A Randomized, Multicenter, Double-Blind, Parallel, Non-Inferiority Clinical Study to Compare the Efficacy and Safety of Unicenta and Melsmon for Menopausal Symptom Improvement.

This study was conducted to evaluate the efficacy and safety of Unicenta in female subjects with menopausal symptoms by analyzing the changes in the Kupperman index (primary endpoint) and hormonal changes (secondary endpoint). It was a randomized, multi-center, double-blind, parallel, non-inferiority clinical study conducted at two different tertiary medical centers. A Unicenta injection was shown to be non-inferior to Melsmon based on the Kupperman index in both the intent-to-treat and per-protocol populations (p = 0.789 and p = 0.826, respectively). Additionally, there were no statistically significant differences in hormone levels (estradiol, follicular-stimulating hormone) or in the evaluation of facial flushes. There was no statistically significant difference in the incidence rate of adverse events between the two groups (p = 0.505). The study demonstrated that Unicenta is not inferior to Melsmon in terms of the change in the Kupperman index after 12 days of injection. The efficacy and safety of Unicenta were shown, resulting in the improvement of menopausal symptoms.

Molecular Mechanism and Prevention Strategy of Chemotherapy- and Radiotherapy-Induced Ovarian Damage.

Fertility preservation is an emerging discipline, which is of substantial clinical value in the care of young patients with cancer. Chemotherapy and radiation may induce ovarian damage in prepubertal girls and young women. Although many studies have explored the mechanisms implicated in ovarian toxicity during cancer treatment, its molecular pathophysiology is not fully understood. Chemotherapy may accelerate follicular apoptosis and follicle reservoir utilization and damage the ovarian stroma via multiple molecular reactions. Oxidative stress and the radiosensitivity of oocytes are the main causes of gonadal damage after radiation treatment. Fertility preservation options can be differentiated by patient age, desire for conception, treatment regimen, socioeconomic status, and treatment duration. This review will help highlight the importance of multidisciplinary oncofertility strategies for providing high-quality care to young female cancer patients.

Nontuberculous mycobacterial infection in a clinical presentation of Fitz-Hugh-Curtis syndrome: a case report with multigene diagnostic approach.

BACKGROUND: Fitz-Hugh-Curtis syndrome (FHCS) is caused by inflammation of perihepatic capsules associated with pelvic inflammatory disease. In recent years, infections with nontuberculous mycobacteria (NTM) have been increasingly occurring in immunocompromised and immunocompetent patients. However, NTM has never been reported in patients with FHCS. We present the first case of a patient with extrapulmonary NTM infection in a clinical presentation of FHCS. CASE PRESENTATION: A 26-year-old Korean woman presented with right upper quadrant and suprapubic pain. She was initially suspected to have FHCS. However, she was refractory to conventional antibiotic therapy. Laparoscopy revealed multiple violin-string adhesions of the parietal peritoneum to the liver and miliary-like nodules on the peritoneal surfaces. Diagnosis of NTM was confirmed by the polymerase chain reaction analysis results of biopsy specimens that showed caseating granulomas with positive acid-fast bacilli. Treatment with anti-NTM medications was initiated, and the patient's symptoms were considerably ameliorated. CONCLUSIONS: An awareness of NTM as potential pathogens, even in previously healthy adults, and efforts to exclude other confounding diseases are important to establish the diagnosis of NTM disease. NTM infection can cause various clinical manifestations, which in the present case, overlapped with the symptoms of perihepatic inflammation seen in FHCS.

Anti-proliferative effect of Klimaktoplan® on human breast cancer cells.

