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Biomedical subjects

Lars-Ake Mattsson

Publications and source records attributed to Lars-Ake Mattsson.

11 recordsLinked to original sources
PubMed2006

Benefits and risks of long-term low-dose oral continuous combined hormone therapy.

OBJECTIVES: Current recommendations for hormone therapy (HT) are mainly based on findings from studies using standard dose regimens in older women who had a different health profile from those who start HT soon after the onset of menopause. METHODS: We, therefore, reviewed controlled trials assessing the efficacy, safety and tolerability of low-dose oral continuous combined HT (cc-HT) started for treatment of climacteric symptoms. This review is limited to oral cc-HT regimens over sequential regimens as most postmenopausal women prefer not to have a return of uterine bleeding, and to studies of at least 2 years in duration. RESULTS: Low-dose cc-HT is effective in alleviating climacteric symptoms and in maintaining bone density over prolonged periods, although no data were available regarding fracture risk. No increased risk of coronary heart disease, venous thrombo-embolism or stroke during the use of low-dose cc-HT was reported in the long-term studies and no definitive evidence for an increased risk of breast cancer was found. Breakthrough bleeding during the first months of use is less common than with standard dose HT and amenorrhoea is achieved in most women over time. These regimens are safe for the endometrium and are well tolerated, with a low incidence of adverse events compared with standard doses. CONCLUSIONS: Current evidence from controlled trials indicates that low-dose oral cc-HT appears effective and safe. This makes it a good choice for the alleviation of climacteric symptoms, and for this purpose long-term administration of low-dose cc-HT does not seem to impose serious health risks. However, more long-term study data and direct head-to-head comparisons between various low-dose preparations are needed to support or rectify the safety aspects.

Breast Neoplasms↗
PubMed2006

Scientific evidence changes prescribing practice--a comparison of the management of the climacteric and use of hormone replacement therapy among Swedish gynaecologists in 1996 and 2003.

OBJECTIVES: To study changes in attitudes, knowledge and management strategies concerning hormone replacement therapy (HRT) among gynaecologists in Sweden. DESIGN: Comparative questionnaire study. SETTING: National survey. POPULATION: Practising gynaecologists. METHODS: In 1996, gynaecologists in Sweden (n= 1323) were invited to return a postal questionnaire concerning their attitudes, knowledge and management strategies concerning HRT. They were also asked about their own use of HRT. In 2003, a similar questionnaire was sent to practising gynaecologists (n= 1320) in Sweden. MAIN OUTCOME MEASURES: Attitudes to and personal use of HRT. RESULTS: The response rate was 76% in 2003 when 11% of the gynaecologists thought that all women without contraindications should be offered HRT compared with 44% in 1996 and 89% found it difficult to evaluate pros and cons with HRT in a clinical situation (74% in 1996). More gynaecologists in 2003 believed that HRT increased the risk for breast cancer (95% vs 71%). Twenty-five percent in 2003 stated that risk factors for osteoporosis were absolute indications for HRT (60% in 1996). Current ischaemic heart disease was considered to be an indication for HRT by 7% in 2003 (60% in 1996). In 2003, current use of HRT was reported by 71% of female menopausal gynaecologists (88% in 1996). CONCLUSIONS: Swedish gynaecologists were more cautious in their management strategies concerning HRT in 2003 compared with 1996, probably influenced by results from the Heart and Estrogen/Progestin Replacement Study (HERS) and Women's Health Initiative (WHI) studies. Current use of HRT was still high among female gynaecologists, although it had decreased since 1996.

Adult↗
PubMed2005

The effect of continuous combined HRT on glucose homeostasis and plasma lipids. A placebo-controlled study in postmenopausal women with type 2 diabetes.

