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Hormone replacement therapy (HRT) plays a large part in maintaining and improving the quality of life (QOL) of postmenopausal women. Despite this obvious role, the use of HRT has stagnated in Japan as well as the United States, since the interim report of the HRT trial of Women's Health Initiative study was published in 2002. The Japan Society of Obstetrics and Gynecology and Japan Society for Menopause and Women's Health formulated the Guidelines for Hormone Replacement Therapy in 2009, which was subsequently revised in 2012, with the aim of organizing perceptions about HRT and allowing people to provide or receive HRT with a sense of security. Later on, in light of changes in indications for HRT and attitudes toward its impact on cancer risks, amendments were made again in 2017. With the establishment of the 2017 guidelines, practitioners in Japan are able to address various issues related to HRT with more appropriate judgment. Moreover, the practice of reliable, safe and effective HRT is expected to promote further efforts toward improvement or maintenance of QOL in patients.

Introduction We conducted a questionnaire survey of Japanese women with migraine who presented at neurology and gynecology headache clinics to assess how the frequency and severity of migraine in pre-, peri-, and postmenopausal women changed as compared with what they experienced in their 20s and 30s. Methods The study group comprised 171 women with migraine (mean age 48.5) at the time of the survey. They were requested to fill out a self-administered questionnaire. Results (1) The current frequency and severity of migraine were claimed to be higher than that in their 20s and 30s. (2) More than 50% of postmenopausal women responded that migraines were currently less frequent than in their 20s and 30s. (3) The largest proportion of postmenopausal women responded that migraine was currently less severe than during any other period. Conclusions Our survey demonstrated that there are trends toward fewer migraine attacks and milder symptoms in postmenopausal Japanese women.

Hormone replacement therapy (HRT) plays a large part in maintaining and improving the quality of life (QOL) of postmenopausal women. Despite this obvious role, the use of HRT has stagnated in Japan as well as the United States, since the interim report of the HRT trial of Women's Health Initiative study was published in 2002. The Japan Society of Obstetrics and Gynecology and Japan Society for Menopause and Women's Health formulated the Guidelines for Hormone Replacement Therapy in 2009, which was subsequently revised in 2012, with the aim of organizing perceptions about HRT and allowing people to provide or receive HRT with a sense of security. Later on, in light of changes in indications for HRT and attitudes toward its impact on cancer risks, amendments were made again in 2017. With the establishment of the 2017 guidelines, practitioners in Japan are able to address various issues related to HRT with more appropriate judgment. Moreover, the practice of reliable, safe and effective HRT is expected to promote further efforts toward improvement or maintenance of QOL in patients.

Postmenopausal osteoporosis is mainly caused by decreased estrogen levels, and progression of disease is associated with irreversible changes. It is therefore extremely important to maintain or improve healthy bone and calcium metabolism during and before the climacteric from a preventive medicine viewpoint. The specific preventive measures are appropriate calcium intake and regular physical exercise. In recent years, women in their twenties are considerably thinner and have a lower calcium intake than women in other age groups, which may lead to a further increase in the number of women with osteoporosis in the future. From the aspect of female hormone secretion, women are at higher risk for osteoporosis than men at any given age. Aggressive intervention should therefore be undertaken to prevent osteoporosis according to life stage in women.

We previously reported an association between dyslipidemia and endometrial cancers. Osteoporosis is also reported to relate with some cancers. A common etiologic event has been proposed between dyslipidemia and osteoporosis. However, the pattern of interrelationships among dyslipidemia, osteoporosis and endometrial cancer is not well understood. To improve the quality of life of endometrial cancer survivors, these relationships should be determined. This study included 179 Japanese menopausal women who underwent bilateral salpingo-oophorectomy, including 114 women with incident endometrial cancer and 65 without endometrial cancer. The women were categorized according to dyslipidemia status. Bone mineral density was measured and compared between groups. Osteoporosis was statistically more frequent in women with hypertriglyceridemia who did not have endometrial cancer. In contrast, osteoporosis was statistically less frequent in women with hypertriglyceridemia who had endometrial cancer. In this cross-sectional study in a Japanese population, osteoporosis was associated with hypertriglyceridemia in post-menopausal women without endometrial cancer, but was less frequent in endometrial cancer survivors with hypertriglyceridemia.

Background: This study aimed to examine family history among Japanese ovarian cancer patients and to investigate the TP53 status of fallopian tube epithelial and ovarian cancer cells in a Japanese BRCA1 mutant case that may be associated with the transformed state in hereditary ovarian cancer. Methods: One hundred and two primary ovarian cancer patients were retrospectively evaluated in this cross-sectional study. The family history of cancer was determined in probands. In a BRCA1 mutant case, p53 immunostaining and direct sequencing, followed by laser-capture microdissection, were performed for the fallopian tube, considered the origin of ovarian cancer. Results: Nine of 102 (8.8%) families were regarded as having hereditary breast–ovarian cancer syndrome, two families (2.0%) were diagnosed with Lynch syndrome and six patients harbored BRCA1 or BRCA2 mutations. One case underwent risk-reductive salpingooophorectomy as a BRCA1 mutant carrier was retrospectively diagnosed as occult cancer. Common TP53 mutations were detected in cancer and fallopian tube epithelial cells in the case. Conclusions: Here, we integrate family cancer history and histology in ovarian cancer cases as well as TP53 status in a BRCA1 mutant case into a discussion regarding carcinogenesis in a Japanese population. The TP53 status for the BRCA1 mutant case examined here supports the recently proposed theory that ovarian cancer develops because of BRCA1 or BRCA2 inactivation and/or TP53 mutations.

