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PubMed2006

Oxidative stress contributes to chronic leg vasoconstriction in estrogen-deficient postmenopausal women.

Basal whole leg blood flow and vascular conductance are reduced in estrogen-deficient postmenopausal compared with premenopausal women. The underlying mechanisms are unknown, but oxidative stress could be involved. We studied 9 premenopausal [23 +/- 1 yr (mean +/- SE)] and 20 estrogen-deficient postmenopausal (55 +/- 1 yr) healthy women. During baseline control, oxidized low-density lipoprotein (LDL), a marker of oxidative stress, was 50% greater in the postmenopausal women (P < 0.001). Basal whole leg blood flow (duplex ultrasound of femoral artery) was 34% lower in the postmenopausal women because of a 38% lower leg vascular conductance (P < 0.0001); mean arterial pressure was not different. Intravenous administration of a supraphysiological dose of the antioxidant ascorbic acid increased leg blood flow by 15% in the postmenopausal women as a result of an increase in leg vascular conductance (both P < 0.001), but it did not affect leg blood flow in premenopausal controls or mean arterial pressure in either group. In the pooled subjects, the changes in leg blood flow and leg vascular conductance with ascorbic acid were related to baseline plasma oxidized LDL (r = 0.46 and 0.53, P < 0.01) and waist-to-hip ratio and total body fat (r = 0.41-0.44, all P < 0.05). Our results are consistent with the hypothesis that oxidative stress contributes to chronic leg vasoconstriction and reduced basal whole leg blood flow in estrogen-deficient postmenopausal women. This oxidative stress-related suppression of leg vascular conductance and blood flow may be linked in part to increased total and abdominal adiposity.

Adult↗

PubMed2002

Effects of continuous combined hormone replacement therapy on inflammation in hypertensive and/or overweight postmenopausal women.

OBJECTIVE: We observed that estrogen did not show cardioprotective benefits in type 2 diabetic postmenopausal women. We hypothesized that hypertensive and/or overweight women may be less likely to realize cardiovascular benefits from estrogen. METHODS AND RESULTS: We administered micronized progesterone (MP) 100 mg or medroxyprogesterone acetate (MPA) 2.5 mg with conjugated equine estrogen (CEE) 0.625 mg daily during 2 months to 35 hypertensive and/or overweight postmenopausal women with a randomized, double-blind, crossover design. With significant changes of lipoproteins, CEE+MP or MPA significantly improved flow-mediated dilation and reduced plasma E-selectin, intercellular adhesion molecule type-1, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha levels (P<0.001, P<0.001, P=0.021, P<0.001, and P<0.001 by ANOVA, respectively), but not C-reactive protein and fibrinogen levels. Of note, there were no significant differences between each therapy regarding these effects. However, the magnitude of improvement of flow-mediated dilation in these women was less than in healthy postmenopausal women and more than in diabetic postmenopausal women reported by our previous studies. The effects of CEE+MP or MPA on inflammatory markers were comparable to healthy postmenopausal women, but not comparable to diabetic postmenopausal women. CONCLUSIONS: Estrogen combined with synthetic progestin significantly improved flow-mediated brachial artery dilator response and reduced inflammation markers in hypertensive and/or overweight women, comparable to estrogen combined with natural progesterone.

Animals↗

PubMed2004

Novel mechanisms responsible for postmenopausal hypertension.

Blood pressure increases in many women after menopause. Hypertension is one of the major risk factors for cardiovascular disease. However, the mechanisms responsible for the postmenopausal increase in blood pressure are yet to be elucidated. Various humoral systems have been proposed to play a role in postmenopausal hypertension, such as changes in estrogen/androgen ratios, increases in endothelin and oxidative stress, and activation of the renin-angiotensin system (RAS). In addition, obesity, type II diabetes, and activation of the sympathetic nervous system are common in postmenopausal women and may also play important roles. However, progress in elucidating the mechanisms responsible for postmenopausal hypertension has been hampered by the lack of a suitable animal model. The aging female spontaneously hypertensive rat (SHR) exhibits many of the characteristics found in postmenopausal women. In this review, some of the possible mechanisms that could play a role in postmenopausal hypertension are discussed, as well as the characteristics of the aged female SHR as a model to study.

