Impaired cardiopulmonary parameters in young women with polycystic ovary syndrome.
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Publications and source records attributed to Stefano Palomba.
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OBJECTIVE: To evaluate the effects of metformin and of clomiphene citrate (CC) on the ovarian blood perfusion and on perifollicular and peri-corpus luteum (CL) vascularity in anovulatory women with polycystic ovary syndrome (PCOS). DESIGN: Prospective cohort study. SETTING: University "Magna Graecia" of Catanzaro. PATIENT(S): Forty anovulatory nonobese patients with PCOS who ovulated under treatment with metformin (850 mg twice daily) plus placebo (metformin group) and 38 under placebo plus CC (150 mg for 5 days; CC group). Another 30 healthy normal cycled women (control group). INTERVENTION(S): Serial transvaginal ultrasonographic examinations. MAIN OUTCOME MEASURE(S): Ovary artery blood flow impedance, dimensions, and vascularization of the dominant follicle and of the CL. RESULT(S): No difference was observed in all parameters in metformin ovulating cycles in comparison with healthy controls. In CC ovulating cycles, ovarian artery impedance, and perifollicular and peri-CL vascularization the results were significantly different from the metformin and control groups. After grouping the stimulated cycles for reproductive outcomes, perifollicular vascularization alone ended up being significantly lower only in CC-stimulated cycles with unfavorable outcome. CONCLUSION(S): In patients with PCOS who ovulate under treatment with metformin, the ovarian blood flows are similar to those observed in healthy women, whereas CC administration reduces the ovarian and, specifically, the perifollicular vascularization.
CONTEXT: Polycystic ovary syndrome (PCOS) is associated with early impairment of vascular structure and a low-grade chronic inflammation. Aldosterone is a well-recognized cardiovascular risk (CVR) factor and is related to inflammatory processes. OBJECTIVE: Our objective was to investigate serum aldosterone levels in PCOS and correlate them to some CVR factors and early atherosclerotic markers. DESIGN AND SETTING: A prospective baseline-controlled clinical study was conducted at the University "Federico II" of Naples School of Medicine (Naples, Italy). PATIENTS: Fifty PCOS women age- and body mass index-matched with 50 healthy women were enrolled. MEAN OUTCOME MEASURES: Anthropometric, hormonal, and metabolic patterns, including plasma aldosterone, renin, and C-reactive protein, were measured in each subject. Intima-media thickness was also evaluated in each patient and control. RESULTS: Aldosterone levels were significantly increased (P < 0.001) in PCOS compared with healthy women (10.5 +/- 3.2 vs. 5.7 +/- 2.5 ng/dl). In PCOS, a significant (P < 0.001) direct correlation between plasma aldosterone and homeostasis model assessment, C-reactive protein, intima-media thickness, and mean blood pressure was found. On the other hand, high-density lipoprotein cholesterol and potassium were inversely (P < 0.001) related to serum aldosterone. Multiple linear regression analysis showed that the area under the curve for insulin and homeostasis model assessment was linearly related to aldosterone in PCOS. CONCLUSION: PCOS women show an insulin resistance related increase in serum aldosterone levels.
BACKGROUND: Previous data on the efficacy of clomiphene citrate, the most commonly used drug for treating anovulatory infertility in patients with polycystic ovary syndrome (PCOS), have shown a discrepancy between ovulation and pregnancy rates. In the present subanalysis (of a larger previously published randomized controlled trial), the effect of clomiphene citrate on several ultrasonographic markers of uterine receptivity in PCOS patients who ovulated under treatment was studied. METHODS: Thirty-three PCOS women who ovulated under 150 mg daily clomiphene citrate and 33 healthy controls were studied. Uterine, subendometrial and endometrial blood flows, endometrial thickness and pattern were assessed using serial ultrasonographic assessments. The data were analysed before and after grouping the clomiphene citrate-stimulated ovulatory cycles for reproductive outcome [unfavourable (ovulation alone or early pregnancy loss) or favourable outcome (clinical pregnancy and/or live birth)]. RESULTS: Both before and during treatment, uterine vascularity assessed at all sites was significantly lower in the PCOS group than in controls. Endometrial thickness and pattern were impaired in the PCOS group under clomiphene citrate treatment. A significant difference in all ultrasonographic parameters was observed between cycles ending in unfavourable versus those ended in favourable outcome. CONCLUSIONS: Clomiphene citrate administration alters several surrogate ultrasonographic parameters of uterine receptivity, and this effect could be crucial for its efficacy.