BACKGROUND: Hyperandrogenicity in women is a risk factor for cardiovascular disease and noninsulin-dependent diabetes mellitus (NIDDM). Estradiol alone decreases hyperandrogenicity and have beneficial effects on glucose metabolism and plasma lipids in postmenopausal women with type 2 diabetes. OBJECTIVES: To analyse effects on glucose homeostasis and plasma lipids by 2 mg estradiol and 1mg norethisterone acetate (NETA) given as a daily tablet during 6 months in postmenopausal women with type 2 diabetes. DESIGN: Randomised, double-blind, placebo-controlled, cross-over design. MATERIAL AND METHODS: Thirty-one postmenopausal women with type 2 diabetes, glycosylated haemoglobin (HbA1c) of 6% or more and sex hormone-binding globulin (SHBG) values of 60 nmol/L or less were included. Anthropometric variables, blood pressure, sex steroid hormones, HbA1c, serum and lipoprotein lipids, plasminogen activator inhibitor 1 (PAI-1) and insulin-like growth factor 1 (IGF-1) were measured. An oral glucose tolerance test (OGTT) was performed and blood glucose, insulin and C-peptide were analysed. All measurements were taken at baseline and after each 6-month period. RESULTS: An increase of SHBG and a decrease in free testosterone and PAI-1 levels was induced by the estradiol/NETA treatment compared with placebo. Lipoprotein(a) decreased but otherwise lipid metabolism was unaffected. No differences were recorded in glucose homeostasis between active treatment and placebo. CONCLUSION: Estradiol/NETA therapy decreased hyperandrogenicity in postmenopausal women with type 2 diabetes. Lipoprotein(a) and PAI-1 which are independent risk factors for coronary heart disease decreased. No changes in glucose homeostasis were found.

Aged↗
PubMed2005

Intrahepatic cholestasis of pregnancy: a randomized controlled trial comparing dexamethasone and ursodeoxycholic acid.

Intrahepatic cholestasis of pregnancy (ICP) is characterized by troublesome maternal pruritus, elevated serum bile acids (> or =10 micromol/L) and increased fetal risk. Recently we determined a cutoff level of serum bile acids, > or =40 micromol/L, to be associated with impaired fetal outcome. We have now studied the effects of ursodeoxycholic acid (UDCA) and dexamethasone on pruritus, biochemical markers of cholestasis, and fetal complication rates in a double-blind, placebo-controlled trial. For this purpose, 130 women with ICP were randomly allocated to UDCA (1 g/day for three weeks), or dexamethasone (12 mg/day for 1 week and placebo during weeks 2 and 3), or placebo for 3 weeks. Pruritus and biochemical markers of cholestasis were analyzed at inclusion and after 3 weeks of treatment. Fetal complications (spontaneous preterm delivery; asphyxial events; and meconium staining of amniotic fluid, placenta, and membranes) were registered at delivery. An intention-to-treat analysis showed significant reduction of alanine aminotransferase (ALT) (P = .01) and bilirubin (P = .002) in the UDCA group only. In a subgroup analysis of ICP women with serum bile acids > or =40 micromol/L at inclusion (n = 34), UDCA had significant effects on pruritus (-75%), bile acids (-79%), ALT (-80%), and bilirubin (-50%) as well, but not on fetal complication rates. Dexamethasone yielded no alleviation of pruritus or reduction of ALT and was less effective than UDCA at reducing bile acids and bilirubin. In conclusion, 3 weeks of UDCA treatment improved some biochemical markers of ICP irrespective of disease severity, whereas significant relief from pruritus and marked reduction of serum bile acids were only found in patients with severe ICP.

Adult↗
PubMed2005

Changes in attitudes, knowledge and hormone replacement therapy use: a comparative study in two random samples with 6-year interval.

