Progress in genome-wide association studies of age at natural menopause.

Menopause is not only the end of reproductive life, it is also related to diseases such as hyperlipidaemia, atherosclerotic cardiovascular disease, osteoporosis and breast cancer. Traditional epidemiological studies have found that heredity is the main determinant of age at natural menopause (ANM). Early studies on genetic factors were limited to candidate gene studies. Menopause age is not inherited by a single gene, but is the result of multiple gene effects. With the development of genomic technology, the Reproductive Genetics Consortium conducted several genome-wide association studies on ANM in people of European descent, and found that defects in DNA damage repair pathways were the main genetic mechanism. In recent years, due to the ethnic heterogeneity of ANM, there has been further development of global studies into multi-ethnic and trans-ethnic genome-wide association studies. Further genetic and epidemiological studies, including polygenetic score and genetic mechanism research, should be conducted to investigate the pathogenesis and mechanism with respect to menopause and its related diseases.

Prevalence of metabolic syndrome and its components in Chinese women with premature ovarian insufficiency.

OBJECTIVES: To assess the prevalence of metabolic syndrome (MetS) and its components in Chinese women with premature ovarian insufficiency (POI) and to explore the metabolic profile of Chinese women with POI. METHODS: 118 POI women aged 20-38 years and 151 age-and-BMI-matched control women were recruited. Measurements included body height, weight, waist circumference (WC), hip circumference (HC), blood pressure, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG) and fasting insulin (FINS). Prevalence and components of MetS and metabolic indices were compared between the two groups. RESULTS: The prevalence of MetS in POI women and age-and-BMI-matched control women was 16.9% and 11.3%, respectively, which was not significantly different (p > .05). The prevalence of hypertriglyceridemia and high fasting glucose was significantly higher in POI than control (17.8% vs. 9.3%, p = .039; 16.9% vs. 6.6%, p = .008), without significant differences in the prevalence of other components of MetS (p > .05). The levels of TG, FINS, and HOMA-IR in POI were significantly higher than in control (p < .05) but without significant differences in WC, WHR, SBP, DBP, TC, HDL-C, LDL-C, and FPG (p > .05). HOMA-IR was positively correlated with WC, DBP, TG, and FPG and negatively correlated with HDL-C in both POI women and control (p < .05). CONCLUSIONS: POI women presented with more unfavorable cardiovascular risk factors (higher prevalence of hypertriglyceridemia and high fasting glucose; higher TG, FINS, and HOMA-IR). So, women diagnosed with POI should always be covered with special care of metabolic profile.

Prevalence of diminished ovarian reserve in Chinese women with follicular cysts and menstrual disorders.

OBJECTIVES: To assess the prevalence of diminished ovarian reserve (DOR) in Chinese women with follicular cysts and menstrual disorders and relationship to hormonal markers. METHODS: 117 women with follicular cysts and menstrual disorders, aged 24 ∼ 53 (39.19 ± 6.61) years; measurements of height, weight, follicle-stimulating hormone (FSH), luteinizing hormone (LH), E2, progesterone (Po), prolactin (PRL), total testosterone, AMH, follicular cyst diameter, endometrial thickness. Three age groups were compared: 1) 21 ∼ 30 years, 2) 30 ∼ 40 years, 3) > 40 years. RESULTS: Total prevalence of DOR 86.3%, in the groups 50%, 81.6%, and 98.4%, in group-3 significantly higher than in group-1 and 2. 34.2% of the 117 patients complained of cessation of regular menstruations or amenorrhea, 65.8% of abnormal uterine bleeding. Follicular cysts disappeard in cycle-1 for 98 (83.8%) and in cycle-2 for 117 (100%) patients. AMH decreased with age, significantly different between the three groups. Total testosterone in group-1 and 2 was significantly higher than in group-3. In total AMH had a negative correlation with age and E2 (p < 0.01) and positive correlation with total testosterone (p < 0.05). CONCLUSIONS: Assessing ovarian reserve with follicular cysts and menstrual disorders is important because often pointing to DOR. The overall prevalence of DOR was high; even young women (<40 years) with follicular cysts and menstrual disorders had a low level of AMH. So AMH can be used as a marker to define DOR with higher sensitivity than other markers like FSH and E2. Primarily, these results only apply to Chinese women and should be confirmed in further studies.