Aged↗

PubMed2006

Effects of a new hormone therapy, drospirenone and 17-beta-estradiol, in postmenopausal women with hypertension.

Drospirenone (DRSP), a progestin with antialdosterone activity, has been developed for hormone therapy in combination with 17-beta-estradiol (E2) in postmenopausal women. We evaluated the antihypertensive efficacy and safety of various doses of DRSP and E2 and estradiol alone in postmenopausal women with hypertension using ambulatory and clinic blood pressure (BP) monitoring. This was a randomized, double-blind clinical trial of 3 doses of DRSP combined with estradiol, estradiol alone, and placebo in 750 postmenopausal women with stage 1 to 2 hypertension between 45 to 75 years. Ambulatory and clinic BPs, potassium, aldosterone, and lipid measurements and adverse events were evaluated in postmenopausal women with stages 1 to 2 hypertension during 8 weeks of double-blind therapy. DRSP and E2 induced dose-related reductions in the ambulatory and clinic systolic BP with physiological increases in serum aldosterone. Significant decreases in 24-hour systolic pressure were observed at doses of 2 and 3 mg of DRSP combined with estradiol but not by estradiol alone or 1 mg of DRSP with estradiol. There were no significant changes from baseline in potassium in any treatment group. Small, significant reductions in total and low-density lipoprotein cholesterol occurred on all of the active treatments, and serum triglycerides did not change. Adverse event rates were low and similar across treatment groups. In conclusion, these data show that DRSP combined with E2 significantly reduces BP in postmenopausal women with hypertension and did not induce significant increases in serum potassium. These characteristics may lead to a new benefit for this novel hormone therapy in postmenopausal women with hypertension.

Aged↗

PubMed2001

Electron paramagnetic resonance investigation on modulatory effect of 17beta-estradiol on membrane fluidity of erythrocytes in postmenopausal women.

Many studies have shown that estrogen may exert cardioprotective effects and reduce the risk of hypertension and coronary events. On the other hand, it has been proposed that cell membrane abnormalities play a role in the pathophysiology of hypertension, although it is not clear whether estrogen would influence membrane function in essential hypertension. The present study was performed to investigate the effects of 17beta-estradiol (E(2)) on membrane fluidity of erythrocytes in normotensive and hypertensive postmenopausal women. We determined the membrane fluidity of erythrocytes by means of an electron paramagnetic resonance and spin-labeling method. In an in vitro study, E(2) significantly decreased the order parameter for 5-nitroxide stearate and the peak height ratio for 16-nitroxide stearate obtained from electron paramagnetic resonance spectra of erythrocyte membranes in normotensive postmenopausal women. The finding indicates that E(2) might increase the membrane fluidity of erythrocytes. The effect of E(2) was significantly potentiated by the NO donor, S-nitroso-N-acetylpenicillamine, and a cGMP analogue, 8-bromo-cGMP. In contrast, the change in the membrane fluidity evoked by E(2) was attenuated in the presence of the NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester, and asymmetric dimethyl-L-arginine. In hypertensive postmenopausal women, the membrane fluidity of erythrocytes was significantly lower than that in normotensive postmenopausal women. The effect of E(2) on membrane fluidity was significantly more pronounced in the erythrocytes of hypertensive postmenopausal women than in the erythrocytes of normotensive postmenopausal women. The results of the present study showed that E(2) significantly increased the membrane fluidity and improved the microviscosity of erythrocyte membranes, partially mediated by an NO- and cGMP-dependent pathway. Furthermore, the greater action of E(2) in hypertension might be consistent with the hypothesis that E(2) could have a beneficial effect in regulating rheological behavior of erythrocytes and could have a crucial role in the improvement of the microcirculation in hypertension.

Aged↗

PubMed2006

Efficacy and safety of alendronate and risedronate for postmenopausal osteoporosis.

