Akt-mTOR Signaling Mediates Abnormalities in the Proliferation and Apoptosis of Ovarian Granulosa Cells in Patients with Polycystic Ovary Syndrome.

BACKGROUND/AIMS: Abnormal apoptosis of granulosa cells (GCs) is thought to involve in the pathogenesis of polycystic ovary syndrome (PCOS); however, the associated cellular and molecular mechanisms remain unclear. METHODS: Primary GCs were obtained from healthy women and women with PCOS. The cell proliferation and apoptosis were analyzed in insulin-stimulated and insulin receptor gene (INSR) siRNA-transfected GCs. The protein expression of Akt-mTOR-S6K1 signal molecules was measured by Western blot. RESULTS: This study showed that 1 nM of insulin significantly stimulated cell proliferation, induced cell apoptosis, and decreased the telomerase activity in GCs from both the healthy women and PCOS patients (p < 0.001), but silencing of INSR expression blocked the effects of insulin. Insulin induced significantly more apoptosis in GCs from PCOS patients than from healthy women (p < 0.01). Insulin significantly increased the ratio of p-Akt/Akt, the expression of mTOR protein, and the ratio of p-S6K1/S6K1 in GCs from normal control than in cells from PCOS patients (p < 0.001). CONCLUSION: Insulin-induced apoptosis of GCs, less activation of Akt-mTOR signaling, and reduction of telomerase activity may be associated with the pathogenesis of PCOS.

Prevalence and predictors of metabolic abnormalities in Chinese women with PCOS: a cross- sectional study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common condition estimated to affect 5.61% of Chinese women of reproductive age, but little is known about the prevalence and predictors in Chinese PCOS patients. This study aimed to determine the prevalence and predictors of the metabolic abnormalities in Chinese women with and without PCOS. METHODS: A large-scale national epidemiological investigation was conducted in reproductive age women (19 to 45 years) across China. 833 reproductive aged PCOS women, who participated in the healthcare screening, were recruited from ten provinces in China. Clinical history, ultrasonographic exam (ovarian follicle), hormonal and metabolic parameters were the main outcome measures. RESULTS: The prevalence of metabolic syndrome (MetS) as compared in PCOS and non-PCOS women from community were 18.2% vs 14.7%, and IR (insulin resistance) were 14.2% vs 9.3% (p < 0.001) respectively. After adjusting for age, the indicators (central obesity, hypertension, fasting insulin, SHBG, dyslipinaemia) for metabolic disturbances were significantly higher in PCOS than in non-PCOS groups. Using multivariate logistic regression, central obesity and FAI were risk factors, while SHBG was a protective factor on the occurrence of Mets and IR in PCOS women (OR: 1.132, 1.105 and 0.995). CONCLUSIONS: The risk factors of the metabolic syndrome and insulin resistance were BMI and FAI for PCOS women, respectively. The decrease of SHBG level was also a risk factor for insulin resistance in both PCOS and metabolic disturbance.

Prevalence of polycystic ovary syndrome in women in China: a large community-based study.