OBJECTIVE: With the health concerns of menopausal hormone replacement therapy, alternatives have been sought. Klimaktoplan® is a homeopathic formulation consisting of four main components and has been used for relief of menopausal symptoms for a long time. The study investigated the safety of Klimaktoplan® through its effect on the proliferation of breast cancer (MCF-7) and non-malignant mammary epithelial cells (MCF-10A). METHODS: MCF-7 and MCF-10A cells were cultured in 312.5, 625, and 1,250 µg/ml Klimaktoplan®. 17-Beta estradiol (E2) and medroxyprogesterone 17-acetate (MPA) were used for comparison with Klimaktoplan®. E2 only (0.001, 0.01, and 0.1 µM), and the combination of E2 (0.001, 0.01, and 0.1 µM) and MPA (0.01, 0.1, and 1 µM) were tested. Control cells for Klimaktoplan® and E2 groups were treated with dimethylsulfoxide (DMSO), and DMSO + ethanol was used for the combination group. Cellular proliferation was evaluated by the formation of insoluble formazan after incubation of 4 days. RESULTS: Klimaktoplan® had a concentration-dependent anti-proliferative effect on breast cancer cells at 625 and 1,250 µg/ml, while not affecting proliferation of non-malignant mammary cells at any tested concentration. The effect of lactose was evaluated as lactose (the adjuvant of Klimaktoplan®) affect cell growth. E2 and lactose increased the proliferation of both malignant and non-malignant cells. The effect of E2 + MPA on the proliferation of malignant and non-malignant mammary cells was lower than estradiol only, but was higher than control. CONCLUSIONS: Klimaktoplan® has an anti-proliferative effect on breast cancer cells, but not for non-malignant mammary epithelial cells, unlike E2 and E2 + P. With further research, KP would be a good alternative or additive in women with menopausal symptoms who wish to avoid conventional E or E + P hormone therapy.

Association of senescence-associated secretory phenotype proteins with ovarian reserve among middle-aged/older women.

OBJECTIVE: This study aimed to examine the association of circulating senescence-associated secretory phenotype proteins, secreted by senescent cells, with indicators of women's ovarian reserve. METHODS: This secondary analysis of cross-sectional baseline survey data was undertaken by the Korean Genome and Epidemiology Study Cardiovascular Disease Association Study. A total of 223 women (aged 40-82 y), without any history of oophorectomy, hysterectomy, or other medical conditions that could lower the ovarian reserve, were enrolled in this analysis. Chronological age (years), menopausal status, and serum anti-müllerian hormone (ng/mL) level were used to assess the associations among biological aging, accelerated menopausal aging, and ovarian reserve. RESULTS: Of the 223 women participants (53.4 ± 11.0 y), 147 (46.4 ± 3.9 y) and 76 (67.0 ± 6.9 y) were premenopausal and postmenopausal, respectively. Serum levels of senescence-associated secretory phenotype proteins were generally higher in postmenopausal, than in premenopausal, women. In the analyses adjusted for chronological age and body mass index, 17 senescence-associated secretory phenotype proteins were associated with menopausal status. However, in premenopausal women, no association trends with the level of anti-müllerian hormone were detected for a total of 28 senescence-associated secretory phenotype proteins. CONCLUSIONS: In a cohort of middle-aged/older women, the level of circulating senescence-associated secretory phenotype proteins indicated chronological age and menopausal status. Yet, serum levels of senescence-associated secretory phenotype protein potentially have limited predictive value for ascertaining ovarian reserve in premenopausal women.

Moderate intensity walking exercises reduce the body mass index and vascular inflammatory factors in postmenopausal women with obesity: a randomized controlled trial.

Postmenopause, the secretion of female hormones changes, causing excessive fat accumulation in the body and leading to chronic inflammation, which increases the incidence of cardiovascular diseases (CVD). Walking is an easily accessible daily exercise and effective non-pharmacological treatment for reducing obesity and the incidence of CVD. The aim of this study was to investigate the effect of moderate intensity walking exercises on body composition, vascular inflammatory factors, and vascular endothelial growth factor (VEGF) in postmenopausal women with obesity. Twenty-six older postmenopausal women with obesity (ages 68-72) were randomly assigned to control (n = 12, BMI 26.06 ± 1.37) or exercise (n = 14, BMI 26.04 ± 1.94) groups. Following a 12-week moderate intensity walking exercise program, we measured the participants' body composition with an InBody S10 analyzer and assessed blood sera using enzyme-linked immunosorbent assays. There was a significant clustering by weight (p < 0.01), body mass index (p < 0.01), percentage body fat (p < 0.001), high-sensitivity C-reactive protein (p < 0.05), interleukin-6, and tumor necrosis factor-α (p < 0.05) being significantly decreased in the exercise group. Although VEGF levels did not change significantly, a tendency to increase was observed in participants that exercised. Our results indicate that walking exercise may help prevent CVD in postmenopausal women with obesity by reducing obesity and vascular inflammatory factors.

