Healthy Postmenopausal Japanese Women Research Articles

The effect of maltobionic acid on bone metabolism markers in healthy Japanese postmenopausal women: A randomized double-blind placebo-controlled crossover study.

Osteoporosis is characterized by compromised bone strengthpredisposing to an increased risk of fracture and is a disease with a high incidence in postmenopausal women. Frequent estrogen deficiency, particularly in postmenopausal women, induces osteoclast activation and is a major contributor to reduced bone mineral density. Maltobionic acid (MB) reportedly promotes mineral resorption and maintains bone mineral density in human clinical trials, although no studies have confirmed that MB improves bone metabolism in humans. Therefore, this study aimed to investigate the effects of MB administration on bone‐resorption markers in healthy Japanese postmenopausal women. This was a randomized, double‐blind, placebo‐controlled, crossover trial. Twenty‐six healthy adult Japanese women who realized that they had passed through more than 1 year of natural menopause and were aged 40–69 years were categorized into three groups. The experimental groups were allowed to consume maltobionic acid syrup 4 g (MB syrup 4 g group), maltobionic acid syrup 2 g plus maltose syrup 2 g (MB syrup 2 g group), and maltose syrup 4 g (placebo group) for 4 weeks. All 26 participants completed the intervention. Continuous ingestion of MB syrup 2 g or 4 g for 4 weeks significantly reduced the levels of bone‐resorption markers deoxypyridinoline (DPD) and urinary N‐telopeptide (u‐NTx), and significantly increased the bone formation marker osteocalcin (OC) compared with the placebo group. Maltobionic acid (MB) intake may improve bone metabolism and reduce bone health problems, including osteoporosis, in postmenopausal, adult Japanese women. (UMIN‐CTR ID: UMIN000038627).

Single- and Multiple-Dose Pharmacokinetics and Safety of Vilaprisan in Healthy Postmenopausal Japanese Women: A Randomized Clinical Trial.

As the prevalence of some gynecological conditions depends on patient characteristics such as race/ethnicity, it is important to study therapies for these conditions in diverse populations. The study described in this article was conducted to investigate the safety, tolerability, and pharmacokinetics of vilaprisan, a selective progesterone receptor modulator, in Japanese women in Japan. It supplements two comparable studies that were conducted in healthy postmenopausal European and Chinese women, respectively. In this exploratory randomized, placebo-controlled, double-blind, ascending-dose study, five groups of healthy postmenopausal Japanese women received vilaprisan as immediate-release tablets (1, 5, or 15 mg as a single dose or 1 or 5 mg/day for 28 days) or placebo tablets (single dosing: 8 subjects/dose step, thereof 2 subjects randomized to placebo; multiple dosing: 12subjects/dose step, thereof 4 subjects randomized to placebo). Blood samples for pharmacokinetic profiles were collected over 14-19 days. Safety assessments were based on adverse event data, vital signs, electrocardiograms, clinical laboratory tests, and transvaginal ultrasound examinations. 48 participants were randomized, treated, and analyzed. Vilaprisan was rapidly absorbed, reaching maximum plasma concentrations (Cmax) between 1and 3 h post dose. Post maximum, plasma concentrations rapidly declined, indicating pronounced distribution into tissues. The exposure of vilaprisan increased roughly dose-proportionally: The geometric mean(geometric coefficients of variation) areas under the concentration time curves from time zero to infinity (AUC∞) after single administration of 1, 5, or 15mg vilaprisan were 67µg·h/l (34%), 249µg·h/l (15%), and 788µg·h/l (37%), respectively. The AUC in the dosing interval after multiple administrations (AUC24,md) of 1mg/day was 76µg·h/l (59%), and the AUC24,md after 5 mg/day was 311 µg·h/l (20%). Geometric mean Cmax values also increased roughly dose-proportionally: They amounted to 6µg/l (22%), 16µg/l (33%), and 52 µg/l (27%) after single administration and to 8µg/l (28%) and 31µg/l (22%) after multiple administrations of the above doses. Mild adverse events were observed, similar to those observed in other clinical studies of vilaprisan. Overall, vilaprisan was safe and well tolerated. The exposure in Japanese women was similar to that observed in European and Chinese women in separate studies. 15 Nov 2011 (no registration number assigned).

