<Emphasis Type="Bold">Reproductive Endocrinology:</Emphasis> Uterine Perfusion and Hormonal Pattern in Patients with Polycystic Ovary Syndrome

Purpose: To evaluate whether polycystic ovary syndrome (PCOS) patients with different pulsatility index (PI) of uterine artery showed differences in their hormonal pattern. Methods: Eighty-eight PCOS-affected patients and 15 controls were submitted to Doppler flow measurement of uterine artery; LH, FSH PRL, estradiol, and androgens concentration determination; and BMI evaluation during early follicular phase. Results: The mean PI of uterine artery of PCOS patients was significantly higher than control group (2.97 ± 0.9 vs. 1.89 ± 0.2 respectively). The distribution of the PI'values was significantly different in the PCOS-affected patients and in control group. The plasma levels of DHEAS and BMI were significantly higher in PCOS patients with PI 3 than in PCOS patients with PI < 3. Conclusion: High resistance in the uterine artery is present in PCOS patients, but a wide range PI values of uterine artery is present. BMI and DHEAS seem to be factors interfering with uterine perfusion.     

The evaluation of blood flow in uterine arteries in girls with polycystic ovary syndrome by transvaginal color Doppler ultrasonography]

OBJECTIVE: The aim of this study was to evaluate of blood flow in uterine arteries in girls with PCOS and to determine whether uterine blood flow variations are associated with endocrine findings typical of PCOS. METHODS: Seventy two girls with clinical, endocrinologic and ultrasonographic features of PCOS (mean age 18.8 +/- 1.3 years) were examined. The control subject consisted of twenty girls with regular, ovulation cycles. None of these girls had received hormonal treatment for at least 6 months before the study. Pelvic ultrasound examination was made in each patient with Acuson 128 XP/10 with the 4/5/7 MHz transvaginal transducer. Examination was performed in early follicular phase. Blood flow was made in each patient in the ascending branches of uterine arteries. Index values pulsatility index (PI) and resistance index (RI) were used for the purpose of better comparison of the data. Associations between values of PI and RI and hormones (testosterone, luteinizing hormone) were examined. RESULTS: No significant differences between PI and RI of the left and right uterine artery was observed. PI in PCOS girls was mean 3.19 +/- 0.52 ranged from 2.1 to 4.3, in control girls PI was mean 2.33 +/- 0.36 ranged from 1.6 to 3.1. The PI was positively correlated (r = 0.435, p < 0.01) with testosterone and PI was positively correlated (r = 0.450, p < 0.001) with LH. The RI in PCOS patients was mean 0.87 +/- 0.04 ranged from 0.74 to 0.93, in control girls 0.72-0.87, mean 0.80 +/- 0.04. The RI was positively correlated (r = 0.466, p < 0.001) with testosterone and RI was positively correlated (r = 0.492, p < 0.001) with LH. CONCLUSIONS: The elevated uterine artery resistance was observed in girls with PCOS.     

Doppler study of the uterine arteries and ovarian stroma in patients with polycystic ovary syndrome

Doppler analysis of the uterine arteries and ovarian stroma was performed by transvaginal ultrasound in 24 patients with polycystic ovary syndrome (PCOS) and 22 ovulatory women. Vascularization of the ovarian stroma was more abundant in patients with PCOS than in control women, but no significant difference in the mean pulsatility index (PI) was observed between groups (1.14 +/- 0.28 for the PCOS group and 1.05 +/- 0.19 for the control group). The mean PI of the uterine arteries was significantly higher in the PCOS group (PI = 3.7 +/- 0.8) than in the control group (PI = 2.9 +/- 0.4). In the patients with PCOS, no correlation was observed between PI and luteinizing hormone, testosterone or androstenedione levels. Obesity had no effect on uterine artery PI, with no significant differences in this index when the 3 groups were subdivided into obese and non-obese groups.     