Objective: Previous studies have reported an association between endometrial cancer and the risk of metabolic syndrome; however, the pattern of endometrial cancer-associated dyslipidemia is not well understood. The standard therapy for endometrial cancer is total abdominal hysterectomy and bilateral salpingo-oophorectomy. Premenopausal bilateral salpingooophorectomy may cause adverse events, including dyslipidemia. Gynecologists have to care dyslipidemia in endometrial cancer survivors at cancer follow-up clinic. Methods: This study included 693 patients who had undergone bilateral salpingooophorectomy, and included 412 women with incident endometrial cancer and 281 controls. We divided the patients into two categories according to whether they had a premenopausal or postmenopausal bilateral oophorectomy. Serum lipid levels were measured and statistically analyzed. Results: Hypertriglyceridemia was statistically more frequent in patients who had undergone bilateral salpingo-oophorectomy both before and after menopause than in the corresponding non-endometrial cancer controls. High levels of low-density lipoprotein cholesterol and a high low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio were statistically more frequent in patients who had undergone bilateral salpingo-oophorectomy before menopause than in non-endometrial cancer controls. Conclusions: Our report highlights the importance of the relationship between endometrial cancer and lipid metabolism, which may aid in preventing cerebrovascular or cardiovascular diseases due to dyslipidemia and improving the quality of life in endometrial cancer survivors.

Background Risk-reducing salpingo-oophorectomy is currently regarded as the most certain primary method for preventing ovarian cancer among BRCA1/2 mutation carriers with hereditary breast and ovarian cancer syndrome. However, risk-reducing salpingo-oophorectomy has rarely been performed in Japan. Methods We developed the first system in Japan for performing risk-reducing salpingo-oophorectomy for BRCA1/2 mutation carriers at our university hospital in 2008. Results The indication for risk-reducing salpingo-oophorectomy for patients with hereditary breast/ovarian cancer syndrome is currently limited in Japan. This situation may be because of the limited number of genetic counseling units, the limited number of facilities that can perform BRCA1/2 genetic testing and the fact that prophylactic surgery is not covered by health insurance in Japan. Conclusions Recent treatment guidelines for breast cancer in Japan recommended risk-reducing salpingo-oophorectomy for BRCA1/2 mutation carriers. Risk-reducing salpingo-oophorectomy should be performed in the framework of the standard therapeutic modality for BRCA1/2 mutation carriers in the near future.

The aim of the study was to clarify the prevalence and severity rates of symptoms and investigate whether symptoms varied in relation to body mass index (BMI).The study group composed of 1,969 women, aged 40 to 60 years, who presented at our department from 1993 through 2014. The participation rate was 98%. The presence or absence of symptoms was evaluated by having the participants complete the Keio Questionnaire, a self-administered questionnaire. To allow the results to be compared according to ovarian function, serum levels of follicle-stimulating hormone and estradiol were measured. Participants were classified into three groups according to BMI: underweight, normal weight, and overweight. Symptoms were also compared among these subgroups.The most common symptom was general fatigue. Vasomotor symptoms differed significantly between pre- and postmenopause status. When symptoms were analyzed according to BMI, the severity rates of the following symptoms were significantly higher in the overweight group than in the normal weight and underweight groups: hot flushes, sweats, joint pain, numbness, and incontinence. On the contrary, the underweight group had significantly higher severities of cold constitution, nervousness, and wrinkled skin than did the other groups. In addition, an increase in BMI was associated with an increased severity of vasomotor symptoms.The prevalence and severities of shoulder stiffness, considered a characteristic symptom in Japanese women, were high. Increased BMI was shown to be associated with a higher severity of vasomotor symptoms, joint pain, nervousness, and urinary symptoms.

A randomized controlled trial was performed to compare the short-term effects of alendronate (ALN) and ECT on pain and quality of life (QOL) in postmenopausal women with osteoporosis. Back pain and QOL [Short-Form Health Survey (SF-8)] significantly improved at 1, 3, and 6 months in both groups, with greater improvements in the ALN group than in the ECT group. These results suggested that ALN reduced back pain and improved QOL more markedly than ECT in postmenopausal osteoporotic women with back pain.Intramuscular ECT is known to reduce pain via the central nervous system. A multicenter randomized controlled trial was performed to compare the short-term effects of ALN and ECT on pain and QOL in postmenopausal women with osteoporosis.One hundred and 94 postmenopausal osteoporotic women with back pain (mean age 79.8 years, range 60-96 years) were randomly divided into two groups: the ALN group (35 mg weekly) and the ECT group (intramuscular 20 units a week). The duration of the study was 6 months. The trial was completed in 97 (100%) women of the ALN group and 96 (99.0%) women of the ECT group. Urinary levels of cross-linked N-terminal telopeptide of type I collagen (NTX), serum alkaline phosphatase (ALP), face scale score (FSS, back pain), and SF-8 (QOL) were monitored.Urinary NTX levels significantly decreased at 3 months in the ALN group, but not in the ECT group. Serum ALP levels significantly decreased at 6 months in the both groups, with a greater reduction in the ALN group. The FSS and SF-8 significantly improved at 1, 3, and 6 months in both groups, with greater improvements in the ALN group than in the ECT group.ALN suppressed bone turnover, reduced back pain, and improved QOL more markedly than ECT in postmenopausal osteoporotic women with back pain.

OBJECTIVE: An inhibitory effect of hyperprolactinemia on the hypothalamo-pituitary-gonadal axis has been suggested as a mechanism of bone loss in schizophrenia, but this has not been confirmed. In this study, which was conducted in Tokyo, Japan, from February to May 2005, we examined the possible causes of reduced bone mineral density (BMD) in male patients with schizophrenia. METHOD: The BMD of the radius of 74 male patients (aged 31-78 years) who met the diagnostic criteria for DSM-IV schizophrenia was measured by dual-energy x-ray absorptiometry. Levels of prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, estradiol, and 1,25-dihydroxy vitamin D (VitD) were also measured. Pedometers were used to measure the impact of exercise. RESULTS: Study subjects showed lower BMD in all age groups compared with reference values in healthy persons. There was no significant difference in the Z score among low, medium, and high exercise groups. 87% of the subjects had hyperprolactinemia, and VitD levels were normal in all subjects except 1. The high PRL group had lower levels of FSH and LH, and significantly lower levels of estradiol (p < .05), compared with the normal PRL group. In the high PRL group, there was a significant negative correlation between the duration of treatment and the Z score (p < .05). CONCLUSION: Male patients with schizophrenia had lower BMD than normal individuals irrespective of the amount of exercise or the level of VitD. The results support the hypothesis that inhibition of the hypothalamo-pituitary-gonadal axis by hyperprolactinemia contributes to the mechanism of the bone loss and suggest that the longer the duration of hyperprolactinemia, the greater the reduction in BMD.