Safety Profiles, Pharmacokinetics, and Changes in Bone Turnover Markers After Twice‐Weekly Subcutaneous Administration of Teriparatide in Healthy Japanese Postmenopausal Women: A Single‐Blind Randomized Study

Once‐weekly injection of 56.5‐μg teriparatide formulation is a potent therapeutic agent for osteoporosis treatment. However, this treatment has an issue of difficulty in continuing the treatment by its adverse side effects including nausea, vomiting, and headaches. To reduce these adverse side effects, we conducted a randomized, single‐blind, placebo‐controlled study to examine the pharmacokinetics, changes in bone turnover markers, and safety profiles of twice‐weekly 28.2‐μg teriparatide injections. Different dosing intervals of the twice‐weekly 28.2‐μg injections were also studied. A total of 100 healthy Japanese postmenopausal women were enrolled in this multiple‐dosing study. The systemic exposure of teriparatide acetate in the twice‐weekly 28.2‐μg injection was half that of the once‐weekly 56.5‐μg injection. Changes in bone turnover markers in the twice‐weekly 28.2‐μg injection were comparable to those in the once‐weekly 56.5‐μg injection. Incidences of adverse events including nausea, vomiting, and headaches were lower in the twice‐weekly 28.2‐μg injections than those in the once‐weekly 56.5‐μg injection. Findings were similar in the twice‐weekly 28.2‐μg injections regardless of the dosing interval. Thus, the new dosing regimen using twice‐weekly 28.2‐μg injections maintained comparable efficacy to the once‐weekly 56.5‐μg injections; however, it improved the safety profile and contributed to better continuity of care with teriparatide.

Effect of Bacillus subtilis C-3102 on bone mineral density in healthy postmenopausal Japanese women: a randomized, placebo-controlled, double-blind clinical trial.

Gut microbiota influence the host immune system and are associated with various diseases. In recent years, postmenopausal bone loss has been suggested to be related to gut microbiota. In the present study, we investigated the treatment effect of the probiotic Bacillus subtilis C-3102 (C-3102) on bone mineral density (BMD) and its influence on gut microbiota in healthy postmenopausal Japanese women. Seventy-six healthy postmenopausal Japanese women were treated with a placebo or C-3102 spore-containing tablets for 24 weeks. When compared with the placebo, C-3102 significantly increased total hip BMD (placebo = 0.83 ± 0.63%, C-3102 = 2.53 ± 0.52%, p=0.043). There was a significant group-by-time interaction effect for urinary type I collagen cross-linked N-telopeptide (uNTx) (p=0.033), a marker of bone resorption. Specifically, the C-3102 group showed significantly lower uNTx when compared with the placebo group at 12 weeks of treatment (p=0.015). In addition, in the C-3102 group, there was a trend towards a decrease in the bone resorption marker tartrate-resistant acid phosphatase isoform 5b (TRACP-5b) when compared with the placebo group at 12 weeks of treatment (p=0.052). The relative abundance of genus Bifidobacterium significantly increased at 12 weeks of treatment compared with the baseline in the C-3102 group. The relative abundance of genus Fusobacterium was significantly decreased in the C-3102 group at 12 and 24 weeks of treatment compared with the baseline. These data suggested that C-3102 improves BMD by inhibiting bone resorption and modulating gut microbiota in healthy postmenopausal women.

Royal Jelly Supplementation Improves Menopausal Symptoms Such as Backache, Low Back Pain, and Anxiety in Postmenopausal Japanese Women.

Objectives This study aimed to evaluate the effect of Royal Jelly (RJ) at a dose of 800 mg/day on menopausal symptoms in healthy Japanese postmenopausal women with placebo-controlled design. Material and Methods A total of 42 healthy Japanese postmenopausal women have been recruited for this study. The subjects were randomized to oral treatment with either 800 mg of protease-digested lyophilized powder of RJ (enzyme-treated RJ) or placebo (800 mg of dextrin) daily for 12 weeks. The level of menopausal symptoms has been evaluated every 4 weeks, using menopausal symptoms questionnaire of Japanese women. Independent t-test was used to evaluate statistical significance of the treatment effects between the two groups. Results and Conclusion All of the 42 women have completed the trial. There were significant differences related to the anxiety score (P = 0.046) and backache and low back pain score (P = 0.040) between 800 mg/day enzyme-treated RJ and placebo-treated groups after 12 weeks of administration, and no significant differences were found between the two groups in 4 weeks after intervention. No side effects were observed in either group. This study demonstrates that enzyme-treated RJ supplementation with doses of 800 mg/day is effective in relieving menopausal symptoms such as anxiety, backache, and low back pain in Japanese postmenopausal women.