Significance of Doppler ultrasonography in the diagnosis of polycystic ovary syndrome

OBJECTIVE: To investigate the importance of transvaginal color Doppler ultrasonography of uterine and intraovarian arteries in the clinical diagnosis of polycystic ovary syndrome (PCOS). MATERIAL & METHOD: This study was planned as a cohort, controlled, prospective study. A total of 80 participants (40 with PCOS and 40 as a control group) were enrolled in the study. A Doppler system with a 6.0 MHz transvaginal probe was used when performing ultrasonography (USG) and Doppler examinations. Ovarian size and volume, number of follicles and stromal echogenity were evaluated by USG. Doppler flow studies were targeted to uterine and intraovarian arteries and the pulsatility index (PI) was assessed. The concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), total testosterone (T) and dihydroepiandrostenedione sulphate (DHEAS) were measured by immunometric methods. RESULTS: The mean values of the number of follicles and the ovarian volume of both the right and left ovaries were higher in the group with PCOS than the control group (p < 0.05). The mean PI values of the right and left ovaries, respectively, were 0.84 +/- 0.23 and 1.09 +/- 1.17 in the group with PCOS, and 0.88 +/- 0.14 and 0.92 +/- 0.15 in the control group. The mean PI values of the right and left uterine arteries, respectively, were 3.25 +/- 0.98 and 3.33 +/- 1.12 in the group with PCOS, and 3.17 +/- 0.93 and 3.2 +/- 1.38 in the control group (p > 0.05). The correlation analysis of the ovarian volume, the number of follicles and Doppler parameters revealed that there was a positive correlation and statistically significant difference between the right ovarian volume and right uterine artery PI in the group with PCOS and the left ovarian volume and left uterine artery PI in the control group (p > 0.05). The mean stromal PI of the ovarian and uterine arteries were 0.96 +/- 0.61 and 3.29 +/- 1.02 in the group with PCOS and 0.9 +/- 0.12 and 3.19 +/- 1.14 in the control group, respectively (p > 0.05). In the group with PCOS, the mean ovarian volume and the mean number of follicles were 11.46 +/- 4.43 and 13.91 +/- 4.11, respectively, whereas they were 7.63 +/- 2.44 and 5.55 +/- 2.34 in the control group (p < 0.05). CONCLUSION: It is not beneficial to use color Doppler transvaginal ultrasonography in the clinical diagnosis of patients with PCOS.     

Treatment with flutamide improves hyperinsulinemia in women with idiopathic hirsutism.

OBJECTIVE: To investigate insulin metabolism and its modifications induced by the administration of flutamide, a specific antiandrogen compound, in women with idiopathic hirsutism (IH) and in nonobese women with polycystic ovary syndrome (PCOS). DESIGN: Prospective, randomized trial. SETTING: Endocrinological Centre of the Department of Obstetrics and Gynecology, University of Caligari, Caligari, Italy. PATIENT(S): Thirty-two women with normal body mass index participated in the study: 11 with clinical and hormonal features of PCOS and 21 age- and weight-matched normally cycling women with IH (n = 11) and without IH (n = 10, controls). INTERVENTION(S): Each subject with PCOS or IH was assigned randomly to receive either flutamide tablets (250 mg twice a day) or placebo for > or =5 months. Twelve subjects (6 with PCOS, 6 with IH) received flutamide and 10 (5 with PCOS, 5 with IH) received placebo. All subjects ingested 75 g of glucose and then underwent an oral glucose tolerance test (OGTT), 3-7 days after spontaneous or medroxyprogesterone acetate (5 mg daily for 5 days)-induced menses. In women with PCOS or IH, the OGTT was repeated at the fourth month of treatment. MAIN OUTCOME MEASURE(S): Fasting and OGTT-stimulated levels of glucose, insulin, and C peptide. RESULT(S): Both fasting and OGTT-stimulated levels of insulin and C peptide were significantly higher in women with PCOS and in those with IH than in controls. Placebo did not modify parameters of glucose metabolism. Flutamide was capable of significantly blunting fasting and OGTT-stimulated secretion of insulin only in women with IH. CONCLUSION(S): Hyperinsulinemia exists in women with IH as well as in nonobese women with PCOS. Treatment with flutamide can completely reverse hyperinsulinemia only in women with IH, which suggests that the efficacy of the drug is dependent on peripheral androgen hyperactivity.     

