Effect of intracervical anesthesia on pain associated with the insertion of the levonorgestrel-releasing intrauterine system in women without previous vaginal delivery: a RCT.

STUDY QUESTION: Is the pain associated with levonorgestrel-releasing intrauterine system (LNG-IUS) insertion reduced by intracervical anesthesia in women without previous vaginal birth? SUMMARY ANSWER: Intracervical anesthesia was not associated with reduced pain in women without previous vaginal birth. WHAT IS KNOWN ALREADY: The pain associated with the insertion of intrauterine contraceptives (IUCs) is a limiting factor for the use of these contraceptives by some women. No prophylactic pharmacological intervention has proven efficacy in relieving pain during or after the insertion of IUCs. However, previous studies included women with previous vaginal delivery, and injectable intracervical anesthesia was not evaluated in any of these studies. STUDY DESIGN, SIZE, DURATION: This was a randomized, open, parallel-group clinical trial that evaluated 100 women without previous vaginal delivery who wished to use the LNG-IUS for the first time. These women were evaluated immediately after LNG-IUS insertion and then 2 h and 6 h later. PARTICIPANTS/MATERIALS, SETTING, METHODS: The 100 women were randomized into two groups: (i) use of a non-steroidal anti-inflammatory drug (NSAID) (ibuprofen, 400 mg) 1 h prior to LNG-IUS insertion; or (ii) 2% lidocaine intracervical injection 5 min prior to LNG-IUS insertion. The women were evaluated immediately after LNG-IUS insertion and then 2 h and 6 h after insertion. Two pain scales were used (the visual analogue scale and the facial pain scale) in addition to assessing the ease of insertion (as rated by the provider) and the level of discomfort during the procedure (as rated by the patient). Multivariate logistic regression was performed to analyze the predictors associated with moderate/severe pain. MAIN RESULTS AND THE ROLE OF CHANCE: The pain and discomfort associated with LNG-IUS insertion, and the ease of insertion of the LNG-IUS did not differ between the groups. Nulliparity was more associated with moderate/severe pain [adjusted odds ratio (OR): 3.1 (95% confidence interval (CI): 1.3-7.80]. Injectable intracervical anesthesia use reduced the risk of moderate/severe pain by 40% [adjusted OR: 0.6 (95% CI: 0.2-1.4)]. The difference between the mean pain score in the intracervical anesthesia group and the NSAID group was <10%; thus, the effect size of the intervention was not significant. LIMITATIONS, REASONS FOR CAUTION: Intracervical anesthesia was compared with an oral medication in this study. Intracervical injection of a saline solution or even a dry needling as the placebo for a double-blind study could be a more adequate control; however, this approach was not a protocol approved by the institutional review board. Considering that the majority of the insertions were easy (>80% in both groups), the results may not be extrapolated to difficult insertions with moderate/severe pain where local anesthesia may have a role. WIDER IMPLICATIONS OF THE FINDINGS: The findings can be generalized to most insertions in nulliparous women or in those without a previous vaginal delivery. There is currently no evidence to recommend the routine use of prophylactic intracervical anesthesia prior to LNG-IUS insertion; there is no evidence that this treatment reduces insertion-related pain. STUDY FUNDING/COMPETING INTERESTS: RAF and CSV give occasional lectures for Bayer Healthcare. This study received funding from the National Institute of Hormones and Women's Health, National Council for Scientific and Technological Development (CNPq). TRIAL REGISTRATION NUMBER: NCT02155166.

Preventing Microbial Contamination during Long-Term In Vitro Culture of Human Granulosa-Lutein Cells: An Ultrastructural Analysis.

Purpose. To investigate whether the addition of antibiotic/antimycotic during human granulosa-lutein cells (GLCs) isolation and cell-plating procedures prevents microbial contamination after 144 h of culture and also evaluate the effects of contamination on GLCs ultrastructure and steroid secretion. Methods. GLCs obtained from five women submitted to assisted reproductive techniques (ARTs) were isolated with PBS supplemented with antibiotic/antimycotic or PBS nonsupplemented and cultured for 144 h. GLCs were evaluated by transmission electron microscopy (TEM), and estradiol (E2) and progesterone (P4) secretion was assayed by chemiluminescence. Results. Although no contaminating microorganisms were identified by light microscopy, TEM analyses revealed several bacterial colonies in culture dishes of GLCs isolated with only PBS. Bacterial contamination disrupted the adherence of the GLCs to the culture plate interfering with monolayer formation affecting the growth pattern of GLCs. Various cellular debris and bacteria were observed, and no organelles were found in the cytoplasm of infected cells. While bacterial contamination decreased estradiol media levels, it increased progesterone, as compared with noncontaminated group. Conclusion. Taken together, our data showed that the addition of a high dose of antibiotic/antimycotic during the isolation and cell-plating procedures prevents microbial contamination of long-term GLCs culture as its effects on cells growth and function in vitro.

VIP expression in vessels of the vaginal wall: relationship with estrogen status.