Introduction : Bilateral salpingo-oophorectomy (BSO) is a risk factor for osteoporosis. Previous studies have reported an association between genetic polymorphisms and the risk of developing osteoporosis. However, the relationship between osteoporosis and genetic polymorphisms in Japanese women treated with BSO is not well understood. To improve the quality of life for post-BSO patients, it is important to determine the genetic factors that influence their risk for osteoporosis. The aim of this study was to investigate the association between gene variations of estrogen metabolism-related genes and osteoporosis in surgically menopausal patients, which may improve the quality of life for surgically menopausal patients. Material and methods : This study included 203 menopausal women treated with BSO because of gynecologic disorders. One hundred and twenty-six women with artificial (surgical) menopause, who had undergone BSO in the premenopausal period, were compared with 77 women with natural menopause, who had undergone BSO in the postmenopausal period. The women were tested for bone mineral density to diagnose osteoporosis. Polymorphisms of estrogen receptor 1 ( ESR1 ) and UDP-glucuronosyl transferase (UGT) genes UGT2B17 and UGT1A1 were analyzed, and their association with bone mass and osteoporosis was statistically evaluated. Results : No significant association was found between osteoporosis and polymorphisms in ESR1 , UGT2B17 , or UGT1A1 in both groups, suggesting that BSO might be a more significant physiological factor in influencing bone mass density compared to genetic variations. Conclusions : These results suggest that the ESR1 , UGT2B17 , and UGT1A1 polymorphisms are not genetic factors affecting osteoporosis in postmenopausal Japanese women.

This paper deals with optimal design strategy of the connected control method for flexible structures with same dynamic properties. One of the authors had already proposed effectiveness of connected control method for vibration control of flexible structures arranged in parallel. However, its control performance reduces as the natural frequencies of structures become closer. Therefore, the authors have presented a modified control mechanism in which the actuators are connected to the structures with a difference in its connecting position using long arms. However, its optimal design strategy of vibration control device has not been established yet. In this report, the optimal design strategy of passive control is derived. Computer simulations and experiments are carried out and the effectiveness of the presented optimal design strategy is confirmed.

OBJECTIVE To gain insight into the characteristics and current status of climacteric symptoms reported by middle-aged and older women in Japan, we surveyed women presenting at our menopause clinic. DESIGN The participants included 1,069 women, ranging in age from 40 to less than 60 years (mean age, 50.2 y). Climacteric (indefinite) symptoms were objectively assessed with the use of the Keio questionnaire, which grades the severity of 40 types of symptoms classified into 20 subgroups. The total scores obtained for the 40 symptoms were used to calculate symptom prevalence and severity. To evaluate ovarian function, concentrations of estradiol and follicle-stimulating hormone (FSH) in sera were measured. RESULTS The most frequent symptom was general fatigue, reported by 88.2% of the women. Shoulder stiffness was the symptom rated to be severe by the highest percentage of women (38.1%). The prevalence and severity of hot flushes (and sweats) were slightly higher in perimenopausal and early postmenopausal women than in premenopausal and late postmenopausal women. The prevalence and severity of hot flushes and sweats were higher in women with estradiol 40 mIU/mL than in those with estradiol > or = 25 pg/mL and FSH < or = 40 mIU/mL. CONCLUSION General fatigue and shoulder stiffness, symptoms with low hormone dependence, are the two most frequent climacteric symptoms in our clinic. Hot flushes and sweats, symptoms with high hormone dependence, are also common symptoms.

Aim: Psychosocial elements are often found in the background of patients with menopausal disorders, and counseling based on these elements is essential for effective treatment. In the study presented here an attempt was made to extract psychosocial factors from Japanese cases of menopausal disorders in which the patients exhibited the impact of psychiatric elements and required counseling. Methods: A total of 97 cases in which the patients received counseling for the treatment of undefined complaints at our menopause clinic were analyzed. During counseling the patients were interviewed in regard to psychosocial factors and underwent psychological tests. Results: About half of them were found to have experienced various interpersonal problems as well as health-related problems. The frequency of problems such as empty nest syndrome and loss of relatives or friends was relatively low. Work-related anxiety or hardships of life were frequent among the premenopausal patients, while concern about aging was often noted in their postmenopausal counterparts. The incidence of empty nest syndrome was high among the ovariectomized women, but worry about aging was frequently reported by those undergoing natural menopause. Conclusion: This preliminary study revealed that problems related to families and the patient's health account for a large part of the psychosocial factors affecting the development of menopausal disorders in Japan. Incorporating these findings into counseling will make outpatient clinics services more acceptable to such patients.

Background: This prospective observational study was designed to determine whether the bone mineral density (BMD) of the lumbar spine decreases before menopause. Methods: The change in BMD of the second through fourth lumbar vertebrae (Δ%L2–4BMD) over the course of 12 months was measured in 197 pre- and perimenopausal Japanese women aged 48.2 ± 2.3 (mean ± SD) years. Results: Overall, Δ%L2–4BMD decreased significantly, with a greater decrease seen in perimenopausal women. This group also had a significantly higher level of FSH (p < 0.05, t = 7.356), a significantly lower level of estradiol (p < 0.05, t = 4.245), and significantly higher levels of the bone metabolic markers, alkaline phosphatase (p < 0.05, t = 3.841), calcium (p < 0.05, t = 3.939), and osteocalcin (p < 0.05, t = –3.295). Overall, there was a significant positive correlation between osteocalcin and Δ%L2–4BMD (r = –0.194, p = 0.0479). Conclusion: A subset of perimenopausal women with transient decreases in ovarian function that do not respond to increased FSH may be at increased risk for abnormally low BMD, and may benefit from early management of bone mass.

