Comparison of Drospirenone- with Cyproterone Acetate-Containing Oral Contraceptives, Combined with Metformin and Lifestyle Modifications in Women with Polycystic Ovary Syndrome and Metabolic Disorders: A Prospective Randomized Control Trial.

Many hormonal contraceptives have been associated with changes in carbohydrate metabolism. Alterations may include decreased glucose tolerance and increased insulin resistance, which are risk factors for Type 2 diabetes mellitus and cardiovascular disease. These issues have been raised primarily with contraceptives containing estrogen. To evaluate the effect of hormonal contraceptives on carbohydrate metabolism in healthy women and those at risk for diabetes due to overweight. In February 2012, we searched the computerized databases MEDLINE, POPLINE, CENTRAL, and LILACS for studies of hormonal contraceptives and carbohydrate metabolism. We also searched for clinical trials in ClinicalTrials.gov and ICTRP. Previous searches also included EMBASE. All randomized controlled trials were considered if they examined carbohydrate metabolism in women without diabetes who used hormonal contraceptives for contraception. Comparisons could be a placebo, a non-hormonal contraceptive, or another hormonal contraceptive that differed in drug, dosage, or regimen. Interventions included at least three cycles. Outcomes included glucose and insulin measures. We assessed all titles and abstracts identified during the literature searches. The data were extracted and entered into RevMan. We wrote to researchers for missing data. For continuous variables, the mean difference (MD) was computed with 95% confidence interval (CI) using a fixed-effect model. For dichotomous outcomes, the Peto odds ratio with 95% CI was calculated. We found 31 trials that met the inclusion criteria. Twenty-one trials compared combined oral contraceptives (COCs); others examined different COC regimens, progestin-only pills, injectables, a vaginal ring, and implants. None included a placebo. Of 34 comparisons, eight had any notable difference between the study groups in an outcome.Twelve trials studied desogestrel-containing COCs, and the few differences from levonorgestrel COCs were inconsistent. A meta-analysis of two studies showed the desogestrel group had a higher mean fasting glucose (MD 0.20; 95% CI 0.00 to 0.41). Where data could not be combined, single studies showed lower mean fasting glucose (MD -0.40; 95% CI -0.72 to -0.08) and higher means for two-hour glucose response (MD 1.08; 95% CI 0.45 to 1.71) and insulin area under the curve (AUC) (MD 20.30; 95% CI 4.24 to 36.36).Three trials examined the etonogestrel vaginal ring and one examined an etonogestrel implant. One trial showed the ring group had lower mean AUC insulin than the levonorgestrel-COC group (MD -204.51; 95% CI -389.64 to -19.38).Of eight trials of norethisterone preparations, five compared COCs and three compared injectables. In a COC trial, a norethisterone group had smaller mean change in glucose two-hour response than a levonorgestrel-COC group (MD -0.30; 95% CI -0.54 to -0.06). In an injectable study, a group using depot medroxyprogesterone acetate had higher means than the group using norethisterone enanthate for fasting glucose (MD 10.05; 95% CI 3.16 to 16.94), glucose two-hour response (MD 17.00; 95% CI 5.67 to 28.33), and fasting insulin (MD 3.40; 95% CI 2.07 to 4.73).Among five recent trials, two examined newer COCs with different estrogen types. One showed the group with nomegestrel acetate plus 17β-estradiol had lower means than the levonorgestrel group for incremental AUC glucose (MD -1.43; 95% CI -2.55 to -0.31) and glycosylated hemoglobin (HbA1c) (MD -0.10; 95% CI -0.18 to -0.02). Two trials compared extended versus conventional (cyclic) regimens. With a dienogest COC, an extended-use group had greater mean change in AUC glucose (MD 82.00; 95% CI 10.72 to 153.28). In a small trial using two levonorgestrel COCs, the lower-dose group showed smaller mean change in fasting glucose (MD -3.00; 95% CI -5.89 to -0.11), but the obese and normal weight women did not differ significantly. Current evidence suggests no major differences in carbohydrate metabolism between different hormonal contraceptives in women without diabetes. We cannot make strong statements due to having few studies that compared the same types of contraceptives. Many trials had small numbers of participants and some had large losses. Many of the earlier studies had limited reporting of methods.We still know very little about women at risk for metabolic problems due to being overweight. More than half of the trials had weight restrictions as inclusion criteria. Only one small trial stratified the groups by body mass index (obese versus normal).