Sexual function in Chinese women with different clinical phenotypes of polycystic ovary syndrome.

Objective: To investigate sexual function stratified according to four clinical phenotypes of polycystic ovary syndrome (PCOS) and its association with clinical and quality of life parameters, and to compare these with healthy controls in Chinese women with PCOS. Methods: A cross-sectional study was designed in 1000 PCOS women and 500 control women aged 18-45 years. PCOS women were grouped into four clinical phenotypes according to the Rotterdam Criteria. FSFI (Female Sexual Function Index), SF-12 (the 12-item short form health survey) and clinical and hormonal characteristics likely to affect sexual function were determined. Results: 809 PCOS women and 385 control women with complete parameters were evaluated after screening. Phenotype A had a lower total FSFI mean score (23.14 ± 3.22) compared with phenotype D and control group (p < 0.05). The control group had the highest total FSFI mean score (24.98 ± 3.78). For the percentage at risk of sexual dysfunction, phenotype A (87.5%) and phenotype B (82.46%) had a higher risk of female sexual dysfunction (FSD) than that in phenotype C (75.34%), phenotype D (70.56%) and control group (61.30%) (p < 0.05). SF-12 mental domain scores were significantly lower in phenotypes A and B compared with phenotypes C and control group (p < 0.05). Infertility treatment, bioavailable testosterone, psychological factors, age and waist circumference presented negative correlation with female sexual function. Conclusions: The risk of FSD in PCOS women seemed to be associated with PCOS clinical phenotypes. The classical PCOS phenotype with oligo-ovulation and hyperandrogenism had a higher risk of sexual dysfunction.

Plasma visfatin and apelin levels in adolescents with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that usually begins during adolescence. Patients may have severe metabolic disorders. OBJECTIVE: To investigate the levels of visfatin and apelin in adolescent girls with PCOS and to explore the importance of visfatin and apelin in glucose and lipid metabolism. METHODS: A total of 88 girls (aged 12-20 years) were prospectively and consecutively recruited during two years for the PCOS group (n = 44) and the control group (n = 44). Serum visfatin, apelin and other metabolic parameters were measured. Receiver operator characteristics (ROC) curve analysis was performed to reveal the diagnostic potential. RESULTS: Visfatin, apelin and indicators of glucose and lipid-metabolism were not different for PCOS patients compared to control. However, insulin resistance (IR) in the PCOS-group was more frequent (p < 0.05). Visfatin in non-IR patients was higher than in IR-patients in the PCOS-group (p < 0.05). However, there was no difference in apelin levels between IR and non-IR patients in the PCOS-group (p > 0.05). ROC-curve analyses demonstrated that the optimal value of visfatin for predicting IR in PCOS-patients was 7.14 ng/mL, with 78.1% sensitivity and 68.7% specificity. In the PCOS-group, visfatin was positively correlated with high density lipoprotein cholesterol (HDL-C), and negatively correlated with HOMA-IR, apolipoprotein B (Apo-B), cholesterol (CHO), low density lipoprotein cholesterol (LDL-C) and CHO/HDL-C ratio (p < 0.05). Apelin had no correlation with all indices (p > 0.05). CONCLUSIONS: Higher visfatin levels may prevent IR in adolescent PCOS patients, showing a positive predictive value for IR and also reflecting a beneficial effect on lipids. It is a possible protective factor at certain stages of metabolic syndrome.

Diagnostic value of anti-Müllerian hormone combined with androgen-levels in Chinese patients with polycystic ovary syndrome.

