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Biomedical subjects

M Hammar

Publications and source records attributed to M Hammar.

At least 19 recordsLinked to original sources

Postmenopausal women without previous or current vasomotor symptoms do not flush after abruptly abandoning estrogen replacement therapy.

BACKGROUND: Most but not all women suffer from vasomotor symptoms around menopause. The exact mechanisms behind these symptoms are unknown, but the rate of decline in estrogen concentrations has been suggested to affect the risk of hot flushes. OBJECTIVE: The objective was to assess whether vasomotor symptoms were induced in women without previous such symptoms, when the women were given combined estradiol and progestagen therapy for 3 months, whereafter therapy was abruptly withdrawn. MATERIALS AND METHOD: After randomization, 40 postmenopausal women without previous or current vasomotor symptoms were treated transdermally with either 50 micrograms/day 17 beta-estradiol or placebo during 14 weeks. During the 13th and 14th weeks, treatment was combined with oral medroxyprogesterone acetate 10 mg/day. Serum estradiol and follicle-stimulating hormone (FSH) concentrations were analysed before and after 12 weeks of therapy. Climacteric symptoms were assessed at the same intervals as well as 8 weeks after the end of therapy. RESULTS: All women had low pretreatment levels of estradiol and high FSH concentrations. During estradiol therapy estradiol levels increased significantly, whereas FSH only decreased slightly. No woman developed vasomotor symptoms after withdrawal of therapy. CONCLUSION: Postmenopausal women without previous or current vasomotor symptoms did not develop such symptoms when estrogen replacement therapy was first instituted and then abruptly stopped. Probably other factors than the rate with which estrogen concentrations decrease determine whether or not a woman will develop vasomotor symptoms. Evidently, estrogens can be prescribed to a woman who has no vasomotor symptoms, without much risk of inducing such symptoms if she decides to abandon therapy, even after 3 months of treatment.

Administration, Cutaneous

Sex differences in neuropeptide distribution in the rat brain.

We have investigated possible sex differences in the regional concentrations of neuropeptides in the rat brain. Immunoreactive neurotensin (NT), neurokinin A (NKA), galanin (GAL), calcitonin gene-related peptide (CGRP), substance P (SP) and neuropeptide Y (NPY) were measured by radioimmunoassay in frontal cortex, occipital cortex, hippocampus, striatum, hypothalamus and pituitary in male and female pre- and postpubertal rats. Sex differences were found for NPY (p < 0.001), NT (p < 0.01) and GAL (p < 0.05), in particular in hippocampus, striatum, hypothalamus and pituitary, but not for CGRP, SP and NKA. Results from analysis of neuropeptides in one sex may not be entirely applicable to the other.

Animals

Acupuncture treatment of vasomotor symptoms in men with prostatic carcinoma: a pilot study.

PURPOSE: Most men who undergo castration therapy for prostatic carcinoma will have vasomotor symptoms that usually persist for years. Vasomotor symptoms are elicited from the thermoregulatory center, possibly due to a decrease in hypothalamic opioid activity induced by low sex steroid concentrations. Acupuncture treatment in women, which stimulates hypothalamic opioid activity, alleviates vasomotor symptoms. We report on men treated with acupuncture for relief of vasomotor symptoms after castration therapy. MATERIALS AND METHODS: We asked 7 men with vasomotor symptoms due to castration therapy to receive acupuncture treatment 30 minutes twice weekly for 2 weeks and once a week for 10 weeks. Effects on flushes were recorded in logbooks. RESULTS: Of the 7 men 6 completed at least 10 weeks of acupuncture therapy and all had a substantial decrease in the number of hot flushes (average 70% after 10 weeks). At 3 months after the last treatment the number of flushes was 50% lower than before therapy. Therapy was discontinued after 10 weeks because of a femoral neck fracture in 1 man and after 3 weeks due to severe back pain in 1. CONCLUSIONS: Acupuncture may be a therapeutic alternative in men with hot flushes after castration therapy and merits further evaluation.

Acupuncture Therapy

The relationship between stress-coping and vasomotor symptoms in postmenopausal women.