Many hormonal contraceptives have been associated with changes in carbohydrate metabolism. Alterations may include decreased glucose tolerance and increased insulin resistance, which are risk factors for Type 2 diabetes mellitus and cardiovascular disease. These issues have been raised primarily with contraceptives containing estrogen. To evaluate the effect of hormonal contraceptives on carbohydrate metabolism in healthy women and those at risk for diabetes due to overweight. In April 2014, we searched the computerized databases MEDLINE, POPLINE, CENTRAL, and LILACS for studies of hormonal contraceptives and carbohydrate metabolism. We also searched for clinical trials in ClinicalTrials.gov and ICTRP. The initial search also included EMBASE. All randomized controlled trials were considered if they examined carbohydrate metabolism in women without diabetes who used hormonal contraceptives for contraception. Comparisons could be a placebo, a non-hormonal contraceptive, or another hormonal contraceptive that differed in drug, dosage, or regimen. Interventions included at least three cycles. Outcomes included glucose and insulin measures. We assessed all titles and abstracts identified during the literature searches. The data were extracted and entered into RevMan. We wrote to researchers for missing data. For continuous variables, the mean difference (MD) was computed with 95% confidence interval (CI) using a fixed-effect model. For dichotomous outcomes, the Peto odds ratio with 95% CI was calculated. We found 31 trials that met the inclusion criteria. No new trials were eligible in 2014. Twenty-one trials compared combined oral contraceptives (COCs); others examined different COC regimens, progestin-only pills, injectables, a vaginal ring, and implants. None included a placebo. Of 34 comparisons, eight had any notable difference between the study groups in an outcome.Twelve trials studied desogestrel-containing COCs, and the few differences from levonorgestrel COCs were inconsistent. A meta-analysis of two studies showed the desogestrel group had a higher mean fasting glucose (MD 0.20; 95% CI 0.00 to 0.41). Where data could not be combined, single studies showed lower mean fasting glucose (MD -0.40; 95% CI -0.72 to -0.08) and higher means for two-hour glucose response (MD 1.08; 95% CI 0.45 to 1.71) and insulin area under the curve (AUC) (MD 20.30; 95% CI 4.24 to 36.36).Three trials examined the etonogestrel vaginal ring and one examined an etonogestrel implant. One trial showed the ring group had lower mean AUC insulin than the levonorgestrel-COC group (MD -204.51; 95% CI -389.64 to -19.38).Of eight trials of norethisterone preparations, five compared COCs and three compared injectables. In a COC trial, a norethisterone group had smaller mean change in glucose two-hour response than a levonorgestrel-COC group (MD -0.30; 95% CI -0.54 to -0.06). In an injectable study, a group using depot medroxyprogesterone acetate had higher means than the group using norethisterone enanthate for fasting glucose (MD 10.05; 95% CI 3.16 to 16.94), glucose two-hour response (MD 17.00; 95% CI 5.67 to 28.33), and fasting insulin (MD 3.40; 95% CI 2.07 to 4.73).Among five recent trials, two examined newer COCs with different estrogen types. One showed the group with nomegestrel acetate plus 17β-estradiol had lower means than the levonorgestrel group for incremental AUC glucose (MD -1.43; 95% CI -2.55 to -0.31) and glycosylated hemoglobin (HbA1c) (MD -0.10; 95% CI -0.18 to -0.02). Two trials compared extended versus conventional (cyclic) regimens. With a dienogest COC, an extended-use group had greater mean change in AUC glucose (MD 82.00; 95% CI 10.72 to 153.28). In a small trial using two levonorgestrel COCs, the lower-dose group showed smaller mean change in fasting glucose (MD -3.00; 95% CI -5.89 to -0.11), but the obese and normal weight women did not differ significantly. Current evidence suggests no major differences in carbohydrate metabolism between different hormonal contraceptives in women without diabetes. We cannot make strong statements due to having few studies that compared the same types of contraceptives. Many trials had small numbers of participants and some had large losses. Many of the earlier studies had limited reporting of methods.We still know very little about women at risk for metabolic problems due to being overweight. More than half of the trials had weight restrictions as inclusion criteria. Only one small trial stratified the groups by body mass index (obese versus normal).

