Carolina Sales Vieira

Safety of the etonogestrel-releasing implant during the immediate postpartum period: a pilot study.

BACKGROUND The effects of etonogestrel (ETG)-releasing contraceptive implant during the immediate postpartum period on maternal safety are unknown. STUDY DESIGN Forty healthy women exclusively breastfeeding were randomized to receive either ETG-releasing implant 24-48 h after delivery (n=20) or depot medroxyprogesterone acetate (DMPA group; n=20) at the sixth week postpartum. We measured blood pressure, maternal and neonatal weight, body mass index (BMI; kg/m(2)), waist circumference (WC), complete blood count, C-reactive protein, interleukin-6, tumor necrosis factor (TNF-alpha), lipid profile, fasting serum glucose and maintenance of exclusive lactation up to the 12th week postpartum. RESULTS Decreases in mean maternal weight, BMI (kg/m(2)) and WC were significantly greater in the ETG-releasing implant group than in the DMPA group during the first 6 weeks postpartum (-4.64+/-2.71 kg vs. -2.6+/-2.45 kg mean+/-SD, p=.017; -1.77+/-1.06 kg/m(2) vs. -0.97+/-0.95 kg/m(2), p=.026; -15.3+/-6.72 cm vs. -9.05+/-5.84 cm, p=.003, respectively). In addition, total cholesterol and HDL, were lower in DMPA users, and TNF-alpha and leukocytes were higher in DMPA users compared to in the implant group, between 6 and 12 weeks after delivery. The newborns of implant users showed a trend towards gaining more weight, as compared with the infants of the DMPA mothers during the first 6 weeks of life (implant group: +1460.50+/-621.34 g vs. DMPA group: +1035.0+/-562.43 g, p=.05). The remaining variables, including the duration of exclusive breastfeeding, were similar between the groups. CONCLUSION The insertion of ETG-releasing contraceptive implant during the immediate postpartum period was not associated with deleterious maternal clinical effects or with significant maternal metabolic alterations or decreased infant weight gain.

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.

High prevalence of polycystic ovary syndrome in women born small for gestational age

BACKGROUND There is evidence that intrauterine growth restriction, resulting in newborn girls that are small for gestational age (SGA), may be related to the onset of polycystic ovary syndrome (PCOS). Thus, we studied whether women born SGA have a higher prevalence of PCOS than women born appropriate for gestational age (AGA). METHODS This was a prospective birth cohort study of 384 women born at term between June 1, 1978, and May 31, 1979, in Ribeirão Preto, Brazil. After exclusion, 165 women effectively participated in this study, of whom 43 were SGA and 122 were AGA. The prevalence of PCOS was analysed. At a mean age of 29 years, the women agreed to follow the study protocol, which included: anamnesis, physical examination, serum tests [follicle stimulating hormone, luteinizing hormone, total and free testosterone, dehydroepiandrostenedione sulphate, 17-OH-progesterone, fasting insulin, sex steroid-binding globulin (SHBG) and fasting glucose] and pelvic ultrasound. Data regarding gestational age, birthweight, age at menarche and maternal data were obtained from the files of the cohort. The adjusted relative risk (RR) values of the SGA, insulin resistance, body mass index, maternal smoking and parity variables were analysed using Poisson regression with robust adjustment of variance for the prediction of PCOS. RESULTS The prevalence of PCOS was higher in the SGA group than in the AGA group [adjusted RR = 2.44, 95% CI (1.39-4.28)]. Hyperandrogenism was more prevalent in the SGA women than in the AGA women (P = 0.011). Circulating SHBG was lower in the SGA women than in the AGA women (P = 0.041), but fasting insulinemia was similar in both groups. CONCLUSIONS The prevalence of PCOS in SGA women was twice as high as in AGA women in our study population.

Effects of the levonorgestrel-releasing intrauterine system on cell proliferation, Fas expression and steroid receptors in endometriosis lesions and normal endometrium

BACKGROUND The objectives of this study were: (i) to evaluate the effects of the levonorgestrel-releasing intrauterine system (LNG-IUS) on both proliferation and apoptosis markers and hormone receptors of the eutopic and ectopic endometrium of women experiencing pain related to endometriosis and (ii) to compare the results with those obtained with GnRH agonist (GnRHa) injections. METHODS Pre- and post-treatment endometrium and endometriosis specimens were obtained from 22 women experiencing pain related to endometriosis who were treated with LNG-IUS (n = 11) or GnRHa (n = 11) for 6 months. Changes in the expression of proliferating cell nuclear antigen, Fas, progesterone receptor (PRA) and estrogen receptor alpha (ER-alpha) were analyzed by immunohistochemistry. RESULTS The cell proliferation index was significantly reduced in the epithelium and stroma of both the eutopic and the ectopic endometrium after treatment with the LNG-IUS and GnRHa. Only LNG-IUS users showed an increased H-score for Fas in the epithelium of the eutopic and ectopic endometrium (P < 0.05). Expression of ER-alpha and PRA by the glandular epithelium was lower in the eutopic endometrium after both treatments, but this reduction was noted in the ectopic endometrium only after LNG-IUS treatments (P < 0.05). No difference was detected between groups for any of the markers. CONCLUSIONS LNG-IUS reduced both cell proliferation and the expression of PRA and ER-alpha and increased Fas expression in the eutopic and ectopic endometrium of patients with endometriosis. Some of these actions were not observed with GnRHa.