OBJECTIVES: To study changes in: (i) the prevalence of hormone-replacement therapy (HRT) and (ii) women's attitudes and knowledge about the climacteric. Design. Cross-sectional comparison was performed on two populations of women both aged 46-62 years and resident in the same urban Swedish population over a period of 6 years. MATERIAL AND METHODS: In 1992, a random sample of 5990 women, from five birth cohorts, 46, 50, 54, 58, and 62 years in the city of Göteborg, were assessed using a postal questionnaire technique. In 1998, the same technique was used and a similar questionnaire was sent to another cohort of women (n=5411) of the same ages, resident in the city of Göteborg. The overall response rate was 76%. Information was obtained regarding climacteric symptoms, HRT use, and attitudes and knowledge. RESULTS: The prevalence of HRT use with medium-potency estrogens had increased from 13% (1992) to 31% (1998). The highest prevalence was reported in women 54 years of age (46%). The most common reasons why women started HRT were: hot flushes and sweats, depression/irritability, sleeping disturbances, and vaginal dryness. Forty-four percent of the women in this study were prepared to consider extended HRT if the treatment was free from withdrawal bleedings (35%, 1992). Eighty percent believed that the risk of osteoporosis decreased during HRT use (61%, 1992) and 68% thought that the risk of breast cancer increased (58%, 1992). CONCLUSIONS: A marked increase in the use of HRT was reported between 1992 and 1998. Women's attitudes to HRT were more positive in 1998 compared to 1992. Knowledge about HRT among women had increased during the same 6-year period.

Body Mass Index↗
PubMed2004

Hormone replacement therapy, calcium and vitamin D3 versus calcium and vitamin D3 alone decreases markers of cartilage and bone metabolism in rheumatoid arthritis: a randomized controlled trial [ISRCTN46523456].

This study aimed to evaluate the effects of hormone replacement therapy (HRT), known to prevent osteoporosis and fractures, on markers of bone and cartilage metabolism. Furthermore, we assessed whether changes in these markers corresponded to alterations in bone mineral density and radiographic joint destructions in postmenopausal women with rheumatoid arthritis. Eighty-eight women were randomized to receive HRT, calcium, and vitamin D3, or calcium and vitamin D3 alone, for 2 years. Bone turnover was studied by analyzing serum levels of C-terminal telopeptide fragments of type I collagen (CTX-I), C-terminal telopeptide of type I collagen (ICTP), bone sialoprotein, and C-terminal propeptide of type I procollagen (PICP) and cartilage turnover by urinary levels of collagen type II C-telopeptide degradation fragments (CTX-II) and cartilage oligomeric matrix protein (COMP) in serum. Treatment with HRT resulted in decrease in CTX-I (P < 0.001), ICTP (P < 0.001), PICP (P < 0.05), COMP (P < 0.01), and CTX-II (P < 0.05) at 2 years. Reductions in CTX-I, ICTP, and PICP were associated with improved bone mineral density. Of the markers tested, CTX-I reflected bone turnover most sensitively; it was reduced by 53 +/- 6% in the patients receiving HRT. Baseline ICTP (P < 0.001), CTX-II (P < 0.01), and COMP (P < 0.05) correlated with the Larsen score. We suggest that biochemical markers of bone and cartilage turnover may provide a useful tool for assessing novel treatment modalities in arthritis, concerning both joint protection and prevention of osteoporosis.

Aged↗
PubMed2004

Intrahepatic cholestasis of pregnancy: Relationships between bile acid levels and fetal complication rates.

Intrahepatic cholestasis of pregnancy (ICP), characterized by pruritus in the second half of pregnancy, entails an increased risk to the fetus. This study was designed to determine the incidence and fetal complication rates in ICP, and to define groups at increased risk. In an prospective cohort study conducted between February 1, 1999, and January 31, 2002, all 45,485 pregnancies in a defined region of Sweden (Västra Götaland) were screened for ICP, defined as otherwise unexplained pruritus of pregnancy in combination with fasting serum bile acid levels > or = 10 micromol/L. Pruritus was reported by 937 (2.1%) women, and ICP was diagnosed in 693 (1.5%). Simple logistic regression analyses showed that the probability of fetal complications (spontaneous preterm deliveries, asphyxial events, and meconium staining of amniotic fluid, placenta, and membranes) increased by 1%-2% per additional micromol/L of serum bile acids. Complementary analyses showed that fetal complications did not arise until bile acid levels were > or = 40 micromol/L. Gallstone disease and a family history of ICP were significantly (P < .001) more prevalent in the group of ICP patients with higher bile acid levels. In conclusion, we found an incidence of ICP in our population of 1.5%. From complication rates recorded prospectively, we could define a mild (81%) and a severe (19%) form of ICP, the latter with bile acid levels > or = 40 micromol/L. No increase in fetal risk was detected in ICP patients with bile acid levels < 40 micromol/L, and we propose that these women be managed expectantly, which would significantly reduce the costs of medical care.