The use of a combination of myoinositol and D-chiroinositol in a ratio of 5:1 (MI/DCI 5:1), manganese and folic acid appears promising for the correction of androgen-dependent dermopathy, regulation of the menstrual cycle, restoration of ovulation in patients planning pregnancy, as well as for improving endocrine and metabolic parameters, carbohydrate and lipid metabolism in patients with polycystic ovary syndrome (PCOS). Objective. To compare the effects of combined oral contraceptives (COCs) and combination of MI/DCI 5:1, manganese and folic acid on endocrine, metabolic and clinical parameters in patients with PCOS. Patients and methods. A prospective open-label clinical trial included 129 patients with PCOS. Patients in group 1 (A, n = 63) were prescribed COCs with antiandrogenic activity containing ethinyl estradiol 20 μg/drospirenone 3 mg; patients in group 2 (B, n = 66) were prescribed the combination of MI/DCI 5:1, manganese and folic acid for 6 months. Lifestyle modifications were also recommended for all patients: physical activity and diet therapy. Results. Low serum androgen levels were observed in both groups. The use of COCs resulted in a more significant reduction in hirsutism according to the Ferriman-Gallwey score and clinical manifestations of acne. Administration of the combination of MI/DCI 5:1 showed good results in improving carbohydrate and lipid metabolism in patients with PCOS. Thus, in group B there was a significant reduction in glucose levels (4.9 ± 0.3 vs. 5.2 ± 0.5 mmol/L, p < 0.01) and fasting insulin (12.1 ± 5.3 vs. 22.2 ± 4.9 mmol/L, p < 0.01), HOMA and CARO indices. No changes in carbohydrate metabolism were observed during COCs administration, but there was an increase in cholesterol levels (6.0 ± 0.7 vs. 5.7 ± 0.5 mmol/L, p < 0.05), low-density lipoproteins (LDL) (3.9 ± 0.4 vs. 3.5 ± 0.6 mmol/L, p < 0.05), and atherogenic coefficient (AC). Lipid profile parameters in group B improved significantly from baseline by reducing cholesterol (5.1 ± 0.6 vs. 5.6 ± 0.6 mmol/L, p < 0.05), triglycerides (1.5 ± 0.4 vs. 1.8 ± 0.3 mmol/L, p < 0.05), and LDL (2.7 ± 0.5 vs. 3.6 ± 0.8 mmol/L, p < 0.01). Diet therapy and administration of the combination of MI/DCI 5:1, manganese and folic acid resulted in a 4.4% decrease in waist circumference and a 4.8% decrease in body mass index (BMI). In contrast, the COCs group showed a 2.1% increase in waist circumference and a 4.7% increase in BMI, which may be related to an increased appetite. In group B, the regularity of menstrual cycle in patients with PCOS was also analyzed. After 6 months of therapy, a regular cycle was observed in 40% of patients vs. 11% of patients at baseline with a mean duration of 33.3 ± 9.4 days (p < 0.05). Conclusion. Lifestyle modification with the combination of MI/DCI 5:1, manganese and folic acid is effective for the correction of endocrine, metabolic, and clinical profile in patients with PCOS and appears to be a promising new alternative to COCs regardless of reproductive planning. Key words: polycystic ovary syndrome, myoinositol, D-chiroinositol, hyperandrogenism, insulin resistance, hirsutism, acne