Minodronate is a potent nitrogen-containing bisphosphonate that can be administered according to a monthly (every 4 weeks) dosing regimen. A 6-month, cluster-randomized, open-label, multicenter, crossover trial was conducted to test the preference of Japanese patients with osteoporosis for monthly bisphosphonate versus weekly bisphosphonate. One hundred and forty-seven patients (postmenopausal women and men) with primary osteoporosis were recruited at eight outpatient clinics. The clinics were randomized into two groups according to the dosing protocol—monthly minodronate followed by weekly alendronate or risedronate for a total of 24 weeks, or weekly alendronate or risedronate followed by monthly minodronate for 24 weeks. Patient preference for either the monthly or weekly bisphosphonate regimen was evaluated using a preference questionnaire. One hundred and fifteen patients (78.2 %) who completed the trial were processed for the analyses. Significantly more patients preferred the monthly bisphosphonate regimen (65.2 %) than the weekly bisphosphonate regimen (15.7 %) (P = 0.007). ‘Dosing schedule fits lifestyle better’ was the most common reason given for the patient preference for both the monthly (32.0 %) and weekly bisphosphonate (33.3 %) regimens. Significantly more patients found the monthly bisphosphonate regimen to be more convenient (73.0 %) than the weekly bisphosphonate regimen (13.9 %) (P < 0.0001). The safety profiles of the two regimens were similar. The present trial demonstrated a strong patient preference for and the convenience of the monthly bisphosphonate regimen over the weekly bisphosphonate regimen in Japanese patients with osteoporosis.

Objectives This study was designed to investigate the current status of vaginal symptoms in Japanese postmenopausal women, and to clarify the significance of vaginal symptoms by analyzing their relationship to other climacteric symptoms. Methods The complaints of 613 women attending a menopause clinic (mean age ± standard deviation 53.5 ± 7.2 years; time since menopause or bilateral oophorectomy 6.4 ± 6.5 years) were evaluated according to the Keio modified menopause index. Results In total, 56.4% of subjects had at least one vaginal symptom. The most frequent vaginal symptom was dyspareunia, followed by vaginal dryness, discharge and itching, and the mean prevalence of the four symptoms was 31.7%. The peak intensity of vaginal symptoms occurred in the sixth decade, or 3–5 years after menopause or oophorectomy. Vaginal symptoms were usually associated with other climacteric symptoms, but some occurred independently. Conclusions A moderate proportion of Japanese postmenopausal women experience vaginal symp...

An optimal scheme of road paving maintenance was investigated by examining the environmental loading and cost considerations of pavement operations over a 30-year life cycle. Results indicated that the application of recycled materials in pavement construction and repair reduced the effects of environmental loading over the life cycle by approximately 40%. Furthermore, it was observed that environmental loading conditions associated with the maintenance repair stage of asphalt paving comprised 50% of the total environmental loading determined for the 30-year life cycle. Conversely, costs of the maintenance repair stage were 40% of the total life cycle costs. Finally, results suggest that environmental load and cost considerations will be improved and made more efficient over a life cycle period if a regular maintenance routine of simple asphalt repairs is established. INTRODUCTION The need to protect the environment is of paramount concern, particularly when a l a rge-scale project such as a road is being undertaken. It is necessary that all aspects of construction and maintenance be monitored in relation to the environment, especially hidden factors, including the production of input materials and assembling vehicles for operational purposes. Unfortunately, very few sources exist that examine the effects of both construction materials and vehicles on the environment. Those papers that investigate both components do not evaluate the environmental issues over the whole life cycle of the road. This study investigates the environmental loading and cost parameters associated with the construction and maintenance of a road over a 30-year life cycle. The cycle includes a number of repair works as well as the optimal maintenance schedule for the road. Furthermore, the evaluation considers the impact of using recycled material in road construction and maintenance work. The Life Cycle Inventory Method is used to determine the environmental loading conditions of a road, while construction and maintenance costs are estimated using statistical tables[1-4] published in 1995 by a variety of organizations. PAVEMENT MAINTENANCE MODELS The costs and environmental impact associated with an asphalt road surface and a concrete road surface were evaluated over a 30-year life cycle. To estimate environmental and cost conditions associated with maintenance repair work, information on a number of parameters was considered. Environmental loading was determined by evaluating the amount of fuel consumed by paving vehicles, the volume of resources used during maintenance procedures, and the transportation of waste material from site. The direct cost of construction was computed by combining labor expenses, material costs, and machine operating expenses. Calculations were based on a minimum traffic density of 3000 larg e vehicles per day in one direction (road classification ‘D’) and a unit execution area of 100m. Only one repair model was selected for the concrete surface, as concrete requires little maintenance over its life cycle. The model repair schedule included an asphalt compound coating 18 years after the road was constructed and surface treatment work 25 years following completion. Four models[5] of asphalt surface repair were evaluated in the analysis. Descriptions of each model are provided in the following section. Asphalt paving case I: pavement is replaced every 10 years following its initial construction; Asphalt paving case II: pavement is replaced 15 years after construction and cutting overlay occurs twice (8 and 23 years after construction); Asphalt paving case III: 13 years following construction, pavement is replaced, surface recycling work is performed 7 years after construction, and surface treatment occurs 23 years after road completion; Asphalt paving case IV: the pavement is not replaced; only 4 small scale repair projects are performed: cutting overlay (12 and 23 years after construction), surface recycling work (year 7) and surface treatment (year 18). Figures 1 to 4 summarise the environmental load and cost estimates for each repair model. Carbon dioxide emissions and energy volume consumption during the repair of asphalt were estimated to be 65% of the total environmental load in case I, and 50% of the total in case II. Conversely, 70% of the total costs in case I were generated during the maintenance repair stage while repairs accounted for 40% of the total costs in case IV. Maintenance repair costs during these stages exceeded the initial construction costs calculated for cases I to III. Furthermore, the environmental load was greater than the load Carbon dioxide emission, kg-C/100m