OBJECTIVE: To establish a cutoff level of AMH which could help for the diagnosis of PCOS, to investigate the predictive value of AMH combined with androgens in Chinese women to diagnose PCOS. MATERIALS AND METHODS: This is a prospective case control study, 550 women recruited (aged 20-40 years), in which 450 PCOS women recruited according to the Rotterdam criteria and 100 non-PCOS women in the control group were from the women for the pregnancy preparation examination. AMH were measured by the Elecsys AMH Plus immunoassay. Androgens and other sex hormone were measured. The validity of AMH toward the diagnosis of PCOS, or AMH combined with total testosterone, free testosterone, bioavailable testosterone and androstenedione was estimated by receiver operating characteristic (ROC)curves, and correlations between paired variables was estimated by Spearman's rank correlation coefficient. RESULTS: The cutoff value of AMH in Chinese reproductive-age women with PCOS is 4.64 ng/mL, AUC under the curve is 0.938, with 81.6% sensitivity, and 92.0% specificity. Total testosterone, free testosterone, bioactive testosterone, and androstenedione are significantly higher in women with PCOS of reproductive age than in controls. The combination of AMH and free testosterone resulted in a higher AUC of 94.8%, with higher sensitivity (86.1%) and excellent specificity (90.3%) for the prediction of PCOS. CONCLUSION: The Elecsys AMH Plus immunoassay, with a cutoff of 4.64 ng/mL, is a robust method for identifying PCOM to aid in PCOS diagnosis. The combination of AMH and free testosterone resulted in a higher AUC of 94.8% for the diagnose of PCOS.

A prospective study on the endometrium properties and the pregnancy rate of infertile women with thin endometrium receiving Fructus ligustri lucidi used in traditional Chinese medicine.

OBJECTIVE: To evaluate whether Zi Gui Nv Zhen capsules (ZGNZC) can increase the fertility rate of Chinese women with infertility due to thin endometrium. METHODS: Prospective, randomized, open-labeled 3-monthly study; 104 patients (aged 20-40 years) receiving either ZGNZC (experimental group, n = 55) or not (control group, n = 49). Main outcomes: thickness/type of the endometrium during ovulation and pregnancy rate. Between-group analysis (A) compares the experimental vs. control group, and within-group analysis (B) compares data at baseline and after study in the experimental group. RESULTS: (A) Between-group-analysis: Patients with ZGNZC had a higher endometrium thickness (0.8 ± 0.27 vs. 0.68 ± 0.10; p < .05) and higher type A endometrium rates (34.2% vs. 13.2%; p < .05) than the control group. Pregnancy rates were higher in the experimental than in the control group (43.6% vs. 22.4%; p < .05). (B) Within-group-analysis: ZGNZC increased endometrium thickness (0.58 ± 0.13 vs. 0.87 ± 0.24 vs. 0.83 ± 0.26 vs. 0.80 ± 0.27), and type A endometrium rates (10.9% vs. 60.0% vs. 49.0% vs. 34.2%) (all p < .05). Univariate analysis of pregnancy with other study parameters showed positive and significant correlations between pregnancy and administration of ZGNZC (p < .05). All hepato-renal biomarkers remained within the norm. There were no adverse events. CONCLUSIONS: In infertile women with thin endometrium who wish to conceive, two months' application of ZGNZC can improve endometrial properties and proliferation, which is necessary for a healthy pregnancy, and increase the clinical pregnancy rate in our prospective randomized observational study.

Effect on the cardiovascular independent risk factor lipoprotein(a) in overweight or obese PCOS patients with ethinyl-estradiol/drospirenone alone or plus orlistat.

