Insulin Resistance in Polycystic Ovary Syndrome Improved by Chinese Medicine Dingkun Pill (): A Randomized Controlled Clinical Trial.

OBJECTIVE: To assess the efficacy and safety of the Chinese medicine Dingkun Pill (, DKP) on insulin resistance in women with polycystic ovary syndrome (PCOS). METHODS: A total of 117 women with PCOS were randomly assigned to Group A (38 women), Group B (40 women), or Group C (39 women) in a randomization sequence with SAS software and a 1:1:1 allocation ratio using random block sizes of 6, and were given 7 g of oral DKP daily (Group A), 1 tablet of Diane-35 orally daily (Group B), or 7 g of oral DKP daily plus 1 tablet of Diane-35 orally daily (Group C). Patients took all drugs cyclically for 21 consecutive days, followed by 7 drug-free days. The treatment course for the 3 groups was continued for 3 consecutive months. Oral glucose tolerance tests (OGTT) were performed before treatment and again after 2 and 3 months of therapy, respectively, and homeostasis model assessment for insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) were calculated. RESULTS: Of 117 women with PCOS, 110 completed the entire course of therapy: 35 in Group A, 36 in Group B, and 39 in Group C. After treatment, all three groups showed significant decreases in fasting glucose: at 1 h glucose decreased significantly in Group A (by 0.5 ± 1.4 mmol/L, P=0.028) and Group C (by 0.5 ± 1.2 mmol/L, P=0.045); while showing a tendency to increase in Group B (by 0.4 ± 1.9 mmol/L, P=0.238). HOMA-IR decreased significantly in Group C [by 0.5 (-2.2 to 0.5) mIU mmol/L2, P=0.034]. QUICKI was significantly increased in Groups A and C (by 0.009 ± 0.02, P=0.033 and by 0.009 ± 0.027, P=0.049, respectively), while no change was observed in Group B. Repeated-measure ANOVA showed that the absolute changes in all parameters (except for glucose at 1 h), including glucose and insulin levels at all time-points during OGTT and in HbA1c, HOMA-IR, and QUICKI, were not significantly different among the 3 groups after treatment (P>0.05). CONCLUSION: DKP or DKP combined with Diane-35 produce a slight improvement in insulin sensitivity compared with Diane-35 alone in PCOS patients (Trial Registration: ClinicalTrials.gov, NCT03264638).

Decreased expression of interleukin-37 in the ectopic and eutopic endometria of patients with adenomyosis.

Previous studies have shown that alterations of cytokines might play a role in the pathogenesis of adenomyosis. This study aims to investigate the expression of interleukin-37 (IL-37), an anti-inflammatory cytokine, in the eutopic and ectopic endometria of patients with adenomyosis. Endometrial specimens were collected from 30 women with adenomyosis and 20 without adenomyosis. The gene and protein expression of IL-37 was measured using a quantitative real-time polymerase chain reaction and immunohistochemistry, respectively. Compared with the control endometria, the protein expression level and gene level of IL-37 was significantly lower in both the ectopic and eutopic endometria of patients with adenomyosis. The gene and protein expressions of IL-37 in ectopic endometria were lower than those in eutopic endometria of patients with adenomyosis. Our results suggest that there was a low level of IL-37 in the eutopic and ectopic endometria of patients with adenomyosis, and an abnormal inflammatory response might occur in the endometria of patients with adenomyosis.

Surgical Therapy of 17α-hydroxylase Deficiency in 30 Patients.

Objective To analyze the clinical features of 17α-hydroxylase deficiency and explore the appropriate timing and methods of surgical treatment. Methods We retrospectively analyzed the clinical data of patients with complete 17α-hydroxylase deficiency,containing Y chromosome material in their karyotype,adimitted to Peking Union Medical College Hospital from January 2004 to December 2014. Results Thirty patients with complete 17α-hydroxylase deficiency were included. Their social gender were all female and the mean age at diagnosis was (16.1±2.7) years. Twenty-six patients (86.7%) presented with primary amenorrhea and hypertension. The development of secondary sexual characteristics was poor and their uterus was absent. The levels of gonadotropin,progesterone,and adrenocorticotropic hormone were elevated in all patients and the levels of estradiol,testosterone,and cortisol were decreased. All patients had undergone laparoscopic gonadectomy. Most (86.7%) of the gonads were located in abdomen,while 13.3% were in inguinal canal. Histopathology confirmed that gonadal malignancy was obsetved in two patients (6.7%): one with leydig cell tumor and the other with sertoli cell tumor. Conclusions Patients with complete 17α-hydroxylase deficiency have specific clinical features. Early diagnosis and timely laparoscopic gonadectomy are critical to prevent gonadal malignancy.

Clinical Features of 32 Patients with XO/XY Gonadal Dysgenesis.