Objective Dingkun Pill (DKP) is a proprietary Chinese medicine that has been utilized for patients with gynecological diseases, and its clinical application has been widely accepted in China. However, the effects of DKP on reproduction and metabolism in women with polycystic ovary syndrome (PCOS) have never been systematically evaluated. Our objective was to evaluate the efficacy and safety of DKP in treating reproductive and metabolic abnormalities with PCOS. Methods We searched in PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and Chinese Biomedical Literature Database up until January 2022 to identify randomized controlled trials (RCTs). The methodological quality of the included RCTs was estimated using the Cochrane collaboration risk-of-bias instrument, and the meta-analysis was performed using RevMan. Results A total of 22 RCTs (including 1994 participants) were identified. DKP, combined with ovulation-inducing drugs (OID) or combined oral contraceptives (COC) was superior to OID or COC alone in improving the pregnancy rate (relative risk (RR) 1.84, 95% CI 1.62 to 2.11 and RR 1.38, 95% CI 1.16 to 1.64, respectively), ovulation rate (RR 1.38, 95% CI 1.03 to 1.84 and RR 1.23, 95% CI 1.11 to 1.37, respectively), endometrial thickness (weighted mean difference (WMD) 2.50, 95% CI 1.91 to 3.09 and WMD 0.62, 95% CI 0.08 to 1.16, respectively), luteinizing hormone (WMD −1.93, 95% CI −2.80 to−.07 and WMD −1.79, 95% CI −2.66 to−0.92, respectively), and testosterone (standardized mean difference (SMD) −2.12, 95% CI −3.01 to−1.24 and SMD −1.21, 95% CI −1.64 to−0.78, respectively). DKP combined with COC led to a greater improvement in homeostasis model assessment-β (WMD 20.42, 95% CI 16.85 to 23.98) when compared with COC alone. There was a significant difference between DKP and COC in terms of decreasing total cholesterol (WMD −0.37, 95% CI −0.72 to−0.02), triacylglycerol (WMD −0.85, 95% CI −1.50 to−0.20), and free fatty acid (WMD −130.00, 95% CI −217.56 to−42.22). However, DKP did not affect the follicle stimulating hormone, fasting blood glucose, fasting insulin, body mass index, waist-to-hip ratio, high-density lipoprotein cholesterol, or low-density lipoprotein cholesterol. Adverse reactions were more common in COC alone compared to DKP and COC in combination (RR 0.22, 95% CI 0.07 to 0.63). Conclusion DKP shows promise in modifying reproductive and metabolic parameters in patients with PCOS and may be used as a primary choice in conventional or complementary therapies for PCOS. The quality of the evidence analyzed was suboptimal, and therefore, our results should be interpreted cautiously. More prospective large-scale and well-designed RCTs, as well as longer intervention durations are required in the future to draw more reliable conclusions.

Improvement in quality-of-life questionnaire measures in obese adolescent females with polycystic ovary syndrome treated with lifestyle changes and oral contraceptives, with or without metformin

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in reproductive-aged women, characterized by hyperandrogenism, oligo/anovulation, and polycystic ovarian morphology. Combined oral contraceptives (COCs), along with lifestyle modifications, represent the first-line medical treatment for the long-term management of PCOS. Containing low doses of estrogen and different types of progestin, COCs restore menstrual cyclicity, improve hyperandrogenism, and provide additional benefits such as reducing the risk of endometrial cancer. However, potential cardiometabolic risk associated with these agents has been a concern. COCs increase the risk of venous thromboembolism (VTE), related both to the dose of estrogen and the type of progestin involved. Arterial thrombotic events related to COC use occur much less frequently, and usually not a concern for young patients. All patients diagnosed with PCOS should be carefully evaluated for cardiometabolic risk factors at baseline, before initiating a COC. Age, smoking, obesity, glucose intolerance or diabetes, hypertension, dyslipidemia, thrombophilia, and family history of VTE should be recorded. Patients should be re-assessed at consecutive visits, more closely if any baseline cardiometabolic risk factor is present. Individual risk assessment is the key in order to avoid unfavorable outcomes related to COC use in women with PCOS.