INTRODUCTION: This paper discusses the efficacy and safety of alendronate and risedronate in the treatment of postmenopausal osteoporosis. METHODS: The literature was searched with the PubMed from 1996 to the present, with respect to strictly conducted systematic reviews with homogeneity, meta-analyses with homogeneity, and randomized controlled trials (RCTs) with narrow Confidence Interval. RESULTS: According to the results of large randomized controlled trials (RCTs), bisphosphonates (alendronate, risedronate, and ibandronate), raloxifene, calcitonin, parathyroid hormone (PTH), and strontium ranelate effectively prevent vertebral fractures in postmenopausal women with osteoporosis. Because raloxifene has been shown to be effective in preventing the initial vertebral fracture in postmenopausal osteoporotic women without prevalent vertebral fractures, it is considered in the treatment of postmenopausal women with mild osteoporosis or osteopenia with some risk factors for fractures. RCTs have also demonstrated that alendronate, risedronate, PTH, and strontium are useful to prevent non-vertebral fractures and that alendronate and risedronate prevent hip fractures, thus alendronate or risedronate are primarily considered as the first-line drugs in the treatment of elderly women with osteoporosis having some risk factors for falls. While it has been suggested that PTH may be considered in patients with severe osteoporosis, the use of PTH in the treatment for osteoporosis is limited to 2 years or less, and it may be appropriate to use other anti-resorptive drugs after the completion of PTH treatment to maintain the skeletal effects gained during the treatment. RCTs have demonstrated that the incidence of gastrointestinal tract adverse events in postmenopausal osteoporotic women treated with bisphosphonates and placebo are similar, and also the long-term efficacy and safety of alendronate and risedronate. CONCLUSION: The evidence derived from the literature, based on strict evidence-based medicine guidelines, suggests that there is long-term efficacy and safety with alendronate and risedronate in the treatment of osteoporosis in postmenopausal women.

Alendronate↗

PubMed1995

Comparison of markers for bone formation and resorption in premenopausal and postmenopausal subjects, and osteoporosis patients.

Recently, the biochemical markers for bone metabolism have been developed and are expected to reflect the minor change of bone turnover. We compared bone formation markers: alkaline phosphatase-(Alp), bone gla-protein(BGP), carboxy-terminal propeptide of type I collagen(PICP); and bone resorption markers: carboxy-terminal telopeptide of type I collagen(ICTP), pyridinoline(Pyr), deoxypyridinoline(Dpyr) to see if they reflected the effects of aging and menopause in 95 premenopausal and 66 postmenopausal healthy subjects. We also compared the bone turnover in 29 vertebral osteoporosis patients. All markers except ICTP significantly increased with age in the healthy subjects. Alp, BGP, PICP, Pyr, and Dpyr were significantly higher in the postmenopausal group than in the premenopausal group. BGP, Pyr, and Dpyr in premenopausal subjects in their 50s were already significantly increased compared with BGP, Pyr, and Dpyr in premenopausal subjects in their 30s and 40s. To evaluate the discrimination power of the six markers in the postmenopausal subjects and in patients with osteoporosis, the z scores of six markers were calculated against the premenopausal group. z-scores of bone resorption markers(ICTP, Pyr, and Dpyr) were much higher than those of bone formation markers (Alp, BGP, and PICP) in patients with osteoporosis, even though z-scores of bone resorption markers were similar to those of bone formation markers in postmenopausal subjects. In conclusion, Alp, BGP, PICP, Pyr, and Dpyr had good performance in postmenopausal status. Resorption markers increased more than formation markers in osteoporosis subjects, and the bone turnover in osteoporosis subjects was more uncoupled than in postmenopausal subjects.

Adult↗

PubMed1996

Concentrations of estrone, estradiol, and estrone sulfate and evaluation of sulfatase and aromatase activities in pre- and postmenopausal breast cancer patients.