OBJECTIVE: This study aimed to assess the effect on the cardiovascular independent risk factor Lipoprotein(a) [Lp(a)] in overweight or obese polycystic ovary syndrome (PCOS) patients with ethinyl-estradiol/drospirenone (EE/DRSP) alone or plus orlistat. METHODS: In this randomized controlled prospective study, 66 PCOS patients with overweight or obesity were matched according to age and BMI. All participants were randomly divided into two groups to receive EE/DRSP plus Orlistat (n = 33) or EE/DRSP alone (n = 33) for 3 months. Changes in cardiovascular risk factors including Lp(a), CRP, LDL-C, anthropometric assessments, variations in sex hormones related parameters, and in glucolipid metabolic index were evaluated after the intervention. RESULTS: Lp(a) and CRP were significantly decreased at 3 months only in the EE/DRSP plus Orlistat group. There were significant reductions in LDL-C, weight, BMI, waist circumference (WC), body fat percentage (BFP), FT in both groups compared to baseline. However, these reductions were significantly greater in EE/DRSP plus Orlistat group. The levels of HDL-C, TG, and SHBG significantly increased, while TT and LH significantly decreased in both groups over time. TC, FINS, FPG were not significantly changed in both groups after the intervention. CONCLUSIONS: This is the first study found that EE/DRSP plus Orlistat could significantly decrease Lp(a) in overweight or obese PCOS patients. This result can be assessed as particularly important, because Lp(a) is well-known as an independent risk factor predicting an increased risk of cardiovascular diseases (CVDs).

Effect of orlistat during individualized comprehensive life-style intervention on visceral fat in overweight or obese PCOS patients.

ObjectiveTo investigate the effect of orlistat combined with drospirenone/ethinylestradiol tablets (DRSP/EE) on the visceral fat area (VFA) compared to DRSP/EE-alone in overweight or obese patients with polycystic ovary syndrome (PCOS).Methods90 PCOS patients [body mass index (BMI) ≥24kg/m2] were recruited for a prospective, open-label, 1:2 paired 3-monthly study. All were included during the per-protocol defined recruitment time and numbered according to the entry-order: group-1: No.1-60, orlistat plus DRSP/EE; group-2: No.61-90, DRSP/EE-alone. Both groups received the same comprehensive intervention in terms of individualized, standardized management and lifestyle monitoring such as diet and exercise. Primary study-endpoint was VFA, secondary endpoints were anthropometric indices, sex hormones and glucolipid metabolism. Within- and between-group analyses were performed.ResultsVFA [cm2] in group-1 after treatment decreased significantly (p = 0.001), and the between-group comparison was highly significant (p = 0.001). Body weight, hip circumference (HC), BMI, body fat (BF), free testosterone (FT) and low-density lipoprotein-cholesterol (LDL-C) significantly decreased in both groups (within-group analysis); the decrease in group-1 was significantly greater than in group-2 (p < 0.05). Systolic and diastolic blood pressure (SBP/DBP) and fasting plasma glucose (FPG) in group-1 were significantly decreased, significantly more in group-1 than in group-2 (p < 0.05).ConclusionThis study is the first to investigate the effect of orlistat combined with DRSP/EE in overweight or obese PCOS patients compared with using DRSP/EE-alone. Orlistat combined with DRSP/EE was better than using DRSP/EE-alone in reducing VFA, body weight, FT, BP and FPG, which provides evidence for the choice of rational drug use in clinical practice.

Is anti-Mullerian hormone a useful biomarker in the diagnosis of polycystic ovary syndrome in Chinese adolescents?

OBJECTIVE: (1) To investigate anti-Mullerian-hormone (AMH) in adolescents with polycystic ovary syndrome (PCOS) compared to age-matched girls without PCOS; (2) to determine whether AMH is a valuable marker for diagnosing PCOS and to explore the best cutoff value in adolescents; (3) using a multivariate predictive model for the diagnosis of PCOS. METHODS: Ninety girls (aged 10-20 years) recruited during two years for the PCOS-group (n = 45) or control-group (n = 45). PCOS diagnostic criteria according guidelines of the Endocrinology Expert Group, Obstetrics/Gynecology Branch of the Chinese Medical Association. Serum AMH and other sex hormones were measured. Logistic regression analysis to estimate the odds ratio of AMH and other variables for the diagnosis of PCOS. Receiver operator characteristics (ROC) curve analysis was performed to reveal the diagnostic potential. RESULTS: (A) AMH was significantly higher in PCOS patients than in controls (10.21 ± 5.85 ng/ml vs. 4.31 ± 2.84 ng/ml, p < .001). In PCOS-group, total testosterone (TT), free testosterone (FT) and biologically active testosterone (BioT) were significantly higher than in controls (p < .001). (B) Logistic regression suggests that AMH and TT are correlated with the diagnosis of PCOS (p < .05). (C) ROC curve analyses demonstrated that the optimal value of AMH for predicting PCOS was 6.32 ng/mL, with 69.8% sensitivity and 80.5% specificity. Furthermore, AMH combined with TT can provide 83.7% sensitivity and 80.5% specificity for diagnosing PCOS in adolescents. CONCLUSIONS: AMH may be a useful biomarker for the diagnosis of PCOS in Chinese adolescent girls. A cutoff value of 6.32 ng/mL best discriminated between PCOS patients and controls. Besides AMH a multivariate predictive model should include TT.

