Comparison of the five different definitions of equol producers: The relationship between blood and urine equol concentrations and blood parameters in 466 healthy men and women.

BACKGROUND AND AIMS: No studies have compared various definitions of "equol producers" until now. Therefore, we aimed to explore the accuracy of five different definitions of equol producers (EQP) and their associations with health benefits. METHODS: This is a cross-sectional study of 466 healthy Japanese men and women aged between 22 and 88 years. Equol producer proportions were calculated from their serum and urine isoflavone concentrations using five commonly used definitions. We then examined their accuracy, and associations with the blood parameters. RESULTS: Proportions of equol ranged from 29 % in the most stringent definition to 47.6 % in the most sensitive definition. EQP identified under all definitions had significantly low serum PSA1 levels compared to nonequol producers (NEQP). The most stringent definition, which is defined as the urinary equol level of 1.0 µM and above, corresponded to the highest median serum equol level and was associated with better health outcomes. Male EQP identified by this definition seemed to have reduced risk of LDL2-hypercholesterolemia by 50 %, and female EQP identified by this definition seemed to have lower risk of high hs-CRP,3 compared to NEQP. Both the first and second stringent definition, which is defined as the serum equol level of 1.0 ng/mL and above, was associated with lower thyroid stimulating hormone level. CONCLUSIONS: More stringent definitions were associated with better parameters in general. Combined with the dietary inquires, a reliable definition for equol producer is crucial to evaluate the health benefits of equol.

Comparison of blood and urine concentrations of equol by LC‒MS/MS method and factors associated with equol production in 466 Japanese men and women.

Equol is produced from daidzein by the action of gut bacteria on soy isoflavones. However, not all people can produce equol, and metabolism differs even among the producers. We aimed to examine the equol producer status in both men and women, and investigate the relationships among the serum and urinary isoflavones as well as to other biomedical parameters. In this study, we measured the equol and daidzein concentrations from the blood and urine of 292 men and 174 women aged between 22 and 88 years by liquid chromatography-tandem mass spectrometry (LC‒MS/MS). We then analysed the cut-off value for equol producers in both sexes, the relationship of serum and urinary equol concentrations, and other parameters, such as sex, age, endocrine function, glucose metabolism, lipid metabolism, and renal function with regards to equol-producing ability, among the different age groups. Equol producers were defined as those whose log ratio of urinary equol and daidzein concentration or log (equol/daidzein) was -1.42 or higher. Among 466 participants, 195 were equol producers (42%). The proportion of equol producers was larger in women. The cut-off value for equol producers was consistent in both sexes. Positive relationships were noted between serum and urinary equol levels in equol producers of both sexes; however, such a relationship was not detected in nonproducers. Lipid and uric acid abnormalities were more common with non equol producers in both men and women. Prostate specific antigen (PSA) levels in men were significantly lower in equol producers, especially in those in their 40 s. This study suggests a relationship between equol-producing ability and reduced risk of prostate disease as well as positive effects of equol on blood lipids and uric acid levels. However, lack of dietary information and disperse age groups were major drawbacks in generalizing the results of this study.

An online survey on coping methods for genitourinary syndrome of menopause, including vulvovaginal atrophy, among Japanese women and their satisfaction levels.

BACKGROUND: This study aimed to explore the current situation and existing issues regarding the management of vulvovaginal atrophy (VVA) or the genitourinary syndrome of menopause (GSM). A nationwide web-based questionnaire survey was conducted among 1,031 Japanese women aged 40 years or older. MATERIALS AND METHODS: Eligible women were asked to complete a questionnaire about how they dealt with their symptoms and how satisfied they were with their coping methods. RESULTS: Of those highly conscious of their GSM symptoms (n = 208; 20.2%), 158 had sought medical consultation (15.3%), with only 15 currently continuing to seek consultation (11.5%). Of the specialties consulted, gynecology was the most frequently consulted (55%). Furthermore, those unwilling to seek medical consultation despite their symptoms accounted for the greatest proportion (n = 359; 34.8%), with 42 (23.9%) having never sought consultation. Topical agents, e.g., steroid hormone ointments/creams, were the most frequent treatments provided by the clinics (n = 71; 40.3%), followed by oral and vaginal estrogens (n = 27; 15.5%), suggesting that estrogen therapy was not the first choice of treatment at the clinics. While 65% of patients treated at the clinics reported satisfaction with the treatments, this was inconsistent with the fact that many were reported to have remained untreated and very few continued with treatment. CONCLUSIONS: Survey results suggest that GSM, including VVA, remains underdiagnosed and undertreated in Japan. Medical professionals should deepen their understanding of GSM and raise their level of care to select the appropriate treatment for the condition.