This report concerns the evaluation of various estrogens, estrone (El), estradiol (E2), and estrone sulfate (E1S), as well as E1S-sulfatase and aromatase activities in pre- and postmenopausal women with breast cancer. The levels (in picomoles per g; mean +/- SEM) of the various estrogens in the breast tissue from premenopausal patients (n = 11) are: El, 1.4 +/- 0.5; E2, 1.2 +/- 0.6; and E1S, 1.2 +/- 0.3. In postmenopausal patients (n = 23), the values are, respectively, 1.0 +/- 0.4, 1.4 +/- 0.7, and 3.3 +/- 1.9. These concentrations of estrogens in the tumors of postmenopausal patients are significantly higher than those found in plasma. The activity of E1S-sulfatase in both pre- and postmenopausal patients was 50-200 times higher than that of aromatase. E1S-sulfatase and aromatase activities are significantly higher in post-menopausal than in cycling patients. It is concluded that despite the low levels of circulating estrogens in postmenopausal patients, the tissue concentrations of these steroids are several-fold higher than those in plasma, suggesting tumor accumulation of these estrogens. The physiopathology and clinical significance of these high levels of the various estrogens (E1, E2, and E1S) as well as sulfatase and aromatase activities in postmenopausal patients with breast cancer is yet to be explored.

Adult↗

PubMed1997

Selective growth hormone/placental lactogen gene transcription and hormone production in pre- and postmenopausal human ovaries.

In addition to effects of pituitary-derived gonadotropins, human GH modulates and regulates intraovarian reproductive processes in a dose-dependent manner via the endocrine GHRH/GH/insulin-like-growth-factor I (IGF-I) axis. Based on increasing evidence that ovarian regulation involves a complex system of putative para/autocrine factors, we investigated the possibility of gene-selective intraovarian GH/placental lactogen (PL) hormone production, with emphasis on differences between pre- and postmenopause. Analysis of both premenopausal (n = 8) and postmenopausal (n = 10) ovarian-derived messenger ribonucleic acid by reverse transcription-PCR, which amplifies all major gene products of the five-member GH/PL gene cluster GH-N, GH-V, PL-A/B, and PL-L, revealed specific transcripts in all specimens. Their share in gene selective expression by analytical restriction enzyme digestion was determined. The expression pattern of GH/PL messenger ribonucleic acid shows PL-A/B > GH-N, which sets it apart from those of pituitary and placenta. Local production of the respective protein hormones was verified by two time-resolved immunofluorometric assays for human PL-A/B and GH-N; significant amounts of these hormones were detected in cytosolic extracts of premenopausal (n = 6; 555.5 +/- 171 ng PL-A/B and 0.8 +/- 0.6 ng GH-N/g tissue wet wt) and postmenopausal (n = 6; 5.2 +/- 2.7 ng PL-A/B and 0.9 +/- 0.6 ng GH-N/g tissue wet wt) ovaries. No difference was observed between pre- and postmenopausal ovarian GH-N contents, but PL values were 2-3 orders of magnitude lower in postmenopausal tissue (P < 0.001). Serum levels of healthy premenopausal (n = 21) and postmenopausal (n = 16) women were less than 0.02 ng PL/mL. In summary, ovarian-derived GH-N and PL-A/B synthesis correlates well with the established local cascade of GHRH, GHRH receptor, GH receptor, IGF-I, and IGF-I receptor as a putative para/autocrine regulator of ovarian reproductive function.

Adult↗

PubMed1998

Prolactin pulsatile characteristics in postmenopausal women.