Infertile women with endometriosis possess differences in cytokine levels in various tissues.

OBJECTIVE: (1) To characterize the cytokine expression profiles of endometriosis related infertile women in comparison to fertile women with endometriosis; (2) to investigate the correlation of the cytokine levels from different tissues. METHODS: 100 stage IV endometriosis patients were recruited and grouped by infertility status (n = 50, separately). Concentrations of TNF-α, TGF-ß1, IL-10, and IL-17A from the serum, peritoneal fluid (PF), eutopic, and ectopic endometrium samples were measured. RESULTS: (1) In the infertile group, the concentrations of IL-10 within serum, PF and eutopic endometrium were all significantly higher (p = .022 and <.01, .013, respectively), the levels of TGF-ß1 in serum and eutopic endometrium samples were both higher (p = .025 and p < .01), the levels of IL-17A in the PF, eutopic, and ectopic endometrium were all lower (p < .01, all). (2) Significant positive correlation was observed between IL-17A from PF and the ectopic endometrium (p = .014), IL-17A from PF and eutopic endometrium (p < .01). The PF IL-10 levels positively correlated with those in the serum (p = .007). CONCLUSIONS: This is the first study comparing the levels of cytokines within four different tissues of endometriosis women with or without infertility. The study revealed that endometriosis-related infertile women possess significant differences in cytokine levels in comparison to fertile women with endometriosis. The levels of inflammatory factors from different tissues had certain positive correlations. Infertility may indicate the progress of the disease.

Efficacy and safety of Zi Gui Nv Zhen® capsules used in TCM for fertility preservation in patients with diminished ovarian reserve.

OBJECTIVE: To evaluate for the first time whether Zi Gui Nv Zhen® capsules (ZGNZC), until now used in traditional Chinese medicine (TCM) for menopausal complaints, can increase the fertility of Chinese women with diminished ovarian reserve (DOR). METHODS: Prospective, randomized, open-labeled 3-monthly study; 109 DOR patients (aged 20-40 years) receiving either ZGNZC (experimental group, n = 75) or not (control group, n = 34). Main outcomes: markers for ovarian function, thickness/type of the endometrium during ovulation, and pregnancy rate. Between-group analysis (A) comparing experimental vs. control group and within-group analysis (B) comparing data at baseline and after study in each of both groups. RESULTS: (A) Between-group-analysis: patients with ZGNZC had a higher endometrium thickness (0.75 vs. 0.62; p<.05) and higher anti-Müllerian hormone (AMH, 0.50 vs. 0.40; p<.05) than control group. Pregnancy rates were higher in the experimental than the control group (26.7% vs. 14.7%; n.s.). (B) Within-group-analysis: ZGNZC decreased levels of follicle-stimulating hormone (FSH, 11.42 vs. 8.69), increased estradiol-levels (E2, 56.09 vs. 73.36), and type A endometrium rates (5.3% vs. 39.7%) (all p< .05) and increased antral follicle count (AFC, 2 vs. 3). All hepato-renal biomarkers remained within the norm. The tolerability was good. There were no adverse events. CONCLUSIONS: In women with DOR who wish to conceive, three months' application of ZGNZC can improve ovarian function and oocyte quality by adjusting the neuroendocrine system, can improve endometrial properties and proliferation, necessary for a healthy pregnancy, and increased the clinical pregnancy rate in our prospective randomized observational study.

Long-time low-temperature transportation of human ovarian tissue before cryopreservation.