Evaluation of the efficacy of Lactobacillus-containing feminine hygiene products on vaginal microbiome and genitourinary symptoms in pre- and postmenopausal women: A pilot randomized controlled trial.

As estrogen level decreases with aging, the vaginal mucosa gets thinner, and collagen amount decreases. In addition, the population of Lactobacillus in the vagina declines, increasing the risk of atrophic vaginitis, bacterial vaginosis, and genitourinary symptoms in the postmenopausal women. In this study, we evaluated the effects of Lactobacillus-containing feminine hygiene products on vaginal microbiome and genitourinary symptoms in pre- and postmenopausal women. This was a pilot randomized controlled trial in 35 premenopausal and 35 postmenopausal healthy women. For 4 weeks, treatment 1 group (14 premenopausal and 16 postmenopausal women) used the Lactobacillus-containing feminine soap and cream, and treatment 2 group (15 premenopausal and 14 postmenopausal women) used Lactobacillus-containing feminine gel in addition to soap and cream. The remaining 6 premenopausal and 5 postmenopausal women served as controls without using any products. We then compared the changes in the vaginal microbiota, genitourinary symptoms, and other related biomarkers after completion of treatment. Vaginal pH and pathogenic flora were reduced in both treatment groups compared to control group, which was more significant in the treatment 2 group of postmenopausal women. Genitourinary symptoms significantly improved in 60% of premenopausal women in treatment 1 group and 81.3% of postmenopausal women in treatment 2 group, compared to control group (0%, p = 0.043 and p<0.01 respectively). Overactive bladder symptom scores were significantly improved after using the products in eleven out of twelve postmenopausal women suspected of having overactive bladder. The use of Lactobacillus-containing feminine products was associated with improved vaginal ecosystem and urogenital health compared to control group, especially in those women using feminine gel.

Age-Related Changes, Influencing Factors, and Crosstalk Between Vaginal and Gut Microbiota: A Cross-Sectional Comparative Study of Pre- and Postmenopausal Women.

Objective: The ideal vaginal environment is maintained by Lactobacillus species, which keep the vagina clean and free of infections, boost fertility and immunity. Age-related decline in estrogen affects Lactobacillus population, leading to dominance of nonoptimal species and increased diversity in vaginal microbiota. In this study, we compared the differences between the vaginal microbiota of pre- and postmenopausal women. We also examined the relationships between vaginal and gut microbiota, their relationships with sex hormones and equol-producing ability. Materials and Methods: This was a cross-sectional study of 35 premenopausal and 35 postmenopausal women (age range: 27-76 years). We compared parameters such as the composition of the gut and vaginal microbiota, vaginal pH, estradiol, follicular stimulating hormone, and urinary equol concentration. Results: In the vaginal microbiota of premenopausal women, Lactobacillus species constituted ∼71.98%, and nonoptimal species constituted ∼16.87%. They were 10.08% and 26.78%, respectively, in the vaginal microbiota of postmenopausal women. The proportion of Lactobacillus was significantly low, whereas microbial diversity and vaginal pH were significantly high (p < 0.0001) in postmenopausal women. The compositions of the vaginal microbiota were significantly different in pre- and postmenopausal women. However, such differences were not noticeable in the gut microbiota. Urinary equol production had no significant correlation with vaginal microbiota, although it had significant relationships with gut microbiota in postmenopausal women. In both groups, the proportions of vaginal Lactobacillus were inversely correlated with vaginal microbial diversity and vaginal pH. Conclusion: Postmenopausal women had significantly low Lactobacillus and high nonoptimal species in their vaginal flora, whereas such age-related differences were not identified in gut microbiota. Urinary equol concentration had significant correlation with gut microbiota in postmenopausal women only. This study was registered with the University Hospital Medical Information Network (UMIN) Clinical Trial Registry (Trial registration No.: UMIN000043944).

Effects of an equol-containing supplement on advanced glycation end products, visceral fat and climacteric symptoms in postmenopausal women: A randomized controlled trial.

