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Biomedical subjects

Britt-Marie Landgren

Publications and source records attributed to Britt-Marie Landgren.

15 recordsLinked to original sources

Small artery endothelial dysfunction in postmenopausal women: in vitro function, morphology, and modification by estrogen and selective estrogen receptor modulators.

OBJECTIVE: Our objective was to assess vascular endothelial function and morphology in resistance vasculature from healthy pre- and postmenopausal women in vitro and to determine potential mechanisms of vascular protection by estrogenic compounds. METHODS: Arteries (approximately 220 microm) were dissected from sc fat biopsies obtained from healthy premenopausal and postmenopausal women. Flow-mediated dilatation, agonist-induced endothelium-dependent and -independent relaxation, and myogenic responses to changes in intraluminal pressure were evaluated before and after incubation (3 h) with 17beta-estradiol, propyl pyrazole triol [a selective estrogen receptor-alpha (ERalpha) agonist], raloxifene (a second-generation selective ER modulator), and the phytoestrogen genistein, using pressure myography technique. In addition, endothelial morphology was assessed in arteries from pre- and postmenopausal women, and distribution of ERs within the artery wall from postmenopausal women was evaluated. RESULTS: Functional and morphological disturbances of endothelial function were observed in small arteries from postmenopausal women. Incubation with 17beta-estradiol improved postmenopausal resistance artery function, an effect mimicked by propyl pyrazole triol but not raloxifene or genistein. Immunohistochemical staining revealed similar expression of ERalpha and ERbeta in the smooth muscle of arteries from postmenopausal women; however, ERalpha was dominant in endothelium. CONCLUSIONS: The resistance arteries from postmenopausal women show functional and morphological abnormalities. ERalpha may contribute to vascular protection by estrogens in the peripheral resistance circulation in postmenopausal women. Selective ERalpha agonists warrant further investigation as therapeutic agents for prevention of cardiovascular disease in postmenopausal women.

Adult↗

Does body mass index, smoking, lipoprotein levels, surgically induced menopause, hormone replacement therapy, years since menopause, or age affect hemostasis in postmenopausal women?

BACKGROUND: Controversy still exists as to the relative importance of menopausal status and lifestyle factors for the risk of coronary heart disease in women. OBJECTIVE: The purpose of this study was to assess the influence of body mass index (BMI), smoking,lipoprotein levels, surgically induced menopause, hormone replacement therapy (HRT), years since menopause, and age on hemostasis in apparently healthy postmenopausal women. METHODS: Lipoproteins (total cholesterol [TC], low-density lipoprotein cholesterol, high-density lipoprotein cholesterol [HDL-C], triglycerides [TG]), and hemostatic factors (fibrinogen, von Willebrand factor antigen [vWFag], coagulation factors VIIag [FVIlag] and VIIa [FVIIa], plasminogen activator inhibitor 1 [PAI-1]) were each measured once. A forward, stepwise, multiple regression analysis was used to assess variations in hemostatic parameters. RESULTS: A group of 292 healthy Stockholm women recruited from the census register participated in the Stockholm Female Coronary Risk Study as controls. Of these women, 260 participated in the present study. BMI, smoking, lipoprotein levels, surgically induced menopause, and years since menopause (1-5 y) were found to be associated with a 31% increase in fibrinogen levels. A 7% increase in FVIIa levels was attributed to TC, BMI, and HRT. Years since menopause (1-15 y), TG, TC, BMI, and HRT were associated with an increase of up to 26% in FVIIag levels. A 9% increase in vWFag correlated with HDL-C and years since menopause (1-10, 11-14, and > or =15 y). BMI and TG explained a 21% and 3% increase, respectively, in PAI-1 levels. Neither the use of HRT nor years since menopause had any influence on hemostasis. CONCLUSION: BMI, high levels of TC and TG, and low HDL-C levels appear to be more important than hormonal status in their impact on hemostatic variables in healthy postmenopausal women.

Adult↗

The effect of physical training on bone mineral density in women with endometriosis treated with GnRH analogs: a pilot study.

