Gustavo Mafaldo Soares

Increased arterial stiffness in nonobese women with polycystic ovary syndrome (PCOS) without comorbidities: one more characteristic inherent to the syndrome?

Background  Polycystic ovary syndrome (PCOS) is associated with adverse metabolic effects. Some cardiovascular disease (CVD) risk markers are increased in women with PCOS. However, early markers of atherosclerosis are also associated with obesity and insulin resistance, which are related to PCOS. These markers may result either directly from PCOS or indirectly as a consequence of the comorbidities associated with the syndrome.

Both a combined oral contraceptive and depot medroxyprogesterone acetate impair endothelial function in young women.

BACKGROUND The study was conducted to determine whether the use of a combined oral contraceptive (COC) or depot medroxyprogesterone acetate (DMPA) interferes with endothelial function. STUDY DESIGN The study was conducted on 100 women between the ages of 18 and 30 years. Fifty women had not used hormonal contraception (control group) for at least 12 months, 25 were current users of a COC (ethinylestradiol 30 mcg+levonorgestrel 150 mcg) and 25 were current users of DMPA (150 mg) for at least a 6-month period. All women were evaluated for brachial flow-mediated dilation (FMD), intima-media thickness, carotid distensibility and stiffness index, arterial pressure, body mass index, waist circumference, heart rate and lipid profile. RESULTS A significant difference in FMD was observed between the COC and control groups (6.4+/-2.2% vs. 8.7+/-3.4%, p<.01) and between the DMPA and control groups (6.2+/-2.1% vs. 8.7+/-3.4%, p<.01). The DMPA group had lower values of total cholesterol (TC) and low-density lipoprotein (LDL-C) than COC users and the control group (TC: DMPA=139.9+/-21.5 mg/dL vs. controls=167.1+/-29.2 mg/dL vs. COC=168.2+/-37.5, p=.001; LDL-C: DMPA=85.3+/-20.1 mg/dL vs. controls=102+/-24.5 mg/dL vs. COC=106.7+/-33.3 mg/dL, p=.01). The control group had higher levels of high-density lipoprotein (HDL-C) than the DMPA and COC groups (controls=52.4+/-14.1 mg/dL vs. DMPA=42.2+/-7.2 mg/dL vs. COC=45.4+/-9.1 mg/dL, p=.001). No significant differences were observed regarding the other variables. CONCLUSIONS FMD was lower among COC and DMPA users, suggesting that these hormonal contraceptives may promote endothelial dysfunction.

Metabolic and cardiovascular impact of oral contraceptives in polycystic ovary syndrome

Chronic anovulation, polycystic ovarian morphology and hyperandrogenism are the diagnostic criteria for polycystic ovary syndrome (PCOS). Metabolic disturbances are more common in PCOS women who are prone to develop metabolic syndrome and to present higher levels of some cardiovascular disease risk marker. Oral contraceptives are widely used in PCOS, but conflicting data have been reported regarding their impact on carbohydrate and lipid metabolism on PCOS women. This paper presents a critical evaluation of combined oral contraceptives (COCs) metabolic effect – carbohydrate metabolism and insulin sensitivity, lipid metabolism, haemostasis, body weight, arterial pressure and cardiovascular impact – on PCOS women. Because of the paucity of data on the impact of COCs on cardiovascular and metabolic parameters in PCOS patients, most of there commendations are based on studies involving ovulatory women. The use of low‐dose COCs is preferable in PCOS, especially among patients with glucose intolerance, insulin resistance and uncomplicated diabetes mellitus. Although reported as a side effect of COCs, marked weight gain has not been confirmed among users. However, when arterial hypertension or elevated risk for thromboembolism is present, progestogen‐only hormonal contraceptives should be used instead of COCs. Regarding dyslipidaemia, COCs reduce low‐density lipoprotein and total cholesterol and elevate high‐density lipoprotein and triglycerides, and therefore are not recommended for women with high triglycerides levels. The choice of a COC, which alleviates the PCOS‐induced hyperandrogenism without significant negative impact on cardiovascular risk, is one of the greatest challenges faced by gynaecologists nowadays.