INTRODUCTION: Equol, an isoflavone derivative whose chemical structure is similar to estrogen, is considered a potentially effective agent for relieving climacteric symptoms, for the prevention of lifestyle-related diseases, and for aging care in postmenopausal women. We investigated the effect of an equol-containing supplement on metabolism and aging and climacteric symptoms with respect to internally produced equol in postmenopausal women. METHODS: A single-center, randomized controlled trial (registration number: UMIN000030975) on 57 postmenopausal Japanese women (mean age: 56±5.37 years) was conducted. Twenty-seven women received the equol supplement, while the remaining received control. Metabolic and aging-related biomarkers were compared before and after the 3-month intervention. Climacteric symptoms were assessed every month using a validated self-administered questionnaire in Japanese postmenopausal women. RESULTS: Three months post-intervention, the treatment group showed significant improvement in climacteric symptoms compared to the control group (81% vs. 53%, respectively, p = 0.045). We did not observe any beneficial effect on metabolic and aging-related biomarkers in the intervention group. However, in certain populations, significant improvement in skin autofluorescence, which is a measurement of AGE skin products, and visceral fat area was observed, especially among equol producers. CONCLUSION: Women receiving equol supplementation showed improved climacteric symptoms. This study offered a new hypothesis that there may be a synergy between supplemented equol and endogenously produced equol to improve skin aging and visceral fat in certain populations.

Inter-relationship between diet, lifestyle habits, gut microflora, and the equol-producer phenotype: baseline findings from a placebo-controlled intervention trial.

OBJECTIVE: Equol is an active metabolite of isoflavones produced by gut microbiota. It is beneficial to health; however, equol-producing ability varies greatly among individuals. These variations depend on the host's gut microbiota and lifestyle habits including diet. We investigated the relationship between the gut microbiota, lifestyle habits including diet, and equol-producing ability in postmenopausal Japanese women. METHODS: We studied 58 postmenopausal Japanese women aged 48 to 69 years who visited the Sendai Medical Center in January, 2018. Self-administered questionnaires assessed their recent and remote food intake histories and lifestyle habits. Fecal microbiome analysis was performed using a next-generation sequencer. Urinary equol was measured using an immunochromatographic strip test. Women with urinary equol concentration >1.0 µM were defined as equol producers. RESULTS: Equol-producing bacteria were identified in 97% (56) of women; however, only 13 (22%) were equol producers. Equol producers showed significantly higher microflora diversity (P = 0.002), and significantly different recent and remote food intake patterns compared with equol nonproducers. Higher consumption of foods such as meat, fish, soy, vegetables, and Japanese snacks positively affected microbial diversity and equol production, whereas a high intake of Ramen and smoking showed negative effects. CONCLUSION: Equol production might not depend on the quantity, but on the quality of equol-producing bacteria. High microbial diversity might enhance equol production. Increasing microbial diversity through healthy lifestyle habits and habitual consumption of a wide variety of foods might be useful to maintain a healthy gut environment for equol production.

Effects of Equol Supplement on Bone and Cardiovascular Parameters in Middle-Aged Japanese Women: A Prospective Observational Study.

OBJECTIVE: To examine changes in the bone and cardiovascular parameters and tolerability in middle-aged Japanese women taking equol supplement for a year. DESIGN: This was a prospective observational study. SUBJECTS AND SETTING: Participants were 74 women receiving outpatient care at Hamasite Medical Clinic, Minato-ku, Tokyo, from 2013 to 2015. INTERVENTIONS: Participants received per oral equol-containing supplement, 10 mg/day. OUTCOME MEASURES: The primary outcome measures were percent changes in bone and cardiovascular parameters after 1 year supplementation with equol. The secondary measures included factors affecting the parameter changes and adverse effects associated with equol use for a year. RESULTS: Reduction in arterial stiffness was observed after 12 months of equol supplement (1402.3 cm/s vs.1367.3 cm/s, p < 0.001). Significant reductions in respective parameters were observed in women with moderate and high risk for arteriosclerosis (median [95% confidence interval]: -3.2% [-5.79 to -0.74]; -12.65% [-18.52 to -4.28]; respectively); hypertriglyceridemia -45.53% [-70.24 to -5.58]; bone resorption risk (-15.15% [-23.71 to 1.56]; and bone fracture risk -26.68% [-76.43 to -5.99]. All 15 women with high baseline parathyroid hormone levels had achieved a median of 50% [-54.11 to -31.69] reduction from their baseline values. These associations were further confirmed in the results of multiple linear regression analysis. There were no reported adverse events or abnormal findings in the blood chemistry, Pap smear, mammography, and transvaginal ultrasound during periodic follow-ups. CONCLUSION: One year equol supplement was tolerable and induced improvement of certain bone and cardiovascular parameters, especially in higher risk groups. Further controlled studies are needed to explore long-term equol use for wellbeing of middle-aged women.