癌肉腫は子宮悪性腫瘍の中でも発生頻度は低いものの, 予後がきわめて悪く, しかも術前に癌肉腫と診断される頻度は低い. 今回われわれは, 術前に子宮体部癌肉腫と診断しえた症例を経験したので報告する. 症例は62歳女性で, 下腹部痛を主訴に当科を受診した. 初診時膣腔を占拠する壊死状の腫瘍を認めたが, 子宮頸部および内膜細胞診はclassII, 子宮内膜組織診でも壊死組織を認めるのみであった. 入院後腫瘍が自然脱落し, その病理組織学的検索によって癌肉腫と診断され, 手術時の摘出標本により子宮に通常存在しない骨肉腫成分を含んだ異所性癌肉腫と最終診断した. 手術による摘出標本の捺印細胞診では, 腫瘍細胞は重積性を示す細胞集団と孤立散在性を呈する細胞の二つのパターンで出現した. 重積性を示す細胞は, N/C比大で核クロマチンは細顆粒状, 核小体は明瞭にて腺癌細胞と同定した. 孤立散在性を示す細胞は, 円形ないし類円形で, 核は大型類円形で大小不同, 核型不整, 増量したクロマチンと著明な核小体を有し, 非上皮性腫瘍細胞と同定した. 癌肉腫は組織構築上, 術前診断としては癌腫成分のみ診断されることが多いが, 今回われわれは肉腫成分をも診断しえた1例を経験した.

In vitro studies have shown that ipriflavone affects both bone formation and bone resorption, but the effect in early-stage postmenopausal women with low bone mass and a high turnover of bone metabolism is unknown. In this prospective study, we randomly assigned 60 patients with postmenopausal osteopenia or osteoporosis to receive either 600 mg/day of ipriflavone or 0.8 g/day calcium lactate, and compared the effects on bone mineral density (BMD) from the 2nd to 4th lumbar vertebrae (L2–4) and bone metabolic markers before and after one year of treatment. In the iprifravone-treated (IP) group, L2–4 BMD was similar before and after treatment (0.78 and 0.77 g/cm2, respectively), but in the calcium lactate-treated (CL) group, L2–4 BMD decreased significantly from 0.81 to 0.79 g/cm2 after 1 year of treatment (p < 0.0001). Furthermore, the rate of the decrease in L2–4 BMD was significantly greater in the CL group than in the IP group (p < 0.01). The median deoxypyridinoline (Dpd) level was significantly lower after 1 year of treatment (5.8 mmol/mmol creatinine [Cr]) than the baseline value (10.2 mmol/mmol Cr) in the IP, but not in the CL group, suggesting that IP treatment suppresses bone resorption.

Objectives: Menopause is associated with a rise in serum lipid concentrations. We compared a regimen of pravastatin alone with pravastatin and hormone therapy in postmenopausal women with hyperlipidemia. Methods: We performed a double-blind, randomized, multicenter controlled study in postmenopausal women with hyperlipidemia. The women were randomly assigned to receive pravastatin alone (M group; n =25) or pravastatin and hormone replacement therapy (HRT) (MC group; n =32) for 12 weeks. Serum lipid and estrogen concentrations were measured at baseline and after 4 weeks and 12 weeks of treatment. Results: The two groups were similar with respect to baseline demographic characteristics such as age, height, and body weight. As compared with baseline, the total cholesterol (TC) concentration was 15.0% lower at 4 weeks and 17.7% lower at 12 weeks in the M group and 15.1% lower at 4 weeks and 18.3% lower at 12 weeks in the MC group. The low-density-lipoprotein cholesterol (LDL-C) concentration decreased by 25.0% at both 4 weeks and 12 weeks in the M group and by 26.8% at 4 weeks and 30.0% at 12 weeks in the MC group. Serum TC and LDL-C concentrations were significantly lower in the MC group than in the M group after 4 weeks of treatment, but there was no significant difference between the groups in serum lipid concentrations after 12 weeks. Pravastatin combined with HRT was therefore suggested to lower serum lipid concentrations earlier than pravastatin alone. There were no significant differences between the treatment groups in serum high-density-lipoprotein cholesterol concentrations or triglyceride concentrations after the initiation of therapy. In the MC group, there was a significant positive correlation between the percentage change in serum lipid concentrations and that in estrogen concentrations, suggesting that the HRT-induced rise in estrone (E1) as well as that in estradiol (E2) contributed an improved serum lipid profile. TC and E2, and LDL-C and serum E1 had significant negative correlation at 12 weeks and 4 weeks, respectively. Pravastatin had no apparent effect on endogenous estrogen levels and was not associated with any side effects, which confirmed that pravastatin is safe, either alone or in combination with HRT. Conclusions: The combination of pravastatin and HRT in the management of hyperlipidemia in postmenopausal women is very useful therapeutically, because it additionally provides the broad benefits of HRT, without compromising the lipid lowering effects of either treatment.

It has become significant to illustrate the environmental load emissions and the costs by waste recycling system, and to improve the actual recycling processes in various industries. Objective of this study is to evaluate the carbon dioxide emission and costs in the construction processes of new and recycled pavement. Three kinds of materials (asphalt, cement, and aggregate) are put into road building. We reached the recycling effects in the carbon dioxide emission and construction costs by applying these materials to some model cases of the traffic volume. The following results were obtained in this study.(1) Recycling of pavement waste asphalt is effective for reducing 56% of carbon dioxide emission.(2) Recycling of pavement waste aggregate increases carbon dioxide emission but it is greatly effective for saving resources consumption.(3) While the recycled asphalt pavement is expected to have some advantages in reducing carbon dioxide emission and construction costs, it was founded the recycled concrete pavement to increase carbon dioxide emission and construction costs.

Prescription of a bisphosphonate (BP) with monthly dosing has recently been approved in Japan. The value of this approach for improvement of medication adherence was investigated in patients undergoing drug therapy for osteoporosis. A questionnaire was distributed to patients receiving treatment for osteoporosis at 8 medical facilities (5 orthopedic, 2 gynecology, and one internal medicine). Responses were collected from 1,300 patients. After exclusion of those who missed an item on the questionnaire or took drugs other than oral drugs, responses from 1,151 patients were analyzed. The most frequently used drug for treatment of osteoporosis was a once-weekly BP. Of the 1,151 patients, 38.4 % reported forgetting to take their current drug. The most frequent concern was ‘I cannot feel an effect’, but 73.2 % answered ‘I have no concerns’. Regarding the most appropriate dosing regimen for long-term treatment, 60.3 % selected once-weekly and 24 % selected once every 4 weeks. Based on a recommendation by a physician of a drug to be taken monthly, 32.5 % wanted to switch, 31.8 % were undecided, and 35.7 % wanted to continue with their current drug. The desire for a change was higher among patients currently taking a once-weekly BP (52.3 %) than among patients taking a daily BP (29.5 %) or a SERM (19.4 %). This survey revealed patients’ preferences in osteoporosis drug therapy. It is important to select a drug for osteoporosis based on the efficacy and the drug regimen preferred by the individual patient.