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.

Effects of the levonorgestrel-releasing intrauterine system on cardiovascular risk markers in patients with endometriosis: a comparative study with the GnRH analogue.

BACKGROUND The study was conducted to evaluate the cardiovascular risk markers associated with endometriosis and the influence of the levonorgestrel intrauterine system (LNG-IUS) compared with the GnRH analogue (GnRHa) leuprolide acetate on these risk markers after 6 months of treatment. STUDY DESIGN This was a randomized, prospective, open clinical study, with 44 patients with laparoscopically and histologically confirmed endometriosis. Patients were randomized into two groups: the LNG-IUS group, composed of 22 patients who underwent LNG-IUS insertion, and the GnRHa group, composed of 22 patients who received a monthly GnRHa injection for 6 months. Body mass index; systolic and diastolic arterial blood pressure; heart rate; and laboratory cardiovascular risk markers such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), C-reactive protein (CRP), homocysteine (HMC), lipid profile, total leukocytes and vascular cell adhesion molecule (VCAM) were measured before and 6 months after treatment. RESULTS After 6 months of treatment, a significant reduction in pain score occurred in both groups with no significant difference in improvement between the two medications evaluated. In the LNG-IUS group, from pretreatment to posttreatment period, there was a significant reduction in the levels (mean+/-SD) of VCAM (92.8+/-4.2 to 91.2+/-2.7 ng/mL, p=.04), CRP (0.38+/-0.30 to 0.28+/-0.21 mg/dL, p=.03), total cholesterol (247.0+/-85.0 to 180.0+/-31.0 mg/dL, p=.0002), triglycerides (118.0+/- 76.0 to 86.5+/-41.5 mg/dL, p=.003), low-density lipoprotein cholesterol (160.5+/-66.0 to 114.5+/-25.5 mg/dL, p=.0005) and high-density lipoprotein cholesterol (63.0+/-20.5 to 48.5+/-10.5 mg/dL, p=.002). The GnRHa group showed an increase in HMC levels (11.5+/-2.9 to 13.0+/-2.7 mumol/L, p=.04) and a reduction in IL-6 levels (4.3+/-3.9 to 2.3+/-0.8 pg/mL, p=.005), VCAM (94.0+/-3.8 to 92.0+/-1.6 ng/mL, p=.03) and total leukocytes (7330+/-2554 to 6350+/-1778, p=.01). In the GnRH group, the remaining variables, including lipid profile, did not show any statistical difference. CONCLUSIONS This study shows that some cardiovascular risk markers are influenced by both GnRHa and the LNG-IUS, but the latter had a greater positive impact on the lipid profile, which could lead to a favorable effect during long-term treatment.

Unfavorable lipid profile in women with endometriosis

Similar to dyslipidemia, the oxidative stress and intrinsic inflammatory status may be associated with the development of endometriosis. Thus, we performed a cross-sectional study and found that women with endometriosis had an increased low-density lipoprotein (LDL) and non-high-density lipoprotein (HDL) cholesterol levels compared with controls presumably without endometriosis.

Effect of antiretroviral therapy including lopinavir/ritonavir or efavirenz on etonogestrel-releasing implant pharmacokinetics in HIV-positive women.

Objective:Data on the interaction between the etonogestrel (ENG) implant and antiretroviral therapy are lacking. We evaluated the effect of 2 highly active antiretroviral therapy (HAART) regimens (1 including efavirenz and the other ritonavir-boosted lopinavir) on the pharmacokinetic (PK) parameters of an ENG-releasing implant in HIV-positive women. Design:Prospective nonrandomized PK study. Methods:Forty-five HIV-positive women who desired to use ENG implants were included: 15 had received zidovudine/lamivudine + lopinavir/ritonavir for ≥3 months (LPV/r-based HAART group), 15 had received zidovudine/lamivudine + efavirenz for ≥3 months (EFV-based HAART group), and 15 had not received HAART (non-HAART group). PK parameters were measured using ultra-performance liquid chromatography–mass spectrometry at baseline and 2, 4, 6, 8, 10, 12, 16, 20, and 24 weeks after implant placement. Results:The EFV-based HAART regimen was associated with a reduction in the bioavailability of ENG, which showed decreases of 63.4%, 53.7%, and 70% in the area under the curve (AUC), maximum concentration (Cmax), and minimum concentration (Cmin) of ENG, respectively, compared with the non-HAART group. The LPV/r-based HAART regimen was associated with an increase in ENG bioavailability, which showed 52%, 60.6%, and 33.8% increases in the ENG AUC, Cmax, and Cmin, respectively, compared with the non-HAART group. Conclusions:The coadministration of EFV decreased the bioavailability of ENG released from the implant, which could impair contraceptive efficacy. However, the coadministration of LPV/r increased the bioavailability of ENG released from the implant, which suggests that this antiretroviral combination does not impair the ENG implant efficacy.

Ultrasonographic and laboratory markers of metabolic and cardiovascular disease risk in obese women with polycystic ovary syndrome

To evaluate whether the presence of polycystic ovary syndrome (PCOS) alters multiple ultrasonographic and laboratory markers of metabolic and cardiovascular disease risk in obese women without any other health condition that could interfere with combined oral contraceptive (COC) eligibility criteria.

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.