Relationship between equol producer status and metabolic parameters in 743 Japanese women: equol producer status is associated with antiatherosclerotic conditions in women around menopause and early postmenopause.

OBJECTIVE: Equol, an active metabolite possessing estrogen-like activity, is produced by the action of intestinal flora on soy isoflavones. There is an increasing evidence regarding its efficacy in the relief of menopausal symptoms, suppression of decreased bone mineral density, and lipid profile improvement. Only those with equol-producing capacity, however, seem to benefit. Thus, we examined the relationship between equol producer status and parameters associated with lifestyle-related diseases in women from their 20s to 80s. METHODS: This cross-sectional study was conducted among 743 women (21-89 y; average age: 52.5 ±â€Š11.8 y) who have undergone health screening at Tokyo Midtown Medical Center and given consent to participate in the study. The relationship between equol producer status and metabolic parameters was assessed. RESULTS: In our study, 236 women (32%) were equol producers. Equol producers had significantly lower triglycerides and higher high-density lipoprotein cholesterol levels compared with nonproducers. Equol-producing women in their 50s showed significantly lower body fat level, visceral fat area, triglyceride levels, pulse wave velocity, uric acid levels, and high sensitivity C-reactive protein levels. In addition, women in their 60s showed significantly higher levels of high-density lipoprotein cholesterol. In multivariate logistic regression, for women in their 50s, equol production was significantly associated with lower arterial stiffness and uric acid levels, and a high ratio of eicosapentaenoic acid to arachidonic acid, whereas it was significantly associated with lower urinary N-telopeptides in their 60s. CONCLUSIONS: Equol producer status was associated with favorable metabolic parameters, in women in the early phase postmenopause, with the transitional periods noted with declining intrinsic estrogen levels.

Relationship between skipping breakfast and bone mineral density in young Japanese women.

UNLABELLED: BACK GROUND AND AIMS: It is well known that insufficient nutrient intake leads to poor bone status. To find a simple evaluation method for prevention of nutrition intake disorder, a cross-sectional study with 275 healthy Japanese female students aged 19-25 was conducted. METHODS: Anthropometric parameters, bone mineral density (BMD) at lumbar and total hip, bone metabolic markers and physical activity were measured in study participants and the frequency of skipping meals (breakfast, lunch, supper), and absolute values for nutrient intakes were assessed using a Diet History Questionnaire. RESULTS: The frequency of skipping breakfast significantly correlate to total energy intake (ρ= -0.276, p<0.001). BMI, total intake of energy, intake of protein, intake of phosphate, and energy expenditure positively correlated significantly to BMD at lumbar and total hip (p<0.05) using simple linear regression. BMI (regression coefficient (b))=0.088, p<0.001), bone alkaline phosphatase (b= -0.050, p=0.012), total energy expenditure (b=0.019, p<0.001), and frequency of skipping breakfast (b= -0.018, p=0.048) were independent risk factors for lower total hip BMD by multiple regression analysis. The total hip BMD in participants who skipped breakfast three or more times was significantly lower than in those who did not skip breakfast (p=0.007). CONCLUSIONS: In conclusion, managing the frequency of skipping breakfast and reducing it to <3 times per week may be beneficial for the maintenance of bone health in younger women.

Familial correlation of bone mineral density, birth data and lifestyle factors among adolescent daughters, mothers and grandmothers.

This study aimed to clarify the relationship between skeletal or lifestyle factors among Japanese daughter-mother, mother-grandmother and daughter-grandmother pairs. We performed a cross-sectional study in a cohort of Japanese adolescent daughters (12-18 years of age), their mothers (339 pairs) and grandmothers on their mothers' side (34 pairs). Gestational age, birth weight, age at menarche and presence of menarche or menopause were surveyed in the participants. Height, body weight and lumbar 2-4 bone mineral density (BMD) were measured. Dietary intake and current physical activity were assessed by using questionnaires. Gestational age and age at menarche were significantly correlated among daughters, mothers and grandmothers (P < 0.001). BMD was significantly correlated between daughters and mothers (P < 0.001), while it was not significantly correlated between daughters and grandmothers or between mothers and grandmothers. Dietary intake of calcium and vitamin D, and the frequency, duration and intensity of current physical activity were significantly correlated between daughters and mothers (P < 0.05), although no significant correlation was found between daughters and grandmothers, or between mothers and grandmothers. The parameters for exercise indicated a positive correlation for BMD in the daughters and the mothers, but not in the grandmothers. The results suggested that estrogen deficiency decreases familial correlation for BMD after menopause. Achieving high BMD through exercise may be important for prevention of postmenopausal osteoporosis in premenopausal low-height mothers.