Pulsatile PRL secretion undergoes diurnal variation, with maximal PRL release in the evening during sleep in both women and men. However, the impact of the menopause on PRL pulsatile dynamics are largely unknown. To characterize diurnal PRL pulsatile secretion in postmenopausal women, we performed frequent venous sampling over 24 h every 10 min for serum PRL in 7 postmenopausal women (age, 56 +/- 4 yr) and in 2 control groups, 8 men (age, 25 +/- 8 yr) and 22 cycling women (age, 28 +/- 5 yr), at 3 phases of the menstrual cycle. Standard TRH tests (200 microg, i.v.) were administered at 0900 h after completion of the 24-h sampling, and PRL levels were then obtained at 0, 10, 20, 30, and 60 min in all subjects. PRL pulse characteristics were similar between the postmenopausal women and men. Mean serum PRL levels and PRL pulse frequency were significantly higher in the cycling women than in either postmenopausal women or men over 24 h and during either the day or night periods. Mean serum PRL levels and pulse frequency were significantly higher during the night compared to those during the day in all groups. Pulse amplitude was higher during the night vs. the day in all groups and was highest in the cycling women. PRL responses to TRH administration were greatest in cycling women. These data demonstrate that PRL pulse dynamics are significantly different between postmenopausal women and cycling women, and endogenous estrogen levels may have an important role in this difference. Pulsatile PRL secretion is similar between postmenopausal women and men, suggesting that estrogen levels modulate PRL dynamics across genders.

Adult↗

PubMed1998

Bowel dysfunction in postmenopausal women.

BACKGROUND/AIMS: The perimenopausal and postmenopausal states are frequently accompanied by a variety of symptoms of hormonal imbalance. Although vasomotor, vaginal and genitourinary symptoms prevail, gastrointestinal complaints such as abdominal bloating may occur. In this study, we investigated the nature and prevalence of gastrointestinal and irritable bowel syndrome (IBS)-type complaints in women going through their climacteric and postmenopausal periods. PATIENTS/METHODS: 228 women (170 postmenopausal and 58 premenopausal) who presented for evaluation at a primary care practice limited to women's health were evaluated prospectively by a previously validated gastrointestinal symptoms questionnaire designed to evaluate symptoms suggestive of IBS. At the time of their participation in the study, none of these women was presenting for evaluation of abdominal or genitourinary symptoms. RESULTS: Thirty-eight percent of postmenopausal women reported altered bowel function, in contrast to 14% of premenopausal ones (p < 0.001). Despite this, the two groups did not differ in regards to the occurrence of abdominal pain, diarrhea or constipation, suggestive of IBS. The prevalence of IBS-type complaints peaked to 36% during the climacteric period (40-49 years). Laxative usage (9.4% prevalence), gaseousness/excessive flatulence (48% prevalence) and heart-burn/acid regurgitation (34% prevalence) were also more common among postmenopausal women. Estrogen use did not affect gastrointestinal symptoms in any of the two groups. CONCLUSIONS: Although the possible role of aging on symptom perception-regardless of hormonal status-cannot be ruled out, these results suggest that peri- and postmenopausal women have a high prevalence of altered bowel function and IBS-like gastrointestinal complaints that should be carefully assessed. If the diagnosis of IBS is confirmed, appropriate treatment may improve patients' symptoms, although this approach requires further study.

Abdominal Pain↗

PubMed1999

Etidronate and alendronate in the treatment of postmenopausal osteoporosis.

OBJECTIVE: To review the clinical trials evaluating the efficacy of etidronate and alendronate in the treatment of established postmenopausal osteoporosis. DATA SOURCE: A MEDLINE search was performed (from 1966 through September 1998) using the search terms bisphosphonates, etidronate, alendronate, and postmenopausal osteoporosis. English-language articles were considered for review. STUDY SELECTION AND DATA EXTRACTION: Prospective, randomized, double-blind, placebo-controlled clinical trials using fracture as an end point were selected to review the efficacy of etidronate and alendronate in the treatment of postmenopausal osteoporosis. Results for the outcomes of bone mineral density (BMD) and fracture are summarized. DATA SYNTHESIS: Etidronate and alendronate increase spinal BMD in postmenopausal women with osteoporosis. In one study, etidronate decreased the number of women sustaining new radiographic vertebral fractures over two years, but this effect was lost after three years of treatment. Alendronate reduces the number of radiographic vertebral fractures in postmenopausal women with a low bone mass. In women with preexisting fractures, alendronate decreases the number of patients with radiographic vertebral fractures, clinical (i.e., symptomatic vertebral and nonvertebral) fractures, and hip fractures. A significant reduction in the overall number of nonvertebral fractures has not been demonstrated in clinical trials evaluating either alendronate or etidronate. CONCLUSIONS: No studies have directly compared the efficacy of alendronate and etidronate and the results of long-term clinical trials (i.e., >5 y) have not been published. Based on the results obtained in clinical trials using fracture as an end point, alendronate appears to be the bisphosphonate of choice. Safety profiles and cost should also be considered in the choice of etidronate or alendronate for the treatment of postmenopausal osteoporosis.