Resistência à insulina em mulheres com síndrome dos ovários policísticos modifica fatores de risco cardiovascular

PURPOSE: to evaluate whether the presence of insulin resistance (IR) alters cardiovascular risk factors in women with polycystic ovary syndrome (POS). METHODS: transversal study where 60 POS women with ages from 18 to 35 years old, with no hormone intake, were evaluated. IR was assessed through the quantitative insulin sensitivity check index (QUICKI) and defined as QUICKI <0.33. The following variables have been compared between the groups with or without IR: anthropometric (weight, height, waist circumference, arterial blood pressure, cardiac frequency), laboratorial (homocysteine, interleucines-6, factor of tumoral-α necrosis, testosterone, fraction of free androgen, total cholesterol and fractions, triglycerides, C reactive protein, insulin, glucose), and ultrasonographical (distensibility and carotid intima-media thickness, dilation mediated by the brachial artery flux). RESULTS: Eighteen women (30%) presented IR and showed significant differences in the following anthropometric markers, as compared to the women without IR (POS with and without IR respectively): body mass index (35.56±5.69 kg/m2 versus 23.90±4.88 kg/m2, p<0.01), waist (108.17±11.53 versus 79.54±11.12 cm, p<0.01), systolic blood pressure (128.00±10.80 mmHg versus 114.07±8.97 mmHg, p<0.01), diastolic blood pressure (83.67±9.63 mmHg versus 77.07±7.59 mmHg, p=0.01). It has also been observed significant differences in the following laboratorial markers: triglycerides (120.00±56.53 mg/dL versus 77.79±53.46 mg/dL, p=0.01), HDL (43.06±6.30 mg/dL versus 40.45±10.82 mg/dL, p=0.01), reactive C protein (7.98±10.54 mg/L versus 2.61±3.21 mg/L, p<0.01), insulin (28.01±18.18 µU/mL versus 5.38±2.48 µU/mL, p<0.01), glucose (93.56±10.00 mg/dL versus 87.52±8.75 mg/dL, p=0.02). Additionally, two out of the three ultrasonographical markers of cardiovascular risk were also different between the groups: carotid distensibility (0.24±0.05 mmHg-1 versus 0.30±0.08 mmHg-1, p<0.01) and carotid intima-media thickness (0.52±0.08 mm versus 0.43±0.09, p<0.01). Besides, the metabolic syndrome ratio was higher in women with IR (nine cases=50% versus three cases=7.1%, p<0.01). CONCLUSIONS: POS and IR women present significant differences in several ultrasonographical, seric and anthropometric markers, which point out to higher cardiovascular risk, as compared to women without POS and IR. In face of that, the systematic IR evaluation in POS women may help to identify patients with cardiovascular risk.

The effects of 2 mg chlormadinone acetate/30 mcg ethinylestradiol, alone or combined with spironolactone, on cardiovascular risk markers in women with polycystic ovary syndrome

BACKGROUND Polycystic ovary syndrome (PCOS) is an endocrine disorder associated with metabolic dysfunction and changes in cardiovascular risk markers, and using oral contraceptives (OCs) may exert a further negative effect on these alterations in patients with PCOS. Thus, the primary objective of this study was to assess the effects on arterial function and structure of an OC containing chlormadinone acetate (2 mg) and ethinylestradiol (30 mcg), alone or combined with spironolactone (OC+SPL), in patients with PCOS. STUDY DESIGN This was a randomized, controlled clinical trial. Fifty women with PCOS between 18 and 35 years of age were randomized by a computer program to use OC or OC+SPL. Brachial artery flow-mediated vasodilation, carotid intima-media thickness and the carotid artery stiffness index were evaluated at baseline and after 6 and 12 months. Serum markers for cardiovascular disease were also analyzed. The intragroup data were analyzed using analysis of variance with Tukeys post hoc test. A multivariate linear regression model was used to analyze the intergroup data. RESULTS At 12 months, the increase in mean total cholesterol levels was greater in the OC+SPL group than in the OC group (27% vs. 13%, respectively; p=.02). The increase in mean sex hormone-binding globulin levels was greater in the OC group than in the OC+SPL group (424% vs. 364%, respectively; p=.01). No statistically significant differences between the groups were found for any of the other variables. CONCLUSION The addition of spironolactone to an OC containing chlormadinone acetate and ethinylestradiol conferred no cardiovascular risk-marker advantages in young women with PCOS.