Variations in circulating osteoprotegerin and soluble RANKL during diurnal and menstrual cycles in young women.

BACKGROUND/AIMS: Physiological bone turnover shows diurnal variations and changes within the menstrual cycle. The aim of this study was to assess the variability of osteoprotegerin (OPG) and soluble RANKL (sRANKL) serum levels during diurnal and menstrual cycles. METHOD: Blood was collected from 15 young women at 6-hour intervals between 08.00 and 20.00 h during the follicular phase. Moreover, to compare the follicular and luteal phases, blood was also collected at 14.00 h during the luteal phase. Serum bone-specific alkaline phosphatase (BAP), N-telopeptide of type I collagen (NTX), OPG and free sRANKL were measured. RESULTS: No diurnal variations in BAP, OPG, sRANKL and sRANKL/OPG ratio were detected. NTX was significantly higher in the morning than in the afternoon and at night (p = 0.02). There were no menstrual variations in either. CONCLUSIONS: The consistent absence of diurnal variations in circulating OPG and sRANKL levels may reflect the absence of diurnal variation in their expression in the bone microenvironment. In this case, the nocturnal rise and the fall in bone resorption in the luteal phase should be accounted for by other factors than RANKL/OPG-mediated factors. Timing of sampling is unlikely to influence the results of circulating OPG and sRANKL measurement.

Influence of maternal genetic and lifestyle factors on bone mineral density in adolescent daughters: a cohort study in 387 Japanese daughter-mother pairs.

We conducted a cross-sectional study in a cohort of Japanese adolescent schoolgirls (12-18 years of age) and their mothers (387 pairs). Age, lumbar bone mineral density (BMD), birth and menarche-related status, height, body weight and lifestyles were surveyed in the participants. The values of BMD, height and body weight were converted to standard deviation (SD) by age. There were 49 (12.7%) pre-menarche and 338 (87.3%) post-menarche daughters. BMD-SD, height-SD, vitamin D intake and vitamin K intake were significantly correlated between the pre-menarche daughters and mothers (P < 0.05), while BMD-SD, birth weight, age at menarche and all lifestyle-related factors were significantly correlated between the post-menarche daughters and mothers (P < 0.05). BMD-SD in the pre-menarche daughters was affected by BMD-SD in mothers (R (2) = 0.069, P = 0.033) and their own height-SD (R (2) = 0.199, P = 0.001) (model R (2) = 0.340), independently. BMD-SD in the post-menarche daughters was affected by BMD-SD in mothers (R (2) = 0.073, P < 0.001) as well as by their own age at menarche (R (2) = 0.020, P = 0.001), height-SD (R (2) = 0.022, P < 0.001), body weight-SD (R (2) = 0.081, P < 0.001) and intensity of exercise (R (2) = 0.015, P = 0.045) (model R (2) = 0.372), independently. The results suggest that BMD is strongly correlated between daughters and mothers and that a greater age at menarche leads to lower peak bone mass. It was also suggested that maintaining high-intensity physical activity and adequate body weight is important in achieving maximum BMD as factors amenable to intervention in post-menarche daughters.

Association between lumbar bone mineral density and vascular stiffness as assessed by pulse wave velocity in postmenopausal women.

Recent studies have showed a significant correlation between vascular calcification and bone mineral density (BMD). Therefore, an investigation was carried out on the association between arterial stiffness, lumbar BMD and bone metabolic markers in Japanese postmenopausal women. Brachial-ankle PWV (baPWV) and BMD of the lumbar spine and serum bone-specific alkaline phosphatase (BAP) levels in 143 postmenopausal women were measured, where there was a significant negative correlation between baPWV and BMD (r = -0.21; P = 0.0135). An additional analysis included the remaining 75 subjects, but excluded subjects with hypertension and obesity. Here, a more negative correlation between baPWV and BMD (r = -0.315; P = 0.006), and a positive correlation between baPWV and BAP (r = 0.248; P = 0.032) were also significant. A group analysis, where the women were age matched and stratified into three groups of different bone density, i.e., normal BMD, osteopenic and osteoporotic, were further made. This showed lower PWV values in the normal BMD group than in the other two groups. A study also showed that the tertile with the highest BAP was associated with significantly higher PWV values than the other tertiles. However, when the multiple linear regression analysis was carried out, there was no correlation between PWV and BAP values. Low BMD and arterial stiffness show some correlation, suggesting that BAP may reflect the degree of arterial stiffness present.