BACKGROUND: The effect of physical training on bone mineral density (BMD) in women with endometriosis treated with gonadotropin-releasing hormone (GnRH) analogs was studied. METHODS: Nineteen Caucasian premenopausal women aged 23-38 years were included in the study. The subjects were all treated with 21.6 mg goserelin during 6 months. The patients were randomized to physical training n=8 or to a control group n=11. The total period of training was 12 months, whereas GnRH treatment was terminated after 6 months. BMD was measured in the femoral neck area and the lumbar spine using dual X-ray absorptiometry (DEXA). This was performed just before treatment, after 6 months and after 12 months. Six women fulfilled the training during 12 months of observation. In the control group 10 women were followed up for 12 months. RESULTS: After 6 months the women in the physical training group were 2.1% below baseline. Six months later these women had gained BMD in the femoral neck and were 0.6% below baseline. Those in the control group lost 2.8% after 6 months and were 3.6% below baseline after 12 months. The difference in loss of BMD after 12 months between the groups was significant 0.029. In the spine there was no significant difference between the two groups. CONCLUSIONS: Physical training in women with endometriosis was found to rebuild bone after treatment with GnRH analogs when compared to a control group. This effect could be demonstrated 6 months after cessation of GnRH treatment.

Absorptiometry, Photon↗

Role of progestins in contraception.

Progestins have been used for contraception for more than 30 years. The main goal was to develop a contraceptive method devoid of the metabolic or clinical side-effects associated with the use of estrogens. The development of new contraceptive methods and formulations is time-consuming and requires devotion, belief, and also strong economical basis. As a result of this endeavor new methods have been developed: oral progestins, implants, injectables, intrauterine hormonal systems, and vaginal rings. Progestin-only contraceptives may be preferable in some situations, which have absolute or relative contraindications to estrogen, side-effects to estrogen containing hormonal contraception, lactation, and comfort and feasibility of formulations for long-term use. At present, emergency contraception is also performed with progestin.

Cervix Mucus↗

Ecological effects of perorally administered pivmecillinam on the normal vaginal microflora.

The knowledge of the effects of antimicrobial agents on the normal vaginal microflora is limited. The objective of the present study was to study the ecological impact of pivmecillinam on the normal vaginal microflora. In 20 healthy women, the estimated day of ovulation was determined during three subsequent menstrual cycles. Microbiological and clinical examinations were performed on the estimated day of ovulation and on day 3 in all cycles and also on day 7 after ovulation in cycles 1 and 2. Anaerobic and facultative anaerobic gram-positive rods, mainly species of lactobacilli and actinomycetes, dominated the microflora. One woman was colonized on the third day of administration with a resistant Escherichia coli strain, and Candida albicans was detected in one woman on days 3 and 7 in cycle 2. No other major changes in the normal microflora occurred during the study. Administration of pivmecillinam had a minor ecological impact on the normal vaginal microflora.

Actinobacteria↗

Physical training and hormone replacement therapy reduce the decrease in bone mineral density in perimenopausal women: a pilot study.

The effects of physical training and hormone replacement therapy (HRT) on bone mineral density in perimenopausal women were studied. Sixty perimenopausal women were randomized to either physical training (n = 20), HRT (n = 20), or control group (n = 20). The study period was 18 months. Bone mineral density (BMD) in the femoral neck and lumbar spine was measured using dual-energy X-ray absorptiometry (DXA). DXA was performed before treatment and after 6 and 18 months. Blood samples for analysis of the bone markers U-deoxypyridinoline and osteocalcin were collected at the same time points. After 18 months, BMD in the spine had not decreased in either the training group or in the HRT group. In the control group, spine BMD had significantly decreased (p = 0.0014). U-Deoxypyridinoline and osteocalcin were increased significantly in the control group (p = 0.0198, p = 0.0295, respectively). No significant changes in bone marker levels were found in the training group or the HRT group. We found that both HRT and physical training can prevent loss of spine BMD in perimenopausal women over a period of 18 months. HRT remains a cornerstone in the treatment of vasomotor symptoms and preservation of BMD. However, HRT can only be used for limited periods of time due to the potential serious adverse effects. This study indicates a beneficial effect of physical activity on spine BMD in the perimenopausal period, and highlights its potential as an alternative to HRT during this period.

