Influence of body mass on the hypothalamic-pituitary-adrenal-axis response to naloxone in patients with polycystic ovary syndrome

OBJECTIVE: To evaluate the influence of body mass on the hypothalamic-pituitary-adrenal (HPA)-axis response to naloxone in polycystic ovary syndrome (PCOS). DESIGN: Controlled clinical study. SETTING: Academic research environment. PATIENT(S): Ten lean and 10 obese women with PCOS compared with 7 lean and 8 obese control subjects matched for body mass index. INTERVENTION(S): Each patient received an IV bolus of naloxone at a dosage of 125 microg/kg. MAIN OUTCOME MEASURE(S): Samples were collected 30 minutes before and 0, 15, 30, 60, 90, and 120 minutes after injection: ACTH and cortisol levels were measured in all plasma samples. RESULT(S): No significant differences were found in the ACTH and cortisol responses to opioid blockade between lean women with PCOS and lean as well as obese control subjects; conversely, obese patients with PCOS showed a higher ACTH and cortisol responses to naloxone compared with all other groups. CONCLUSION(S): Hypothalamic-pituitary-adrenal-axis abnormalities of PCOS may be central in origin and abdominal obesity seems to play a key role in the HPA-axis hyperactivity of women with PCOS when naloxone is administered.     

Intratumoral color Doppler analysis in endometrial carcinoma: is it clinically useful?

OBJECTIVE: The aim was to study the effectiveness of subjective color Doppler evaluation and spectral Doppler parameters in preoperative characterization of endometrial carcinomas. METHODS: Seventy-six patients with endometrial carcinoma were preoperatively analyzed by color Doppler ultrasound in order to subjectively evaluate the amount of intratumoral blood flow (color score) and to analyze the lowest resistance index (RI), the highest peak systolic velocity (PV), and the highest time averaged maximum velocity (TAMVX). These parameters were analyzed according to clinico-pathological characteristics. RESULTS: In 13 patients no intratumoral arterial vessels were detected by color Doppler examination. No lymph node metastases were found in this group of patients. Positive nodes were found in 24% of patients with detectable arterial vessels, although the difference did not reach the statistical significance. No differences were found in spectral Doppler parameters (RI, PV, TAMVX) according to tumor characteristics or nodal involvement. A higher percentage of cases with a color score of 3 was found in stage >I than in stage I patients (69 vs 42%, P < 0.05), and in patients with myometrial invasion greater than 50% than in those with less than 50% invasion (72 vs 38%; P = 0.05). CONCLUSIONS: Nodal metastases were found in 24% of patients with detectable vessels at color Doppler examination. Subjective analysis of vessel density correlated >50%, myometrial invasion, but spectral Doppler analysis was not predictive of surgical stage, tumor grade, myometrial invasion, or lymph node metastases. These results do not support the use of preoperative intratumoral blood flow analysis as a clinical test in evaluating tumor characteristics or in predicting lymph node metastases.     

Naltrexone effect on pulsatile GnRH therapy for ovulation induction in polycystic ovary syndrome: a pilot prospective study

The aim of the present study was to analyze the opioid influence on LH pulsatility in polycystic ovary syndrome (PCOS) patients and to evaluate the effectiveness of a long-term opioid antagonist (naltrexone) treatment in improving the pulsatile GnRH therapy which is successful in this syndrome. Ten obese women affected by PCOS participated in the study. Patients were hospitalized during the early follicular phase and underwent an oral glucose tolerance test (OGTT) with 75 g of glucose and a pulse pattern study followed by a GnRH test (100 pg i.v.). All patients were then treated for ovulation induction with pulsatile administration of GnRH (5 microg/bolus every 90 min). Since pregnancies did not occurr in any patient, after spontaneous or progestin-induced menstrual cycles, all patients received naltrexone at a dose of 50 mg/day orally for 8 weeks and during treatment repeated the basal protocol study and the ovulation induction cycle with the same modalities. The naltrexone treatment significantly reduced the insulin response to OGTT and the LH response to GnRH bolus, whereas it did not affect the FSH and LH pulsatility patterns. Concerning the ovulation induction by pulsatile GnRH, naltrexone treatment was able to improve, although not significantly, the ovulation rate (60% pre-treatment vs 90% post-treatment). Furthermore, the maximum diameter of the dominant follicle and the pre-ovulatory estradiol concentration were higher after long-term opioid blockade (follicular diameter 19.5+/-1.76 mm pre-treatment vs 21.6+/-2.19 mm post-treatment, p<0.001; maximum estradiol level 728.7+/-288.5 pmol/l pre-treatment vs 986.4+/-382.1 pmol/l post-treatment, p<0.05). During the naltrexone-pulsatile GnRH co-treatment two pregnancies occurred. In conclusion, our data show that naltrexone-pulsatile GnRH co-treatment is able to improve the ovarian responsiveness to ovulation induction in obese PCOS patients when compared to pulsatile GnRH alone. This action seems to be related to a decrease of insulin secretion. Further randomized studies should be performed in order to obtain significant conclusions on the possible clinical application.     