RESEARCH QUESTION: Can the low-temperature transport time of removed human ovarian tissue be prolonged until cryopreservation? DESIGN: Fresh ovarian cortex from nine premenopausal patients was either slow-frozen immediately or stored at 4°C for 24 or 48 h before slow-freezing. The fresh and frozen-thawed biopsies were evaluated by follicle counting via calcein staining, histologic analyses via haematoxylin and eosin staining, and apoptosis via terminal deoxynucleotidyl transferase-mediated dUDP nick-end labelling (TUNEL). The fresh cortex was assessed by reactive oxygen species (ROS) and total antioxidant capacity (TAC) assay to detect oxidative stress. The frozen-thawed cortex biopsies were also evaluated by quantitative PCR for messenger RNA (mRNA) expression of BCL-2, BAX, TNFa, HIF-1a, BMP15 and GDF9, and Western blot for detection of BCL-2, BMP15, GDF9 and CASPASE-3. The frozen-thawed cortex was cultured in vitro for 4 days, anti-Müllerian hormone and glucose were assessed in the supernatant, and ROS and TAC assay detected any oxidative stress in the cortex. RESULTS: In the fresh cortex, there were no significant differences between the three groups. In the frozen-thawed cortex, there were no significant differences between the three groups regarding follicle viability, TUNEL, mRNA expression of TNFa, HIF-1a or BMP15. GDF9 mRNA and BAX/BCL-2 were lower and higher at 48 h than at 0 h, respectively. However, the protein expression of BCL-2, CASPASE-3, GDF9 and BMP15 were no different. In the cultured cortex, ROS, TAC and glucose uptake were no different across the three groups. CONCLUSION: Ovarian tissue transportation was validated for 24 h in the procedure used in clinical practice. This study showed that 4-8°C transportation for 24 or 48 h does not seem to damage the ovarian tissue. However, ovarian tissue transportation beyond 48 h needs to be further studied for conclusions to be made.

Menopausal symptoms among Chinese peri- and postmenopausal women: a large prospective single-center cohort study.

BACKGROUND: The prevalence and intensity of menopausal symptoms differ depending on ethnicity, culture, and country. Epidemiological data from China are scarce. OBJECTIVE: To compare the prevalence and severity of menopausal symptoms in peri- and postmenopausal Chinese women. METHODS: This was a prospective two year cohort study that included all eligible women from 31 Chinese provinces attending our 'Menopause Clinic', the first official specialized center in China. Structured questionnaires containing seven domains with 41 items in total were used to assess the following menopausal symptoms using descriptive analysis: negative mood, cognitive symptoms, sleep disorder, vasomotor symptoms (VMS), urogenital symptoms, autonomic nervous disorder, and limb pain/paresthesia. RESULTS: A total of 4063 women with a mean age of 50.53 ± 6.57 (n = 2107 perimenopausal and 1956 postmenopausal) participated. All menopausal symptoms were more severe in postmenopausal women (p<.05). Independent of menopausal status, urogenital symptoms, often combined with sexual problems, were the most common complaints (in prevalence and severity), followed by sleep disorder, cognitive symptoms (especially hypomnesia), negative mood, autonomic nervous disorder, limb pain/paresthesia and, as the rarest complaint, VMS. CONCLUSIONS: Urogenital symptoms among midlife Chinese women are common, frequently also in combination with sexual dysfunction, although many do not often complain about these in the first place. Postmenopausal women presented more prevalent and severe menopausal symptoms. In contrast to Western countries, VMS are rare among our population. A multidisciplinary approach and use of hormonal and non-hormonal therapies should be considered for these women.

Importance of active and passive smoking as one of the risk factors for female sexual dysfunction in Chinese women.