来曲唑联合氯米芬对PCOS患者子宫卵巢血流动力学影响

目的:经阴道超声观察来曲唑联合氯米芬(CC)治疗多囊卵巢综合征(PCOS)的血流动力学变化,探讨来曲唑联合CC治疗PCOS的临床价值。方法:来曲唑联合CC治疗49例PCOS患者,经阴道超声观察子宫内膜厚度,优势卵泡个数,子宫动脉和优势侧卵巢基质收缩期血流峰值(PSV)、舒张末期血流速(EDV)、搏动指数(PI)、阻力指数(RI)及卵巢基质血流信号数。结果:来曲唑联合CC治疗PCOS有较高排卵率和妊娠率,使PCOS患者形成了子宫卵巢血流的周期性变化。结论:来曲唑联合CC用药能改善PCOS的子宫卵巢血流,促进PCOS患者排卵,利于妊娠并能减少流产的发生。     

Impaired uterine perfusion associated with metabolic disorders in women with polycystic ovary syndrome

BACKGROUND: Risk factors for cardiovascular disease, including chronic anovulation, obesity, hyperandrogenism, hyperinsulinemia, and dyslipidemia, are commonly observed in women with polycystic ovary syndrome (PCOS). We evaluated uterine perfusion and its correlation with clinical and biochemical parameters in women with PCOS. METHODS: We performed a pulsed Doppler study on uterine arterial blood flow in 25 women with PCOS and 45 control women with regular menstrual cycles. PCOS was diagnosed based on oligomenorrhea, polycystic ovaries determined by means of ultrasonography, and elevated luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratio. RESULTS: Women with PCOS had a significantly higher body mass index (BMI) and serum testosterone, and showed insulin resistance and dyslipidemia, including increased total cholesterol, triglyceride, low-density lipoprotein-cholesterol (LDL-C), and decreased high-density lipoprotein-cholesterol (HDL-C). The uterine arterial pulsatility index (PI) in women with PCOS was significantly higher than that in the control women during the follicular phase. The PI was correlated with BMI, LH/FSH ratio, or LDL-C/HDL-C ratio, whereas it was inversely correlated with the HDL-C level. Women with PCOS had reduced endometrial thickness and elevated uterine arterial PI in the luteal phase, in which implantation occurs. CONCLUSIONS: Elevation of uterine arterial blood flow resistance is associated with risk factors for cardiovascular events. Furthermore, the impaired uterine perfusion in the luteal phase may cause endometrial dysfunction in women with PCOS.     

Raloxifene reduces impedance to flow within the uterine artery in early postmenopausal women: a 2-year randomized, placebo-controlled, comparative study

OBJECTIVE: We sought to investigate the long-term effect of raloxifene and continuous combined hormone replacement therapy (ccHRT) on impedance to flow within the uterine artery in postmenopausal women. STUDY DESIGN: A prospective, randomized, double-blind, placebo-controlled 2-year study was performed in 95 postmenopausal women. They received either 60 mg of raloxifene daily (raloxifene 60 group), 150 mg of raloxifene daily (raloxifene 150 group), ccHRT, or placebo. At baseline and thereafter every 6 months, color Doppler ultrasonography was used to measure the pulsatility index (PI) of the uterine artery. RESULTS: After 24 months of treatment, compared with placebo, significant decreases were found in the PI in the raloxifene 150 group (P = .021) and in the ccHRT group (P = .007). In the raloxifene 150 group compared with the placebo group, after 6 and 24 months, decreases were observed in median PI of -5% and -15%, respectively, and in the ccHRT group decreases of -2% and -19%, respectively, were found. CONCLUSION: Long-term use of 150 mg of raloxifene daily or ccHRT reduces impedance to flow within the uterine artery. This indicates that high-dose raloxifene may exert cardiovascular protection.     

Uterine restoration by radiation sequelae regression with combined pentoxifylline-tocopherol: a phase II study

Objective: To determine whether combined pentoxifylline (PTX) and tocopherol (vitamin E) treatment can improve uterine radiation-induced sequelae, resulting in an improved embryo implantation rate.

Design: Retrospective phase II clinical trial.

Setting: Volunteers in an oocyte donation program in a public hospital.

Patient(s): Six women aged 31 ± 4 years, who were irradiated 25 years previously for childhood cancer with 20 to 40 Gy including the pelvic area.

