A Comparative Study of Pyrolysis Liquids by Slow Pyrolysis of Industrial Hemp Leaves, Hurds and Roots.

This study assessed the pyrolysis liquids obtained by slow pyrolysis of industrial hemp leaves, hurds, and roots. The liquids recovered between a pyrolysis temperature of 275-350 °C, at two condensation temperatures 130 °C and 70 °C, were analyzed. Aqueous and bio-oil pyrolysis liquids were produced and analyzed by proton nuclear magnetic resonance (NMR), gas chromatography-mass spectrometry (GC-MS), and atmospheric pressure photoionization Fourier transform ion cyclotron resonance mass spectrometry (APPI FT-ICR MS). NMR revealed quantitative concentrations of the most abundant compounds in the aqueous fractions and compound groups in the oily fractions. In the aqueous fractions, the concentration range of acetic acid was 50-241 gL-1, methanol 2-30 gL-1, propanoic acid 5-20 gL-1, and 1-hydroxybutan-2-one 2 gL-1. GC-MS was used to compare the compositions of the volatile compounds and APPI FT-ICR MS was utilized to determine the most abundant higher molecular weight compounds. The different obtained pyrolysis liquids (aqueous and oily) had various volatile and nonvolatile compounds such as acetic acid, 2,6-dimethoxyphenol, 2-methoxyphenol, and cannabidiol. This study provides a detailed understanding of the chemical composition of pyrolysis liquids from different parts of the industrial hemp plant and assesses their possible economic potential.

Classification of Wood Chips Using Electrical Impedance Spectroscopy and Machine Learning.

Wood chips are extensively utilised as raw material for the pulp and bio-fuel industry, and advanced material analyses may improve the processes in utilizing these products. Electrical impedance spectroscopy (EIS) combined with machine learning was used in order to analyse heartwood content of pine chips and bark content of birch chips. A novel electrode system integrated in a sampling container was developed for the testing using frequency range 42 Hz-5 MHz. Three electrode pairs were used to measure the samples in x-, y- and z-direction. Three machine learning methods were used: K-nearest neighbor (KNN), decision tree (DT) and support vector machines (SVM). The heartwood content of pine chips and bark content of birch chips were classified with an accuracy of 91% using EIS from pure materials combined with a k-nearest neighbour classifier. When using mixed materials and multiple classes, 73% correct classification for pine heartwood content (four groups) and 64% for birch bark content (five groups) were achieved.

Lifestyle factors and site-specific risk of hip fracture in community dwelling older women--a 13-year prospective population-based cohort study.

BACKGROUND: Several risk factors are associated to hip fractures. It seems that different hip fracture types have different etiologies. In this study, we evaluated the lifestyle-related risk factors for cervical and trochanteric hip fractures in older women over a 13-year follow-up period. METHODS: The study design was a prospective, population-based study consisting of 1681 women (mean age 72 years). Seventy-three percent (n = 1222) participated in the baseline measurements, including medical history, leisure-time physical activity, smoking, and nutrition, along with body anthropometrics and functional mobility. Cox regression was used to identify the independent predictors of cervical and trochanteric hip fractures. RESULTS: During the follow-up, 49 cervical and 31 trochanteric fractures were recorded. The women with hip fractures were older, taller, and thinner than the women with no fractures (p < 0.05). Low functional mobility was an independent predictor of both cervical and trochanteric fractures (HR = 3.4, 95% CI 1.8-6.6, and HR = 5.3, 95% CI 2.5-11.4, respectively). Low baseline physical activity was associated with an increased risk of hip fracture, especially in the cervical region (HR = 2.5, 95% CI 1.3-4.9). A decrease in cervical fracture risk (p = 0.002) was observed with physically active individuals compared to their less active peers (categories: very low or low, moderate, and high). Moderate coffee consumption and hypertension decreased the risk of cervical fractures (HR = 0.4, 95% CI 0.2-0.8, for both), while smoking was a predisposing factor for trochanteric fractures (HR = 3.2, 95% CI 1.1-9.3). CONCLUSIONS: Impaired functional mobility, physical inactivity, and low body mass may increase the risk for hip fractures with different effects at the cervical and trochanteric levels.