OBJECTIVE: The objective was to assess whether menopausal women with vasomotor symptoms had a lower stress-coping than menopausal women without symptoms and if stress-coping changed when vasomotor symptoms had been effectively treated with estrogens. The objective was also to assess whether menopausal women, effectively treated for vasomotor symptoms, had a higher neuroticism score than women without such symptoms. METHODS: Two groups of physically and mentally healthy postmenopausal women were recruited from the outpatient clinic at the Department of Obstetrics and Gynaecology, University Hospital of Linköping, Sweden. Sixteen women with vasomotor symptoms (target group) were treated with oral 17 beta-estradiol, 2 mg/day during 3 months. A comparison group was formed comprising 17 women without vasomotor symptoms. The Kupperman Index was used to cover menopausal characteristics in all women at baseline as well as at the second visit after 3 months. Stress-coping was measured by means of the Stress Coping Inventory, which is an instrument developed to measure of the individual's appraisal of having adaptive resources for handling stressful situations. At the second visit all women were also asked to complete the Eysenck Personality Inventory. RESULTS: Women in the target group had a significantly lower stress-coping than women in the comparison group at baseline as well as after 3 months. Stress-coping did not change after estrogen therapy, although the vasomotor symptoms had virtually disappeared. Women in the target group successfully treated for vasomotor symptoms, had a significantly higher neuroticism score compared to the comparison group. CONCLUSIONS: Differences in behaviour patterns and personality are probably two reasons why some women report or seek advice due to vasomotor symptoms and some women do not. Stress-coping in women with moderate to severe vasomotor symptoms is unaffected by estrogens.

Adaptation, Psychological

Postmenopausal women with vasomotor symptoms have increased urinary excretion of calcitonin gene-related peptide.

OBJECTIVES: To establish whether 24 h urinary excretion of the potent vasodilator calcitonin gene-related peptide (CGRP) was higher in postmenopausal women with vasomotor symptoms compared to the level in women without symptoms. We also wanted to establish whether urinary excretion of CGRP changed during the menstrual cycle in women of fertile age. MATERIAL AND METHODS: Thirteen postmenopausal women with and 13 women without vasomotor symptoms were included. Urine was collected over 24 h and CGRP excretion was measured utilizing radio-immunoassay technique. Twenty-four hour CGRP excretion was also measured in ten fertile women with regular cycles in early follicular, preovulatory and midluteal phase. RESULTS: Twenty-four hour urinary excretion of CGRP was significantly higher in women with vasomotor symptoms compared to non-flushing women (median 7.16 vs 5.15 pmol/24 h; P = 0.028). CGRP concentrations were stable throughout the ovulatory cycles. CONCLUSION: The 24 h urinary excretion of CGRP is higher in women with vasomotor symptoms than in women without these symptoms. CGRP may be the mediator of vasodilator signals originating from the thermoregulatory center.

Calcitonin Gene-Related Peptide

Physical exercise and vasomotor symptoms in postmenopausal women.

BACKGROUND: The mechanisms causing postmenopausal vasomotor symptoms are unknown, but changes in hypothalamic beta-endorphins have been suggested to be involved. beta-endorphin production may be increased by regular physical exercise. OBJECTIVE: To assess if physically active women suffered from vasomotor symptoms to a lower extent than sedentary women. MATERIAL AND METHODS: All women (n = 1323) in the ages ranging from 55-56 years in the community of Linköping Sweden, were included. In a questionnaire these women were asked about their physical exercise habits and their complaints from vasomotor symptoms. Only those 793 women who had reached a natural menopause were grouped into sedentary, moderately or highly active women, based on a physical activity score. RESULTS: Only 5% of highly physically active women experienced severe hot flushes as compared with 14-16% of women who had little or no weekly exercise (P < 0.05; relative risk 0.26; CI 95%: 0.10-0.71). This was not explained by differences in body mass index, smoking habits or use of hormone replacement therapy. Women who used hormone replacement therapy were more physically active than non-users (P < 0.05). CONCLUSION: Fewer physically active women had severe vasomotor symptoms compared with sedentary women. This may be due to a selection bias but also to the fact that physical exercise on a regular basis affects neurotransmitters which regulate central thermoregulation.

Estrogen Replacement Therapy

Follow-up of patients with low back pain during pregnancy.