<b>Optimizing a Single Monthly Dose of Risedronate Based on its Weekly Dose in Healthy Japanese Postmenopausal Women </b>

<b>Optimizing a Single Monthly Dose of Risedronate Based on its Weekly Dose in Healthy Japanese Postmenopausal Women </b>

Relationship of pharmacokinetics, changes of bone turnover markers and BMD/fractures efficacy during treatment with anabolic agents;Teriparatide daily and once weekly subcutaneous injections.

Teriparatide(recombinant human PTH1-34, 20 μg daily subcutaneous injection)has been approved for osteoporosis patients at high risk of fracture in many countries including Japan. Teriparatide daily injection therapy has been reported to increase BMD, improve microarchitecture of bone, and reduce the risk of new vertebral fractures and that of non-vertebral fractures. Pharmakokinetic(PK)study after a single Teriparatide injection of the daily dose in healthy Japanese postmenopausal women(n=18)revealed very rapid achievement of peak blood level(median of tmax=0.25 hr)followed by fast disappearance from the blood(mean t1/2=0.708 hr, n=17). Consistent with these PK characteristics, a rapid increase in bone formation marker and later increase in bone resorption marker has previously been observed, which was described as a bone anabolic window. More recently, once weekly subcutaneous injection of teriparatide acetate(56.5 μg)has been reported to reduce the risk of new vertebral fractures compared with placebo and has been approved in Japan. PK study after injection of the higher weekly dose in healthy Japanese postmenopausal women(n=10)revealed a relatively slow achievement of the peak blood level(mean tmax=0.875 hr)compared to daily injections, followed by relatively slow disappearance from the blood(mean t1/2=1.295 hr). Consistent with these PK characteristics, an initial(<24 hr)transient decrease of bone formation markers(serum osteocalcin and P1NP)and transient increase of bone resorption markers(serum NTX and urinary CTX)were observed. However, afterword, the bone formation and resorption markers were increased and decreased, respectively, for longer than 1 week from the baseline levels. The relationship of pharmacokinetics, changes of bone turnover markers and BMD/fractures efficacy during daily versus weekly teriparatide treatment needs to be clarified.

Effects of short-term fructooligosaccharide intake on equol production in Japanese postmenopausal women consuming soy isoflavone supplements: a pilot study

BackgroundRecent studies suggest that some of the clinical effectiveness of soy or daidzein, which is a type of isoflavone, may be attributed to a person’s ability to produce equol from daidzein. Equol, which is a metabolite of one of the major soybean isoflavones called daidzein, is produced in the gastrointestinal tract by certain intestinal microbiota where present. Habitual dietary patterns may alter the intestinal bacterial profile, and influence the metabolism of isoflavones and the production of equol. Fructooligosaccharides (FOS) have a prebiotic activity as well as being a dietary fibre. The purpose of the present study was to determine whether FOS supplementation increases equol production in equol producers and stimulates equol production in equol non-producers in Japanese postmenopausal women.MethodsA soy challenge was used to assess equol-producer status prior to the start of the study in healthy postmenopausal Japanese women. The study involved 4 separate groups in randomised crossover design. First, subjects were classified as equol producers (n = 25) or non-producers (n = 18), and then they were randomly assigned to the FOS or control group. All subjects received a daily dose of 37 mg isoflavone conjugates in the capsule (21 mg aglycone form) and either FOS (5g/day) or sucrose as control, in a randomised crossover study design. Equol -production was assessed by testing the serum and urine before and after the 2-week supplementation period.ResultsThe analyses were conducted on 34 subjects completed the study, 21 (61.8%) were classified as equol producers, and 13 (38.2%) as non-producers. Significant differences were observed in the interaction effect of time × equol state after 1 week of intervention (p = 0.006). However there were no effects after 2 weeks of intervention (p = 0.516). Finally, in both equol producers and non-producers, FOS supplementation did not affect the serum equol concentration or the urinary equol to daidzein concentration ratios.ConclusionsWe have reported that FOS intervention (5 g/day for 2 weeks) does not significantly modulate the capacity of intestinal microbiota to produce equol in postmenopausal Japanese women, in either equol producers or non-producers in this pilot study. Further larger investigations that explore the roles of specific intestinal microbiota in equol production will enable the establishment of dietary conditions that are required to enhance equol production.