Possible risk factor for postmenopausal women: postprandial hypertriglyceridemia.

AIM: To explore the clinical implications of postprandial hypertriglyceridemia in postmenopausal Japanese women. METHODS: Postprandial blood samples were collected from 91 women at their initial visit, with fasting blood samples collected within the following month to examine their lipid profiles. These women were grouped into normotriglyceridemia (fasting/postprandial triglycerides [TG] < 150; n = 36), mild postprandial hypertriglyceridemia (fasting TG < 150, postprandial TG > or = 150, < 225; n = 27), moderate postprandial hypertriglyceridemia (fasting TG < 150, postprandial TG > or = 225; n = 19) and hypertriglyceridemia (fasting TG > or = 150; n = 9) by using 225 mg/dL as the cut-off value for postprandial hypertriglyceridemia. RESULTS: The subjects were 54.1 +/- 7.8 years old; their duration of menopause, 6.0 +/- 7.7 years; body mass index, 21.4 +/- 4.0 kg/m(2); postprandial TG concentration, 189 +/- 110 mg/dL; and fasting TG concentration, 109 +/- 50 mg/dL. Approximately 50% (n = 46) of the women had normal fasting TG (fasting TG < 150), but high postprandial TG (postprandial TG > or = 150). Approximately 10% (n = 9) of the women had hypertriglyceridemia (fasting TG > or = 150 mg/dL). In those with postprandial hypertriglyceridemia (n = 46), postprandial TG negatively correlated with high-density lipoprotein cholesterol (HDL-C), while fasting TG showed no such correlation with HDL-C. CONCLUSION: Postprandial TG may provide a better understanding of lipid metabolism in postmenopausal women.

Peripheral arterial thrombosis induced by chemotherapy in ovarian carcinoma coexisted with endometrial carcinoma.

INTRODUCTION: Most patients with peripheral arterial occlusion have underlying atherosclerosis. Peripheral arterial thrombosis induced by chemotherapy in gynecological malignancies is rare. CASE REPORT: A 60-year-old woman was diagnosed with ovarian carcinoma coexisting with endometrial carcinoma after surgical histopathological examination. Chemotherapy was started on postoperative day 11. On day 2 of chemotherapy, she developed bilateral lower extremity cyanosis. Thrombocytopenia due to chemotherapy was diagnosed and treated with repeated platelet transfusions. Anticoagulant therapy was also continued. However, the patient worsened steadily and died of liver dysfunction due to multiple liver metastases. CONCLUSION: Although arterial thrombosis induced by chemotherapy is rare, it is important for physicians to consider this possibility in the course of treatment with cytotoxic agents because this complication has serious health implications.

Immunohistochemical characteristics of mature ovarian cystic teratomas in patients with postoperative recurrence.

Because a mature teratoma could recur, we studied the clinical, pathological, and immunohistochemical characteristics of mature ovarian cystic teratomas of 121 patients who underwent surgeries between 1994 and 2002. Recurrence was defined as cases that required secondary surgeries for mature ovarian cystic teratomas. A total of 10 patients were grouped as recurrence, and 111 patients were grouped as non-recurrence. The recurrence group was generally younger (mean, 22.9 +/- 1.26 vs. 32.8 +/- 1.15 years; p < 0.05), had higher tridermal components, and had greater central nervous system (CNS) component expression rate (9 vs. 48%, p < 0.05) compared with the non-recurrence group. The time between primary and secondary surgery averaged 9 years. Our result showed that maturation of teratomas reduced the number of neurons and increased glia. The process is similar to the aging process of brains. The presence of tridermal components and a high synaptophysin/glial fibrillary acidic protein (SP/GFAP) ratio suggested that recurrent ovarian teratomas were capable of both neuronal and glial differentiations. Nestin was expressed in the astrocyte from both the recurrence and non-recurrence groups. Thus, we concluded that nestin was not a useful marker for predicting recurrence and that attention should be given when a high ratio of SP/GFAP is found in lesions.