Absorptiometry, Photon↗

Circulating angiogenic factors during periovulation and the luteal phase of normal menstrual cycles.

OBJECTIVE: To measure serial serum concentrations of the angiogenic factors vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and angiogenin (ANG) in the periovulatory and secretory phase of normal menstrual cycles in healthy women and to determine their peaks, which might reflect the stage of their critical angiogenic action. DESIGN: Prospective study. SETTING: University departments of obstetrics and gynecology. PARTICIPANT(S): Thirty-three healthy Swedish women with regular menstrual cycles. INTERVENTION(S): Serial blood samples were collected from each woman. Luteinizing hormone surge was identified by testing morning urine. MAIN OUTCOME MEASURE(S): Circulating levels of VEGF, bFGF, and ANG. RESULT(S): Circulating peak concentrations were determined for VEGF on day 0 and 9 after ovulation, for bFGF on day 1 before ovulation and day 9 after ovulation, and for ANG on day 3 after ovulation. CONCLUSION(S): Circulating VEGF increased in a stage-dependent cyclic fashion. Basic FGF peaked during the late proliferative and mid secretory phase. Circulating ANG showed increased expression around the early secretory phase of the cycle.

Adult↗

Menopause transition: Annual changes in serum hormonal patterns over the menstrual cycle in women during a nine-year period prior to menopause.

To examine the hormonal characteristics of menstrual cycles in healthy women approaching menopause, serum hormone profiles were investigated annually in this longitudinal study of 13 healthy women between 4 and 9 yr before menopause and the year of the menopause. Serum FSH, LH, estradiol, progesterone, total inhibin, inhibins A and B, and prolactin were determined in blood samples collected annually three times weekly for 4 wk beginning with the onset of menses. Menstrual bleeding diaries covering this 4- to 9-yr period were also collected allowing the prospective identification of the final menstrual period. A change in serum hormone patterns was observed in cycles approaching menopause, exemplified by an increasing number of cycles of prolonged length with a prolonged follicular phase resulting in a failure to detect a luteal phase rise in serum progesterone within the 4-wk collection period. These prolonged cycles (designated B cycles based on a previous work) were analyzed separately and compared with the remaining ovulatory (D) cycles. No B cycles were identified in any women earlier than 27 cycles from menopause. The proportion of B cycles increased as menopause approached, reaching 62% in the last 10 cycles. The proportion of D cycles decreased accordingly. The B cycles during the initial 4-wk collection period were characterized by elevated FSH, LH, FSH/inhibin A and FSH/inhibin B ratios, and longer duration, although cycle length/subject was not significantly different presumably due to the small number of B cycles. The D cycles showed no changes in hormonal profiles over the 4- to 9-yr time period. These data indicate that there is a time-related change in the character of menstrual cycles as menopause approaches, with an increasing proportion of cycles observed with prolonged follicular phases that may either be delayed ovulatory cycles or anovulatory cycles. The increase in the proportion of B cycles with elevated early follicular phase FSH levels and low inhibin/FSH ratios toward menopause provides a basis for the apparent early increase in serum FSH and decrease in serum inhibins observed previously in studies of the menopause transition based on sampling confined to the follicular phase only. The data amplify and clarify current concepts of the endocrine basis of the menopause transition.

Estradiol↗

Coexpression of pinopodes and leukemia inhibitory factor, as well as its receptor, in human endometrium.