The present study was designed to investigate the differences in serum levels of sex steroids, bone metabolism, and bone mineral density (BMD) between 22 premenopausal subjects and 21 age- and body size-matched postmenopausal subjects. Dual photon absorptiometry (DPA) demonstrated total body BMD significantly decreased in postmenopausal subjects. It was also found that not only spinal BMD as assessed by DPA, but also total third lumbar BMD and third lumbar trabecular BMD as measured by quantitative computed tomography (QCT) significantly decreased in these subjects. In postmenopausal subjects, the urinary-hydroxyproline/creatinine ratio increased significantly, which suggested that bone resorption had been stimulated, and serum levels of alkaline phosphatase (ALPase) and osteocalcin also significantly increased, which suggested a stimulation of bone formation. Consequently, the reduction in BMD was thought to result from a negative balance of bone resorption versus bone formation, or a high turnover of bone metabolism. Androgens were not confirmed to participate in these changes in bone metabolism, but the reduction in serum levels of estradiol, as a major factor, and the reduction in serum levels of estrone, as a participating factor, were assumed to result in an increase in bone resorption in excess of bone formation.

A total of 22 female patients under age 60 who showed a decrease in bone mineral density (BMD) after menopause and/or bilateral oophorectomy received 600 mg/day ipriflavone (IP) for 1 year, and the effects on bone metabolism and BMD were observed. Although estrogen levels were low in these patients, a significant rise in serum calcitonin and a decrease in serum calcium were observed. Osteocalcin, a bone formation indicator, also showed a significant increase. These findings suggest IP both inhibits bone resorption and promtes bone formation not only in vitro but also in vivo. BMD of cancellous bone was measured using quantitative computed tomography (QCT). Cancellous bone is believed to most sensitively reflect changes in bone metabolism because of its high rate of metabolic turnover [1]. The patients who had not received IP showed a significant decrease in BMD, while those who had received IP showed only a slight decrease. These observations suggest that IP can be used successfully to reduce the rapid decrease in bone density associated with menopause and/or bilateral oophorectomy.

Summary The present study was designed to investigate in a comparative manner whether menopause or oophorectomy (OPX) would be a more osteoporosis-inducing factor with regard to sex steroids, bone metabolism and bone mineral density (BMD), including postmenopausal subjects, OPX subjects and ageand body-size-matched premenopausal controls. Serum levels of estradiol (E 2 ), testosterone (TS) and dehydroepiandrosterone (DHEA) were found to decrease in both the postmenopausal and OPX subjects without any significant difference between them, while serum levels of estrone (E 1 ) and androstenedione (Δ 4 ), which have been reported to be related to bone metabolism, were significantly lower in the OPX subjects than in the postmenopausal subjects. According to the indices representing bone formation and bone resorption, as well as the changes in serum levels of Ca-regulating hormones, bone metabolic balance seemed to be slightly more negative in the former than in the latter. However, there was no difference between these two groups of subjects with regard to BMD in lumbar vertebral spongy portion which sensitively reflects the changes in total lumbar BMD and bone metabolism and in which compressive fracture is apt to occur. This fact suggests that these two groups of subjects may be managed in the same way in clinical practice. In other terms, the menopause, a natural event in women, influences BMD as much as OPX, which is the greatest risk factor in osteoporosis, does.

Aim: To assess lipoprotein(a) [Lp(a)] dynamics before and after menopause and to examine long-term changes during hormone replacement therapy (HRT) in middle-aged and older Japanese women. Methods: (1) Serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and Lp(a) concentrations of 526 patients were compared. The patients were divided into 3 groups on the basis of menopausal status (premenopause, perimenopause, postmenopause). (2) Serum markers of lipid metabolism were measured at baseline and at 6-month intervals in 161 postmenopausal women who continuously received HRT with conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA) for 4 years. (3) Changes in serum concentrations of markers were compared among 120 women with hypercholesterolemia who were randomly assigned to receive HRT (CEE plus MPA, or transdermal estradiol plus MPA) or pravastatin. Results: (1) Lp(a) concentrations were significantly higher in the postmenopausal women than in the premenopausal or perimenopausal women. (2) The mean Lp(a) concentration after 6 months of HRT decreased by about 19%, and similar levels were maintained for 4 years (3). The mean Lp(a) concentration after 6 months of HRT decreased by 19.9% in the CEE plus MPA group, but did not change significantly in the transdermal estradiol plus MPA group or the pravastatin group. Conclusion: Our results suggest that HRT with CEE plus MPA is useful for the management of elevated serum Lp(a) concentrations in middle-aged and older women. However, follow-up studies are needed to determine whether this finding is related to the future prevention of coronary heart disease events.

We conducted a prospective, randomized, multicenter, open-label 2-year trial with 76 postmenopausal women agedor =60 years with low (T-score less than -1) lumbar bone mineral density (BMD). The hormone replacement therapy (HRT) group received a low dose of conjugated estrogen (CEE) at a dose of 0.31 mg/day +/- medroxyprogesterone acetate (MPA) 2.5 mg/day. Group HRT/D received the same dose of HRT together with alfacalcidol in a daily dose of 1.0 microg/day. Changes in lumbar BMD measured by dual energy X-ray absorptiometry (DXA) were followed every 6 months for 2 years. The lumbar BMD of group HRT increased 3.37% [95% confidence interval (CI) 1.6%-5.2%], 4.00% (95%CI 1.6%-6.4%), and 2.32% (95%CI -0.7% to 5.3%) at 12, 18, and 24 months, respectively, when the baseline value was taken as 0%. Lumbar BMD of group HRT/D showed a significant increase beyond 6 months. The percent increases for this group at 6, 12, 18, and 24 months were 6.18 (95%CI 1.3%-6.6%), 6.18% (95%CI 3.9%-8.5%), 7.17% (95%CI 4.3%-10.0%), and 8.75% (95%CI 6.0%-11.5%), respectively. In addition, there was a significant difference in the changes of the lumbar BMD between the two groups at 24 months, suggesting that the combination of HRT and alfacalcidol is more effective than HRT alone in terms of the BMD effect. This study is the first prospective trial demonstrating an additive effect of alfacalcidol on lumbar BMD in postmenopausal women receiving low-dose HRT. It suggests that the combination therapy can be considered to be a promising mode of treatment for bone loss after menopause.