OBJECTIVE: To assess possible risk factors for female sexual dysfunction (FSD), aiming especially at smoking in China. METHODS: Female Sexual Function Index (FSFI) for assessing FSD; 621 women (24-75 years) divided into 'group FSD' (FSFI≤ 26.55) and 'group No FSD' (FSFI > 26.55). Univariate and multivariate analysis to detect potential risk factors for FSD. RESULTS: Active smoking was the strongest risk factor after multiple adjustments (OR= 6.226, 95%CI = 1.561 ∼ 24.822), but passive smoking also was significantly associated with a risk of FSD (OR = 1.887, 95%CI = 1.092 ∼ 3.260) (p < .05). Other risk factors included age (OR = 1.040, 95%CI = 1.005 ∼ 1.076), medical comorbidities (OR= 1.688, 95%CI =1.044 ∼ 2.729), postmenopausal stage (OR= 2.021, 95%CI = 1.073 ∼ 5.717), and dissatisfied marital relations (OR= 3.771, 95%CI = 1.768 ∼ 8.045). The prevalence of FSD for smokers regarding disorders of sexual arousal, orgasm and sexual satisfaction increased in active smokers; sexual desire disorder, sexual arousal disorder and pain in secondhand smokers (p < .05). CONCLUSION: The risk of FSD was closely related to depletion of ovarian function. Active smokers had the highest risk, but passive smoking also had a significant relationship to FSD. Although female smokers are rare in China, 'husband smoking' is frequent. Thus, our results should have significant healthcare consequences.

How much total ovarian tissue can be removed without compromising ovarian function? An animal study.

OBJECTIVE: Removal of ovarian tissue is a new option for fertility preservation for certain cancer patients in China. The aim was to investigate the impact of stepwise removed tissue on hormone levels and follicles in rats. METHODS: Six to ten-week old rats were divided into six groups (% total ovarian tissue): 1 = control (100%), 2 (75%), 3 (50%), 4 (25%), 5 (12.5%), 6 (0%, bilateral ovariectomy). Blood test was carried out fortnightly to assess estradiol (E2), progesterone (P), follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), and inhibin B (INHB). Ovaries are obtained from surgical resections and from rats sacrificed after 12 weeks. RESULTS: During 12 weeks, groups 4, 5, and 6 had higher FSH and lower AMH and INHB values compared to control (p< .05), but in group 4 E2 and P was not significantly different from control (p> .05). All ovarian function parameters stopped in groups 5 and 6. Follicle morphology was not significantly different between baseline and 12 weeks after surgery in groups 1-5. CONCLUSIONS: For the first time, we demonstrated that even up to 75% of total ovarian tissue can be removed without impact on E2 and P production in rats, which, if confirmed in women, would mean that hazardous (or possibly contraindicated in cancer patients) hormone therapy is not required to avoid the negative consequences of hormone depletion.

Lumbar bone mineral density measured by quantitative computed tomography (QCT): association with abdominal adipose tissue in different menopausal periods of Chinese women.

OBJECTIVE: To investigate the correlation between abdominal adipose tissue and lumbar bone mineral density (BMD) in different menopausal periods of Chinese women. METHODS: 230 women were included in this cross-sectional study. Subjects were divided into a perimenopausal and postmenopausal group. Lumbar BMD was measured by QCT to assess total adipose tissue (TAT), visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). The concomitant variables age, body mass index (BMI), and endocrine hormones were also considered. Multiple linear regression was used to assess the relationship between abdominal adipose tissue and BMD. RESULTS: In the perimenopausal group, Spearman correlation analysis showed that there was no significant association among TAT, SAT, VAT, and BMD (all p > .05). In the postmenopausal group, BMD was negatively correlated with TAT, SAT, and VAT. In both groups, after adjustment for age and BMI, multiple linear regression analysis showed that VAT was negatively correlated with BMD (p < .05). In contrast, there was no significant correlation with TAT, SAT, and BMD. CONCLUSIONS: High VAT volume is associated with low lumbar BMD in both perimenopausal and postmenopausal women. TAT and SAT have no significant correlation with lumbar trabecular BMD.

Sexual dysfunction in Chinese women at different reproductive stages and the positive effect of hormone replacement therapy in the early postmenopause.