Objective To summarize the clinical features of XO/XY gonadal dysgenesis. Method We retrospectively analyzed the clinical data of patients with XO/XY gonadal dysgenesis admitted to Peking Union Medical College Hospital from January 2008 to May 2015. Results Totally 32 patients with XO/XY gonadal dysgenesis were included. The social gender was female in all subjects and the age 6 to 33 years. Patients presented mainly with primary amenorrhea or short stature,and usually had specific somatic signs of Turner's syndrome. The breast development of 27 patients (84.38%) was less than level 3. The armpit hair was sparse or absent in 28 patients (87.5%) and the pubic hair was sparse or absent in 26 patients (81.25%).Other findings include naive vulva (n=18,56.25%)) and enlarged clitoris (n=5,15.63%). The average level of follicle stimulating hormone was (78.56±35.62) mIU/ml,the luteinizing hormone level was (20.23±11.35) mIU/ml,the estradiol level was (9.94±8.21) pg/ml,and the testosterone level was (0.24±0.18) ng/ml. All patients received prophylactic gonadectomy. The histopathology results showed a variety of gonads,and gonadal malignancy were observed in 4 patients.Conclusions Patients with XO/XY gonadal dysgenesis manifest primary amenorrhea or short stature,poorly developed secondary sexual characteristics,and elevated gonadotropin level. The gonads have increased risk of gonadal malignancy.

Aberrantly expressed long noncoding RNAs in the eutopic endometria of patients with uterine adenomyosis.

OBJECTIVE: Adenomyosis is a common gynecologic disease. Alterations in the eutopic endometria might play an important role in the pathogenesis of adenomyosis. Long non-coding RNA (lncRNA) represents key regulators of gene expression. Our goal was to identify differentially expressed long noncoding RNA and messenger RNA (mRNA) in the eutopic endometria of subjects with adenomyosis on a genome-wide scale. STUDY DESIGN: The expression level of lncRNAs and mRNAs in the eutopic endometria from women with adenomyosis and from that of normal control subjects were detected by Affymetrix Human Transcriptome Array 2.0. Bioinformatics analysis was done for further investigation. Three up-regulated and three down-regulated lncRNAs were randomly chosen for validation by quantitative real-time polymerase chain reaction. RESULTS: A total of 165 lncRNAs and 612 mRNAs were aberrantly expressed in the eutopic endometria of subjects with adenomyosis. Pathway analysis indicated that 40 pathways corresponded to up-regulated transcripts and 39 pathways corresponded to downregulated transcripts. A list of genes that might play roles in the pathogenesis of adenomyosis were produced by comparing the difference between co-expression networks. Expression of six chosen lncRNAs was validated by quantitative real-time polymerase chain reaction. CONCLUSION: This study show for the first time that the lncRNA expression profile is altered in women with adenomyosis and provides new biological foundations for further mechanistic studies in this enigmatic disorder.

Increased Expression of Interleukin 37 in the Eutopic and Ectopic Endometrium of Patients With Ovarian Endometriosis.

INTRODUCTION: Endometriosis is a chronic inflammatory condition. Interleukin (IL) 37 is a member of the IL-1 family and an anti-inflammatory cytokine. This study investigated the gene and protein expression of IL-37 in the eutopic and ectopic endometrium of women with ovarian endometriosis and in the endometrium of patients without endometriosis. METHODS: Eutopic and ectopic endometria (n = 24) were collected from patients with ovarian endometriosis, and control endometria (n = 15) were obtained from women without endometriosis. Quantitative real-time polymerase chain reaction was used to measure the gene expression levels of IL-37, and immunohistochemistry was performed to assess the protein expression levels of IL-37. RESULTS: The gene and protein expression levels of IL-37 in both eutopic and ectopic endometrium of women with ovarian endometriosis were significantly higher than in the endometrium of patients without endometriosis. Compared to the eutopic endometrium of patients with ovarian endometriosis, IL-37 gene and protein expression levels were significantly higher in the ectopic endometrium. CONCLUSION: These findings suggest that increased expression of IL-37 was present in eutopic and ectopic endometrium of women with ovarian endometriosis, which might be involved in the inflammatory process of endometriomas.

Gonadal malignancy in 202 female patients with disorders of sex development containing Y-chromosome material.

The objective of this study was to examine risks for gonadal malignancy in a large sample of adult female patients with disorders of sex development (DSD). A retrospective-observational study was conducted from July 1992 to March 2015 and 202 women with DSD were enrolled. Tumor risks for different types of DSD were measured. We found that the patients' total gonadal-malignancy risk was 18.3% (37/202). Tumors included gonadoblastoma (n = 11), seminoma (n = 8), dysgerminoma (n = 5), choriocarcinoma (n = 1), sertoli cell tumors (n = 11), and leydig cell tumors (n = 1). The incidence of gonadal malignancy in patients with complete androgen insensitivity syndrome (CAIS), pure 46, XY gonadal dysgenesis, 45 X/46 XY mixed gonadal dysgenesis, 17α-hydroxylase/17, 20-lyase deficiency and partial androgen insensitivity syndrome (PAIS) were 27.1% (13/48), 22.4% (15/67), 10.9% (5/46), 10% (2/20) and 9.5% (2/21), respectively. Our results suggest that the incidence of gonadal malignancy increases with age for female patients with Y-chromosome material. Upon diagnoses, immediate, prophylactic gonadectomies should be considered for adult female patients with DSD containing Y chromosome material if they cannot receive regular follow-ups.