Correction: Rheu et al. Effect of Fermented Sarco Oyster (Crassostrea gigas) Extract on Muscle Strength Enhancement in Postmenopausal Females: A Randomized, Double-Blind, Placebo-Controlled Trial. Int. J. Environ. Res. Public Health 2022, 19, 16450.

There was an error in the original publication [...].

Comparison of Surgical Outcomes between Single-Port Laparoscopic Surgery and Da Vinci Single-Port Robotic Surgery.

BACKGROUND: The aim of this study is to compare the surgical outcomes of single-port laparoscopic surgery (SPLS) and single-port robotic surgery (SPRS). METHODS: We retrospectively analyzed patients who underwent a hysterectomy, ovarian cystectomy, or myomectomy with SPLS or SPRS from January 2020 to July 2022. Statistical analyses were performed using the SPSS chi-square test and student's t-test. RESULTS: A total of 566 surgeries including single-port laparoscopic hysterectomy (SPLH; n = 148), single-port robotic hysterectomy (SPRH; n = 35), single-port laparoscopic ovarian cystectomy (SPLC; n = 207), single-port robotic ovarian cystectomy (SPRC; n = 108), single-port laparoscopic myomectomy (SPLM; n = 12), and single-port robotic myomectomy (SPRM; n = 56). The SPRH, SPRC, and SPRM groups had a shorter operation time than the SPLS group, although the results were not statistically significant (SPRH vs. SPLH, p = 0.134; SPRC vs. SPLC, p = 0.098; SPRM vs. SPLM, p = 0.202). Incisional hernia occurred as a postoperative complication in two patients only in the SPLH group. Postoperative Hb changes were lower in the SPRC and SPRM groups than in the SPLC and SPLM groups (SPRC vs. SPLC, p = 0.023; SPRM vs. SPLM, p = 0.010). CONCLUSIONS: Our study demonstrated that the SPRS had comparable surgical outcomes when compared to the SPLS. Therefore, the SPRS should be considered a feasible and safe option for gynecologic patients.

Efficacy and safety of oxiracetam in patients with vascular cognitive impairment: A multicenter, randomized, double-blinded, placebo-controlled, phase IV clinical trial.

BACKGROUND: Oxiracetam may have a modest effect on preventing cognitive decline. Exercise can also enhance cognitive function. This trial aims to investigate the effect of oxiracetam on post-stroke cognitive impairment and explore whether this effect is modified by exercise. Furthermore, the mechanisms that mediate this effect will be investigated through a neural network analysis. METHODS: This is a multicenter, randomized, double-blind, placebo-controlled phase IV trial. Patients who complained of cognitive decline 3 months after stroke and had a high risk of cognitive decline were eligible. Patients were randomly assigned to receive either 800 mg of oxiracetam or placebo twice daily for 36 weeks. After randomization, a predetermined exercise protocol was provided to each participant, and the degree of physical activity was assessed using wrist actigraphy at 4, 12, 24, and 36 weeks. Resting-state functional MRI was obtained in baseline and 36-week follow-up. Co-primary endpoints are changes in the Mini-Mental State Examination and Clinical Dementia Rating-Sum of Boxes. Secondary endpoints include changes in the NINDS-CSN VCIHS-Neuropsychology Protocol, Euro QoL, patient's global assessment, and functional network connectivity. If there is a significant difference in physical activity between the two groups, the interaction effect between physical activity and the treatment group will be examined. A total of 500 patients were enrolled from February 2018, and the last patient's final follow-up was completed in September 2022. CONCLUSION: This trial is meaningful not only to prove the efficacy of oxiracetam, but also evaluate whether exercise can modify the effects of medication and how cognitive function can be restored. Trial registrationhttp://cris.nih.go.kr (KCT0005137).

The relationship between fat depot-specific preadipocyte differentiation and metabolic syndrome in obese women.