OBJECTIVES: The aims of the study were to investigate female sexual dysfunction (FSD) at different reproductive stages and the effect on FSD of hormone replacement therapy (HRT). METHODS: Participants (N = 524) were divided into six groups according to the Stages of Reproductive Aging Workshop (STRAW + 10): reproductive age (R), early (ET)/late (LT) menopausal transition, early (EP)/late (LP) postmenopause and early postmenopause in women using HRT (EP-HRT; oestradiol sequentially combined with dydrogesterone). The Female Sexual Function Index (FSFI) was used to assess FSD. Univariate and multivariate logistic regression analysis was carried out to predict FSD risk factors. RESULTS: There was an increase in FSD in groups EP and LP, but not in groups R, ET and LT; most FSFI scores were lower in groups EP and LP than in groups R, ET and LT (p < .05). There was no difference in FSD between groups EP and LP, but lubrication and pain scores were higher in group EP (p < .05). The prevalence of FSD was lower in group EP-HRT; most FSFI scores were higher in group EP-HRT compared with group EP as control (p < .05). Further risk factors for FSD were identified as neutral and dissatisfied marital relations, lower educational level and smoking (p < .05). CONCLUSION: We report a clear association between deteriorating sexual function and increasing STRAW + 10 classification, suggesting the consequence of decreasing ovarian function. HRT containing 'natural hormones' was shown to have a beneficial effect on FSD. The results are reported here for the first time in Chinese women.

[Clinical evaluation of progestogens used in Menopausal Hormone Therapy (MHT)]. / Klinische Beurteilung der Gestagene in der Menopausalen Hormontherapie (MHT).

Clinical evaluation of progestogens used in Menopausal Hormone Therapy (MHT) Abstract. Primary indication for progestogens in MHT is to avoid estrogen-induced endometrial cancer. Progesteron has the least endometrial efficacy but is used increasingly (together with transdermal estradiol) because it is neutral in vascular and metabolic systems and possibly may have a lower risk of breast cancer. Comparable is dydrogesterone, the retro-isomer of progesterone, but with higher endometrial efficacy. However, also other progestogens (including tibolone) are used to take advantage of the androgenic, anti-androgenic and anti-mineralocorticoid "partial effects". Based on the results of the Women's Health Initiative Study the use of progestogens in MHT can cause an increased risk of breast cancer and coronary artery disease. Using different progestogens this is confirmed in various observational studies, which also suggest an increased progestogen-dependent risk of stroke. Since with every MHT early start can reduce cardiovascular risk or even act preventive, the decisive question remains, if there may be a screening regarding already known mechanisms for hormone-dependent development of breast cancer, at least for patients with increased risk of breast cancer. For this, new own research results are described.

PGRMC1 in animal breast cancer tissue and blood is associated with increased tumor growth with norethisterone in contrast to progesterone and dydrogesterone: four-arm randomized placebo-controlled xenograft study.

Progesterone receptor membrane component 1 (PGRMC1) is mediating strong breast cancer cell proliferation induced by certain synthetic progestogens which we have shown within already published in vitro studies. Aim was now to use an animal model, to compare tumor growth using progesterone and its isomer dydrogesterone with norethisterone, which elicited in our in vitro studies the strongest proliferating effect. For the first time, we wanted to investigate if growth can be correlated both with blood concentrations and tissue expression of PGRMC1 to identify if PGRMC1 could be a new tumor marker. Prospective, randomized, blinded, placebo-controlled four-arm study (45-50 days); PGRMC1-transfected or empty-vector T47D- and MCF7-xenotransplants were each treated with estradiol (E2) +placebo; E2 + progesterone; E2 + norethisterone; E2 + dydrogesterone; blood PGRMC1 assessed by a novel ELISA, tissue expression by immunohistochemistry. PGRMC1-transfected tumors further increased with E2 + norethisterone but not with E2-dydrogesterone or E2-progesterone. In both PGRMC1-xenograft groups (T47D, MCF7) with E2/norethisterone, the blood concentrations and tissue expression of PGRMC1 were higher than in all other 14 groups (p < .05), with positive significant correlation between blood PGRMCI concentrations and tissue PGRMC1 expression. In the presence of PGRMC1, certain progestogens could increase the growth of breast tumor, which now also should be tested in clinical studies.