Aging↗

PubMed2000

Hormone replacement therapy in a postmenopausal woman with epilepsy.

OBJECTIVE: To prospectively evaluate the effects of hormone replacement therapy (HRT) on seizure activity in a postmenopausal woman with epilepsy. BACKGROUND: Postmenopausal women are at an increased risk for cardiovascular disease and osteoporosis secondary to a lack of estrogen's protective effects. As a result, women without known contraindications often take HRT to counteract this risk. Postmenopausal women with epilepsy are at a greater risk for osteoporosis because of the negative effects that certain antiepileptic drugs have on bone density. Clinical studies and experience have shown that hormonal variances across a woman's lifetime play a significant role in seizure activity, but the effects of HRT in postmenopausal women with epilepsy are unknown. CASE SUMMARY: We report the case of a 51-year-old postmenopausal white woman with epilepsy who presented with frequent vasomotor flushing. To determine individual effects of HRT on seizure activity, therapy was initiated in two three-month phases, with monthly evaluation. A weekly transdermal patch of estradiol 0.1 mg/d was initiated for the first three months. During the second three months, the regimen was expanded to include oral medroxyprogesterone acetate 2.5 mg once daily. Antiepileptic medications and their dosages remained constant. HRT was associated with a decreased incidence of seizures, cessation of vasomotor flushing, improved sleep, and a positive impact on the lipid profile. CONCLUSIONS: This case report describing the prospective addition of HRT in a postmenopausal woman with epilepsy suggests that HRT can be initiated in certain women to achieve therapeutic benefits without adversely affecting seizure activity.

Epilepsy↗

PubMed2004

Oral daily ibandronate prevents bone loss in early postmenopausal women without osteoporosis.

UNLABELLED: Oral daily ibandronate was investigated for the prevention of bone loss in postmenopausal women without osteoporosis (n = 653). BMD at the lumbar spine and hip were significantly increased (3.1% and 1.8%, respectively; p < or = 0.0001 versus placebo) with 2.5 mg ibandronate after 24 months. Oral ibandronate is a promising option for the prevention of postmenopausal bone loss. INTRODUCTION: Further strategies to manage patients most at risk from developing postmenopausal osteoporosis are required. The objectives of this multicenter, double-blind, randomized, placebo-controlled study were to examine the efficacy, tolerability, and optimal dose of oral daily ibandronate in the prevention of bone loss in postmenopausal women. MATERIALS AND METHODS: In total, 653 women (mean bone mineral density [BMD] T-score > -2.5 at the lumbar spine), who had been postmenopausal for at least 1 year, were allocated to one of four strata based on time since menopause and baseline lumbar spine BMD. Women were randomized to receive calcium (500 mg daily) plus either placebo (n = 162) or ibandronate 0.5 mg (n = 162), 1 mg (n = 166), or 2.5 mg (n = 163) as once-daily oral treatment for 2 years. The primary endpoint was the mean percent change in lumbar spine BMD with ibandronate versus placebo. RESULTS AND CONCLUSIONS: After 2 years, oral daily ibandronate produced a dose-related and sustained maintenance or increase in BMD at the lumbar spine and hip (total hip, femoral neck, trochanter), together with a dose-related reduction in the rate of bone turnover. The greatest nominal increases in spinal and hip BMD were observed with the 2.5-mg dose, which produced statistically significant BMD gains compared with placebo at 6 months and all subsequent time-points at the spine and hip (3.1% and 1.8% increase in lumbar spine and total hip BMD, respectively, versus placebo; p < or = 0.0001 after 24 months). Oral daily ibandronate was well tolerated with an incidence of upper gastrointestinal adverse events similar to placebo. No safety concerns were identified. In summary, oral daily ibandronate 2.5 mg decreases bone turnover, preserves or increases BMD in the spine and proximal femur, and is well tolerated. Oral ibandronate provides a promising option for the prevention of bone loss in postmenopausal women.