Obesidade e alteração da estrutura arterial em mulheres jovens com síndrome dos ovários micropolicísticos

PURPOSE to compare echographical cardiovascular risk factors between obese and non-obese patients with micropolycystic ovarian syndrome (MPOS). METHODS in this transversal study, 30 obese (Body Mass Index, BMI>30 kg/m(2)) and 60 non-obese (BMI<30 kg/m(2)) MPOS patients, aging between 18 and 35 years old, were included. The following variables were measured: flow-mediated dilatation (FMD) of the brachial artery, thickness of the intima-media of the carotid artery (IMT), anthropometric data, systolic arterial pressure (SAP) and diastolic arterial pressure (DAP). The women had no previous medical treatment and no comorbidity besides MPOS and obesity. For statistical analysis, the non-paired tand Mann-Whitneys tests were used. RESULTS obese weighted more than non-obese patients (92.1+/-11.7 kg versus 61.4+/-10.7 kg, p<0.0001) and had a larger waist circumference (105.0+/-10.4 cm versus 78.5+/-9.8 cm, p<0.0001). The SBP of obese patients was higher than that of the non-obese ones (126.1+/-10.9 mmHg versus 115.8+/-9.0 mmHg, p<0.0001) and the IMT was also bigger (0.51+/-0.07 mm versus 0.44+/-0.09 mm, p<0.0001). There was no significant difference between the groups as to FMD and carotid rigidity index (beta). CONCLUSIONS obesity in young women with MPOS is associated with higher blood pressure and alteration of arterial structure, represented by a thicker intima-media of the carotid artery.

Oral Contraceptive Containing Chlormadinone Acetate and Ethinylestradiol Reduces Plasma Concentrations of Matrix Metalloproteinase‐2 in Women with Polycystic Ovary Syndrome

Biochemical markers of cardiovascular disease, including matrix metalloproteinases (MMPs), are altered in women with polycystic ovary syndrome (PCOS), with many of these alterations thought to be due to excess androgen concentrations. Despite oral contraceptives (OCs) being the first‐line pharmacological treatment in women with PCOS and the importance of MMPs in many physiological conditions and pathological states, including cardiovascular diseases, no study has yet evaluated whether OCs alter plasma concentrations of MMPs. We therefore assessed whether treatment with an OC containing the anti‐androgenic progestogen alters MMP profiles in women with PCOS. We analysed 20 women with PCOS who wanted hormonal contraception (OC‐PCOS group), 20 ovulatory women who required hormonal contraception (OC‐control group) and 20 ovulatory women who wanted non‐hormonal contraception (non‐OC‐control group). OC consisted of cyclic use of 2 mg chlormadinone acetate/30 μg ethinylestradiol for 6 months. Plasma concentrations of MMP‐2, MMP‐9, TIMP‐1 and TIMP‐2 were measured by gelatin zymography or enzyme‐linked immunoassays. OC treatment for 6 months significantly reduced plasma MMP‐2 concentrations in the OC‐control and OC‐PCOS groups and TIMP‐2 and TIMP‐1 concentrations levels in the OC‐control group (all p < 0.05), but had no effects on MMP‐9 concentrations or on MMP‐2/TIMP‐2 and MMP‐9/TIMP‐1 ratios in any group (all p > 0.05). These findings indicated that long‐term treatment with an OC containing chlormadinone acetate plus ethinylestradiol reduced plasma MMP‐2 concentrations in both healthy and PCOS women. As the latter have imbalances in circulating matrix MMPs, treatment of these women with an OC may be beneficial.

Exercise and reproductive function in polycystic ovary syndrome: protocol of a systematic review

BackgroundAlthough many post-participation outcomes in different types of physical training (e.g., aerobic and strength) have been previously investigated for the treatment of polycystic ovary syndrome, there is no recent systematic review of the relationship between various types of intervention and the reproductive function of women with PCOS. The current paper describes a systematic review protocol on the benefits of physical exercise and dietary or drug interventions on endocrinological outcomes in women with PCOS.MethodsPubMed/MEDLINE, Science Direct, Bireme, Scopus, Web of Science, ProQuest, Cochrane Library (Cochrane Systematic Reviews Database, Cochrane Central Register of Controlled Studies (CENTRAL) databases will be searched. Studies randomized controlled trials reporting on intervening changes in exercise interventions with or without interventions compared such as diet, medication and acupuncture on the menstrual cycle, and fertility in women with PCOS will be included. Results will be on the decrease of the characteristics of hyperandrogenism, insulin resistance, and obesity. Studies published since 2010 and in the English language will be included.DiscussionThis systematic review will identify improvement strategies and types of interventions that are geared toward improving endocrine and consequently metabolic parameters. Thus, the use of such strategies may increase the types of low-cost non-drug therapies that aid in the treatment of PCOS.Systematic review registrationPROSPERO CRD42017058869