CONTEXT: Insulin resistance is a feature of polycystic ovary syndrome (PCOS), and it is related to mitochondrial function, particularly with maximal oxygen consumption (VO(2max)). At the moment, no evaluation of cardiopulmonary functional capacity in young patients with PCOS has been performed. OBJECTIVE: Our objective was to assess cardiopulmonary functional capacity in young PCOS overweight patients. DESIGN AND SETTING: We conducted a prospective baseline-controlled clinical study at University Federico II of Naples, School of Medicine (Naples, Italy). PATIENTS: Forty-five PCOS patients were matched with 45 healthy women for age (mean +/- sd, 21.3 +/- 2.0 vs. 21.6 +/- 1.9 yr, respectively) and body mass index (29.4 +/- 3.6 vs. 29.0 +/- 3.4 kg/m(2), respectively). MEAN OUTCOME MEASURES: We assessed hormonal and metabolic pattern and functional capacity by cardiopulmonary exercise testing to evaluate maximal oxygen consumption (VO(2max)), oxygen consumption at anaerobic threshold (VO(2AT)), and the maximal workload at peak exercise. RESULTS: VO(2max) (17.0 +/- 3.7 vs. 26.8 +/- 3.5 ml/kg.min), oxygen consumption at anaerobic threshold (13.9 +/- 3.0 vs. 21.2 +/- 3.8 ml/kg.min), and maximal workload at peak exercise (101.3 +/- 25.2 vs. 135 +/- 22.6 W) were significantly (P < 0.001) reduced in PCOS subjects compared with healthy women. The multiple linear regression analysis showed that only homeostasis model assessment appears to have a strong negative linear relation with VO(2max) in PCOS. No relation was found in controls. CONCLUSIONS: Our data demonstrate a reduced cardiopulmonary functional capacity in young PCOS patients.
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OBJECTIVE: To assess and compare the laparoscopic uterine nerve ablation (LUNA) and the vaginal uterosacral ligament resection (VUSR) in postmenopausal women with chronic pelvic pain (CPP). STUDY DESIGN: Eighty postmenopausal women with intractable and severe midline CPP were randomized to undergo LUNA or VUSR. Costs of two surgical procedures were assesses. Cure rate, severity of CPP, and deep dyspareunia were also evaluated after 6 and 12 months from surgery. RESULTS: The mean cost of LUNA resulted significantly higher in comparison with VURS (2078+/-637 versus 1497+/-297, P<0.001). The cure rate was not significantly different between the two groups at 6 (33/40, 82.5% versus 35/40, 87.5% for groups A and B, respectively; P=0.530; RR 0.94, 95% CI 0.78-1.13), and 12 months (27/36, 75.0% versus 28/38, 73.7%, for groups A and B, respectively; P=0.901; RR 0.90, 95% CI 0.78-1.33) of follow-up. At same times, a significant (P<0.01) decrease in severity of CPP and deep dyspareunia was observed in both groups with no difference between them. CONCLUSIONS: Both LUNA and VUSR are equally effective surgical treatments in postmenopausal women with central CPP but VUNR is significantly cheaper than LUNA.