BackgroundLifestyle modification (diet, exercise, and behavioral interventions) is the first-line treatment for polycystic ovary syndrome (PCOS). The benefits of face-to-face lifestyle modification intervention in a short time have been demonstrated. However, few studies have investigated the mobile technology effects on lifestyle modification in PCOS. Therefore, we examined the effect of transtheoretical model-based mobile health application intervention program for PCOS.MethodsA randomised controlled, single-blind trial, was carried out from October 2018 to March 2019, which included 122 participants recruited from gynecology outpatient clinics of affiliated Hospital of Zunyi Medical University in Guizhou. The study participants were randomised into intervention (n = 61) and control groups (n = 61). Participants in the intervention group undertook a TTM-based mobile health application program in addition to routine care, and participants in the control group received only routine care.ResultsFifty-one participants in the intervention group and 49 in the control group completed the study. Compared to the control group, participants in the intervention group showed statistically significant decrease for BMI (P < 0.05), WC (P < 0.05), SAS (P < 0.05), and SDS (P < 0.05) scores at 6-month and 12-month, respectively. Behavior stage change of exercise and diet among paticipants with PCOS was significant at 6 months (c2 = 43.032, P < 0.05) and 12th months (c2 = 49.574, P < 0.05) between the intervention and control groups.ConclusionsThis study showed that the TTM-based mobile health application program can decrease BMI, WC, anxiety, and depression, and improve exercise and diet adherence in patients with PCOS in the long term. The TTM-based mobile health application program can be applied for lifestyle modification in women with PCOS.Trial registration This study was approved by the ethics committee NO.[2019]1-028 in March 2018 and was registered at the Chinese Clinical Trial Registry (website: www.chictr.org.cn, registry number: ChiCTR2000034572)

Polycystic Ovary Syndrome (PCOS) is a complex hormonal disorder that is associated with heightened metabolic risks. While oxidative stress (OS) is known to play a role in PCOS, the precise nature of the relationship between PCOS and increased OS remains not entirely understood. Combined oral contraceptives (COCs) are the first-line treatment to regulate menstrual cycles and androgen levels, but their impact on oxidative stress requires further study. We conducted a transcriptomic analysis using RNAseq and assessed the levels of various oxidative stress (OS) markers in serum samples from women with PCOS and controls and whether they were using combined oral contraceptives (COCs), including enzymatic activities, FRAP, and 8-isoprostane (8-iso). A total of 359 genes were differentially expressed in women with PCOS compared to control women. Genes differentially expressed were enriched in functions related to inflammation and, interestingly, oxidative stress response. In controls, 8-iso levels were increased in women using COCs, whereas in women with PCOS, 8-iso levels were reduced in those using oral contraceptives (191.1 ± 97 vs. 26.4 ± 21 pg/mL, p: <0.0001). Correlation analyses showed a trend for a negative correlation between 8-iso and Ferriman score in women with PCOS consuming COCs (r = -0.86, p = 0.06) and a negative correlation between GSH and hyperandrogenism in women with PCOS (r = -0.89, p = 0.01). These results reveal the presence of lipid peroxidation in women with PCOS, which was modified by the use of COCs, providing new insights into the pathophysiology of PCOS in the Chilean population.

Polycystic ovary syndrome (PCOS) is a heterogeneous clinical entity that is defined as the association of hyperandrogenism with chronic anovulation in women without specific underlying diseases of the adrenal or pituitary glands. PCOS is also associated with a metabolic disturbance (insulin resistance). The nature of the complex interrelation of obesity, insulin resistance and endocrine abnormalities in PCOS remains unresolved. However, several studies link obesity, body fat distribution and nutritional habitus with the hormonal and metabolic profiles of PCOS. Moreover, intervention studies have suggested that reducing weight and/or hyperinsulinaemia either by diet alone or by a combination of diet and drugs improves hirsutism, fertility and the hormonal and metabolic profiles of PCOS. In fact, the evaluation of nutritional factors in PCOS is helpful for the screening of metabolic abnormalities and the management of women with PCOS. A point of particular interest in the management of PCOS is that the choice of contraception remains difficult in these high cardiovascular risk women. The impact of pills with ethinyl oestradiol on weight, body fat distribution and carbohydrate metabolism in women with PCOS has not been thoroughly evaluated. The lack of prospective studies to evaluate long-term metabolic and cardiovascular tolerance necessitates care and the assessment of other hormonal possibilities.