OBJECTIVE: Vasoactive intestinal peptide (VIP) is a neuropeptide with elevated expression in regions that control urogenital functions. Estrogen appears to modulate VIP expression in various organs, but this effect has not been demonstrated in the vaginal wall. The aim of this study was to evaluate the influence of estrogen status on VIP expression in vessels of the vaginal wall. METHODS: Surgical specimens were removed from the vaginal walls of 18 premenopausal women and 12 postmenopausal women who were given surgery for genital prolapse grade I or II. Vaginal specimens were stained with estrogen receptor-alpha (ER-α) and VIP antibodies. Levels of follicle stimulating hormone (FSH), estradiol, prolactin, fasting glucose and serum thyroxine stimulating hormone were also measured. Estrogen status was assessed on the basis of FSH and ER-α scores. RESULTS: The vaginal walls of premenopausal women had significantly higher ER-α scores than those of menopausal women (premenopausal group, 3.6 ± 2.2; menopausal group, 1.4 ± 1.8; p = 0.01). Premenopausal women also had significantly higher levels of VIP in the vaginal wall than menopausal women (p = 0.02). Increasing age was associated with lower level of VIP staining (odds ratio 0.88; 95% confidence interval 0.78-0.99). CONCLUSION: Levels of ER-α and VIP expression in the posterior vaginal wall were higher in premenopausal than in menopausal women, but VIP expression was not associated with estrogen status. Age was an independent predictor of VIP staining in vaginal wall biopsies.

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.

Use of the etonogestrel-releasing implant is associated with hypoactivation of the coagulation cascade.

BACKGROUND: The role of progestogens in haemostasis is controversial. Our objective is to evaluate the haemostatic effects of an etonogestrel-releasing implant. METHODS: This open-label, self-controlled, longitudinal study involved 20 healthy women receiving subcutaneous etonogestrel-releasing implants. At baseline, 1, 3 and 6 months, we measured the following: activated partial thromboplastin time; prothrombin time; thrombin time; fibrinogen; coagulation factors II, V, VII, VIII, IX, X and XI; von Willebrand factor; activated protein C (APC); antithrombin; free protein S; plasminogen activator inhibitor type 1 (PAI-1); alpha2-antiplasmin; thrombin-antithrombin (TAT) complex; prothrombin fragment 1 + 2 (F1 + 2); D-dimers; APC resistance. Statistical analyses included the Friedman test and ANOVA. RESULTS: Levels of APC (P < 0.01), factor II (P = 0.02), factor VII (P = 0.006), factor X (P = 0.01) and F1 + 2 (P < 0.001) were reduced, whereas those of PAI-1 (P = 0.01) and factor XI (P = 0.006) were transitory increased. All of these values, however, remained within normal ranges. Surprisingly, TAT concentrations fell below the normal range (P < 0.001). CONCLUSIONS: Our findings suggest that the etonogestrel-releasing implant does not induce a prothrombotic pattern during the first six months of use, and that its use is associated with a reduction in thrombin generation.

Autonomic modulation of heart rate of young and postmenopausal women undergoing estrogen therapy.

The aim of the present study was to determine whether estrogen therapy (ET) reduces alterations of the autonomic control of heart rate (HR) due to hypoestrogenism and aging. Thirteen young (24 +/- 2.6 years), 10 postmenopausal (53 +/- 4.6 years) undergoing ET (PM-ET), and 14 postmenopausal (56 +/- 2.6 years) women not undergoing ET (PM) were studied. ET consisted of 0.625 mg/day conjugated equine estrogen. HR was recorded continuously for 8 min at rest in the supine and sitting positions. HR variability (HRV) was analyzed by time (SDNN and rMSSD indices) and frequency domain methods. Power spectral components are reported as normalized units (nu) at low (LF) and high (HF) frequencies, and as LF/HF ratio. Intergroup comparisons: SDNN index was higher in young (median: supine, 47 ms; sitting, 42 ms) than in PM-ET (33; 29 ms) and PM (31; 29 ms) women (P < 0.05). PM showed lower HFnu, higher LFnu and higher LF/HF ratio (supine: 44, 56, 1.29; sitting: 38, 62, 1.60) than the young group in the supine position (61, 39, 0.63) and the PM-ET group in the sitting position (57, 43, 0.75; P < 0.05). Intragroup comparisons: HR was lower in the supine than in the sitting position for all groups (P < 0.05). The HRV decrease from the supine to the sitting position was significant only in the young group. These results suggest that HRV decreases during aging. ET seems to attenuate this process, promoting a reduction in sympathetic activity on the heart and contributing to the cardioprotective effect of estrogen hormones.

Comparison of anaerobic threshold determined by visual and mathematical methods in healthy women.