Long-term outcomes of exercise: follow-up of a randomized trial in older women with osteopenia.

BACKGROUND: Long-term evidence from randomized trials of the effectiveness of exercise in preventing disability and fall-related fractures in elderly people has been lacking. METHODS: We performed extended follow-up of 160 women (aged 70-73 years at baseline) with osteopenia in a population-based, randomized, controlled exercise trial. The trial was conducted from April 1 through April 30, 2001. Follow-up was conducted from May 1, 2001, through December 31, 2005. Mean total time in observation was 7.1 years. Primary outcome measures were femoral neck bone mineral density, postural sway, and leg strength. Secondary outcome measures were hospital-treated fractures and functional ability measures. Outcomes were measured annually using masked assessors. RESULTS: There was a significant difference between groups in favor of exercise in terms of postural sway (group × time interaction, P = .005), walking speed (group × time interaction, P < .001), and Frenchay Activities Index score (group x time interaction, P = .001). The bone mineral density decreased similarly across time in both groups. The incidence rate of fractures during the total follow-up among women in the exercise group vs women in the control group was 0.05 vs 0.08 per 1000 person-years (Poisson incidence rate ratio, 0.68; 95% confidence interval, 0.34-1.32). There were no hip fractures in the exercise group, whereas 5 hip fractures occurred in the control group. One woman in the exercise group and 8 women in the control group died (Poisson incidence rate ratio, 0.11; 95% confidence interval, 0.01-0.85). CONCLUSION: Mainly home-based exercises followed by voluntary home training seem to have a long-term effect on balance and gait and may even protect high-risk elderly women from hip fractures. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00655577.

Risk factors for cervical and trochanteric hip fractures in elderly women: a population-based 10-year follow-up study.

We evaluated the contribution of lifestyle-related factors, calcaneal ultrasound, and radial bone mineral density (BMD) to cervical and trochanteric hip fractures in elderly women in a 10-year population-based cohort study. The study population consisted of 1,681 women (age range 70-73 years). Seventy-two percent (n = 1,222) of them participated in the baseline measurements. Calcaneal ultrasound was assessed with a quantitative ultrasound device. BMD measurements were performed at the distal and ultradistal radius by dual-energy X-ray absorptiometry. Forward stepwise logistic regression analysis was used to find the most predictive variables for hip fracture risk. During the follow-up, 53 of the women had hip fractures, including 32 cervical and 21 trochanteric ones. The fractured women were taller and thinner and had lower calcaneal ultrasound values than those without fractures. High body mass index (BMI) was a protective factor against any hip fractures, while low functional mobility was a risk factor of hip fractures. Specifically, high BMI protected against cervical hip fractures, while low physical activity was a significant predictor of these fractures. Similarly, high BMI protected against trochanteric fractures, whereas low functional mobility and high coffee consumption were significant predictors of trochanteric fractures. Cervical and trochanteric hip fractures seem to have different risk factors. Therefore, fracture type should be taken into account in clinical fracture risk assessment and preventative efforts, including patient counseling. However, the study is not conclusive due to the limited number of observed fractures during follow-up, and the results have to be confirmed in future studies.

Associations of genetic lactase non-persistence and sex with bone loss in young adulthood.