OBJECTIVE: To report the effect of metformin treatment on a patient with recurrent miscarriage (RM) and polycystic ovary syndrome (PCOS). DESIGN: Case report. SETTING: University department of obstetrics and gynecology, Italy. PATIENT(S): A woman complaining of RM who had PCOS and insulin resistance. INTERVENTION(S): Clinical, biochemical, and instrumental assessments. MAIN OUTCOME MEASURE(S): Administration of metformin hydrochloride before and throughout pregnancy. RESULT(S): After 3 months of treatment, the patient became pregnant. The pregnancy had a physiologic development, and at 39 weeks of gestation, the patient spontaneously delivered a healthy infant. CONCLUSION(S): Metformin has shown to be effective in an insulin-resistant PCOS woman with RM.
Polycystic ovary syndrome (PCOS) is not only a reproductive problem but a complex, endocrine, multifaceted disease with several health complications. Cardiovascular abnormalities represent important long-term sequelae of PCOS.
To date, clomiphene citrate (CC) remains the first therapeutical step for inducing ovulation in anovulatory PCOS patients. Metformin alone or combined with CC is a valid second step approach, whereas the laparoscopic ovarian diathermy can be useful only in selected cases.
BACKGROUND: Laparoscopic ovarian diathermy (LOD) has been used successfully as a first-, second- and third-line treatment for ovulation induction in women with polycystic ovary syndrome (PCOS). However, little is known about the predictors for LOD efficacy. The aim of the present study was to evaluate reproductive outcomes in clomiphene citrate (CC)-resistant PCOS patients treated with LOD according to ovarian and chronological age. METHOD: A total of 60 non-obese, primary infertile, CC-resistant women with PCOS were enrolled and treated with LOD. During the following 6 months, all patients underwent ovulation monitoring and timed intercourse. If spontaneous ovulation did not occur within 3 months from surgery, CC (100 mg/day) was administered for 5 days from day 3 of the remaining cycles. The ovulation, abortion and pregnancy rates were assessed and analyzed with patients categorized according to chronological age (group A, <25 years; group B, 25-30 years; group C, 30-35 years; group D, >35 years) and ovarian age (group 1, follicle stimulating hormone (FSH) < 10 mIU/ml; group 2, FSH > 10 mIU/ml). RESULTS: At the end of the study, total ovulation, pregnancy and abortion rates were 57.1, 13.0 and 18.2%, respectively. No difference in all reproductive outcomes was observed between groups A, B and C, whereas the efficacy of LOD was significantly lower in group D. A significant difference in all clinical endpoints was detected between groups 1 and 2. CONCLUSIONS: Our data show that chronological age >35 years and basal FSH value > 10 mIU/ml are related to poor reproductive prognosis in CC-resistant PCOS patients treated with LOD.
In the past and currently, there are several applications of oral contraceptives (OCs) in the field of infertility. The aim of the present descriptive review is to analyze the old and new uses of OCs in infertile patients undergoing simple or multiple ovulation-induction programs. Available data seem to indicate that OCs given before treatment could be effective in patients who are resistant to clomiphene citrate and in poor responders. In addition, the use of OCs is useful for scheduling in vitro fertilization programs downregulated with gonadotropin-releasing hormone-antagonists.
Polycystic ovary syndrome (PCOS) is a good example of obesity-related cardiovascular complication affecting young women. PCOS is not only considered a reproductive problem but rather represents a complex endocrine, multifaceted syndrome with important health implications. Several evidences suggest an increased cardiovascular risk of cardiovascular disease associated with this syndrome, characterized by an impairment of heart structure and function, endothelial dysfunction and lipid abnormalities. All these features, probably linked to insulin-resistance, are often present in obese PCOS patients. Cardiovascular abnormalities represent important long-term sequelae of PCOS that need further investigations.