OBJECTIVE: Obesity is strongly associated with metabolic syndrome, but not all obese individuals display a clustering of metabolic risk factors. Recent studies have shown that in vitro subcutaneous (SC)-preadipocyte differentiation is negatively associated with obesity. These results suggest that impaired adipogenesis is an important factor linking obesity to metabolic disorders. We examined whether in vitro preadipocyte differentiation is associated with metabolic syndrome, independent of obesity. DESIGN/PATIENTS/MEASUREMENTS: Paired adipose tissue samples were obtained from the 13 nonobese women and the 65 obese women. The CD34(+)/CD31(-) cells were isolated from the stromal-vascular fraction of both SC and omental (OM) fat depots by immune magnetic separation, and the subset was cultured with a differentiation cocktail. Then, we analysed the relationship between the degree of preadipocyte differentiation and metabolic factors. RESULTS: Obese women without metabolic syndrome (n = 37) had significantly higher SC-preadipocyte differentiation than equally obese women with metabolic syndrome (n = 28); however, OM-preadipocyte differentiation was similar in both groups. SC-preadipocyte differentiation was strongly correlated with triglycerides, HDL cholesterol, homoeostasis model assessment of insulin resistance and OM-adipocyte size. However, OM-preadipocyte differentiation was not correlated with any of these parameters. CONCLUSIONS: This study identified that SC-preadipocyte differentiation is associated with metabolic syndrome independent of obesity, whereas OM-preadipocyte differentiation is not. These findings suggest that, in the setting of obesity, an enhanced adipogenic capacity of SC depots could be protective for metabolic syndrome. Our data underscores an interaction between adipose tissue homoeostasis and metabolic disorder.

A 12-week after-school physical activity programme improves endothelial cell function in overweight and obese children: a randomised controlled study.

BACKGROUND: Endothelial dysfunction is associated with childhood obesity and is closely linked to the amount and function of endothelial progenitor cells. However, it remains unclear whether endothelial progenitor cells increase with after-school exercise in overweight and obese children. The purpose of this study was to investigate the effects of an after-school exercise programme on endothelial cell function in overweight and obese children. METHODS: A total of 29 overweight/obese children (12.2 ± 0.1 years) were randomly divided into control (i.e. no after-school exercise, n = 14) and after-school exercise (n = 15) groups. The 12-week after-school exercise intervention consisted of 3 days of combined aerobic and resistance exercise per week. Each 80-minute exercise programme included 10 minutes of warm-up and 10 minutes of cool-down after school. CD34(+) (a cell surface marker on hematopoietic stem cells), CD133(+) (a cell surface marker on hematopoietic progenitor cells) and CD34(+)/CD133(+) (considered as endothelial progenitor cells) were measured at baseline and after 12 weeks using flow cytometry. RESULTS: Increased percentages of CD34(+), CD133(+) and CD34(+)/CD133(+) cells were observed in the after-school exercise group (p = 0.018; p = 0.001; p = 0.002, respectively) compared with the control group. Carotid intima-media thickness decreased after 12 weeks in the after-school exercise group (p = 0.020) compared with the control group. CONCLUSIONS: This study provides preliminary evidence that a combined after-school exercise programme may represent an effective intervention strategy for improving vascular repair and endothelial cell function, leading to improved cardiovascular health in overweight and obese children. TRIAL REGISTRATION: Current Controlled Trials ISRCTN19037201.

Estradiol treatment increases M2-like visceral adipose tissue macrophages in obese ovariectomized mice regardless of its anorectic action.

Estradiol (E2) treatment has been known to induce changes in food intake, energy expenditure, and weight gain. However, its direct effects on adipose tissue macrophages (ATM) in vivo are not fully understood. Thus, we aimed to explore this aspect at cellular and molecular levels in ovariectomized obese mice. We examined the changes in ATMs after eight weeks of a high-fat diet (HFD) in male, female, and ovariectomized (OVX) mice. After eight weeks, osmotic pumps were inserted into OVX mice to provide two weeks of E2 treatment. We additionally set up a vehicle Pair-Fed (PF) control group that supplied the same amount of HFD consumed by the E2-treated group. We then investigated the in vivo phenotypic changes of visceral adipose tissue (VAT) macrophages. The percentage of M1-like ATMs decreased by the anorectic effect of E2, while M2-like ATMs increased regardless of the anorexia. E2 treatment increased the expression of anti-inflammatory genes but decreased pro-inflammatory genes in VAT. Monocyte recruitment and local proliferation contributed to M2-like ATMs. Furthermore, M2-like phenotypes were induced by E2 treatment in human macrophages. E2 treatment increases M2-like macrophages and improves the tissue milieu of VAT regardless of the anorectic reaction of E2.