Some studies have reported that after attainment of peak bone mass (PBM), slow bone loss may occur in both men and women; however, findings are inconsistent. Genetic factors play a significant role in bone loss, but the available evidence is conflicting. Genetic lactase non-persistence (lactase C/C(-13910) genotype) is suggested to increase risk for inadequate calcium intake predisposing to poorer bone health. We investigated whether this genotype is associated with PBM and bone loss in young Finnish adults. Subjects belong to the Cardiovascular Risk in Young Finns Study that is an ongoing multi-centre follow-up of atherosclerosis risk factors. From the original cohort, randomly selected subjects aged 20-29 participated in baseline bone mineral density (BMD) measurements (n=358), and in follow-up measurements 12 years later (n=157). Bone mineral content (BMC) and BMD at lumbar spine (LS) and femoral neck (FN) were measured at baseline and follow-up with dual energy X-ray absorptiometry (DXA). Lactase C/T(-13910) polymorphism was determined by PCR and allele-specific fluorogenic probes. Information on lifestyle was elicited with questionnaires. During the follow-up, bone loss at both bone sites was greater in males (LS BMD: -1.1%, FN BMD: -5.2%) than in females (LS BMD: +2.1%, FN BMD: -0.7%) (both bone sites p=0.001). Younger age predicted greater loss of FN BMC and BMD in females (p=0.013 and p=0.001, respectively). Increased calcium intake predicted FN BMD gain in both sexes (in females B=0.007 g/cm(2)/mg, p=0.002; in males B=0.006, p=0.045), and increased physical activity LS BMD gain in females (B=0.091 g/cm(2)/physical activity point, p=0.023). PBM did not differ between the lactase genotypes, but males with the CC(-13910) genotype seemed to be prone to greater bone loss during the follow-up (LS BMD: C/C vs. T/T p=0.081). In conclusion, bone loss in young adulthood was more common in males than in females and seemed to occur mainly at the femoral neck. Young males with the lactase CC(-13910) genotype may be more susceptible to bone loss; however, calcium intake predicts changes in bone mass more than the lactase genotype.

Estrogen replacement therapy decreases plasma adiponectin but not resistin in postmenopausal women.

The effects of estrogen replacement therapy (ERT) to cardiovascular disease risk are still unclear. Low adiponectin and high resistin plasma concentrations are reported to be associated with atherosclerosis. However, it is not known how ERT affects plasma adiponectin and resistin concentrations. Seventy-three hysterectomized, nondiabetic, postmenopausal women were randomized in a double-blind, double-dummy study to receive either peroral estradiol valerate or transdermal 17beta-estradiol gel for 6 months. Biochemical measurements were determined from samples taken before and after the therapy. Peroral estradiol valerate therapy decreased adiponectin concentrations from 13.6 to 11.6 mg/L (P = .008), whereas transdermal 17beta-estradiol gel had no effect (12.7 vs 12.2 mg/L). Neither treatment changed the resistin concentrations significantly. Plasma concentrations of estradiol and estrone did not correlate with adiponectin or resistin concentrations before or after therapy. The change in adiponectin concentration correlated significantly with the changes in waist-hip ratio, very low-density lipoprotein triglycerides, and insulin-like growth factor 1 in the peroral estradiol valerate group. The changes in these variables and the change in estradiol concentration explained 43.1% (P = .001) of the variability in the change of plasma adiponectin, the change in very low-density lipoprotein triglycerides being the strongest determinant (beta = -.407, P = .011). The results show that peroral ERT can decrease plasma adiponectin levels. However, ERT does not seem to influence plasma resistin concentrations.

A 10-year follow-up of the effect of continuous-combined hormone replacement therapy and its discontinuation on bone in postmenopausal women.

OBJECTIVE: To establish the effect on bone mineral density (BMD) of long-term (nine years) continuous-combined hormone replacement therapy (ccHRT) with estradiol valerate/medroxyprogesterone acetate (E(2)V/MPA) and follow-up one year after discontinuation of ccHRT. STUDY DESIGN: A total of 279 women were treated with daily dosages of E(2)V + MPA: 1 mg + 2.5 mg (n = 69), 1 mg + 5 mg (n = 70) or 2 mg + 5 mg (n = 140) (Indivina), Orion Pharma, Espoo, Finland) for 8.5 years; all subjects received the lowest dosage for the next six months. BMD was measured at baseline, between 6 and 12 months, annually until the end of study and at one-year postdiscontinuation of ccHRT. Main outcome measure Change in BMD during nine years of treatment with ccHRT and at one-year postdiscontinuation of ccHRT. RESULTS: Progressive increase of vertebral BMD was observed with all dosage regimens throughout nine years, with corresponding reduction in the proportion of women fulfilling criteria for osteoporosis or osteopaenia. Femoral neck BMD reached a peak at about five to six years, whereas in the lumbar spine the BMD increase was sustained until the end of the study treatment. Mean BMD declined after cessation of ccHRT use but remained substantially above baseline levels. In a subset of women (n = 58) there was a rapid (> or =4%) loss of vertebral BMD in the year after termination of ccHRT use. These women had lower than average BMD at baseline but no other factor was identified that distinguished them from the overall study population. CONCLUSIONS: Low-dose ccHRT in postmenopausal women is associated with increases in lumbar spine BMD for at least nine years. These gains are not sustained after cessation of therapy but the rate of BMD loss varies between individuals.