Intervention(s): Four women had taken hormone replacement therapy for primary amenorrhea, and two had retained their natural cycle. Treatment consisted of at least 12 months of pentoxifylline at 800 mg/day combined with 1000 IU/day of tocopherol.

Main Outcome Measure(s): Endometrial thickness, uterine volume, and uterine artery blood flow were assessed by ultrasonography before and after pentoxifylline-tocopherol treatment, under usual estrogen-progesterone (OP) administration.

Result(s): This treatment was well tolerated. All six patients improved significantly in endometrial thickness (6.2 ± 0.6 vs. 3.2 ± 1.1 mm), myometrial dimensions (44 [± 5] × 30 [± 3] × 20 [± 2] vs. 30 [± 7] × 22 [± 3] × 16 [± 2] mm), and diastolic uterine artery flow.

Conclusion(s): In young women who want to bear children, the combination of pentoxifylline and vitamin E can reduce fibroatrophic uterine lesions after childhood irradiation.     

A randomized controlled study comparing the endocrine effects of pulsatile intravenous gonadotropin-releasing hormone after gonadotropin-releasing hormone agonist pretreatment versus clomiphene citrate in patients with polycystic ovary syndrome

Objective: To compare the endocrine changes in the follicular phase in infertile patients with polycystic ovary syndrome (PCOS) treated with either pulsatile IV GnRH after GnRH-agonist (GnRH-a) down-regulation or clomiphene citrate (CC).

Design: Subgroup analysis within a randomized, controlled, multicenter study.

Setting: Women referred to the Infertility Clinic, Catharina Hospital Eindhoven, The Netherlands.

Patient(s): Twenty-eight infertile patients with PCOS.

Intervention(s): Patients were randomly assigned to pulsatile IV GnRH (10–20 μg/90 min) after GnRH-a down-regulation or CC (50–150 mg; cycle days 3–7). Patients were monitored on alternate days with ovarian sonography and serum concentrations of E₂, LH, and FSH. Serum P and sonography confirmed ovulation.

Main Outcome Measure(s): Serum concentrations of E₂, LH, and FSH were assessed before treatment was started and after each ovarian sonography.

Result(s): In ovulatory cycles, no statistically significant differences were observed during the follicular phase comparing serum concentrations of E₂, LH, and FSH between the treatments. However, a significant increase in LH occurred in the GnRH group.

Conclusion(s): No significant endocrine differences were observed between GnRH and CC treatment. However, there was a significant increase in the serum LH concentration during the follicular phase in the GnRH group. Increments of LH in the GnRH group may be due to recovery of endogenous LH secretion.     

Postprandial triglyceride response in patients with polycystic ovary syndrome: relationship with waist-to-hip ratio and insulin

Objective: To examine the postprandial triglyceride response to a high-fat meal in women with polycystic ovary syndrome (PCOS) compared with a matched control group.

Design: Controlled clinical study.

Setting: Department of Endocrinology and Pathophysiology, School of Medicine, Universidad de Los Andes.

Patient(s): 18 Hispanic women with PCOS (nine overweight and nine nonobese) and 9 healthy control women.

Intervention(s): Biometric measures and blood sample collection.

Main Outcome Measure(s): Insulin and glucose levels during a standard oral glucose tolerance test. Plasma triglyceride, cholesterol, and high-density lipoprotein cholesterol levels were measured at baseline and at 4, 5, and 6 h after a high-fat meal.

Result(s): Both obese and nonobese PCOS women had higher waist-to-hip ratios than controls. PCOS women had higher levels of fasting and postglucose insulin and fasting triglyceride and postprandial triglyceride response and had lower levels of postprandial high-density lipoprotein cholesterol response, but no significant differences within PCOS groups were observed.

Conclusion(s): An expanded postprandial hypertriglyceridemia in PCOS women is related to a higher waist-to-hip ratio and insulin resistance, regardless of obesity, and contributes to increase the risk for coronary artery disease.     

Doppler analysis of uterine perfusion and ovarian stromal blood flow in polycystic ovary syndrome

Objective

To investigate blood flow velocity in the ovarian stromal artery and uterine artery in women with polycystic ovary syndrome (PCOS) and to correlate these velocities with clinical and biochemical parameters.