Under the current diagnostic criteria for primary osteoporosis, patients are diagnosed as having osteopenia if their bone density is between 70 and 80% of the average bone density of young adult women. Osteopenia is essentially a precursor for osteoporosis, and because prevention is the basis of osteoporosis treatment, halting the progression of osteopenia into osteoporosis is very important. In other words, the risk factors associated with osteoporosis in each patient must be assessed, and if rapid bone mass loss is expected or confirmed, drug therapy should then be actively administered.

Aim: To examine the status and characteristics of climacteric symptoms reported by generally healthy middle-aged to elderly women in Japan, those living in Saitama Prefecture were surveyed . Methods: The subjects comprised 398 women ranging in age from 40 to

This paper deals with vibration control using the optimal design strategy of the connected control device for flexible structures with same dynamic properties. One of the authors had already proved effectiveness of connected control method for vibration control of flexible structures arranged in parallel. However, its control performance is degraded as the natural frequencies of structures become closer. To overcome this problem, the authors present a modified control mechanism in which the actuators are connected to the structures with differences in its connecting position by using long arms named “supporting structures”. However, the optimal design strategy for vibration control device has not been established yet. In this report, the optimal design strategy of passive control is presented. Computer simulations and the experiments are carried out and the effectiveness of the presented vibration control designed by the connected control device is confirmed.Copyright © 2005 by ASME

Our objective was to assess the effects of 6 months' treatment with two types of gonadotropin-releasing hormone (GnRH) analogues on lumbar bone mineral density (BMD) and bone metabolism. We studied 27 women who had been given a diagnosis of endometriosis or uterine myoma. The subjects received drug therapy for 6 months and were subsequently followed up for 1 year. The BMD of the lumbar spine (L2, L3, L4) was measured by dual energy X-ray absorptiometry four times: at baseline, after 6 months, after 12 months, and after 18 months. The serum concentrations of sex steroids and bone metabolic markers were measured at the same times as BMD. Compared with the baseline value, the mean decrease in the buserelin group L2-4 BMD was 3.7% at 6 months, 1.7% at 12 months, and 0.4% at 18 months. In the leuprolide group, L2-4 BMD decreased respectively by 5.1%, 6.2%, and 4.3%. Serum concentrations of calcium increased significantly after 6 months of treatment (P < 0.05) and returned to the baseline level at 12 months in both groups. In the leuprolide group, the intact osteocalcin concentration after 6 months was significantly higher than the baseline value, and after 12 months, it decreased to the baseline level. Our results indicate that the effect on BMD of 6 months' treatment with GnRH analogues virtually resolves by 1 year after treatment, provided that drugs affecting bone metabolism are not given during this period.

Aim: To examine current depressive tendencies among Japanese patients visiting a menopause clinic with complaints of climacteric symptoms. Methods: The subjects were 389 Japanese women (age range: 45–60 years; mean: 51.4 ± 3.8 years) who visited the menopause clinic in Department of Obstetrics and Gynecology, Keio university hospital, reporting climacteric symptoms. Their depressive tendencies were examined with the SDS (Self-rating Depression Scale, filled out by the patient). Results: The SDS was computed to be 42.4 ± 9.9. Ninety-three (23.9%) suffered from an intermediate or higher level depressive tendency; 132 (33.9%) had a mild depression; and 164 (42.2%) were free of any depressive tendency. It was concluded that more than one-half of the subjects suffered from some form of depression. Correlations between age, time after menopause/oophorectomy, and depressive tendency were ambiguous. In comparing the total scores of SDS for pre-, peri-, and postmenopause groups, the incidence of probable depression was higher in the second group, but no significant differences were noted among each group. When the parameters were compared in relation to their hormonal environments, the natural menopause group rated significantly higher in the scores related to sleep disturbance, hopelessness and dissatisfaction than the premenopause group. The number of those who probably exhibited mild or more exaggerated depression was significantly lower in the surgical menopause group in comparison with the natural menopause group. Conclusion: A depressive tendency occurred frequently among Japanese patients with menopausal disorders. It is important to evaluate the mental status of these patients with the aid of an appropriate tool.

To investigate if menopause and oophorectomy may represent different risk factors for bone resorption/loss.The urinary levels of pyridinoline (Pyr) and deoxypyridinoline (D-pyr), the serum levels of type I carboxy-terminal pyridinoline cross-linked telopeptide (ICTP), and lumbar bone mineral density (BMD), were compared in 80 Japanese women after menopause or oophorectomy. These women were divided into four groups of 20 women each as follows: early postmenopausal stage (early physiologic menopause3 years before study entry); late postmenopausal stage (physiologic menopauseor = 3 years before study entry); early postoophorectomy stage (oophorectomyor = 03 years before study entry); or late oophorectomy stage (oophorectomy3 years before study entry).Lumbar BMD was significantly lower in the late groups compared to their respective early groups and was lowest in the late postoophorectomy group. The ratio of D-pyr/creatinine (Cr) was not significantly different among the four groups. The ratio of Pyr/Cr was significantly higher in the early postoophorectomy subjects compared with either late group. The serum level of ICTP was significantly higher in the early postoophorectomy group compared to all other groups.These findings suggest that serum ICTP may be useful in detecting changes in bone resorption after oophorectomy and that women are at greater risk for bone resorption after oophorectomy than after physiologic menopause, although this difference appears to diminish with time.