Effect of Fermented Sarco Oyster (Crassostrea gigas) Extract on Muscle Strength Enhancement in Postmenopausal Females: A Randomized, Double-Blind, Placebo-Controlled Trial.

A randomized controlled trial (RCT) was conducted to evaluate the effect of fermented sarco oysters (FSO) on muscle strength in postmenopausal females with low muscle mass. Fifty-two female participants were randomly divided into the experiment group (EG) or control group (CG). For 12 weeks, the EG was subjected to 1000 mg of FSO extract daily while the CG consumed the placebo extract. The muscle extension and flexion at an angular velocity of 60°/s and with respect to grip strength, body composition, and muscle growth-related blood factors were measured at the baseline and after the trial. The difference in the quadriceps muscle extension at an angular velocity of 60°/s, grip strength on both the left and right side, and insulin-like growth factor-1(IGF-1) between groups were significantly higher in the EG compared with the CG. However, no differences were found in body composition, blood pyruvate, lactate, or high-sensitivity C-reactive protein (hsCRP) concentration between the two groups. In conclusion, FSO supplements may improve muscle strength in postmenopausal females with relatively reduced muscle strength without a change in muscle mass.

Relationship between uric acid and metabolic syndrome according to menopausal status.

OBJECTIVE: Uric acid, the levels of which have been shown to increase after menopause, has been associated with metabolic syndrome. The prevalence of metabolic syndrome has also been determined to increase after menopause. Therefore, we surmised that menopausal status-specific analyses for the characterisation of the relationship between uric acid and the metabolic syndrome were warranted. METHODS: We included 1644 patients: 1018 premenopausal women and 626 postmenopausal women, all of whom participated in annual health examinations at Anam Hospital in Seoul, Korea, from January 2008 through December 2008. RESULTS: On the multivariate logistic regression analysis, uric acid was identified as an independent risk factor for metabolic syndrome in both premenopausal and postmenopausal women. Uric acid levels had different relationships with blood pressure based on menopausal status, however, no such relationships with fasting glucose or age were found. CONCLUSIONS: Increased uric acid levels were associated with increased risk for metabolic syndrome in both premenopausal and postmenopausal women. In studies regarding uric acid and metabolic syndrome in women, the effects of menopausal status should be considered.

Ovarian hyper-response to administration of an GnRH-agonist without gonadotropins.

Several case reports have indicated that a small subgroup of patients may develop ovarian hyperstimulation following the administration of gonadotropin-releasing hormone agonists (GnRHa) without gonadotropins. However, since only few such cases have been published, it is unclear what course to follow in subsequent cycles after ovarian hyperstimulation in the first cycle using only GnRHa. A 33-yr-old woman was referred to in vitro fertilization for oocyte donation. A depot preparation (3.75 mg) of tryptorelin without gonadotropins induced ovarian multifollicular enlargement with high estradiol level, and was followed by human chorionic gonadotropin administration and oocyte retrieval. In a subsequent cycle of the same patient, a low dose of tryptorelin (0.05 mg) did not induce ovarian hyperstimulation, and resulted in clinical pregnancy. This report shows potential management of ovarian hyperstimulation following the administration of GnRHa without gonadotropins.

Genomic Consideration in Chemotherapy-Induced Ovarian Damage and Fertility Preservation.

Chemotherapy-induced ovarian damage and fertility preservation in young patients with cancer are emerging disciplines. The mechanism of treatment-related gonadal damage provides important information for targeting prevention methods. The genomic aspects of ovarian damage after chemotherapy are not fully understood. Several studies have demonstrated that gene alterations related to follicular apoptosis or accelerated follicle activation are related to ovarian insufficiency and susceptibility to ovarian damage following chemotherapy. This may accelerate follicular apoptosis and follicle reservoir utilization and damage the ovarian stroma via multiple molecular reactions after chemotherapy. This review highlights the importance of genomic considerations in chemotherapy-induced ovarian damage and multidisciplinary oncofertility strategies for providing high-quality care to young female cancer patients.