Methods

A prospective study was carried out in 55 patients with PCOS and 42 age-matched women who did not have PCOS. Clinical, biochemical, and hormonal characteristics, and utero-ovarian Doppler ultrasound blood flow parameters were determined, and correlations between the parameters were evaluated.

Results

Ovarian stromal blood flow was higher (P < 0.01) and uterine perfusion was lower (P < 0.01) in women with PCOS compared with women who did not have PCOS. Ovarian stromal artery pulsatility index (PI) was inversely correlated with levels of dehydroepiandrosterone sulfate (DHEAS) and insulin-like growth factor-1, and with the luteinizing hormone/follicle-stimulating hormone ratio. There was a positive correlation between uterine artery PI and DHEAS level.

Conclusion

Doppler analysis of the uterine and intraovarian arteries may provide additional information about the etiopathogenesis of PCOS and partly explain the clinical implications of the condition.     

Successful pregnancy after transient ovarian failure following treatment of symptomatic leiomyomata

Objective: To report a case of transient ovarian failure after treatment of symptomatic leiomyomata and review other iatrogenic causes of transient ovarian failure.

Design: Case report and literature review.

Setting: University-affiliated private practice.

Patient(s): A 35-year-old woman with symptomatic leiomyomata.

Intervention(s): Bilateral uterine artery embolization with subsequent abdominal myomectomy to treat unchanged regular heavy menstrual flow.

Main Outcome Measure(s): Ovarian function.

Result(s): Because medical therapy failed to control her menorrhagia, the patient proceeded with uterine artery embolization. She had persistent menorrhagia after bilateral uterine artery embolization and underwent exploratory laparotomy and myomectomy. After surgery, she had amenorrhea, hot flushes, and elevated FSH levels for 3 months. Ovarian function recovered after a short course of oral contraceptives, and the patient conceived without assistance.

Conclusion(s): Several interventions can affect normal ovarian function and can lead to permanent or transient ovarian failure. Possible causes of transient ovarian failure are radioactive iodine treatment, radiation, chemotherapy, pelvic surgery, stress, and uterine artery embolization. Before these interventions are applied, the possibility of ovarian failure and available preventive measures should be discussed with the patient.     

The risk of hepatotoxicity during long-term and low-dose flutamide treatment in hirsutism

Objective  Flutamide is an effective drug in treatment of hirsutism. Hepatotoxicity occasionally may occur with therapeutic doses (750–1500 mg/day), 3 months after initiation of treatment. Monitoring of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels is recommended to obviate serious hepatotoxicity. Materials and methods  Two hundred and fourteen patients with mean age of 20.9 ± 2.34 years suffering from hirsutism were included in the study. Of these 214 women, 117 had diagnosis of polycystic ovarian syndrome (PCOS), and 97 had diagnosis of idiopathic hirsutism. Thirty age-matched (mean age 20.3 ± 2.0 years) normal women without signs of hirsutism and with normal menstrual cycle served as control group. Hirsutism was assessed using modified Ferriman–Gallwey method at the beginning and at the end of the treatment. Serum levels of luteinizing hormone (LH), follicle stimulant hormone (FSH), prolactine (PRL), estradiol (E2), androstenodion (A), testosteron (T), dehydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEAS), dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone (17-P), sex hormone binding protein (SHBG), and ACTH were measured. Pelvic ultrasonography was performed for diagnosis of PCOS. Fifty-seven patients with PCOS (group 1) were given flutamide 125 mg/day + oral contraceptive. Sixty patients with PCOS (group 2) were given flutamide 250 mg/day + oral contraceptive. Forty-seven patients with IH (group 3) were given flutamide 125 mg/day alone, and 50 patients with IH (group 4) were given flutamide 250 mg alone. Thirty women in control group (group 5) were given placebo only. ALT and AST levels were measured in the beginning of the treatment, and repeated after 3, 6, 9 and 12 months. Results  No incidence of increase in AST or ALT levels (≥45 U/L) was observed in any of the groups. No evidence of hepatotoxicity in any of the 214 hyperandrogenic women was observed on low-dose flutamide for 1 year. Conclusion  We conclude that flutamide in a dosage of 125 or 250 mg daily is a safe drug in the long-term treatment of hirsutism. The follow-up of patients receiving flutamide can be done by monitoring AST or ALT levels for hepatotoxicity.     