Bile Acids and Salts↗
PubMed2003

Hormone replacement therapy in rheumatoid arthritis is associated with lower serum levels of soluble IL-6 receptor and higher insulin-like growth factor 1.

Hormone replacement therapy (HRT) modulates the imbalance in bone remodeling, thereby decreasing bone loss. Sex hormones are known to influence rheumatic diseases. The aim of this study was to investigate the effects of HRT on the serum levels of hormones and cytokines regulating bone turnover in 88 postmenopausal women with active rheumatoid arthritis (RA) randomly allocated to receive HRT plus calcium and vitamin D3 or calcium and vitamin D3 alone for 2 years. An increase in estradiol (E2) correlated strongly with improvement of bone mineral density in the hip (P < 0.001) and lumbar spine (P < 0.001). Both baseline levels and changes during the study of IL-6 and erythrocyte sedimentation rate were correlated positively (P < 0.001). HRT for 2 years resulted in an increase of the bone anabolic factor, insulin-like growth factor 1 (IGF-1) (P < 0.05) and a decrease of serum levels of soluble IL-6 receptor (sIL-6R) (P < 0.05), which is known to enhance the biological activity of IL-6, an osteoclast-stimulating and proinflammatory cytokine. Baseline levels of IL-6 and IGF-1 were inversely associated (P < 0.05), and elevation of IGF-1 was connected with decrease in erythrocyte sedimentation rate (P < 0.05) after 2 years. Interestingly, increase in serum levels of E2 was associated with reduction of sIL-6R (P < 0.05) and reduction of sIL-6R was correlated with improved bone mineral density in the lumbar spine (P < 0.05). The latter association was however not significant after adjusting for the effect of E2 (P = 0.075). The influences of IGF-1 and the IL-6/sIL-6R pathways suggest possible mechanisms whereby HRT may exert beneficial effects in RA. However, to confirm this hypothesis future and larger studies are needed.

Aged↗
PubMed2003

Influence of hormone replacement therapy on disease progression and bone mineral density in rheumatoid arthritis.

OBJECTIVE: Hormone replacement therapy (HRT) is known to exert a positive effect in preventing bone loss and a beneficial effect on the disease activity in rheumatoid arthritis (RA). We evaluated the effects of HRT on bone mineral density (BMD) and on the course of established RA. METHODS: Eighty-eight postmenopausal women with RA were randomly allocated to receive HRT, vitamin D3, and calcium supplementation or vitamin D3 and calcium supplementation alone for 2 years. The effects of additional HRT on laboratory and clinical measures of disease activity, quality of life, and BMD and on radiographic joint damage were investigated. RESULTS: Treatment with HRT suppressed signs of inflammation as shown by reduction in erythrocyte sedimentation rate (ESR) (p = 0.025) and an elevation in hemoglobin concentration (p = 0.007), a better clinical outcome assessed by response on the Disease Activity Score 28 (DAS28) (p = 0.036), increased BMD in the forearm, proximal femur and spine (p < 0.01), and retarded (p = 0.026) progression of joint destruction among patients with radiological progressive disease. No significant effect on quality of life was seen. CONCLUSION: Two years of HRT in women with active RA had significant ameliorating effects on inflammation, DAS28 response, and BMD and was associated with slower progression of radiological joint destruction. The mechanisms by which HRT exerts its effects remain to be elucidated. We suggest HRT can be used in addition to conventional therapy in the management of postmenopausal patients with RA.

Absorptiometry, Photon↗