STUDY QUESTION: What is the prevalence of polycystic ovary syndrome (PCOS) in Han Chinese women from different communities? SUMMARY ANSWER: The prevalence of PCOS in Chinese women aged 19-45 years is 5.6%. WHAT IS KNOWN ALREADY: The prevalence of PCOS is reported to range from 5 to 10% but to the best of our knowledge the Han Chinese population has not been studied. STUDY DESIGN, SIZE, DURATION: A large-scale epidemiological study was carried out between October 2007 and September 2011 in 15 924 Han Chinese women of reproductive age (19-45 years) from the 10 provinces and municipalities in China. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 16 886 women from 152 cities and 112 villages were involved in the study. All study participants received a questionnaire and underwent a physical and transvaginal ultrasound examination. Blood samples were collected from a subsample of women (n = 3565) for analysis of metabolic markers and hormones. Based on the Rotterdam PCOS criteria, we assessed hyperandrogenism (H), chronic anovulation (O) and polycystic ovaries (P). Following diagnosis, women with PCOS were assigned to one of four different phenotypes. Finally, the prevalence and related risks of PCOS among Chinese women were estimated based on all the data sources. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 16 886 women were initially involved in the study and 15 924 eligible participants then completed the study; the overall response rate was 94.3% (15 924/16 886). The prevalence of PCOS in the Chinese community population was 5.6% (894/15 924). Blood samples were analyzed from 833 of these women who were assigned to the four PCOS phenotypes as follows: 19% H + O, 37% H + P, 15% O + P and 29% H + O + P. Comparing the 833 women with PCOS to 2732 women without PCOS indicated that PCOS occurs in younger women (P < 0.05) and these women were prone not only to menstrual problems, hyperandrogenism, PCO and infertility but also metabolic syndrome (MS) and insulin resistance (IR). However, there was no significant difference in the rate of hypertension or hyperlipemia between the two groups. Obese patients with PCOS had a higher rate of MS (16 versus 48%), IR (7 versus 28%), hypertension (8 versus 30%) and hyperlipemia (48 versus 73%) compared with non-obese patients (all P < 0.05), respectively. The rates of metabolic complications in patients with PCOS increased with age. LIMITATIONS, REASONS FOR CAUTION: Age and ethnic origin contribute to the differing manifestations of PCOS; therefore, sampling is one of the most important issues in epidemiological research into PCOS. Owing to the mobility of the Chinese population, the survey among resident populations caused a certain deviation in the age distribution. WIDER IMPLICATIONS OF THE FINDINGS: The prevention and treatment of PCOS, particularly in those who are obese, are essential in Chinese women of reproductive age.

Alcohol intake induces diminished ovarian reserve in childbearing age women.

AIM: To investigate the adverse effects of alcohol on ovarian reserve in women of childbearing age. MATERIAL AND METHODS: Twenty bar hostesses between the ages of 18 and 29 with moderate alcohol consumption for over 3 years and 16 healthy women between the ages of 18 and 28 with alcohol consumption under a healthy standard were recruited. Their ovarian reserve was evaluated by measuring menstrual cycle day three (CD3) serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), prolactin (PRL) and testosterone (TST) levels, and by transvaginal B-ultrasound examination of uterine size, ovarian size and number of antral follicles. RESULTS: Moderate consumption of alcohol significantly increased serum FSH level (P=0.001), but had no effect on serum LH, E2, PRL and TST levels. Moderate alcohol consumption significantly decreased ovarian volume (P=0.000) and number of ovarian antral follicles (P=0.015), but had no effect on uterus size. Moderate alcohol consumption significantly increased the occurrence of menstrual flow abnormalities (P=0.001 and P=0.036, respectively), but had no effect on menstrual cycle. The amount of alcohol consumed positively correlated with FSH, and negatively correlated with ovarian volume and number of antral follicles in women with moderate alcohol consumption. CONCLUSION: Long-term moderate alcohol consumption may lead to diminished ovarian reserve.

[Survey on characteristics of menopause of Chinese women with the age of 40-60 years at gynecological clinic from 14 hospitals].

OBJECTIVE: To investigate the characteristics of menopause of Chinese women with the age of 40-60 years concerning gynecologic clinics in China. METHODS: From Mar.2008 to Sept.2008, a face-to-face questionnaire was conducted in gynecological clinic in perimenopausal and postmenopausal women in 14 hospitals in China, which included general demographic data, menstrual change process, climacteric symptoms and knowledge about menopause. Modified Kupperman index were used to evaluate climacteric symptoms during the recent week and awareness of hormonal replacement therapy were studied. RESULTS: A total of 1641 women were investigated. The ages of onset of menopause transition, climacteric symptoms and natural menopause were (47 ± 4), (46 ± 4), (49 ± 3) years old respectively. Climacteric symptoms could be found in 78.43% (1287/1641) women during menopausal transition, which were mainly mild to moderate symptoms. The top 5 symptoms were fatigue and weakness (71.48%, 1173/1641), irritability (68.68%, 1127/1641), insomnia (67.65%, 1110/1641), muscle and joint pain (64.11%, 1052/1641) and hot flush (57.90%, 950/1641). The climacteric symptoms were not constant during menopausal transition, usually more severe in late transition and postmenopausal periods, during which the moderate and severe symptoms were 59.1% (189/320) and 51.1% (291/570) respectively. Although most symptoms primarily appeared along with menstruation change, there are about 17.5% (172/981) patients experienced climacteric symptoms before menstruation change occurrence. There were 56.39% (733/1300) women had ever heard (mostly from gynecologist) about hormone replacement therapy from Obstetrician and Gynecologist. CONCLUSIONS: Most of the women during menopausal transition had climacteric symptoms, usually mild and moderate ones. Although most symptoms primarily appeared along with menstruation change, there are other patients' experienced climacteric symptoms before menstruation change occurrence.