Effect of Aromatase Inhibitors on Bone Mineral Density in a Japanese Breast Cancer Population

We retrospectively analyzed the bone mineral density (BMD) of postmenopausal Japanese women taking an aromatase inhibitor (AI), exemestane, anastrozole or letrozole, and calculated the decrease rate constant of BMD in each individual to compare the influence of the three AIs on BMD. We also aimed to evaluate the preventive effect of bisphosphonates (BPs) on the AI-induced decrease in BMD. The decrease rate constant of BMD (k(e)) in each individual was determined as a slope of linear regression of the relationship between time and logarithm of BMD value in each patient during the AI therapy. To compensate for the age-related change in BMD level, we estimated the age-related decrease rate constant of BMD (ke,0) in healthy Japanese postmenopausal women from the literature. AIs decreased BMD with a ke value of -0.0329 yr(-1), which was 4.7-fold larger than the k(e,₀) value of -0.00699 yr(-1). No significant difference was detected in the influence on BMD among AIs. Co-administration of BP ameliorated the ke value to -0.0117 yr(-1), a value similar to k(e,₀). The influence of AIs on BMD was quantitatively evaluated by using the decrease rate constant of BMD (k(e)). The present study also suggests that BPs may be useful to prevent the decrease in BMD induced by AIs.

A randomized, double-blind, placebo-controlled, single-dose study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of denosumab administered subcutaneously to postmenopausal Japanese women

Denosumab is a fully human monoclonal antibody that has high affinity for RANK ligand (RANKL). RANKL is the essential mediator of osteoclast formation, function and survival. The safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of denosumab in healthy postmenopausal Japanese women were assessed. This was a randomized, double-blind, dose-escalation study in which 40 subjects received denosumab at doses of 0.03, 0.1, 0.3, 1.0 or 3.0mg/kg, or placebo administered subcutaneously. Blood and urine samples for determination of serum denosumab, CTX-I, NTX-I/Cr, bone specific alkaline phosphatase (bone ALP) and intact parathyroid hormone (iPTH) were collected. The PK and PD time profiles were compared to those obtained in separate studies conducted in the US. No serious adverse events occurred and all subjects completed this study. Denosumab demonstrated nonlinear PK and dose- and concentration-dependent dispositions. The maximum mean decrease from baseline ranged from 65% to 95% for CTX-I concentrations and from 50% to 85% for NTX-I/Cr. Additionally, the changes were dose-dependent. The suppression of bone turnover markers was rapid (within 2 days after dosing) and duration of suppression was dose-dependent. No marked differences in the PK and PD profiles between Japanese and non-Japanese subjects were noted. The observed results indicate that denosumab may have therapeutic potential for conditions resulting from increased bone turnover, such as osteoporosis in Japanese.

Population pharmacokinetic analysis of letrozole in Japanese postmenopausal women

Letrozole is an orally active aromatase inhibitor for the treatment of breast cancer. The objectives of this study were to examine the pharmacokinetic profile of letrozole in Japanese subjects and to identify factors that influence variability in the pharmacokinetics of letrozole using population pharmacokinetic (PPK) analysis. Twenty-five healthy postmenopausal Japanese women were enrolled in the study and received 2.5mg letrozole once daily for 14 or 28days. A PPK model was developed using NONMEM software. Age, body weight (WT), AST, ALT, total bilirubin, serum creatinine (CRE), and genotype of CYP2A6 were studied as covariates. Estrone, estrone sulfate, and estradiol in plasma were measured as pharmacodynamic markers. CYP2A6 genotype, CRE, and AST were significant covariates for apparent systemic clearance (CL/F), and WT was a significant covariate for apparent distribution volume (Vd/F). Population mean estimates of CL/F and Vd/F in subjects without CYP2A6 mutation were 1.03 × (CRE/0.70)(-1.27) × (AST/17.5)(-0.793) L/h and 94.2 × (WT/51.1)(1.12) L respectively. CL/F in subjects possessing 1 and 2 CYP2A6 mutation alleles were 84.3% and 44.8% of the value in the subjects without mutation respectively. Estrogen levels fell to below detection limits in most subjects after letrozole administration. Three mild and transient adverse events (upper respiratory tract inflammation, arthralgia, and vomiting) were reported in the study. CYP2A6 genotype largely influences CL/F of letrozole. Genetic polymorphism of CYP2A6 and body weight will be causes of ethnic difference in PK. However, dose adjustment is not necessary, because of the wide therapeutic range.