Age at menarche in a Korean population: secular trends and influencing factors.

This study was designed to identify the secular trend in the age at menarche and to investigate the possible factors that influence the age at menarche using representative Korean data from the 2005 Korean National Health and Nutrition Survey. Three thousand five hundred sixty-two women born between 1920 and 1985 were enrolled to identify secular trends in the age at menarche and 620 girls born between 1986 and 1995 were recruited to evaluate the factors influencing the age at onset of menarche. Mean age at menarche decreased from 16.90 +/- 1.25 years for women born between 1920 and 1925 to 13.79 +/- 1.37 years for those born between 1980 and 1985, indicating a downward trend of 0.68 years per decade (95% CI, 0.64-0.71) in age at menarche. Mean age at menarche of girls born between 1986 and 1995 was 13.10 +/- 0.06 years as estimated by the Kaplan-Meier method. Among girls born between 1986 and 1995, menarcheal girls had a larger waist circumference, a higher body mass index (BMI), and lower maternal menarcheal age and maternal age at birth than premenarcheal girls. The energy and nutrient intake of protein, sugar, fiber, ash, phosphate, natrium, thiamine, riboflavin, and niacin were greater for menarcheal girls than for premenarcheal girls. These data indicate a decreasing secular trend of age at menarche in a Korean population born between 1920 and 1995. Furthermore, maternal menarcheal age, BMI, maternal age at birth, and nutrition are important variables that appear to influence age at menarche in Korean girls.

Prenatally detected congenital perineal mass using 3D ultrasound which was diagnosed as lipoblastoma combined with anorectal malformation: case report.

We report a case of prenatally diagnosed congenital perineal mass which was combined with anorectal malformation. The mass was successfully treated with posterior sagittal anorectoplasty postnatally. On ultrasound examination at a gestational age of 23 weeks the fetal perineal mass were found on the right side. Any other defects were not visible on ultrasonography during whole gestation. Amniocentesis was performed to evaluate the fetal karyotyping and acetylcholinesterase which were also normal. As the fetus grew up, the mass size was slowly increased more and more. At birth, a female neonate had a perineal mass on the right side as expected. During operation, the anal sphincteric displacement was found near the mass and reconstructed through posterior sagittal incision. This is the first reported case of prenatally diagnosed congenital perineal mass, after birth which was diagnosed as lipoblastoma and even combined with anorectal malformation. This case shows that it can be of clinical importance to be aware of this rare fetal perineal mass in prenatal diagnosis and counseling.

Effect of adiponectin and sex steroid hormones on bone mineral density and bone formation markers in postmenopausal women with subclinical hyperthyroidism.

AIM: The relationship between adiponectin and sex hormones with bone mineral density (BMD) and bone formation markers was investigated in postmenopausal women with subclinical hyperthyroidism (SCH). METHODS: Seventy-five postmenopausal women were selected among the patients who participated in a health screening program in 2007. Thirty-seven control women with normal thyroid function were matched to 38 women with SCH by age, body mass index (BMI), and years since menopause (YSM). The associations between adiponectin and sex hormones with lumbar spine BMD and bone turnover markers were investigated. RESULTS: Adiponectin, testosterone (T; total and free forms), and thyroid-stimulating hormone were significantly different between the women with SCH and euthyroid. After adjusting for age, BMI, and YSM, free T (r = 0.351; P = 0.029) and estradiol (E2; r = -0.368; P = 0.024) had significant associations with bone alkaline phosphatase (B-ALP). Total T (r = 0.388; P = 0.021) and E2 (r = -0.376; P = 0.026) had significant associations with osteocalcin. However, there were no significant associations between adiponectin and sex hormones with the BMD levels in the SCH subjects. CONCLUSION: There were correlations between sex hormones with B-ALP and osteocalcin, but no associations between adiponectin and sex hormones with the lumbar spine BMD in postmenopausal SCH patients.