OBJECTIVE: To determine cell-type-specific expression of leukemia inhibitory factor (LIF) and LIF receptor (LIFR) proteins relative to formation of pinopodes in human endometrial samples. DESIGN: Prospective clinical study. SETTING: Hospital-based unit for reproductive health and university-affiliated reproductive research laboratories. PATIENT(S): Twenty-six healthy fertile women with normal menstrual cycles. MAIN OUTCOME MEASURE(S): Routine blood and urine samples were obtained, and vaginal ultrasonography and endometrial biopsy were performed. Pinopode formation and expression of LIF and LIFR were examined in endometrial samples. RESULT(S): Samples obtained during LH days 6 through 9 had pinopodes at different developmental stages. Both surface and glandular epithelial cells expressed maximal levels of LIF and LIFR protein, in biopsy samples showed fully developed pinopodes. Immunostaining of LIF was more intense in the glandular epithelium, whereas immunostaining of LIFR was most intense in the surface epithelium. Before and after the appearance of pinopodes, LIF and LIFR immunostaining was less intense or faint. Stromal endometrial cells showed faint LIF accumulation. CONCLUSION(S): The simultaneous positive spatial and temporal expression of pinopodes and LIF and LIFR proteins in endometrial samples from healthy women suggests that both molecular and structural cell changes are important in the initiation of human blastocyst implantation.

Adult↗

Development and characterization of an endometrial tissue culture system.

A culture system has been developed for pieces of whole endometrium, comprising many different cell types. The system maintains the integrity of all compartments important for tissue function and allows functional studies of the human endometrium. Endometrial biopsy strips were collected from fertile women. The strips were cut into small pieces and cultured for 8 h on dishes pre-coated with Matrigel. The oxygen concentration was kept low (5%), since it was shown to be beneficial for the culture in preliminary studies. Scanning electron microscopy and immunohistochemical detection of proliferating cell nuclear antigen (PCNA), oestrogen receptor alpha (ERalpha), progesterone receptor (PR) A + B and B and TUNEL were used to characterize the endometrium. During culture, the luminal and glandular epithelial cells began to cover the surface injured when cutting the sample, suggesting a healing process. The luminal epithelial surface appeared normal after culture. There was an increased sensitivity to culture after the implantation window. This new method for culture of endometrial strips in vitro has proven successful and may be used for functional studies of the human endometrium.

Adult↗

Repolarization measures and their relation to sex hormones in postmenopausal women with cardiovascular disease receiving hormone replacement therapy.

Women are more susceptible to the development of Torsades de Pointes ventricular tachycardia and have a longer heart rate-corrected QT interval than men. A causal role for estrogen has been implicated. The purpose of this study was to investigate if hormone replacement therapy (HRT) resulted in any changes in noninvasive depolarization and repolarization measurements, and to study their relation to circulating concentrations of sex hormones. Sixty postmenopausal women with cardiovascular disease (mean age 59 +/- 7 years; range 44 to 75) were randomized to receive oral conjugated estrogens, transdermal estradiol-17-beta (both with addition of progestins), or placebo. QRS, QT, and JT intervals and their dispersion on 12-lead electrocardiograms were analyzed at baseline, and after 6 and 12 treatment cycles of HRT. Blood samples for analyses of serum concentration of estrogens and androgens were obtained on the same occasions. Neither mean RR, QT, QTc, JT, and JTc intervals, nor QT and JT dispersion changed during treatment. There was a significant inverse relation between the mean JTc interval and the serum concentration of estradiol-17-beta, independent of age, testosterone levels, and abdominal obesity. There was also a significant inverse relation between the change in androstenedione levels and the change in QT interval (Spearman -0.35, p = 0.028) or JT interval (Spearman -0.41, p = 0.009) at 6 treatment cycles compared with baseline. In conclusion, treatment with oral conjugated estrogens or transdermal estradiol-17-beta combined with progestins did not alter depolarization or repolarization measurements. However, the inverse relation between repolarization and androgens fits with an effect of androgens on repolarization in postmenopausal women.

Administration, Cutaneous↗

Lipoproteins and BMI: a comparison between women during transition to menopause and regularly menstruating healthy women.