Higher bioavailability of isoflavones after a single ingestion of aglycone‐rich fermented soybeans compared with glucoside‐rich non‐fermented soybeans in Japanese postmenopausal women

There have been conflicting study results concerning how the food matrix affects the bioavailability of isoflavone aglycone and glucoside. In this study the bioavailability of isoflavones after a single ingestion of aglycone-rich fermented soybeans (Fsoy) and glucoside-rich non-fermented soybeans (Soy) was compared. Eleven healthy postmenopausal Japanese women were recruited for a randomised, double-blind, crossover trial and consumed Fsoy or Soy powder dissolved in hot water. Blood samples were collected 0, 1, 2, 3, 4, 6, 8, 12 and 24 h and urine samples from 0 to 48 h after ingestion of the powders. The Fsoy and Soy powders ingested had the same total isoflavone content (95 µmol), but the former was rich in aglycone (90.6 µmol) while the latter was rich in glucoside (81.9 µmol). Serum concentrations of total isoflavones after 1-4 h were significantly higher in the Fsoy group than in the Soy group. The Fsoy group showed significantly higher maximum concentration (Cmax: 2.79 ± 0.13 vs 1.74 ± 0.13 µmol L(-1) ) and area under the curve (AUC(0-24 h) : 23.78 ± 2.41 vs 19.95 ± 2.03 µmol day L(-1) ) and lower maximum concentration time (Tmax: 1.00 ± 0.00 vs 5.00 ± 0.67 h) compared with the Soy group. The cumulative urinary excretion of total isoflavones after 2 h was significantly higher in the Fsoy group than in the Soy group. Individual isoflavones (daidzein, genistein and glycitein) showed similar trends to total isoflavones. Equol (a metabolite from daidzein) did not differ between the two groups. The results of this study demonstrated that the isoflavones of aglycone-rich Fsoy were absorbed faster and in greater amounts than those of glucoside-rich Soy in postmenopausal Japanese women.

Association of a single nucleotide polymorphism in the constitutive androstane receptor gene with bone mineral density

Nuclear receptors play an important role in bone metabolism. In bone cells, the vitamin D receptor (VDR) and the steroid and xenobiotic receptor (SXR) are activated by vitamin D and vitamin K2, respectively. VDR and SXR are the NR1I subfamily members of nuclear receptors. We speculated that the constitutive androstane receptor (CAR), the third member of the NR1I subfamily, also could be implicated in the regulation of bone metabolism. Therefore, we analyzed expression of CAR mRNA in osteoblasts and then examined association of a single nucleotide polymorphism (SNP) in the human CAR gene at intron 2 (IVS2-99C>T, rs2502815) with bone mineral density (BMD). Expression levels of CAR mRNA were analyzed during the culture course of rat primary osteoblasts. Association of an SNP in the CAR gene with BMD was examined in 548 healthy Japanese postmenopausal women. CAR mRNA increased at day 16 and then increased during culture of rat primary osteoblasts. The increase of CAR mRNA was parallel with the increase of alkaline phosphatase expression, a differentiation marker of osteoblasts. As a result of association study of an SNP in the CAR gene at intron 2, subjects with the CC genotype (n = 208) had significantly higher BMD than subjects with the TT or CT genotype (n = 340) (lumbar spine BMD, P = 0.0185; total body BMD, P = 0.0416). CAR mRNA was expressed and regulated in primary osteoblasts. A genetic variation at the CAR gene locus is associated with BMD, suggesting an involvement of the CAR gene in bone metabolism.

Safety, Tolerability and Pharmacokinetics of TAS‐108, a Novel Anti‐Oestrogen, in Healthy Post‐Menopausal Japanese Women: A Phase I Single Oral Dose Study

TAS-108 is a novel steroidal anti-oestrogen, expected to be useful for the treatment of breast cancer. The present study was conducted to investigate the safety, tolerability and pharmacokinetics of TAS-108 following the administration at a single oral dose of 40 mg to up to 120 mg in 12 post-menopausal women and the effect of food on the pharmacokinetics of the drug. All adverse events were mild and involved transient symptoms that resolved without therapeutic intervention. TAS-108 was readily absorbed and plasma levels of TAS-108 steadily declined, apparently in a multi-exponential manner. C(max) and AUC(0-12) were proportionally increased with increasing dose of TAS-108. The C(max) and AUC(0-t) of TAS-108 and its metabolite, deEt-TAS-108, were significantly increased to approximately 150% when TAS-108 was administered after a meal. Food did not affect the elimination half-life of TAS-108 or its metabolites. In this escalating dose-study of TAS-108, the drug was well tolerated by healthy post-menopausal Japanese women. The pharmacokinetics of TAS-108 indicated dose proportionality, and its bioavailability was significantly increased by food intake.