Androgen excess is a key pathogenetic mechanism in polycystic ovary syndrome (PCOS), although hyperinsulinism also contributes to androgen secretion. Therapeutic approaches for adult patients not seeking fertility include combined oral contraceptives (COC), antiandrogens (AA) and/or insulin sensitizers, although these practices are supported by limited high-quality evidence. We aimed to assess the efficacy and safety of these common treatments for PCOS by conducting a meta-analysis of RCTs with the following review questions: Which is the more appropriate therapeutic approach for hyperandrogenic symptoms, hyperandrogenemia, and ovulatory dysfunction in adult women with PCOS not seeking fertility; What is the impact on classic cardiometabolic risk factors of the more common treatments used in those women; Does the combination of the antiandrogenic therapy plus metformin have any impact on efficacy or cardiometabolic profile? We searched PubMed and EMBASE for articles published up to 16 September 2017. After deleting duplicates, the abstracts of 1522 articles were analysed. We subsequently excluded 1446 articles leaving 76 studies for full-text assessment of eligibility. Of them, 43 articles were excluded. Hence, 33 studies and 1521 women were included in the quantitative synthesis and in the meta-analyses. Meta-analyses calculated mean differences (MD), standardized mean differences (SMD), odds ratio (OR) and 95% CIs. Heterogeneity and inconsistency across studies was assessed by χ2 test and Higgins's I2 statistics. Quality and risk of bias of individual studies were assessed according to the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0. We then used the approach recommended by the Grading of Recommendations, Assessments, Development, and Evaluation (GRADE) group to indicate the global quality of evidence for a selection of primary outcomes. Regarding efficacy, the MD in hirsutism score between COC and/or AA and metformin were not significant. The exclusion of one single study including most women with severe hirsutism yielded a significant effect in favour of COC and/or AA. When only those studies including an AA were compared with metformin, there were significant differences favouring antiandrogenic therapy. The combination of COC and/or AA with metformin was similar to COC and/or AA therapy alone in the whole group of patients. Post-intervention OR for the presence of regular menses favoured COC therapy. In terms of cardiometabolic impact, the MD in BMI were in favour of metformin. The negative effect of COC therapy on BMI was blunted by its combination with metformin. The MD in homoeostasis model assessment of insulin resistance (HOMA-IR) were also in favour of metformin therapy compared to COC and/or AA. The combination of COC and/or AA and metformin decreased MD in HOMA with respect to antiandrogenic therapy alone. There were no significant post-intervention SMD in circulating glucose levels between COC and/or AA and metformin. However, adding metformin to COC and/or AA yielded a beneficial effect on fasting glucose levels. Post-intervention OR for abnormal glucose tolerance showed no significant differences between COC and/or AA and metformin, although after excluding studies including an AA as a comparator (without COC) a significant effect in favour of metformin therapy was observed. There were no significant differences among therapies in lipid profile, blood pressure or prevalence of hypertension. The global quality of evidence was very low when addressing the impact of the treatments explored on prevalence of hypertension and lipid profiles, low in the case of hirsutism, BMI and blood pressure values, and high for endometrial protection and glucose tolerance. These data provide further scientific evidence for the choice of treatment of women with PCOS. COC and AA are more effective than metformin for hyperandrogenic symptoms and endometrial protection. Their combination with metformin adds a positive effect on BMI and glucose tolerance. CRD42016053457.