A comparative analysis of arterial blood flow in unexplained infertility,tubal infertility and fertile groups

We aimed to compare ovarian (O), uterine (U) and spiral (S) artery (A) resistance of patients diagnosed as fertile, unexplained infertility (UI) and tubal factor infertility (TFI) in the peri-implantation period and independent from the impact of the treatment. UI (n?=?70), TFI (n?=?75) and fertile (n?=?72) patients’ ovarian, uterine and spiral artery pulsatility index (PI), resistance index (RI) and the endometrial thickness, serum estradiol and progesterone levels were compared. The specificity and sensitivity values were calculated according to determined cutoff values. Both TFI and control groups’ UA PI values were significantly lower than the UI group’s PI values. The highest UA RI values were found in UI group and the lowest values were in the control group. UI and TFI groups’ OA PI/RI values were significantly higher than the control group. Both the control and TFI groups’ SA PI/RI values were significantly lower than UI group’s PI/RI values. UI patients’ uterine and spiral arteries PI values >1.86 and >0.85, RI values >0.80 and >0.53 can be used as a valuable test showing reduced uterine perfusion. Ovarian artery PI values >0.96 and RI values >0.58 can be used as tests showing decreased ovarian perfusion in patients with TFI. In these patients, embryo cryopreservation can be considered.     

The effect of methyldopa treatment on uterine,umblical and fetal middle cerebral artery blood flows in preeclamptic patients

The purpose of this study was to evaluate the efficacy of methyldopa in the treatment of preeclamptic patients. This study was performed on 24 preeclamptic women who were in between 25–36 weeks of gestational age. 24 healthy pregnant women were taken as control group. Before starting treatment, 24 preeclamptic patients were examined with Doppler ultrasound. Pulsatility index, resistance index, systolic/diastolic ratio of uterine, umblical and fetal middle cerebral arteries were measured. Preeclamptic patients were treated with totally 1 g methyldopa per day. After 7 d, patients were reexamined with Doppler ultrasound. The effect of methyldopa on uterine, umblical and fetal middle cerebral artery blood flows were detected. Only one control with Doppler ultrasound was done to the healthy pregnant women. Before methyldopa treatment to the preeclamptic women, pulsatility index (PI), resistance index (RI) and systolic/diastolic ratio (S/D) on uterine and umblical arteries were significantly higher than the control group. However, fetal middle cerebral artery (MCA) values were significantly lower than the control group. When Doppler results of preeclamptic patients before and after the methyldopa treatment were compared, no significant differences in terms of Pulsatility Index, Resistance IndexI and S/D ratio of umblical and fetal middle cerebral arteries were found. However, the results of uterine artery were significantly lower after the treatment in preeclamptic patients. Treatment with methyldopa lowered the uterine artery resistance in preeclamptic patients but did not effect the resistance of umblical and fetal middle cerebral artery. Received: 27 March 2001 / Accepted: 5 June 2001     

Metformin versus flutamide in the treatment of metabolic consequences of non-obese young women with polycystic ovary syndrome: a randomized prospective study.

In addition to the reproductive consequences, polycystic ovary syndrome (PCOS) is characterized by a metabolic disorder in which hyperinsulinemia and insulin resistance are central features. The effects and possible benefits from insulin-sensitizing drugs are not well known, especially in non-obese women with PCOS. This study was designed to evaluate the effects of metformin and flutamide on metabolic parameters and insulin resistance in non-obese women with PCOS. Thirty non-obese women newly diagnosed with PCOS and 15 age- and weight-matched healthy volunteers as controls were included in the study. Patients were assigned randomly to receive flutamide 250 mg daily or metformin 850 mg three times daily. Glucose, insulin, insulin resistance, androgen levels and glucose and insulin responses to an oral glucose tolerance tests (OGTT) were assessed before and after a 4-week therapy period. A positive correlation was found between body mass index and insulin level in patients with PCOS and controls. Follicle stimulating hormone, luteinizing hormone, free testosterone and dehydroepiandrosterone sulfate levels decreased significantly, but insulin resistance levels were not changed after flutamide therapy. Body weight, free testosterone, insulin and insulin resistance levels decreased significantly after metformin therapy. In conclusion, metformin treatment improved insulin sensitivity and decreased androgen levels, and flutamide decreased androgen levels but failed to improve insulin sensitivity in the non-obese women with PCOS.     