One-year endometrial safety evaluation of a continuous combined transdermal matrix patch delivering low-dose estradiol-norethisterone acetate in postmenopausal women.

OBJECTIVE: To evaluate the safety and endometrial protection of low-dose transdermal estradiol (E2)/norethisterone acetate (NETA) patches (Estalis 25/125) in terms of post-treatment incidence of endometrial hyperplasia/cancer after 1 year of treatment in postmenopausal women with intact uteri. METHODS: Patients were randomized to receive either transdermal E2/NETA (delivering daily doses of E2 25 microg and NETA 125 microg; applied every 3-4 days) or oral E2/NETA (E2 1mg and NETA 0.5 mg; given daily) in this open-label study. The primary variable was the incidence of endometrial hyperplasia/cancer based on endometrial biopsies; secondary variables included vaginal bleeding/spotting patterns, patch adhesion, safety and tolerability. RESULTS: Six hundred and seventy-seven patients were randomized (507 in the transdermal group and 169 in the oral group; one did not receive study drug) and >80% completed the study. There were no cases of endometrial hyperplasia or cancer in either group and the upper limit of the one-sided 95% confidence interval in the transdermal group was 0.85%. Over time, both treatments were associated with a decreasing frequency of spotting/bleeding days. The overall incidence of adverse events (AEs) was comparable in both groups, and the majority was mild-to-moderate in intensity. Breast tenderness was the most frequently reported AE (transdermal 19.9% versus oral 28.4%). AEs related to the gastrointestinal system were more frequent with oral E2/NETA, and episodes of spotting and bleeding were more frequent with transdermal E2/NETA. Local skin tolerability of the transdermal matrix system was good. CONCLUSIONS: Transdermal E2/NETA (25 and 125 microg) provided adequate endometrial protection in postmenopausal women when evaluated according to CPMP/CHMP criteria, achieved a high rate of amenorrhea, and was well tolerated.

Cost-effectiveness of continuous combined hormone replacement therapy in long-term use: economic evaluation based on a 9-year study in Finland.

OBJECTIVES: To investigate the cost-effectiveness of continuous combined hormone replacement therapy (ccHRT) (Indivina) in postmenopausal women in Finland treated for up to nine consecutive years in the course of a randomised controlled trial. METHODS: In-study event data were accrued for cardiac and vascular events, cancers and fractures. These event incidence data were applied to first-year direct medical costs for these events, derived from published sources. Reference event incidence data were derived from hospital discharge records and relevant national registries for age-matched women (aged 50-70 years) in Finland with an assumed HRT usage rate of 40%. Cost-effectiveness was expressed as additional cost per quality-adjusted life year (QALY) gained for women on ccHRT compared with the general population. All input data were discounted at 3% per annum. RESULTS: The additional cost per QALY gained for ccHRT was less than 5000 euro throughout the nine calendar years examined and remained well below the threshold of acceptability of 50,000 euro in a range of sensitivity analyses. The lowest dose-combination of ccHRT examined improved quality of life at no greater cost than no treatment. CONCLUSIONS: This appraisal, based on event data from a uniquely long study of ccHRT, indicates that this intervention is cost-effective for the relief of symptoms of menopause.