Effect of Low Dose Vitamin K2 (MK-4) Supplementation on Bio-Indices in Postmenopausal Japanese Women

It has been reported that treatment with a pharmacological dose (45 mg/d) of menaquinone-4 (MK-4) prevents bone loss in postmenopausal women. However, it is not known whether supplementation with low dose MK-4 has beneficial effects on bone metabolism in healthy women. The aim of this study is to examine the effects of the supplementation of 1.5 mg/d MK-4 for 4 wk on bone and lipid metabolism in healthy postmenopausal Japanese women. The study was performed as a randomized double blind placebo-controlled trial. The participants aged 53-65 y were randomly assigned to 2 groups and supplemented with 1.5 mg/d of MK-4 or a placebo for 4 wk (n=20 for each group). The most marked effects of MK-4 intake were observed on serum osteocalcin (OC) concentrations. Serum undercarboxylated OC (ucOC) concentration decreased, and the gamma-carboxylated OC (GlaOC) and GlaOC/GlaOC+ucOC ratio that indicates the degree of OC gamma-carboxylation increased significantly at 2 and 4 wk compared with that at baseline in the MK-4 group. The serum ucOC and GlaOC concentrations in the MK-4 group were significantly different from those in the placebo group at 2 wk. These results suggest that supplementation with 1.5 mg/d MK-4 accelerated the degree of OC gamma-carboxylation. The concentrations of serum lipids and other indices were not different between the groups at either intervention period. Thus, the additional intake of MK-4 might be beneficial in the maintenance of bone health in postmenopausal Japanese women.

Association of a single nucleotide polymorphism in the steroid and xenobiotic receptor (SXR) gene (IVS1‐579A/G) with bone mineral density

Vitamin K2 plays an important role in the bone metabolism. The steroid and xenobiotic receptor (SXR) as a nuclear receptor activated by vitamin K2 as well as rifampicin could increase bone markers such as alkaline phosphatase in human osteoblastic cells. Thus, the SXR could mediate vitamin K2 signaling pathway in bone cells. Therefore, we analyzed expression of the SXR mRNA in human primary osteoblasts and chondrocytes. We also studied association of a single nucleotide polymorphism (SNP) in the SXR gene with bone mineral density (BMD). Expression levels of the SXR mRNA were analyzed during the culture course of human primary osteoblasts and chondrocytes. Association of a SNP in the SXR gene in intron 1 (IVS1‐579A&gt;G) with BMD was examined in 294 healthy postmenopausal Japanese women. The SXR mRNA increased at day 5 and then decreased at day 10 in human primary osteoblasts. Its mRNA gradually increased in human primary chondrocytes until day 10. As an association study of a SNP in the SXR gene (IVS1‐579A/G), the subjects without the A allele (GG; n = 47) had significantly higher total BMD than the subjects bearing at least one A allele (AA + AG; n = 247) (Z score ± SD; 0.635 ± 1.031 versus 0.268 ± 1.061; P = 0.0298). The SXR mRNA was expressed and regulated in primary human osteoblasts and chondrocytes. A genetic variation at the SXR gene locus is associated with BMD, suggesting an involvement of the SXR gene in human bone metabolism.

PII-64Safety and pharmacokinetics of TAS-108; a novel antiestrogen, in healthy Japanese postmenopausal women

PII-64Safety and pharmacokinetics of TAS-108; a novel antiestrogen, in healthy Japanese postmenopausal women

Use of dental panoramic radiographs in identifying younger postmenopausal women with osteoporosis