Conventional ultrasonography and color Doppler velocimetry of uterine leiomyomas

The role of uterine leiomyomas as causative factor of sterility is controversial. Submucosal myomas, in particular, can interfere with fertility and be associated to obstetric complications as abruption of placenta, post-partum metrorrhagia and puerperal sepsis. With ultrasonography, immediate and long-term information can be drawn on changes in the features of myomas. However, to-date, there are no reliable noninvasive exams to assess the nature and growth pattern of myomas. With Doppler velocimetry in ovarian malignancies a vascularization significantly different from that observed in benign tumors, is detected. It has been hypothesized that within benign tumors, as myomatous masses, tissues with different cell proliferation rates could be characterized by different vascular patterns. In a group of myomas shown to have central arterial vessels at Doppler examination, significant correlations were assessed between resistance indices of analyzed vessels and percentage of cell in the proliferative phase evaluated with cytofluorimetry. The myomatous tissue with high cell proliferation rate seems to have higher vascular resistances.     

Insulin in obstetrics: a main parameter in the management of pregnancy

Insulin plays a central role in human pregnancy. Maternal insulin sensitivity decreases with advancing gestation in order to provide glucose and possibly other nutrients for feto-placental growth and energy needs. Moreover, alterations of insulin metabolism are clearly involved in the development of gestational diabetes. In recent years, hyperinsulinaemia has been also proposed as a possible pathogenic factor in the development of gestational hypertension and preeclampsia; furthermore it has also been postulated that there is an involvement of insulin sensitivity in fetal growth restriction. These intriguing data have stimulated our interest in summarizing the physiopathological mechanisms by which the pancreatic hormone could be involved in obstetrics.     

A pilot study of the long-term effects of acipimox in polycystic ovarian syndrome

BACKGROUND: To evaluate the effects of long-term acipimox administration on glucose-induced insulin secretion and peripheral insulin sensitivity in polycystic ovarian syndrome (PCOS), 20 PCOS subjects (eight lean and 12 obese) and 14 body mass index-matched controls (seven lean and seven obese) were investigated. METHODS: Fasting blood samples were collected for basal hormone and lipoprotein assays, after which patients underwent an oral glucose tolerance test (OGTT). The following day a euglycaemic-hyperinsulinaemic clamp was performed. After 4-6 weeks of treatment with acipimox at a dose of 250 mg given orally three times a day, the patients repeated the study protocol. RESULTS: No significant differences were found in the glucose, insulin or C-peptide responses to OGTT before and after anti-lipolytic drug administration in any group, nor was there any effect on insulin sensitivity. Concerning the lipid profile, acipimox administration led to a significant decrease of cholesterol and low-density lipoprotein levels in obese PCOS patients as well as in obese and lean controls. Lower triglycerides were found after the drug administration in both obese groups. Post-treatment free fatty acid levels were not significantly different when compared with basal values. CONCLUSIONS: Acipimox does not appear to be an effective insulin-lowering drug in PCOS, even if it can be used in obese women with PCOS as an additional therapeutic agent to ameliorate the atherogenic lipid profile of the syndrome.     

Evidence of a disturbance of the hypothalamic-pltuitary-adrenal axis in polycystic ovary syndrome: effect of naloxone

OBJECTIVE  A recent report has demonstrated a stronger association between the HLA-DQA1*0501 allele and Graves' disease in Caucasian men than in women. Our aim was to confirm this association in a larger series of male Caucasian patients.
DESIGN  Polymerase chain reaction/sequence specific oligonucleotide probing (PCR/SSOP).
PATIENTS  Fifty men and 70 women with Graves' disease were studied as well as a control group consisting of 57 healthy, unrelated men and women.
METHODS  Genomic DNA was derived from venous blood samples. Appropriately primed DNA was amplified by PCR and the products were subjected to SSOP. The presence of the allele was demonstrated by enhanced chemiluminescence.
RESULTS  A significant association between HLA-DQA1* 0501 and Graves' disease was demonstrated among both the men and women as well as in the combined disease cohort, with HLA-DQA1*0501 conferring a greater relative risk than HLA-DR3 in all three groups. This association persisted when the results from the DR3-negative Graves' patients were analysed in isolation. HLA-DQA1*0501 was heterogeneously distributed between the sexes with significantly more female Graves' patients carrying this allele.
CONCLUSIONS  There is a significant association between HLA-DQA1*0501 and Graves' disease which may be unrelated to the inheritance of this allele on an extended haplotype with HLA-DR3. In contrast to a recent report, HLA-DQA1*0501 was significantly more prevalent among women with Graves' disease than men.     