A 10-year follow-up of postmenopausal women on long-term continuous combined hormone replacement therapy: Update of safety and quality-of-life findings.

OBJECTIVE: To assess the safety and health-related quality of life (HRQOL) of continuous combined hormone replacement therapy (ccHRT) with estradiol valerate/medroxyprogesterone acetate (E(2)V/MPA) over nine years and at follow-up one year after discontinuation. STUDY DESIGN: A total of 419 women were randomized to one of four treatments: once-daily 1 mg E2V/2.5 mg MPA (1 + 2.5 group); 1 mg E2V/5 mg MPA daily (1 + 5 group); 2 mg E2V/2.5 mg MPA daily (2 + 2.5 group); 2 mg E2V/5 mg MPA daily (2 + 5 group) (Indivina, Orion Pharma). For the last six months, all received the 1 + 2.5 dosage. The 2 + 2.5 dosage was discontinued at the end of year 7. A total of 198 women continued after year 7. RESULTS: Annualized percentage rates for cardiovascular events [corrected] and endometrial cancers [corrected] were below national rates for Finland and those reported for the Women's Health Initiative. There were no serious events with the 1 + 2.5 dosage or after ccHRT discontinuation. Climacteric symptoms remained significantly below baseline values after dosage reduction; some symptoms recurred after discontinuation of ccHRT. HRQOL ratings improved with ccHRT, irrespective of dosage, including depressed mood, anxiety, health perception and sexual interest. Scores on a scale assessing daily functioning and enjoyment (Q-LES-Q) improved from year 7 to year 9. They deteriorated during follow-up in women not continuing ccHRT. CONCLUSIONS: Lower dosages of HRT were as effective as higher doses in improving climacteric symptoms and HRQOL ratings and had fewer safety concerns. Following discontinuation of ccHRT, patient satisfaction was variable, with 15% electing to continue or restart HRT and 7% resuming at follow-up. This supports the need for an individualized approach to therapy recommendations.

Effects of ospemifene and raloxifene on biochemical markers of bone turnover in postmenopausal women.

Ospemifene is a novel selective estrogen receptor modulator (SERM) that is initially being developed for the treatment of vaginal atrophy in postmenopausal women. However, it also shows promise in the prevention and treatment of osteoporosis. As a part of a phase II trial, we compared the effects of ospemifene and raloxifene on bone turnover in postmenopausal women. The study was conducted as a randomized, double-blind study in which 118 healthy postmenopausal women received 30 (n = 29), 60 (n = 30), or 90 mg (n = 30) ospemifene or 60 mg (n = 29) raloxifene for 3 months. Bone resorption was assessed by measuring the urinary outputs of N- and C-terminal cross-linking telopeptides of type I collagen (NTX and CTX, respectively). Bone formation was assessed by measuring bone-specific alkaline phosphatase (bone ALP), osteocalcin (OC), procollagen type I N propeptide (PINP), and procollagen type I C propeptide (PICP) in serum. All markers were studied before and at 3 months and 2-4 weeks after cessation of the medication. Urine NTX outputs decreased in all study groups, and the only statistically significant difference in NTX was observed between raloxifene and 30 mg ospemifene, which was reduced more in the raloxifene group. The output of CTX decreased most clearly in 60- and 90-mg ospemifene groups, but no significant differences between study groups emerged. A significant difference was found between the 90-mg ospemifene group and raloxifene in PINP in favor of ospemifene. No other differences in bone formation markers emerged between ospemifene and raloxifene. The study confirms the bone-restoring activity of ospemifene, which is comparable to that of raloxifene.

Hormone therapy: maximizing the benefits.

Despite the ongoing controversy surrounding the findings from recent studies of hormone therapy (HT) and their implications for its use, HT is indisputably highly beneficial for treating climacteric symptoms and vaginal atrophy and in preventing osteoporosis. An apparent small increase in breast cancer risk with combined HT must be balanced against a reduction in the significant morbidity and mortality associated with fractures, combined with improved well-being, quality of life, and potential protection against colorectal cancer and cardiovascular disease. Individualization of HT regimen and dose depending on the woman's wishes and circumstances appears to be one way to maximize the benefits of HT and minimize the risks.