BACKGROUND: In Italy, a recent law has imposed a ban on the fertilization of more than three oocytes at one time, and all resulting embryos produced must be transferred simultaneously. The aim of the present controlled study was to assess the clinical feasibility and efficacy of the perifollicular vascularity assessment for oocyte selection in IVF cycles. METHODS: Fifty-four young primary infertile non-obese women (27 cases and 27 age- and BMI-matched controls) underwent IVF cycles. The choice of the oocytes to fertilize was performed according to perifollicular vascularization in the experimental group, whereas in the control group, the standard morphologic criteria alone were used. The dose of gonadotrophins used, the dominant follicles obtained, the duration of the ovarian stimulation, the number of oocytes retrieved, the number/quality of oocytes fertilized and of cleaved embryos, cycle cancellation, implantation, clinical pregnancy, ongoing pregnancy, multiple pregnancies and ovarian hyperstimulation syndrome rates were assessed in each group. RESULTS: The assessment of perifollicular vascularity was feasible in 88.9% of cases. No difference between groups was detected in any parameter evaluated. CONCLUSION: Power Doppler assessment of perifollicular vascularity seems to have no clinical utility for oocyte selection in IVF cycles for young infertile women.
BACKGROUND: Metformin has been shown to improve fertility in anovulatory patients with polycystic ovary syndrome (PCOS), inducing not only a high ovulation and pregnancy rate but also reducing the incidence of miscarriages. The aim of the present study was to evaluate the uterine effects of metformin in patients with PCOS who ovulated under metformin. METHODS: Thirty-seven non-obese primary infertile anovulatory patients with PCOS and another 30 age- and body mass index-matched healthy women (control group) were studied. PCOS patients were treated with metformin (850 mg twice daily) for 6 months, whereas the control group did not receive any treatment. In these PCOS patients who ovulated whilst under metformin treatment (PCOS group) and in controls, uterine, sub-endometrial and endometrial blood flow, and endometrial thickness and pattern were evaluated using serial ultrasonographic assessments. RESULTS: Before treatment, uterine, sub-endometrial and endometrial blood flows were significantly lower in patients with PCOS than in the control group. All indexes of uterine vascularization were significantly improved in the PCOS group with metformin treatment and were not different from the controls. Nor was any difference in endometrial thickness and pattern detected between PCOS and control groups. After grouping the data of PCOS patients who ovulated under metformin for cycles with favourable/unfavourable reproductive outcome, no difference in any parameter was observed. CONCLUSIONS: Metformin improves all surrogate markers of endometrial receptivity in PCOS patients, without difference between patients who had favourable or unfavourable reproductive outcome.
CONTEXT: Recent data indicate that women affected by the polycystic ovary syndrome (PCOS) are at greater risk for cardiovascular disease and that metformin may improve the metabolic alterations in these patients. OBJECTIVE: The objective of this study was to evaluate the effects of 6 months of metformin administration on endothelial structure and function in women with PCOS. DESIGN: This was a prospective, baseline-controlled, clinical study. SETTING: The study was performed at University Federico II (Naples, Italy). PATIENTS: Thirty young normal-weight women with PCOS without additional metabolic or cardiovascular diseases were studied. INTERVENTIONS: Metformin (850 mg daily) was administered for 6 months. MEAN OUTCOME MEASURES: The main outcome measures were complete hormonal profile, including total testosterone, SHBG, dehydroepiandrosterone sulfate, prolactin, and gonadotropin levels; serum insulin and glucose levels during a 75-g 2-h oral glucose tolerance test; plasma endothelin-1 concentrations (picomoles per liter +/- sd); serum lipid profile; brachial artery baseline diameter (millimeters +/- sd), diameter after reactive hyperemia (millimeters +/- sd), and flow-mediated dilation (percentage +/- sd); and the intima media thickness (millimeters +/- sd) on both common carotid arteries. RESULTS: After treatment, SHBG levels and the free androgen index changed significantly (P < 0.001). High-density lipoproteins and the area under curve for glucose/area under curve for insulin ratio also significantly (P < 0.001) increased, whereas low-density lipoproteins and plasma endothelin-1 levels were significantly (P < 0.001) reduced. No other change was found in any of the biochemical parameters evaluated. A significant difference was observed in brachial artery baseline diameter (3.24 +/- 0.30 vs. 3.0 +/- 0.30), flow-mediated dilation (14.30 +/- 1.90 vs. 15.70 +/- 1.50) (P < 0.01, each), diameter after reactive hyperemia (3.70 +/- 0.30 vs. 3.55 +/- 0.10) (P < 0.05), and intima media thickness (0.53 +/- 0.09 vs. 0.40 +/- 0.07) (P < 0.001) after metformin treatment in comparison with baseline values. CONCLUSIONS: A 6-month course of metformin improves endothelial structure and function in young, normal-weight women with PCOS.
