in bone loss rate between calcium intake tertiles disappeared. In addition, in ANCOVA, the term of interaction between smoking and calcium intake was statistically significant at LS only. In conclusion, smoking seems to impair the bone protective effects of nutritional calcium in postmenopausal women, more clearly in LS than FN.

Relation of androgen receptor gene polymorphism to bone mineral density and fracture risk in early postmenopausal women during a 5-year randomized hormone replacement therapy trial.

In women, the influence of androgens on bone health is not clear. It has been suggested that the androgen receptor (AR) genotype is associated with bone mineral density and serum androgen levels in pre- and perimenopausal women, but the association between AR genotype, bone mineral density, and fracture risk has not been studied in postmenopausal women. Therefore, we studied whether AR polymorphism affects bone mineral density, bone mineral density change, or fracture risk in a 5-year randomized hormone replacement therapy (HRT) trial on 331 early postmenopausal women (mean baseline age, 52.7 +/- 2.3 years). The participants consisted of two treatment groups: the HRT group (n = 151) received a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate with or without vitamin D3, 100-300 IU + 93 mg calcium as lactate/day, and the non-HRT group (n = 180) received 93 mg calcium alone or in combination with vitamin D3, 100-300 IU/day for 5 years. Bone mineral density was measured from lumbar spine and proximal femur (DXA) before and after the 5-year trial. All new symptomatic, radiographically defined fractures were recorded during the follow-up. The length of CAG repeat in exon 1 of AR gene was evaluated after polymerase chain reaction (PCR) amplification. The subjects were divided into three repeat groups according to AR alleles. None of the baseline characteristics were associated with AR gene polymorphism and HRT treatment. The polymorphism did not influence the calculated annual changes of lumbar or femoral neck bone mineral density during the 5-year follow-up in the HRT (p = 0.926 and 0.146, respectively) or non-HRT (p = 0.818 and 0.917, respectively) groups. In all, 28 women sustained 33 fractures during the follow-up. Thus, the numbers of fractures were limited. The AR repeat length variation was not significantly associated with fracture risk in the HRT or non-HRT groups (p = 0.632 and 0.459, respectively; Cox proportional hazards model). In conclusion, AR gene polymorphism was not associated with baseline bone mineral density, 5-year bone mineral density change, or fracture risk in early postmenopausal Finnish women.

Leucine7 to proline7 polymorphism in prepro-NPY gene and femoral neck bone mineral density in postmenopausal women.

Neuropeptide Y (NPY) is a versatile neurotransmitter that has recently been shown to regulate bone metabolism in animal and in vitro studies. We studied the influence of leucine7-to-proline7 (Leu7/Pro7) polymorphism of the NPY signal peptide gene on bone mineral density (BMD) before and after a 5-year hormone replacement therapy (HRT) in 316 early postmenopausal women participating in a randomized controlled trial nested in the population-based Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study. The participants were randomized into two treatment groups: the HRT group (n = 146) received a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate and calcium lactate, 500 mg/day (equal to 93 mg Ca2+) alone or in combination with vitamin D3, 100-300 IU/day. The non-HRT group (n = 170) received calcium lactate, 500 mg alone or in combination with vitamin D3, 100-300 IU/day. BMDs of the lumbar spine (L2-4) and proximal femur were measured by using dual X-ray absorptiometry (DXA). The frequency of Leu7/Pro7 polymorphism was 15.2%. At baseline, there were no significant differences in the lumbar or femoral neck BMD between the subjects who had Leu7Pro7 polymorphism and the normal subjects. 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. After 5 years, the femoral neck BMD was significantly lower in those with the wild-type NPY polymorphism than in those with Leu7/Pro7 polymorphism (P = 0.040) in the non-HRT group. In the HRT group, the changes in BMD were quite modest and not significantly modified by Leu7/Pro7 genotype. We conclude that the Leu7/Pro7 polymorphism in NPY signal gene may favorably affect femoral neck BMD in postmenopausal women.

Does postmenopausal hormone replacement therapy affect cardiac autonomic regulation in osteoporotic women?