Co-involvement of psychological and neurological abnormalities in infertility with polycystic ovarian syndrome.

OBJECTIVE: To investigate psychological distress, serum levels of monoamine neurotransmitters and their metabolites, as well as their correlation with polycystic ovarian syndrome (PCOS). METHODS: Thirty infertility patients with PCOS were assigned as the experimental group and 30 infertility patients without PCOS were assigned as the control group. Psychological distress was self-evaluated in all patients with Symptom Checklist 90 (SCL-90). Serum concentrations of norepinephrine (NE) and its metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxytryptamine (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA), dopamine (DA) and its metabolites homovanillic acid (HVA) and dihydroxy-phenyl acetic acid (DOPAC) were measured by high-performance liquid chromatography. RESULTS: The anxious and depressive subscales of SCL-90 were significantly higher in infertility patients with PCOS than those without PCOS (p < 0.05). The serum concentrations of 5-HT, 5-HIAA and HVA were significantly lower in infertility patients with PCOS than those without PCOS (p < 0.05). Importantly, the phobia subscale scores of SCL-90 positively correlated with serum MHPG level (p < 0.05), while the hostility subscale's scores negatively correlated with serum DOPAC level (p < 0.05). CONCLUSION: Psychological and neurological factors play a crucial role in PCOS.

Chronic alcohol administration increases serum prolactin level and pituitary cell proliferation, and alters hypothalamus neurotransmitters in rat.

OBJECTIVES: Alcohol induces hyperprolactinemia in both alcoholic men and women, but the mechanism is not fully established. The aim is to investigate the mechanism involved in elevation of serum prolactin level after chronic alcohol administration. METHODS: In this study, healthy female SD rats were given alcohol for 8 weeks and checked for serum prolactin level by radioimmunoassay. Interior pituitary cell proliferation was determined by immunohistochemistry score of Ki-67, and hypothalamic neurotransmitters were detected by Coulomb HPLC electrochemical array. RESULTS: We demonstrated that serum prolactin level and wet pituitary weight of alcohol-fed rats were significantly increased. Interior pituitary cell proliferation was significantly enhanced; hypothalamic dopamine, 5-HT and GABA levels were reduced while glutamate level was increased by chronic alcohol administration; hypothalamic noradrenalin level remained unchanged. CONCLUSION: Our study suggested that chronic alcohol administration resulted in elevated serum prolactin level in normal SD rats probably through enhancing pituitary gland cell proliferation combined with altered hypothalamic neurotransmitters that regulate prolactin level.

[Spontaneous abortion and changes of estrogen receptors and progesterone receptors in the endometria of patients with polycystic ovary syndrome].

OBJECTIVE: To explore the relationship between the spontaneous abortion and changes of estrogen receptors (ER) and progesterone receptors (PR) in the endometria of patients with polycystic ovary syndrome (PCOS). METHODS: Thirty-two patients who suffered PCOS combined with infertilitas feminis were enrolled in a experimental group,and 20 patients with tubal infertilitas feminis having the corresponding time period as a control group. The expressions of ER and PR in the endometria were observed by pathological examination and immunohistochemical staining. RESULTS: The expressions of ER and PR in the glands and interstitium of endometrial in the PCOS group were significantly lower than those of the tubal infertilitas feminis group (P=0.004,P=0.001). The expressions of ER and PR in the PCOS group in the glands organ and interstitium of endometrial among 3 different periods were not significantly different (P>0.05). The expressions of ER in the glands of endometrium in the spontaneous abortion group were significantly lower than those of the non-spontaneous abortion group (P=0.02), but there was no statistical difference between the two groups in the interstitium of endometria (P>0.05). The expression of PR in the glands interstitium of endometria showed no statistical difference between the spontaneous abortion group and the non-spontaneous abortion group (P>0.05). CONCLUSION: The decrease of ER and PR of endometrial in the PCOS patients, may be a reason for spontaneous abortion, and the cyclical irregularity of ER and PR in the PCOS patients is another cause of spontaneous abortion.