Detection of central pelvic recurrent disease with transvaginal color Doppler ultrasound in women treated for gynecological malignancy.

OBJECTIVE: To evaluate color Doppler characteristics of small recurrent tumors detected within the central pelvis in follow-up patients treated for gynecological malignancy. PATIENTS AND METHODS: A prospective study was performed on 340 patients who were being monitored following treatment for gynecological malignancies. A selected group of 27 patients, with small pelvic masses located in the central region of the pelvis, underwent a color Doppler examination. A subjective assessment of the vascularization (vascular score), the lowest resistance index (RI), the highest peak velocity (PSV) and the highest time averaged maximum velocity (TAMXV) of the vessels detected within the lesion were analyzed. RESULTS: In 16 patients the pelvic mass was found to be benign while in 11 patients a malignant recurrence was diagnosed. Gray-scale examination could not differentiate between benign and malignant lesions. The color score of tumor recurrences was significantly higher in comparison to that in benign lesions (color score 3 in 54% vs. 0%, P < 0.005). The malignant lesions showed significantly lower mean values of RI and significantly higher mean values of PSV and TAMXV when compared with benign lesions (0.39 +/- 0.09 vs. 0.81 +/- 0.22, P < 0.0001; 19.3 +/- 4.7 vs. 10.5 +/- 5.6 cm/s, P < 0.0001; 8.9 +/- 3.7 vs. 4.3 +/- 2.7 cm/s, P < 0.005). CONCLUSIONS: Color Doppler analysis added to transvaginal gray-scale ultrasonography seems to be a helpful tool in the diagnosis of recurrent tumors in the central region of the pelvis.     

Assessment of insulin sensitivity from measurements in the fasting state and during an oral glucose tolerance test in polycystic ovary syndrome and menopausal patients

BACKGROUND: Polycystic ovary syndrome (PCOS) and menopausal subjects are characterized by an increased cardiovascular and type 2 diabetes mellitus risk, at least partially related to insulin disturbances. The evaluation of insulin resistance in these patients could be useful as primary prevention. The aim of the study was to verify the validity of several indexes of insulin sensitivity in PCOS and menopausal subjects by comparing the data obtained by these indexes to those of euglycemic-hyperinsulinemic clamp studies. METHODS: One hundred PCOS and 110 menopausal subjects were analyzed; all subjects underwent an oral glucose tolerance test (75 g) and euglycemic-hyperinsulinemic clamp study. Seven PCOS patients and 13 menopausal subjects had impaired glucose tolerance or type 2 diabetes mellitus and were excluded from the study. After analysis of correlation coefficients between the evaluated indexes and the clamp studies, the sensitivity and specificity of different cut-off values for each parameter were analyzed by receiver operating characteristic (ROC) curves. RESULTS: The best correlation coefficients with clamp studies were obtained with the Avignon insulin sensitivity index (SiM) (R(s) = 0.7812) in PCOS patients and the Matsuda and De Fronzo index (R(s) = 0.6178) in menopausal patients. The best predictive index of insulin resistance in PCOS was a Avignon insulin sensitivity basal index (SibB) value of 62 or less (78% sensitivity, 95% specificity) and an insulin area under the curve (AUC) of 7,000 microIU/ml or more (>/=50,225 pmol/liter) x 120 min (83% sensitivity, 90% specificity). In the menopausal population, the best predictive performance was obtained by an insulin AUC of 10,000 microIU/ml or more (>/=71,750 pmol/liter) x 240 min (70% sensitivity, 88% specificity). CONCLUSIONS: The presence of high correlation coefficients does not necessarily mean that the indexes of insulin resistance have an optimal predictive performance; this is probably due to the presence of many borderline values. The simple evaluation of insulin AUC seems to effectively replace the euglycemic-hyperinsulinemic clamp in routine clinical practice, allowing results superimposable to those obtained by minimal model analysis.