Eroded or thin inferior cortex of the mandible detected on dental panoramic radiographs may be useful for identifying postmenopausal women with low bone mineral density (BMD) or osteoporosis. The purpose of this study was to evaluate whether these panoramic measurements are useful for identifying low BMD or osteoporosis in postmenopausal women younger than 65 years. We compared the diagnostic performances of panoramic measurements with those of the osteoporosis self-assessment tool (OST) for identifying women with low BMD (T-score of -2.0 or less at either the lumbar spine or the femoral neck) and osteoporosis (T score of -2.5 or less) in 158 healthy Japanese postmenopausal women aged 46 years to 64 years. Mandibular cortical shape (erosion) and width were evaluated on dental panoramic radiographs. Receiver operating characteristic curve analysis was used to determine the optimal cutoff thresholds for cortical width and OST index. The sensitivity and specificity, respectively, for identifying women with low BMD were 82.3% and 55.2% for OST index, 79.0% and 50.0% for cortical width, and 72.6% and 74.0% for cortical shape. The sensitivity and specificity, respectively, for identifying women with osteoporosis were 86.7% and 46.9% for OST index, 90.0% and 45.3% for cortical width, and 86.7% and 65.6% for cortical shape. Likelihood ratio for identifying women with low BMD was 13.90 for thin cortical width (<3.0 mm) and 10.84 for severely eroded cortex. That for identifying women with osteoporosis was 6.40 for thin cortical width and 7.11 for severely eroded cortex. Dentists may be able to refer postmenopausal women younger than 65 years for bone densitometry on the basis of incidental findings on dental panoramic radiographs.

Fat Intake Is Associated with Serum Estrogen and Androgen Concentrations in Postmenopausal Japanese Women

A reduction in fat intake has been associated with decreased estrogen levels in dietary intervention studies. However, previous cross-sectional studies conducted mainly among Western populations did not find a positive association between fat intake and postmenopausal estrogen levels. This study examined the cross-sectional association of fat intake with serum levels of estrone, estradiol, testosterone, and dehydroepiandrosterone sulfate (DHEAS) in women. Study subjects were 324 healthy postmenopausal Japanese women. Diet including fat intake was assessed by a validated semiquantitative FFQ. After controlling for age and other potential breast cancer risk factors, serum estrone was positively associated with the percentage of energy from total fat (P = 0.04). The associations of serum estrone with monounsaturated fat and polyunsaturated fat were of borderline significance (P = 0.05). Serum DHEAS was positively associated with the percentage of energy from total fat (P = 0.007), saturated fat (P = 0.009), monounsaturated fat (P = 0.006), and polyunsaturated fat (P = 0.04). Serum estrone and DHEAS concentrations increased 11.8 and 9.3%, respectively, with a 5% increase in the percentage of energy from total fat. These data suggest that a high intake of fat is associated with higher serum levels of estrone and DHEAS in postmenopausal women.

Long-term hormone replacement therapy delays the age related progression of carotid intima-media thickness in healthy postmenopausal women

Objectives: Carotid intima-media thickness (IMT) is an appropriate intermediate end point to investigate clinically relevant effects on atherogenesis. The study objective was to clarify whether long-term hormone replacement therapy (HRT) modifies the progress of age-related IMT in healthy postmenopausal Japanese women. Methods: One hundred and eighty-eight healthy postmenopausal women aged 42–69 years were recruited into the retrospective study. IMT was measured by B-mode real-time ultrasound in the following three groups of patients. One hundred and fifteen women who were prescribed estrogen plus progestin or estrogen alone were classified into two groups according to the HRT treated period: short-term (<2 years of treatment, n=52) and long-term (≥2 years, n=63) HRT groups. The third group consisted an age-matched women ( n=73), who were never treated with HRT (non-HRT group) as a control. Results: Each group was divided into three subgroups according to age: ≤49 years, 50–59 years and 60 years or older. IMT in patients of age ≥60 years in the non-HRT group was 0.607±0.064 mm and was significantly higher compared with that in the other two age subgroups of non-HRT patients (≤49 years: 0.495±0.051 mm; 50–59 years: 0.505±0.068 mm) ( P<0.05). In the short-term HRT group, IMT of ≥60-year-old-subjects (0.588±0.074 mm) was also significantly higher compared with that in the other two age subgroups (≤49 years: 0.480±0.034 mm; 50–59 years: 0.511±0.062 mm). However, in the long-term HRT group, IMT was not significantly different among the three age subgroups. There was a significant relationship between IMT and age in non-HRT ( r=0.594, P<0.0001) and short-term HRT ( r=0.542, P<0.001) groups, but no significant relationship was observed in the long-term HRT ( r=0.195, P=0.1266) group. Conclusions: In long-term HRT, more than 2 years may delay the age-related increase in IMT in healthy postmenopausal Japanese women.