OBJECTIVE: To identify the long-term risk for low back pain among women with previous severe low back pain during pregnancy. METHODS: In a previous prospective study, 79 pregnant women developed low back pain severe enough to require sick leave. Twelve years later a questionnaire was sent to 62 of these women and 84 controls who did not develop severe low back pain during pregnancy. The questionnaire asked about occupation, low back pain in general and during later pregnancies, and sick leave due to low back pain. There were also questions regarding use of oral contraceptives and its possible relation to low back pain. RESULTS: The response rate was 84% in the back pain group and 80% among controls. The two groups were similar according to the percentage of women having had another pregnancy (33 of 52 [63%] versus 39 of 67 [58%]) but ten (19%) of the women with previous low back pain stated they had refrained from another pregnancy because of their fear of low back pain compared with only one control. Almost all women (31 of 33) with previous severe low back pain experienced the same symptoms in a subsequent pregnancy, compared with 17 of 39 (44%) controls. Even when they were not pregnant, women with previous low back pain suffered more often and used more sick leave due to low back pain (44 of 52 versus 43 of 67, chi2 = 5.68, P < .05). The location (sacroiliac joint or lumbar affection) of the previous low back pain did not affect the long-term prognosis. In a logistic regression model, previous low back pain during pregnancy was the only independent risk factor for low back pain during a subsequent pregnancy, whereas an occupation involving physical demand did not affect the results. However, together with previous low back pain during pregnancy, heavy occupation increased the risk for current nonpregnant low back pain. CONCLUSION: Women with severe low back pain during pregnancy have an extremely high risk for experiencing a new episode of severe low back pain during another pregnancy and when not pregnant.

Adult

Effects of physical activity and acupuncture on calcitonin gene-related peptide immunoreactivity in different parts of the rat brain and in cerebrospinal fluid, serum and urine.

Calcitonin gene-related peptide (CGRP) is a very potent vasodilator in the nervous system, and may be involved in hot flushes experienced by most women around menopause. Flushing post-menopausal women had higher urinary excretion of CGRP before than after successful treatment of their flushes with acupuncture. The prevalence of vasomotor symptoms is lower in physically active women. In a rat model we therefore intended to assess whether acupuncture and exercise affected CGRP concentrations in different parts of the brain and peripherally. The aim of the study was to elucidate the short- and long-term effects of exercise and acupuncture on CGRP concentrations in the nervous system of normal adult rats. In a rat model, we examined the effects of single interventions and long-term treatment with physical exercise and manual or electro-acupuncture on CGRP concentrations in urine, cerebrospinal fluid and serum and different parts of the brain. In all compartments studied, but significantly only in the cerebrospinal fluid, CGRP increased after a single session of physical exercise or electro-acupuncture. Manual acupuncture did not change CGRP concentrations in any compartment. Rats had the highest concentrations of CGRP in the pituitary and hypothalamus but the concentrations did not differ significantly between control rats and those subjected to long-term treatment with manual or electro-acupuncture or running rats. Rats treated with electro-acupuncture had twice the CGRP concentration in the frontal cortex compared to control rats, albeit the difference did not reach statistical significance. Evidently manual and electro-acupuncture have different effects, whereas electro-acupuncture and physical exercise have more similar effects on CGRP production and/or release. To elucidate the role of CGRP in vasomotor symptoms, further studies with older flushing rats should be performed.

Anesthesia, Intravenous

A double-blind, randomised trial comparing the effects of tibolone and continuous combined hormone replacement therapy in postmenopausal women with menopausal symptoms.

OBJECTIVE: To compare the effects of two postmenopausal regimens on menopausal symptoms, bleeding episodes, side effects and acceptability. DESIGN: Double-blind, randomised controlled trial. SETTING: Twenty-nine sites in Denmark, nine in Norway and six in Sweden. PARTICIPANTS: Four hundred and thirty-seven postmenopausal women with menopausal complaints. None of these women had had a hysterectomy. INTERVENTIONS: Daily treatment with tibolone 2.5 mg (n = 218) or 17beta-oestradiol 2 mg plus norethisterone acetate 1 mg (E2/NETA) (n = 219). MAIN OUTCOME MEASURES: Hot flushes, sweating episodes, vaginal dryness, assessment of sexual life and bleeding patterns; at baseline and after 4, 12, 24 and 48 weeks. RESULTS: Treatment with either preparation significantly reduced mean scores for hot flushes, sweating episodes and vaginal dryness. The overall discontinuation rate was 28% (tibolone 25%, E2/NETA 31%; P = 0.14), mostly during the first six months. There was a markedly lower cumulative incidence of bleeding or spotting episodes with tibolone compared with E2/NETA (P < 0.0001), mainly during the first six treatment cycles. CONCLUSIONS: Both tibolone and E2/NETA effectively alleviate menopausal symptoms. However, tibolone caused significantly fewer bleeding or spotting episodes, which were reflected by lower overall rates of bleeding, as well as lower drop-out rates due to bleeding.