BACKGROUND: There are few data in the literature regarding the utility of metfomin before and during gonadotrophin administration in women with polycystic ovary syndrome (PCOS). The aim of the present study was to assess the effect of the pre-treatment and co-administration of metformin in infertile PCOS women treated with controlled ovarian stimulation (COS) followed by timed intercourse (TI) or intrauterine insemination (IUI). METHODS: Seventy insulin-resistant primary infertile women with PCOS were randomized to receive metformin cloridrate (850 mg twice daily; group A) or placebo tablets (two tablets daily; group B) for 3 months. Three trials of COS using highly purified urinary FSH (hpFSH) plus TI/IUI were performed. Number of ampoules of gonadotrophin used, duration of the ovarian stimulation, cycle cancellation, ovulation, pregnancy, abortion, live birth, mono-ovulatory cycles, multiple pregnancies and ovarian hyperstimulation syndrome (OHSS) rates were assessed. RESULTS: No difference between groups was detected in ovulation, cycle cancellation, pregnancy, abortion, live birth, multiple pregnancies and OHSS rates. The mono-ovulatory cycle rates were significantly (P = 0.002) more frequent in group A than in group B, whereas the days of stimulation for non-cancelled cycles and the number of vials of gonadotrophins used were significantly (P < 0.001) higher in group A than in group B. CONCLUSION: In insulin-resistant women with PCOS, metformin pre-treatment and co-administration with hpFSH increases the mono-ovulatory cycles.
Patients with inflammatory bowel disease (IBD) have frequently a bone mineral density (BMD) significantly lower than age-matched healthy subjects. The low BMD observed in IBD patients is related also to a higher incidence of bone fractures. In this prospective randomized study we evaluated the effect of 1-year risedronate administration on bone mass and turnover, and on vertebral fractures in osteoporotic postmenopausal women with IBD in remission. Ninety osteoporotic postmenopausal women were randomized to receive oral risedronate 35 mg/week (risedronate group) or placebo tablets (placebo group; one tab/week). The duration of treatment was 12 months. At entry and after treatment, lumbar spine and hip BMD, and serum osteocalcin (OC) and urinary deoxypyridinoline/creatinine ratio (DPD-Cr) levels were evaluated. Vertebral fractures were assessed from thoracic and lumbar lateral and anterior-posterior spinal radiographs taken at baseline, and from lateral spinal radiographs taken at the end of the study. At study entry, no difference between groups was also detected in BMD and in bone turnover markers. At the end of the study, lumbar spine, trochanter and femoral neck BMD was significantly ( p <0.05) higher in comparison with baseline in the risedronate group, whereas a significant ( p <0.05) decrease was observed in the placebo group. For the same visit, a significant ( p <0.05) difference in lumbar spine, trochanter and femoral neck BMD was detected between groups. After 12-month follow-up, serum OC and urinary DPD-Cr levels were significantly ( p <0.05) lower and higher in comparison with basal values in risedronate and placebo group, respectively. At the same time, a significant ( p <0.05) difference in serum OC and urinary DPD-Cr levels was observed between groups. Throughout the study, the incidence of vertebral fractures was significantly ( p <0.05) lower in the risedronate group than in the placebo group (12.5% vs 34.1%). The relative risk (RR) to develop a new vertebral fracture after 1 year of risedronate administration was of 0.36 (95% confidence interval, 0.14-0.85). In conclusion, risedronate administration is an effective anti-osteoporotic treatment in osteoporotic postmenopausal women with IBD in remission.