This prospective observational study was designed to determine whether the bone mineral density (BMD) of the lumbar spine decreases before menopause.The change in BMD of the second through fourth lumbar vertebrae (delta%L2-4BMD) over the course of 12 months was measured in 197 pre- and perimenopausal Japanese women aged 48.2 +/- 2.3 (mean +/- SD) years.Overall, delta%L2-4BMD decreased significantly, with a greater decrease seen in perimenopausal women. This group also had a significantly higher level of FSH (p0.05, t = 7.356), a significantly lower level of estradiol (p0.05, t = 4.245), and significantly higher levels of the bone metabolic markers, alkaline phosphatase (p0.05, t = 3.841), calcium (p0.05, t = 3.939), and osteocalcin (p0.05, t = -3.295). Overall, there was a significant positive correlation between osteocalcin and delta%L2-4BMD (r = -0.194, p = 0.0479).A subset of perimenopausal women with transient decreases in ovarian function that do not respond to increased FSH may be at increased risk for abnormally low BMD, and may benefit from early management of bone mass.

Objectives: We objectively assessed the effects of counseling on climacteric symptoms in Japanese postmenopausal women. Methods: Symptoms in 44 women (age, 51.4 + 3.4 years; period after menopause, 3.6 + 3.4 years) treated with counseling were evaluated according to the Keio modified menopause index. The response to counseling was compared with that to hormone replacement therapy (HRT). Results: Forty cases (90.9%) showed an improvement in index score. There were no significant relationships between improvement and age, the period after menopause, or the severity or type of symptoms before counseling. The most improved symptom was headache, followed by palpitation and insomnia. Physical symptoms accounted for most of the common symptoms. The pattern of improvement with counseling was markedly different from that with HRT. Conclusions: We suggest that counseling is effective for treating climacteric symptoms, since it improves not only psychological symptoms, but also physical ones. Counseling may deserve evaluation as a complementary treatment to HRT.

Objective: To assess the therapeutic value of treatment with an HMG-CoA reductase inhibitor in women with hypoestrogenic hyperlipidemia caused by menopause. Design: Fifty-six women with total cholesterol (TC) levels of 220 mg/dl or more who were within 7 years of menopause were randomly assigned to receive an HMG-CoA reductase inhibitor (pravastatin 10 mg/day; treated group, 26 patients) or no medical treatment (nontreated group, 30 patients) in this 6-month nonblinded prospective trial. Results: In the treated group, the mean (SD) TC levels decreased significantly from 254.5 ± 22.3 mg/dl at baseline to 204.7 ± 22.2 mg/dl (19.6%), and the mean low-density lipoprotein cholesterol (LDL-C) level decreased significantly from 146.7 ± 30.5 to 104.3 ± 22.5 mg/dl (28.9%); the mean arteriosclerotic index decreased significantly from 2.98 to 2.08 (30.2%). There were no significant changes in either triglyceride levels or high-density lipoprotein cholesterol (HDL-C) levels. In the nontreated group, there were no significant changes in the TC, HDL-C, LDL-C, or triglyceride levels; there was also no change in the arteriosclerotic index. After 6 months, the TC level, LDL-C level, and arteriosclerotic index were significantly lower in the treated group compared with the nontreated group (p < 0.01). Conclusions: The results indicate that the HMG-CoA reductase inhibitor lowered TC and LDL-C levels and was useful in the treatment of hypoestrogenic hyperlipidemia for periods of at least 6 months.

We previously reported that hormonal changes in perimenopausal women are associated with dermatologic changes. In the present study, we evaluated such dermatologic changes by means of dermato-physiological testing methods in perimenopausal women with various types of hormonal conditions. The study group consisted of 46 consecutive women 41-70 years of age (mean, 54.0 years), attending a climacteric outpatient clinic for a healthy check-up is whom no abnormalities were recognized. The women were divided into four groups according to menstrual history and sex-related steroid hormone values: a premenopausal group (n = 9); a perimenopausal group (n = 8); an early menopausal group, in which 5 years or less had elapsed since menopause (n = 12); and a late menopausal group, in which 6 years or more had elapsed since menopause (n = 17). We found that: (1) after menopause the sebum cutaneum content of the forehead decreased significantly, but that of the subocular region was unchanged; (2) the water content of the stratum corneum of the forehead was significantly higher in the late menopausal group than in the premenopausal group and the perimenopausal group, but there were no significant differences among the four groups at the other sites studied; (3) on psychological stimulation, sweat production was found to decrease significantly after menopause; (4) the skin temperature of the forehead and cheek fell significantly after menopause, but that of the nose, back of the foot, and tips of the toes, did not differ significantly among the four groups; (5) The perimenopausal period was associated with increased skin permeability and vascular responsiveness; (6) fingertip plethysmography revealed significant decreases in peripheral circulatory function in the perimenopausal group and the late menopausal group.

Objectives: Reduction in serum level of estrogen has been thought to result in hyperlipidemia which triggers atherosclerosis, and even to lead to cardiovascular diseases, in postmenopausal women. The present study was designed to investigate the influence of bilateral oophorectomy (OPX), which induces as much reduction in serum estrogen level as menopause, upon lipid metabolism, especially the serum levels of total cholesterol. Methods: In 31 OPX subjects and 31 age- and body size-matched premenopausal controls, the serum levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein (VLDL-C), apoprotein-A1 (Apo-A1), apoprotein-B (Apo-B), lipoprotein lipase (LPL) and lipoprotein-a [LP(a)] were measured as indices of lipid metabolism and the index of arteriosclerosis was calculated. Results: TC level was significantly higher in the OPX group than in the premenopausal control group, being 8995±244 (mean±S.E.) mmol/l and 7757±228 mmol/l, respectively. LDL-C and Apo-B levels and the index of arteriosclerosis were all significantly higher in the OPX group than in the premenopausal control groups. However, there were no significant intergroup differences with regard to HDL-C, Apo-A1, LPL and LP(a). Conclusions: The above results demonstrated that, in spite of no reduction in HDL-C, the blood levels of Apo-B, LDL-C and TC change due to OPX. These changes suggest OPX induces cardiovascular diseases and, therefore, follow-up of the changes in lipid metabolism is required, paying special attention to Apo-B and LDL-C.