Aged↗

PubMed2005

The effect of hormone replacement therapy on oxidized low density lipoprotein levels and paraoxonase activity in postmenopausal women.

Oxidized low-density lipoproteins (oxLDL) are involved in initiation of atherosclerosis. Paraoxonase 1 (PON1), the isoenzyme of PON, is located on high-density lipoprotein (HDL) and protects against the oxidative modification of both HDL and LDL by hydrolysing lipid peroxides. Postmenopausal women have a higher risk of cardiovascular events compared with premenopausal women. The aim of this clinical study was to evaluate the effects of hormone replacement therapy (HRT) on oxLDL and PON1 activity in menopausal status. The subjects included 45 healthy postmenopausal women, aged 43 to 57 years, and 30 premenopausal women with regular cycles, aged 31 to 40 years. None of the participating women had a history of hypertension, diabetes mellitus or medications known to affect the cardiovascular system. Twenty five of the postmenopausal women received conjugated estrogens at dose of 0.625 mg/day per oral (P.O.) and medroxyprogesterone acetate (MPA) (1 mg/d P.O.) for 10 days. Twenty of the postmenopausal women received 17-beta estradiol (2 mg/day) and norethysterone acetate (NETA) (5 mg/day P.O.) for 10 days. Fasting blood samples were taken from premenopausal women (baseline) and postmenopausal women after HRT of 6 months to determine serum malondialdehyde (MDA), oxLDL, and PON1 activity. After 6-month therapy, MDA and oxLDL levels showed a statistically significant reduction in the treated groups versus baseline (p <0.05), whereas PON1 activities were increased (p <0.05). Increase in oxidative status may be one of the factors leading to reduction in PON1 activity and increased oxLDL in menopause. HRT may be effective on oxidative stress and lipoprotein metabolism in apparently healthy postmenopausal women.

Adult↗

PubMed2003

Advances in endocrine treatments for postmenopausal women with metastatic and early breast cancer.

For the past 25 years, the estrogen antagonist tamoxifen has been the hormonal treatment of choice for postmenopausal patients with hormone-sensitive metastatic and early breast cancer (EBC). However, tamoxifen is associated with certain tolerability and safety concerns. In addition, the hormonal options after progression are limited, and thus, alternative endocrine treatments have been developed. This review provides a synopsis of the newer alternatives in endocrine therapy of breast cancer: the aromatase inhibitors (AIs) and fulvestrant Faslodex), the estrogen receptor antagonist that downregulates estrogen and progesterone receptors and has no known agonist activity. The third-generation AIs, anastrozole and letrozole, have been shown to be as effective or more effective than megestrol acetate and tamoxifen as second- and first-line therapies for the treatment of postmenopausal patients with metastatic breast cancer, and exemestane has been approved for second-line use. Fulvestrant has been shown to be as effective as anastrozole as second-line therapy for metastatic breast cancer and has been approved in the U.S. for the treatment of postmenopausal women with hormone-receptor-positive metastatic breast cancer following progression on antiestrogen therapy. Anastrozole is the only AI with published clinical trial data and U.S. Food and Drug Administration approval for adjuvant therapy of postmenopausal women with EBC. The 'Arimidex,' Tamoxifen, Alone or in Combination (ATAC) trial, a double-blind, multicenter trial with 9,366 patients, compared tamoxifen with anastrozole, alone and in combination, as adjuvant endocrine treatment for postmenopausal patients with operable, invasive, EBC. The first analysis (at a median follow-up of 33.3 months) showed longer disease-free survival and, in general, better tolerability with anastrozole than with tamoxifen. This pattern was maintained at later analyses with a median follow-up of 47 months for efficacy and 37 months for safety and tolerability. Although longer follow-up is warranted, anastrozole appears to be a well-documented choice of endocrine adjuvant therapy for postmenopausal women with hormone-responsive breast cancer.