Effect of exercise on extraskeletal risk factors for hip fractures in elderly women with low BMD: a population-based randomized controlled trial.

UNLABELLED: We conducted a 30-month population-based, randomized, controlled trial in 160 elderly women at risk for fractures on the basis of a low baseline BMD. Mainly home-based weight-bearing exercise was effective in improving strength, balance, and gait. INTRODUCTION: Evidence on the effect of exercise on extraskeletal risk factors for hip fractures comes mainly from studies in voluntary low-risk women, and no population-based, long-term interventions have been performed in elderly women with low bone mass. The aim of this study was to determine the effect of long-term weight-bearing exercise on balance, muscle strength, and gait in elderly women at risk for fractures on the basis of a low baseline BMD. MATERIALS AND METHODS: A birth cohort of 1690 women 70-73 years of age were invited to the radius and hip BMD measurements; 96 women were excluded because of medical reasons; 160 women with radius and hip BMD values of >2 SD below the reference value were included in the trial. The participants were randomly assigned to 30 months of impact, balancing, and strengthening exercises or to no intervention. Main outcome measures were body sway length and leg strength at month 30. Secondary endpoints included gait speed, endurance, and grip strength. Outcomes were assessed at 0, 12, 24, and 30 months using blinded operators. Repeated-measures ANOVA was used to determine statistical significance. The analyses were performed on an intention-to-treat basis. RESULTS: Body sway increased more in the control group than in the exercise group over time (time-group interaction, p < 0.001). Leg strength improved in the exercise group and decreased in the control group (interaction, p < 0.001). A significant time-group interaction (p < 0.001) in favor of the exercise group was found on the following secondary endpoints: the timed up and go test score, walking speed, and distance walked in 2 minutes. CONCLUSIONS: Weight-bearing exercise is an effective way of modifying extraskeletal risk factors for fractures in elderly women.

Effect of impact exercise on bone mineral density in elderly women with low BMD: a population-based randomized controlled 30-month intervention.

Evidence of the effect of exercise on bone loss comes mainly from studies in voluntary postmenopausal women, and no population-based, long-term interventions have been performed. The purpose of this population-based, randomized, controlled trial was to determine the effect of long-term impact exercise on bone mass at various skeletal sites in elderly women with low bone mineral density (BMD) at the radius and hip. Participants (n=160) were randomly assigned to 30 months either of supervised and home-based impact exercise training or of no intervention. The primary outcome measures were femoral neck, trochanter and total hip BMD, and the secondary outcomes were bone density measures at the radius and calcaneum. Outcomes were assessed at baseline, 12 months and 30 months using blinded operators. The analyses were performed on an intention-to-treat analysis. Mean femoral neck and trochanter BMD decreased in the control group [-1.1%, 95% confidence interval (CI) -0.1% to -2.1% and -1.6%, 95% CI -0.4% to -2.7%], while no change occurred in the exercise group. Mean trochanter BMC decreased more in the control group (-7.7%, 95% CI -9.7% to -5.6% vs. -2.9%, 95% CI -5.3 to -0.9). There were six falls that resulted in fractures in the exercise group and 16 in the control group during the 30-month intervention (P=0.019). A significant bone loss occurred in both groups at the radius and calcaneum. In multivariate analysis, weight gain was associated with increased BMD and BMC at all femur sites both in the exercise group and in the pooled groups. In conclusion, impact exercise had no effect on BMD, while there was a positive effect on BMC at the trochanter. Exercise may prevent fall-related fractures in elderly women with low bone mass.

Decade-long use of continuous combined hormone replacement therapy is associated with better health-related quality of life in postmenopausal women, as measured by the generic 15D instrument.