Anabolic Agents

Curli fibers are highly conserved between Salmonella typhimurium and Escherichia coli with respect to operon structure and regulation.

Mouse-virulent Salmonella typhimurium strains SR-11 and ATCC 14028-1s express curli fibers, thin aggregative fibers, at ambient temperature on plates as judged by Western blot analysis and electron microscopy. Concomitantly with curli expression, cells develop a rough and dry colony morphology and bind the dye Congo red (called the rdar morphotype). Cloning and characterization of the two divergently transcribed operons required for curli biogenesis, csgBA(C) and csgDEFG, from S. typhimurium SR-11 revealed the same gene order and flanking genes as in Escherichia coli. The divergence of the curli region between S. typhimurium and E. coli at the nucleotide level is above average (22.4%). However, a high level of conservation at the protein level, which ranged from 86% amino acid homology for the fiber subunit CsgA to 99% homology for the lipoprotein CsgG, implies functional constraints on the gene products. Consequently, S. typhimurium genes on low-copy-number plasmids were able to complement respective E. coli mutants, although not always to wild-type levels. rpoS and ompR are required for transcriptional activation of (at least) the csgD promoter. The high degree of conservation at the protein level and the identical regulation patterns in E. coli and S. typhimurium suggest similar roles of curli fibers in the same ecological niche in the two species.

Bacterial Outer Membrane Proteins

Impact of oestradiol and progesterone on antioxidant activity in normal human breast epithelial cells in culture.

The risk of developing breast cancer increases after long term use of oestrogen and progestagen, and carcinogenesis in the breast is partly due to oxidative damage to DNA bases. Therefore, we studied the effects of 17 beta-oestradiol and progesterone on the antioxidative status and the vulnerability to oxidative stress exhibited by normal human breast epithelial cells in culture. After exposure to hydrogen peroxide, cells grown with oestradiol alone or with both oestradiol and progesterone showed significantly decreased viability compared to cells grown in medium without added hormones. There was, however, no difference in hydrogen peroxide degradation rate between controls and hormone treated cultures. When desferrioxamine was added, the viability increased and the hydrogen peroxide degradation rate decreased. The levels of several antioxidants were altered in cells grown in the presence of oestradiol and progesterone: the concentrations of glutathione reductase and catalase decreased significantly while the levels of glutathione peroxidase and reduced glutathione did not change. The alterations in enzyme activity and cell vulnerability were more pronounced in cultures treated with a combination of oestradiol and progesterone. We conclude that the redox balance in the cultured normal human breast epithelial cells was altered by treatment with oestradiol and progesterone, and that this change led to the increased death of cells subsequently exposed to hydrogen peroxide. This effect may have implications for sex hormone dependent diseases of the breast.

Adult

[Estrogen and natural products in the treatment of postmenopausal complaints. Oral contraceptives prepare the way for hormonal substitution].

To chart current and previous use of hormone replacement therapy (HRT) and alternative remedies in a postmenopausal population, in relation to previous oral contraceptive (OC) usage, all 1,323 55-56-year-old women living in Linköping in 1995 were sent a questionnaire concerning health status and climacteric symptoms, and previous and/or current use of HRT, OCs and alternative remedies. Current HRT was more common among previous OC users than among those who had never used OCs (41.4 vs. 23.1 percent). As compared with non-HRT users, HRT users were characterised by greater physical activity but less strenuous occupations, and a higher prevalence of hysterectomy. Of the series as a whole, 35 per cent were currently on HRT, half of them having been so for at least two years, and only 5 per cent had abandoned HRT after trying it for some time. Alternative remedies were used by 5 per cent of the women as therapy for climacteric complaints, but about four times as many women had tried such therapy and abandoned it. The sole characteristic feature of alternative remedy usage was that it was less common among hysterectomised women. Of women treated for breast cancer, none used HRT and few used alternative remedies. Thus, in this postmenopausal population, the prevalence of HRT was high, as was the level of compliance. Previous OC usage was probably a determinant of current attitudes toward HRT.

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