[Clinical analysis of 4 treatments for woman polycystic ovarian syndrome with infertility].

OBJECTIVE: To investigate the therapeutic effects of 4 different treatments for woman polycystic ovarian syndrome (PCOS) with infertility. METHODS: One hundred and twenty women PCOS with infertility were divided into 4 Groups : patients in Group 1 were directly treated with clomiphene (CC)/CC + human menopausal gonadotropin (HMG) + human chorionic gonadotropin (HCG) to accelerate ovulation; patients in Group 2 were treated with the same way as Group 1 after taking marvolon for 2 cycles; patients in Group 3 took marvolon for 2 cycles and metformin for 8 weeks, and then were treated the same as Group 1; patients in Group 4 were treated with laparosocopy. The body mess index (BMI), emmenia period, weight, volume of ovary, LH, and T were measured before and after the treatment in all patients. The cycle ovulatory rate and occurrence rate of luteinized unruptued follicle syndrome (LUFS) within 2 months and the pregnancy rate within 6 months after the treatment were also observed. RESULTS: In all patients, BMI, emmenia period, serum T, and serum LH decreased significantly (P <0.05 or 0.01). The body mess indexes were significantly lower in Group 2 and Group 3 than those in Group 4 and Group 1, and Group 4 was also lower than Group 1 (P < 0.05 or 0.01). There was no difference in emmenia period between the 4 groups (P = 0.289). The volumes of ovary were enlarged in Group 1, and they were shrunk in the residual groups, which was significantly lower in Group 4 than in Group 2 and 3 (P < 0.01). The cycle ovulation rates were 53%, 72 %, 78 %, and 76%; the pregnancy rates within 6 months were 20%, 47%, 50%, and 57%, respectively; and they were significantly higher in the Group 2, 3 and 4 than in Group 1 (P <0.01). The occurrence rates of LUFS were 32%, 16%, 15%, and 13%, and they were significantly lower in Group 2, 3 and 4 than in Group 1 (P <0. 01). CONCLUSION: The effects of marvolon or marvolon and metformin are the same as those of laparoscopy not only in controlling the symptoms of PCOS, but also in increasing the cycle ovulation rate, pregnancy rate within 6 months, and decreasing the occurrence rate of LUFS. The symptoms of PCOS can be controlled better, but the cycle ovulation rate and pregnancy rate within 6 months can not be improved when clomiphene is used alone.

Transvaginal ultrasound-guided embryo aspiration plus local administration of low-dose methotrexate for caesarean scar pregnancy.

This study evaluated the effect of transvaginal ultrasound-guided embryo aspiration plus local administration of low-dose methotrexate (MTX) on caesarean scar pregnancy (CSP). Sixty-eight cases of CSP were randomly grouped for (1) systemic administration of MTX plus curettage with hysteroscopy (control group); and (2) transvaginal ultrasound-guided embryo aspiration plus local administration of low-dose MTX (experimental group). Serum ß-HCG and transaminase levels, length of hospital stay, occurrence of hypoleukocytosis, vaginal bleeding and genital infection were analyzed. No statistical differences in the duration needed for ß-HCG normalization, genital infection and length of hospital stay were observed between the two groups. However, the occurrence of massive vaginal bleeding, hypoleukocytosis and elevated transaminase levels were significantly lower in patients who received transvaginal ultrasound-guided embryo aspiration plus local administration of low-dose MTX compared with patients in the control group. Our study suggested that transvaginal ultrasound-guided embryo aspiration plus local administration of low-dose MTX should be recommended as a safe and effective treatment of caesarean scar pregnancy.