OBJECTIVE: To examine quality of life after a decade of continuous combined hormone replacement therapy. STUDY DESIGN: The 15D, a generic health-related quality-of-life (HRQoL) instrument, was used to evaluate trends in HRQoL in women who used continuous combined hormone replacement therapy (ccHRT; Indivina, Orion Pharma, Finland) for up to nine years. These women had a mean age of 56 years of age at the start of therapy. Control data on HRQoL were obtained from age-matched women participating in Finnish population health surveys. RESULTS: Relative to controls, ccHRT was associated with significantly better HRQoL after six and nine years of treatment. Dose minimization at 8.5 years was not associated with a decline in HRQoL in the ensuing six months. One year after discontinuation of ccHRT there was evidence of a decline in HRQoL in women who discontinued ccHRT as planned, whereas HRQoL was maintained in women who had continued or resumed ccHRT during the one-year post-study follow-up. The benefits of ccHRT were apparent in multiple dimensions of the 15D, being largest and most robustly reproduced in the dimension 'discomfort and symptoms'. It is conjectured that the effectiveness of ccHRT in relieving symptoms of menopause may have contributed to the improved HRQoL scores registered in other dimensions, in addition to any direct effects of ccHRT on specific aspects of those other dimensions. CONCLUSIONS: These data indicate that up to 10 years of low-dose ccHRT has sustained value in the enhancement of HRQoL when used by women for whom relief of symptoms of menopause and control of bleeding are primary objectives of treatment.

Estrogen replacement therapy increases plasma ghrelin levels.

Ghrelin is a novel peptide hormone that has GH releasing activity and also other endocrine and metabolic functions. The purpose of this study was to investigate the effects of estrogen replacement therapy on plasma active ghrelin levels in 64 hysterectomized postmenopausal women receiving peroral estrogen (PE) or transdermal estrogen therapy for 6 months. Active ghrelin was measured using commercial RIA. Estrogen therapy increased plasma active ghrelin from 479 +/- 118 to 521 +/- 123 pg/ml (P = 0.002) among all the study subjects. PE therapy increased plasma ghrelin levels from 465 +/- 99 to 536 +/- 104 pg/ml (P = 0.001). Transdermal estrogen therapy did not increase plasma ghrelin levels significantly (from 491 +/- 132 to 509 +/- 138 pg/ml; P = 0.332). The relative changes in plasma ghrelin levels were associated with the relative changes in serum estradiol concentrations (r = 0.299; P = 0.017). During the estrogen therapy, negative associations were found between plasma active ghrelin levels and several plasma lipids (total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, total triglycerides, and very low-density lipoprotein triglycerides). As a conclusion, estrogen replacement therapy increased active plasma ghrelin levels, particularly PE therapy. Additional studies are needed to determine the possible underlying mechanisms.

Long-term safety and tolerability of continuous-combined hormone therapy in postmenopausal women: results from a seven-year randomised comparison of low and standard doses.

OBJECTIVE: To establish the long-term safety profile of four oestradiol valerate/medroxyprogesterone acetate (E(2)V/MPA) regimens. STUDY DESIGN: 419 postmenopausal women in parallel treatment groups started treatment with 1 or 2 mg E(2)V with either 2.5 or 5 mg MPA for 84 cycles of 28 days in a randomised, comparative study. The first 24 month double-blind efficacy period has been previously reported. This report focuses on the open safety period after the first two years until completion of 84 treatment cycles. RESULTS: A total of 275 women (65.6%) completed the seven-year study. All regimens provided good bleeding control and endometrial protection, with no cases of endometrial hyperplasia or cancer diagnosed. All regimens were well tolerated with a low frequency of adverse effects, mostly occurring within the first two years. The most common drug-related adverse events included breakthrough bleeding, headache/migraine, abdominal pain and mood changes. Very few women (n = 4) receiving the lowest dose option (1 mg E(2)V + 2.5 mg MPA) reported adverse effects (p<0.009 vs other groups). No serious cardiovascular events occurred in any of the groups, the incidence of strokes was lower than the national incidence for the age group and the incidence of breast cancer was comparable with the national incidence (95% CI). In the lowest dose group, no women had to stop therapy prematurely due to serious adverse events. CONCLUSIONS: The results support the use of lower doses for longterm hormone therapies.