UNLABELLED: One hundred and forty-three women born 1942 were followed for 5 years during transition to menopause (49--54 years of age). Changes in menopausal status, body mass index (BMI) and circulating lipoproteins cholesterol, (chol), low density lipoprotein (LDL), high density lipoprotein, (HDL) and total triglycerides (TG) were measured, once yearly and compared with a control group of normally menstruating healthy, non-smoking women 23--39 years old. RESULTS: Chol was significantly higher P<0.0001 in the study group visits 1--5 when compared with the controls and higher at visit 4 compared with visit 1(P<0.05) LDL was significantly lower in the study group and at visit 5 compared with visit 2 (P<0.05) HDL was significantly lower at visits 1--3 and 5 when compared with the controls (P<0.001) and to visit 4 (P<0.0001). TG was significantly higher in the study group (P<0.0001) and increased significantly during the 5-year study. BMI was significantly higher in the older women (P<0.001) and increased during 5-years of study (P<0.0001). When multiple stepwise regression analyses were performed at visit 5 using education, menopausal status, use of hormone replacement therapy (HRT), BMI and smoking as predictor variables, postmenopausal status was found to be significantly associated with high LDL (P<0.3), while high BMI significantly predicted low HDL and high TG levels. Perimenopausal status was significantly associated with high HDL levels. CONCLUSION: Age, BMI and menopausal status are significant predictors of circulating lipoprotein levels during transition to menopause.

Adult↗

Co-existence of heparin-binding epidermal growth factor-like growth factor and pinopodes in human endometrium at the time of implantation.

Pinopodes have been suggested to be markers of uterine receptivity. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is expressed in increasing amounts in the secretory phase endometrium and is considered to be important for the human implantation process. The aim of this study was to investigate a possible co-existence of pinopodes and HB-EGF in the normal human endometrium. Endometrial biopsies were obtained from women with normal menstrual cycles. The biopsies were examined by scanning electron microscopy for the detection of pinopodes, by immunohistochemistry for the expression of HB-EGF protein, and by confocal microscopy to determine if HB-EGF was present on the surface of the pinopodes. The expression of HB-EGF in luminal and glandular epithelium was highest when fully developed pinopodes were present. Using confocal microscopy it was shown that HB-EGF was present both inside the luminal epithelial cells and on the surface of pinopodes. These findings suggest that HB-EGF might play a role in both the attachment and penetration steps in the human implantation process. Furthermore, the immunohistochemical staining demonstrates that HB-EGF can be used as a marker for the implantation window.

Adult↗

The relationship between the endocrine characteristics and the regularity of menstrual cycles in the approach to menopause.

OBJECTIVE: There is currently little longitudinal data available on the serum hormonal characteristics of the menstrual cycles observed in women as they approach their final menstrual period (FMP) or menopause. We sought to determine whether the onset of irregular menses, marking the menopause transition, signifies the occurrence of anovulatory, potentially infertile cycles. DESIGN: We studied 12 subjects, initially aged 45 to 47 years, who provided daily menstrual diaries, and had blood samples collected annually, three times weekly for 4 consecutive weeks, over a period of 36 to 98 months until FMP, for measurements of serum follicle-stimulating hormone (FSH), luteinizing hormone, estradiol, and progesterone. The definition of entry into the early menopause transition was the occurrence of more than two cycles, in any consecutive sequence of 10, where cycle length was less than 23 or more than 35 days. Entry into the late transition was determined from the first observation of either 60-day or 90-day amenorrhea. Cycles were characterized endocrinologically as normal ovulatory, abnormal luteal phase, and anovulatory with evidence of ovarian follicular activity. RESULTS: The early transition had an average duration of 47 months from onset until FMP. Ten of the 12 subjects had one or more ovulatory cycles during the transition. Anovulatory cycles with ovarian activity were noted in 9 of the 12 subjects, only after entry into early and/or late transition. CONCLUSIONS: Ovulatory cycles occurred both before and after entry into the early and/or late menopause transition in subjects older than 45 years of age, whereas anovulatory cycles were observed only during the transition. The ovulatory cycles were generally associated with normal menses, whereas anovulatory cycles showed long duration and/or abnormal bleeding patterns. The occurrence of cycle irregularity is associated with an increasing frequency of anovulatory cycles, which herald the occurrence of FMP. No conclusion could be drawn regarding the appropriate definition of entry into the late transition. The definition adopted for entry into the early transition merits further validation.

Anovulation↗