&lt;b&gt;Objectives: &lt;/b&gt;Irregular menstrual cycles are associated with increased cardiovascular mortality. Polycystic ovary syndrome (PCOS) is characterized by androgen excess and irregular menses; androgens are drivers of increased metabolic risk in women with PCOS. Combined oral contraceptives (COCPs) are used in PCOS both for cycle regulation and to reduce the biologically active androgen fraction. We examined COCP use and risk of dysglycemia (pre-diabetes and type 2 diabetes) in women with PCOS. &lt;p&gt;&lt;b&gt;Research Design and Methods: &lt;/b&gt;Utilizing a large UK primary care database (The Health Improvement Network, THIN; 3.7 million patients from 787 practices), we carried out a retrospective population-based cohort study to determine dysglycemia risk (64,051 women with PCOS, 123,545 matched controls), as well as a nested pharmaco-epidemiological case-control study to investigate COCP use in relation to dysglycemia risk (2407 women with PCOS with [=cases] and without [=controls] a diagnosis of dysglycemia during follow-up).&lt;b&gt; &lt;/b&gt;Cox models were used to estimate the unadjusted and adjusted hazard ratio and conditional logistic regression was used to obtain adjusted odds ratios (aORs). &lt;/p&gt; &lt;p&gt;&lt;b&gt;Results: &lt;/b&gt;The adjusted hazard ratio for dysglycemia in women with PCOS was 1.87 (95% CI 1.78-1.97, p&lt;0.001; adjustment for age, social deprivation, BMI, ethnicity, and smoking), with increased rates of dysglycemia in all BMI subgroups. Women with PCOS and COCP use had a reduced dysglycemia risk (aOR 0.72, 95% CI 0.59 to 0.87).&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions: &lt;/b&gt;In this study limited by its retrospective nature and the use of routinely collected electronic general practice record data, which does not allow to exclude the impact of prescription-by-indication bias, women&lt;b&gt; &lt;/b&gt;with PCOS exposed to COCPs had a reduced risk of dysglycemia across all BMI subgroups. Future prospective studies should be considered to further understand these observations and potential causality. &lt;/p&gt;

&lt;b&gt;Objectives: &lt;/b&gt;Irregular menstrual cycles are associated with increased cardiovascular mortality. Polycystic ovary syndrome (PCOS) is characterized by androgen excess and irregular menses; androgens are drivers of increased metabolic risk in women with PCOS. Combined oral contraceptives (COCPs) are used in PCOS both for cycle regulation and to reduce the biologically active androgen fraction. We examined COCP use and risk of dysglycemia (pre-diabetes and type 2 diabetes) in women with PCOS. &lt;p&gt;&lt;b&gt;Research Design and Methods: &lt;/b&gt;Utilizing a large UK primary care database (The Health Improvement Network, THIN; 3.7 million patients from 787 practices), we carried out a retrospective population-based cohort study to determine dysglycemia risk (64,051 women with PCOS, 123,545 matched controls), as well as a nested pharmaco-epidemiological case-control study to investigate COCP use in relation to dysglycemia risk (2407 women with PCOS with [=cases] and without [=controls] a diagnosis of dysglycemia during follow-up).&lt;b&gt; &lt;/b&gt;Cox models were used to estimate the unadjusted and adjusted hazard ratio and conditional logistic regression was used to obtain adjusted odds ratios (aORs). &lt;/p&gt; &lt;p&gt;&lt;b&gt;Results: &lt;/b&gt;The adjusted hazard ratio for dysglycemia in women with PCOS was 1.87 (95% CI 1.78-1.97, p&lt;0.001; adjustment for age, social deprivation, BMI, ethnicity, and smoking), with increased rates of dysglycemia in all BMI subgroups. Women with PCOS and COCP use had a reduced dysglycemia risk (aOR 0.72, 95% CI 0.59 to 0.87).&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions: &lt;/b&gt;In this study limited by its retrospective nature and the use of routinely collected electronic general practice record data, which does not allow to exclude the impact of prescription-by-indication bias, women&lt;b&gt; &lt;/b&gt;with PCOS exposed to COCPs had a reduced risk of dysglycemia across all BMI subgroups. Future prospective studies should be considered to further understand these observations and potential causality. &lt;/p&gt;