Lignocaine aerosol spray in outpatient hysteroscopy: a randomized double-blind placebo-controlled trial

Objective: To assess the efficacy of lignocaine spray during outpatient hysteroscopy in reducing the need for additional anesthesia and reducing the discomfort of the procedure.

Design: A randomized double-blind, placebo-controlled trial.

Setting: An undergraduate university teaching hospital in London.

Patient(s): One hundred twenty patients undergoing outpatient hysteroscopy.

Intervention(s): Application of lignocaine spray to the cervix, cervical canal, and uterine cavity during outpatient hysteroscopy.

Main Outcome Measure(s): The need to use additional anesthesia and the pain experienced at various steps of the procedure.

Result(s): Women treated with active spray experienced significantly less pain when the cervix was grasped with a tenaculum at the start of hysteroscopy. There were no other significant differences in the outcome of hysteroscopy between the placebo and lignocaine groups, although there was a significant reduction in the use of additional anesthesia in both groups compared with historical controls.

Conclusion(s): Lignocaine spray has beneficial effects on cervical but not uterine sensation. Pretreatment with either lignocaine or placebo seems to reduce the need for additional intracervical anesthesia during hysteroscopy.     

Improvement of uterine artery Doppler velocimetry indices after metroplasty in arcuate uteri

OBJECTIVE: Our study aimed to evaluate the effect of metroplasty performed in arcuate uteri on uterine artery Doppler velocimetry. STUDY DESIGN: We performed uterine artery Doppler velocimetry transvaginally before and after metroplasty in 36 women with arcuate uteri. Pulsatility indexes (PI) of uterine arteries were calculated and the presence or absence of a protodiastolic notch was evaluated. RESULTS: Comparing Doppler indexes before and after metroplasty, we found that uterine artery impedance improves as assessed by lower mean PI. We observed that PI after intervention was significantly lower compared with indexes before for mean Doppler index evaluations (mean uterine PI pre: 2.07+/-0.61 and post: 1.49+/-0.24 [p<0.03]). No differences were observed as regards bilateral protodiastolic notch absence or presence. A protodiastolic notch was present in 22 out of 36 women before metroplasty (61%), and a notch was observed in 19 out of 36 (52%) after metroplasty. CONCLUSIONS: Our results suggest that, metroplasty, as well as making the uterine cavity wider, leads to better uterine perfusion.     

A variant of the glucocorticoid receptor gene is not associated with adrenal androgen excess in women with polycystic ovary syndrome

Objective: To determine whether the frequency of the N363S variant of the glucocorticoid receptor (GRL) was increased in women with PCOS and adrenal androgen (AA) excess.

Design: Prospective case-control study.

Setting: University reproductive endocrinology laboratory and outpatient clinic.

Patient(s): Consecutive patients of non-Hispanic white race diagnosed with PCOS (n = 114) and healthy controls (n = 92).

Intervention(s): Blood and DNA sampling before hormonal therapy.

Main Outcome Measure(s): PCOS patient and healthy control genotypes, with the N363S allele representing a variant of GRL.

Result(s): Fifty-four PCOS patients with (DHEAS ≥ 3000 ng/mL) and 55 without (DHEAS ≤ 2,500 ng/mL) AA excess, respectively, were studied. Six of 109 (5.5%) patients studied were found to be heterozygous carriers of the A→G base pair substitution at cDNA position 1220, resulting in the missense mutation N363S. Of these six, four had excessive AA secretion (i.e., excess DHEAS levels). There was no significant difference in the allele frequency of the GRL variant between PCOS patients with and without AA excess and controls (3.7% [95% confidence interval: 1.0%–5.7%], 1.8% [0.2%–6.0%], and 3.3% [2.3%–6.0%]). None of the subjects were found to be homozygous for the N363S allele.

Conclusion(s): The N363S variant of GRL was an uncommon occurrence in our population of healthy women and PCOS patients and did not appear to play a major role in the genetic predisposition to PCOS or to AA excess in PCOS.