Aged↗

PubMed2004

Efficacy of first-line letrozole versus tamoxifen as a function of age in postmenopausal women with advanced breast cancer.

PURPOSE: To compare the efficacy, in regard to time to progression (TTP) and objective response rate (ORR), of letrozole (Femara; Novartis Pharma AG; Basel Switzerland), an oral aromatase inhibitor, with that of tamoxifen (Tamofen; Leiras OY; Turku, Finland) as first-line therapy in younger (<70 years) and older (>/=70 years) postmenopausal women with advanced breast cancer. MATERIALS AND METHODS: Nine hundred seven patients with advanced breast cancer were randomly assigned to receive 2.5 mg letrozole (n = 453) or 20 mg tamoxifen (n = 454) once daily in a double-blind, multicenter, international trial. Among the prospectively planned analyses were analyses of TTP and ORR by age (<70 and >/=70 years). The results of these prospectively planned analyses are reported here. RESULTS: Letrozole was as effective in older postmenopausal women (>/=70 years of age) as it was in younger postmenopausal women (<70 years of age). The overall ORR in the older subgroup was significantly higher in patients treated with letrozole (38%) than in patients treated with tamoxifen (18%). In the younger subgroup of postmenopausal patients, the ORRs were not significantly different (letrozole, 26%; tamoxifen, 22%). TTP was significantly longer for letrozole than for tamoxifen in both age groups (younger: letrozole median TTP, 8.8 months; tamoxifen, 6.0 months; older: letrozole median TTP, 12.2 months; tamoxifen, 5.8 months). Although age was independently prognostic of TTP, there was no significant effect of age on ORR in the presence of other factors. CONCLUSION: The data show that letrozole, 2.5 mg once daily, is as effective in older, postmenopausal women as it is in younger postmenopausal women with advanced breast cancer. In addition, letrozole was more effective than tamoxifen in both younger and older patients.

Adult↗

PubMed2002

Relation between fat distributions and several plasma adipocytokines after exercise training in premenopausal and postmenopausal women.

Circulating concentrations of adipocytokines, such as leptin, tumor necrosis factor-alpha (TNF-alpha), and plasminogen activator inhibitor-1 (PAI-1), vary with exercise training, menopause, or regional variations in adipose tissues. In the present study, the relationships between body fat distributions and some adipocytokines were compared in premenopausal (N = 9) and postmenopausal women (N = 9), before and after exercise training. The training for 10 weeks (that is, 3 days/week) consisted of aqua exercise plus resistance exercise. The training reduced percent fat, body mass index, total fat mass (TFM), subcutaneous fat mass (SFM), and plasma levels of leptin and PAI-1 in both women. Mean value of plasma TNF-alpha tended to increase after training in both women. Plasma leptin levels were lower in postmenopausal than in premenopausal women, independently of training. In premenopausal women, plasma leptin levels correlated well with either TFM or SFM before and after training. Regression analysis of decreases in plasma leptin with a reduced amount of SFM revealed that decreases in plasma leptin depended to a greater extent on a loss of SFM. In postmenopausal women, no significant correlation was found between leptin levels and any of the fat depots. Plasma TNF-alpha levels correlated well with visceral fat mass (VFM) in premenopausal but not in postmenopausal women. Changes in TNF-alpha levels after training correlated well with reduced amount of VFM in premenopausal but not in postmenopausal women. Plasma PAI-1 levels were not different between groups. Moreover, no significant correlation was found between PAI-1 levels and any of the fat depots in both women. Thus, in premenopausal but not in postmenopausal women, changes in plasma concentrations of leptin and TNF-alpha correlate well with specific alterations in relative amount of SFM and VFM after training, respectively. However, no significant relationship between PAI-1 and any of the fat depots was found independently of either menopause or training.

Adipose Tissue↗