OBJECTIVE: Postmenopausal hormone replacement therapy (HRT) has been associated with reduced risk of cardiovascular disease; however, the mechanisms remain obscure, and it is not known whether this applies to regimens containing both estrogen and progestin. One possibility is that estrogen would act via enhancement of cardiac autonomic regulation. DESIGN: In this prospective, controlled study of 6-months duration, 22 osteoporotic, postmenopausal women in the intervention group were treated with combined estradiol hemihydrate corresponding to estradiol 2 mg and norethisterone acetate 1 mg with or without clodronate (HRT group). Nine women in the control group received clodronate only. Indices of heart rate variability (HRV) by power spectral analyses and baroreceptor sensitivity (BRS) by phenylephrine test were measured before and after 3 and 6 months of treatment. RESULTS: The total power of HRV remained identical within the groups, although it was higher at 3 and 6-month measurements in the control group than the HRT group. This was mainly due to lower very low frequency and high frequency power in the HRT group. However, no changes in the low frequency/high frequency-ratio of HRV, an index of sympathovagal balance, were observed between and within the groups. Further, during the intervention, no significant changes in BRS (baseline and 6 months: 5.0 +/- 2.1 and 5.1 +/- 2.5 ms/mmHg) within the HRT group was observed. CONCLUSIONS: The impact of estrogen and progesterone on cardiac autonomic regulation seems to be quite modest. Therefore, cardiac morbidity and mortality are probably not mediated by their effects on cardiac autonomic regulation. However, the effects of estrogen alone or more selective estrogen receptor modulators need yet to be clarified in future studies.

Factors affecting bone loss around menopause in women without HRT: a prospective study.

OBJECTIVES: The present study evaluated the effects of menopause and other putative bone loss modifying factors on bone mineral density (BMD) change. METHODS: The study population, 396 healthy women aged 48-59 years with no history of hormone replacement therapy (HRT) use or any bone affecting disease or medications, was selected from a random sample (n=2025) of the OSTPRE-study cohort (n=13100) in Kuopio, Finland. BMD at lumbar spine (LS) and three areas of proximal femur (femoral neck (FN), Ward's triangle (W), trochanter (T)) was measured with dual X-ray absorptiometry at baseline in 1989-1991 and at 5 years in 1994-1997. RESULTS: 116 women who reported the beginning of menopause during the follow-up (perimenopausal) had the greatest mean annual bone loss (-1.22%/year (LS), -0.87% year (FN), -1.14%/year (W), -0.36%/year (T)). In women under 5 years postmenopausal at baseline (early postmenopausal, n=172) bone loss rate was significantly lower than in perimenopausal women. In women over 5 years postmenopausal at baseline (late postmenopausal, n=108) bone loss rate was significantly further decreased only at lumbar spine. In peri- and postmenopausal women the annual BMD change was best described as a trinomial function of the duration of menopause at all sites (P<0.03). Of the life-style factors studied protective effects were found in weight increase in both spinal and femoral bone (P=0.010/P<0.001), high baseline weight in spine (P<0.001) and high grip strength in femoral neck (P=0.002). CONCLUSION: The beginning of menopause is accompanied by significant bone loss, which decreases in later menopause. Few other physiological and life-style factors were found to significantly contribute to this phenomenon.

Effects of continuous combined hormone replacement therapy and clodronate on bone mineral density in osteoporotic postmenopausal women: a 5-year follow-up.

OBJECTIVE: To determine the effects of HRT with or without clodronate on bone mineral density (BMD) change and bone turnover markers. DESIGN: Prospective, partly randomized trial. SETTING: Kuopio University Hospital, Finland. POPULATION: 167 osteoporotic women (61+/-2.7 years; T-score

Hormone therapy protects from diabetes: the Kuopio osteoporosis risk factor and prevention study.