Lifestyle modification is the primary treatment for overweight and obese women with polycystic ovarian syndrome (PCOS). Developing mobile applications that motivate and provide lifestyle modification advice and evidence-based information for women with PCOS is needed. This study is aimed at the development of an integrated mobile application for lifestyle modifications in women with PCOS. This study is a development study to develop a lifestyle modification mobile application for PCOS based on a systematic review and needs analysis according to the ADDIE model. The survey was conducted consecutively on patients with PCOS who visited a university hospital in Incheon, Republic of Korea from 1November 2020 to 28 February 2021. The questionnaire was developed based on prior literature, and validity was evaluated by experts. The survey investigated respondents' general characteristics, the perceptions and needs, and the preferred components of integrated mobile application for lifestyle modification. The usability of the application was evaluated by experts. STROBE statement has been followed in this study. The lifestyle modification programme was confirmed to be clinical effect through a systematic review. The necessity application and high scores in preference of all components was confirmed in a survey. The mobile application included every amount of intake, exercise time, menstrual period, and daily weight compared with the target weight and BMI. It also included questionnaires on hirsutism and acne, disease information, and communication with the researcher for counselling purposes. The application will motivate users to participate by giving scores according to a goal achievement each day. In usability test, experts evaluate this mobile application as suitable for use. In this study, an integrated mobile application was developed in consideration of the systematic review and needs analysis of women with PCOS. The effectiveness of the application will need to be verified through further research. This study developed an integrated mobile application including diet and exercise therapy, as well as weight and menstrual period management, questionnaires and disease information. In addition, the mobile application motivates women with PCOS to provide personalised counselling and achieve goals. We expect to use it in future studies for women with PCOS in clinical practice.

Purpose: To investigate if there is an effect of combined oral contraceptive (COC) use on serum 25-hydroxy vitamin D [25(OH)D] levels in patients with polycystic ovary syndrome (PCOS).Methods: PCOS was defined by the 2003 Rotterdam criteria. All patients with PCOS were treated with a COC containing 0.035 mg ethinylestradiol and 2 mg cyproterone acetate for 6 months. Serum 25(OH)D levels, HOMA–IR, ovarian volume and antral follicule count were measured before and after the treatment.Results: The median 25(OH)D levels were 9.40 (range 4.40–24.50) μg/l and 7.00 (5.00–13.50) μg/l before and after COC use, respectively. Serum 25(OH)D levels decreased after the treatment; however, the difference was not statistically significant (p = 0.055).Conclusion: This study seems to be the first prospective trial revealing the effect of COC use on serum 25(OH)D levels in women with PCOS. Although the decrease in serum 25(OH)D levels in patients with PCOS with the use of COC alone, did not reach to statistically significance level after 6 months treatment with COC.

Polycystic ovary syndrome (PCOS) is a complex of endocrine disease with several phenotypes, which determines the difficulties in its diagnostics (“diagnosis of exceptions”). This is an interdisciplinary disease, as the consequences of this syndrome can be serious (infertility, cardiovascular diseases, diabetes mellitus and their complications). The reason for this is the fact that PCOS occurs with metabolic disorders, manifested as violations of carbohydrate and fat metabolism.Determination of specific phenotypes of women with PCOS are justified from the point of metabolism. Metabolic disorders in PCOS can prevail throughout life. At the initial stages, these changes may be invisible and not diagnosed. PCOS is often characterized by the presence of insulin resistance and is associated with hyperinsulinemia in most obese patients.PCOS can occur with various forms of obesity, the most important is visceral obesity. This connected with the fact that visceral obesity may present in women with PCOS with no elevated body mass index. Therefore, timely diagnostics of obesity, especially visceral, determines the health consequences of this syndrome.There are certain difficulties in the diagnostics of visceral obesity, but many of them are surmountable in modern conditions. Women with PCOS need the use combined oral contraceptives with both contraceptive and curative purposes. Therefore, the choice of the medicine depending on the clinical situation, the peculiarities of redistribution of adipose tissue is important in clinical practice. With the correct choice of COC, there will be no significant adverse effects on the metabolic profile of patients with PCOS and, possibly, a positive effect on their lipid profile will be observed. And yet, weight loss can lead to spontaneous ovulation in women with PCOS and overweight or obese, so the first choice in treatment of such patients should be diet and lifestyle changes, including an increase of daily physical activity.