ABSTRACT
Diminished ovarian reserve (DOR), generally defined as a decreased number or quality of oocytes, has a significant impact on quality of life and fertility in women. In recent years, the incidence of DOR has been increasing and the ages of patients are younger. The search for an effective DOR treatment has emerged as one of the preeminent research topics in reproductive health. An effective DOR therapy would improve ovarian function, fertility, and quality of life in patients. In this review we evaluated DOR treatment progress both in Western medicine and Chinese medicine, and elucidated the characteristics of each treatment.
Subject(s)
Female , Humans , Medicine, Chinese Traditional , Ovarian Reserve , Quality of Life , Oocytes , Treatment Outcome , Infertility, Female/therapyABSTRACT
BACKGROUND@#Obesity and insulin resistance (IR) are common features of polycystic ovary syndrome (PCOS). Metformin (MET) increases insulin sensitivity, but it is associated with unsatisfactory weight loss. The glucagon-like peptide-1 receptor agonist exenatide has been shown to reduce weight and IR in patients with diabetes. This study aimed to explore the therapeutic effects of exenatide once-weekly (QW) combined with MET on body weight, as well as metabolic and endocrinological parameters in overweight/obese women with PCOS.@*METHODS@#Fifty overweight/obese women with PCOS diagnosed via the Rotterdam criteria were randomized to one of two treatment groups: MET (500 mg three times a day [TID]) or combination treatment (COM) (MET 500 mg TID, exenatide 2 mg QW) for 12 weeks. The primary outcomes were anthropometric changes associated with obesity, and the secondary outcomes included changes in reproductive hormone levels, glucose and lipid metabolism, and C-reactive protein.@*RESULTS@#Forty (80%) patients completed the study. COM therapy was superior to MET monotherapy in reducing weight (P = 0.045), body mass index (BMI) (P = 0.041), and waist circumference (P = 0.023). Patients in the COM group on an average lost 3.8 ± 2.4 kg compared with 2.1 ± 3.0 kg in the MET group. In the COM group, BMI and waist circumference decreased by 1.4 ± 0.87 kg/m2 and 4.63 ± 4.42 cm compared with 0.77 ± 1.17 kg/m2 and 1.72 ± 3.07 cm in the MET group, respectively. Moreover, levels of fasting glucose, oral glucose tolerance test (OGTT) 2-h glucose, and OGTT 2-h insulin were significantly lower with COM therapy than with MET (P < 0.050). Mild and moderate gastrointestinal reactions were the most common adverse events in both groups.@*CONCLUSIONS@#COM therapy was more effective than MET alone in reducing body weight, BMI, and waist circumference, and improving insulin sensitivity in overweight/obese women with PCOS, with acceptable short-term side effects.@*TRIAL REGISTRATION@#ClinicalTrials.gov, NCT04029272. https://clinicaltrials.gov/ct2/show/NCT04029272.
Subject(s)
Female , Humans , Exenatide/therapeutic use , Metformin/therapeutic use , Obesity/drug therapy , Overweight , Polycystic Ovary Syndrome/drug therapyABSTRACT
OBJECTIVE@#To evaluate the effects of Chinese medicine Dingkun Pill () alone or in combination with Diane-35 on patients with polycystic ovary syndrome (PCOS).@*METHODS@#This is a prospective randomized controlled trial conducted at Peking Union Medical College Hospital Beijing, China, from December 2016 to September 2017. Totally 117 PCOS patients were randomly assigned to the Dingkun Pill group (38 cases), Diane-35 group (40 cases), or combined group (39 cases). Patients in the Dingkun Pill group or Diane-35 group took daily 7 g of oral Dingkun Pill or 1 tablet of oral Diane-35, respectively, for 21 consecutive days followed by 7 drug-free days. And the combined group received a combination of Dingkun Pill and Diane-35. The treatment course was 3 months. Fasting plasma glucose and insulin, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), free fatty acids (FFA) and sex hormones were analyzed, quantitative insulin sensitivity check index (QUICKI) was calculated, and menstruation and acne scores were recorded at baseline and after 3-month treatment.@*RESULTS@#Compared with before treatment, QUICKI decreased significantly in the Dingkun Pill and combined groups after 3-month treatment (P0.05).@*CONCLUSIONS@#Dingkun Pill showed better effects than Diane-35 in improving insulin sensitivity, lowering TC and FFA. Diane-35 was more efficient in regulating menstruation and lowering androgen than Dingkun Pill. Combination of Dingkun Pill and Diane-35 may be a better choice to regulate menstruation, lower androgens while improve glucose metabolism in PCOS patients. (Registered on ClinicalTrials.gov, registration No. NCT03264638).
ABSTRACT
BACKGROUND:WWOX,a tumor suppressor gene,can affect the growth of ovarian cancer stem cells;however,there is no report on whether its mechanism of action is related to Hedgehog signaling pathway.OBJECTIVE:To investigate the effect and mechanism of overexpression of WWOX on the apoptosis of ovarian cancer stem cells.METHODS:pcDNA3.1-WWOX (pcDNA3.1-WWOX group) and pcDNA4.0-WWOX (pcDNA4.0-WWOX group) were transferred into ovarian cancer stem cells,respectively;and meanwhile,pcDNA3.1 (pcDNA3.1 group) and pcDNA4.0 (pcDNA4.0 group) were transferred into the cells.A non-transfection group (only with Lipofectamine2000) was set up.After cultured 48 hours,the levels of WWOX in the pcDNA3.1-WWOX group and pcDNA4.0-WWOX group were detected using western blot assay,and the cell proliferation and apoptosis were detected using MTT assay and flow cytometry,respectively.Western blot assay was also used to detect the levels of Hedgehog signaling pathway associated proteins,SHH,PTCH1,Gli-1,SMO and apoptosis-related protein Cleaved Caspase-3 in the cells.Cyclopamine,Hedgehog signaling pathway inhibitor,was used in ovarian cancer stem cells without transfection (cyclopamine group) and after the transfection of WWOX overexpression vector (WWOX+cyclopamine group) followed by 48 hours of culture,and then MTT,flow cytometry and western blot detections were performed.RESULTS AND CONCLUSION:(1) The expression level of WWOX in the pcDNA4.0-WWOX group was significantly higher than that in the pcDNA3.1-WWOX group (t=27.84,P=0.00).The ovarian cancer stem cells which were transfected with pcDNA4.0-WWOX were used to overexpress WWOX in the late experiment.(2) Overexpression of WWOX could inhibit the proliferation of ovarian cancer stem cells and promote the apoptosis of ovarian cancer stem cells.(3) Overexpression of WWOX could inhibit the expression of Gii-1,PTCH1,SMO and SHH in ovarian cancer stem cells,and promote the expression of Cleaved Caspase-3.(4) Cyclopamine could inhibit the expression of SHH,PTCH 1,Gli-1,SMO,and promote the expression of Cleaved Caspase-3.Cyclopamine had obvious inhibitory effect on Hedgehog signaling pathway.(5) Cyclopamine could enhance the apoptosis induced by overexpression of WWOX in ovarian cancer stem cells,and enhance the inhibition of proliferation of ovarian cancer stem cells induced by overexpression of WWOX.To conclude,WWOX effects on proliferation and apoptosis of ovarian cancer stem cells may be related to the inhibition of Hedgehog signaling pathway.