OBJECTIVES: The purpose of this population-based prospective cohort study was to examine the effect of hormone therapy (HT) on incidence of diabetes mellitus (DM). DESIGN AND METHODS: Eight thousand four hundred and eighty-three DM-free post-menopausal women aged 52-62 from the population-based Kuopio osteoporosis risk factor and prevention study were followed for 5 years from 1994-1999. Information about the use of HT and health events was obtained from three repeated questionnaires in 1989, 1994, and 1999. DM morbidity before and during the follow-up was obtained from the Registry of Specially Refunded Drugs of the Finnish Social Insurance Institution. Kaplan-Meyer survival curves and Cox's proportional-hazards models were used to estimate the risk of incident DM in relation to the use of HT. RESULTS: During the follow-up, 40.8% DM-free post-menopausal women had never used HT, 27.3% women were HT past users and 31.9% women had used HT presently during the follow-up. During the follow-up, 162 incident DM cases were recorded. Compared with never users of HT, the adjusted hazard ratio of DM was 0.81 (95% confidence interval (CI) 0.57-1.16) for only past users, 0.53 (95% CI 0.24-1.15) in part-time (during the follow-up <2.5 years) users and 0.31 (95% CI 0.16-0.60) in continuous (during the follow-up 2.5-5.0 years) users of HT. CONCLUSIONS: HT use decreases the incidence of DM in post-menopausal women.

Use of calcium supplements and the risk of coronary heart disease in 52-62-year-old women: The Kuopio Osteoporosis Risk Factor and Prevention Study.

BACKGROUND: To analyse prospectively the effect of calcium or calcium+D supplementation on coronary heart disease (CHD) in 52-62-year-old women. METHODS AND RESULTS: 10,555 52-62-year-old women from the population-based Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) who did not have CHD at baseline were followed for nearly 7 years in 1994-2001. Information about use of calcium supplements and health events was obtained from two repeated questionnaires in 1989 and 1994. Information about causes of death during the follow-up was obtained from the Statistics Finland. Information about CHD and other disease morbidity before and during the follow-up was obtained from the Registry of Specially Refunded Drugs of the Finnish Social Insurance Institution (SII). Cox's proportional-hazards models were used to estimate the risk of CHD morbidity related to the use of calcium supplements. At baseline, 2723 women reported current use of calcium or calcium+D supplementation. During the follow-up, CHD was diagnosed in 513 women. Compared to non-users of calcium/calcium+D supplements, the multivariate adjusted hazard ratio (HR) of CHD was 1.24 (95% CI 1.02-1.52) in women who used these supplements. The multivariate adjusted HR for CHD morbidity in postmenopausal women who used calcium/calcium+D supplements was 1.26 (95% CI 1.01-1.57). CONCLUSIONS: Calcium or calcium+D supplementation appears to increase the risk of CHD among women before old age.

Prognostic significance of iNOS in epithelial ovarian cancer.

OBJECTIVE: To study the association of inducible nitric oxide synthase (iNOS) expression with clinicopathological factors and prognosis in epithelial ovarian cancer. METHODS: The study included 301 patients with primary epithelial ovarian cancer. iNOS expression was evaluated by immunohistochemistry using a mouse monoclonal antibody. RESULTS: iNOS positivity was observed as granular deposits in the cancer cell cytoplasm. The mean percentage of iNOS-positive cells was 50% in primary tumors (n=301), and 62% in metastatic lesions (n=43). iNOS expression correlated significantly with histological subtype of the tumor, as high (> 70%) iNOS expression was observed in mucinous tumors (p=0.009). Poorly differentiated tumors showed a tendency to low (< or = 70%) iNOS expression but without statistical significance. Low iNOS expression associated also significantly with large primary residual tumor (p=0.007) and tumor recurrence (p=0.04). The 10-year prognosis of the patients with high iNOS expression was better in disease-related survival (DRS) (p=0.009). However, in multivariate analysis only FIGO stage, primary residual tumor, and grade of the tumor were independent prognostic factors for DRS, but not the iNOS expression. CONCLUSIONS: A major proportion of human epithelial ovarian cancers expressed iNOS. The positive expression was an indicator of better disease-related survival. However, iNOS positivity could not overcome the importance of clinicopathological factors in prediction of prognosis.