Effects of estrogen replacement therapy on natriuretic peptides and blood pressure.

OBJECTIVE: Estrogen replacement therapy (ERT) has been reported to affect blood pressure. Since natriuretic peptides have natriuretic and vasodilatory activity and also inhibit the renin-angiotensin-aldosterone system and lower blood pressure, it was hypothesized that the changes in blood pressure effected by ERT might be mediated via changes in natriuretic peptides. METHODS: Fifty-eight postmenopausal hysterectomized women were randomized in a double-blind, double-dummy study to receive either peroral estradiol valerate 2 mg/day or transdermal estradiol gel containing 1 mg estradiol/day for 6 months. Blood pressure was measured by using an automatic, oscillometric device. Plasma atrial natriuretic peptide (ANP), N-terminal fragment of proANP (NT-proANP), B-type natriuretic peptide (BNP), aldosterone, and renin were determined by radioimmunoassay. RESULTS: The mean decrease in diastolic blood pressure was -6 mmHg both in the peroral group (n = 26) (P = 0.002) and in the gel group (n = 27) (P = 0.001), and the corresponding decreases in systolic blood pressure were -4 mmHg (P = 0.070) and -7 mmHg (P = 0.028) in the sitting position. Plasma NT-proANP rose from 212 to 264 pmol/l (P = 0.001) on peroral ERT and from 240 to 292 pmol/l (P = 0.008) on transdermal ERT. No significant changes were observed in the plasma ANP, BNP, aldosterone, and renin levels. CONCLUSIONS: Both peroral and transdermal ERT result in elevated plasma levels of NT-proANP, indicating an activation of the natriuretic peptide system. This could explain, at least in part, the lowering of blood pressure during ERT.

Effects of ospemifene, a novel SERM, on hormones, genital tract, climacteric symptoms, and quality of life in postmenopausal women: a double-blind, randomized trial.

OBJECTIVE: Ospemifene, a novel selective estrogen receptor modulator, shows a potential for prevention and treatment of osteoporosis in postmenopausal women. We studied the effects of ospemifene on hormone levels, genital tract organs, climacteric symptoms, and quality of life. DESIGN: A double-blinded study in which 160 postmenopausal women were randomly allocated to receive either ospemifene at three different daily doses (30, 60, or 90 mg) or placebo for 3 months. RESULTS: No significant differences were observed among the study groups in clinical characteristics or parameters reflecting estrogen action at baseline. Ospemifene reduced follicle-stimulating hormone and insulin-like growth factor I levels, whereas estradiol failed to change at all, and luteinizing hormone was reduced only in the 90-mg group of ospemifene. In the vast majority of participants, the endometrium remained atrophic after 3 months of treatment with ospemifene. Although the rate of proliferative endometrium slightly increased in all groups, including placebo, no hyperplasia or bleeding occurred in any participant. Ospemifene had no effect on the appearance of proliferation marker Ki-67 in the endometrium as compared with placebo, and endometrial thickness increased by mean 0.4 to 0.6 mm (P < 0.01, P < 0.05 and P < 0.05 for 30, 60 and 90 mg ospemifene, respectively). Uterine volume slightly increased (8.4%-14.7%) in the ospemifene groups (P > 0.05), perhaps as a result of increased uterine blood flow. The most conspicuous finding was the significant estrogenic effect on vaginal epithelium, as evidenced by an increase in intermediate and superficial cells in repeat Pap smears. Ospemifene was not observed to aggravate climacteric symptoms or cause adverse events, nor did it suppress climacteric symptoms. CONCLUSIONS: Ospemifene at daily doses of 30 to 90 mg did not stimulate endometrium or aggravate hot flashes but clearly had a rather strong estrogenic effect on the vaginal epithelium during a 3-month treatment period. Such effects would be advantageous if ospemifene were found to be effective in the long-term prevention of osteoporosis.