Several methods are used to estimate anaerobic threshold (AT) during exercise. The aim of the present study was to compare AT obtained by a graphic visual method for the estimate of ventilatory and metabolic variables (gold standard), to a bi-segmental linear regression mathematical model of Hinkley's algorithm applied to heart rate (HR) and carbon dioxide output (VCO2) data. Thirteen young (24 +/- 2.63 years old) and 16 postmenopausal (57 +/- 4.79 years old) healthy and sedentary women were submitted to a continuous ergospirometric incremental test on an electromagnetic braking cycloergometer with 10 to 20 W/min increases until physical exhaustion. The ventilatory variables were recorded breath-to-breath and HR was obtained beat-to-beat over real time. Data were analyzed by the nonparametric Friedman test and Spearman correlation test with the level of significance set at 5%. Power output (W), HR (bpm), oxygen uptake (VO2; mL kg(-1) min(-1)), VO2 (mL/min), VCO2 (mL/min), and minute ventilation (VE; L/min) data observed at the AT level were similar for both methods and groups studied (P > 0.05). The VO2 (mL kg(-1) min(-1)) data showed significant correlation (P < 0.05) between the gold standard method and the mathematical model when applied to HR (rs = 0.75) and VCO2 (rs = 0.78) data for the subjects as a whole (N = 29). The proposed mathematical method for the detection of changes in response patterns of VCO2 and HR was adequate and promising for AT detection in young and middle-aged women, representing a semi-automatic, non-invasive and objective AT measurement.

Autonomic modulation of heart rate of young and postmenopausal women undergoing estrogen therapy

The aim of the present study was to determine whether estrogen therapy (ET) reduces alterations of the autonomic control of heart rate (HR) due to hypoestrogenism and aging. Thirteen young (24 ± 2.6 years), 10 postmenopausal (53 ± 4.6 years) undergoing ET (PM-ET), and 14 postmenopausal (56 ± 2.6 years) women not undergoing ET (PM) were studied. ET consisted of 0.625 mg/day conjugated equine estrogen. HR was recorded continuously for 8 min at rest in the supine and sitting positions. HR variability (HRV) was analyzed by time (SDNN and rMSSD indices) and frequency domain methods. Power spectral components are reported as normalized units (nu) at low (LF) and high (HF) frequencies, and as LF/HF ratio. Intergroup comparisons: SDNN index was higher in young (median: supine, 47 ms; sitting, 42 ms) than in PM-ET (33; 29 ms) and PM (31; 29 ms) women (P < 0.05). PM showed lower HFnu, higher LFnu and higher LF/HF ratio (supine: 44, 56, 1.29; sitting: 38, 62, 1.60) than the young group in the supine position (61, 39, 0.63) and the PM-ET group in the sitting position (57, 43, 0.75; P < 0.05). Intragroup comparisons: HR was lower in the supine than in the sitting position for all groups (P < 0.05). The HRV decrease from the supine to the sitting position was significant only in the young group. These results suggest that HRV decreases during aging. ET seems to attenuate this process, promoting a reduction in sympathetic activity on the heart and contributing to the cardioprotective effect of estrogen hormones.

Comparison of anaerobic threshold determined by visual and mathematical methods in healthy women

Several methods are used to estimate anaerobic threshold (AT) during exercise. The aim of the present study was to compare AT obtained by a graphic visual method for the estimate of ventilatory and metabolic variables (gold standard), to a bi-segmental linear regression mathematical model of Hinkley's algorithm applied to heart rate (HR) and carbon dioxide output (VCO2) data. Thirteen young (24 ± 2.63 years old) and 16 postmenopausal (57 ± 4.79 years old) healthy and sedentary women were submitted to a continuous ergospirometric incremental test on an electromagnetic braking cycloergometer with 10 to 20 W/min increases until physical exhaustion. The ventilatory variables were recorded breath-to-breath and HR was obtained beat-to-beat over real time. Data were analyzed by the nonparametric Friedman test and Spearman correlation test with the level of significance set at 5 percent. Power output (W), HR (bpm), oxygen uptake (VO2; mL kg-1 min-1), VO2 (mL/min), VCO2 (mL/min), and minute ventilation (VE; L/min) data observed at the AT level were similar for both methods and groups studied (P > 0.05). The VO2 (mL kg-1 min-1) data showed significant correlation (P < 0.05) between the gold standard method and the mathematical model when applied to HR (r s = 0.75) and VCO2 (r s = 0.78) data for the subjects as a whole (N = 29). The proposed mathematical method for the detection of changes in response patterns of VCO2 and HR was adequate and promising for AT detection in young and middle-aged women, representing a semi-automatic, non-invasive and objective AT measurement.

Análise dos índices espectrais da variabilidade da freqüência cardíaca em homens de meia idade e mulheres na pós-menopausa / Analysis of spectral indexes for heart rate variability in middle-aged men and postmenopausal women

OBJETIVO: Analisar e comparar a variabilidade da freqüência cardíaca (VFC), em repouso, de homens e mulheres de meia-idade. MÉTODOS: Foram estudados 10 homens (54 ± 3,2 anos) e 14 mulheres na pós-menopausa (56 ± 2,6 anos) que não faziam uso de terapia hormonal. A freqüência cardíaca (FC) e os intervalos R-R foram obtidos a partir do eletrocardiograma, batimento a batimento, durante 8 minutos em repouso, nas posições supina e sentada. A VFC foi analisada no domínio da freqüência, usando a transformada rápida de Fourier, por meio da qual foram obtidas as bandas de baixa (BF) e alta freqüência (AF), as quais foram expressas em unidades normalizadas (AFun) e (BFun) e na razão BF/AF. Foram utilizados os testes estatísticos não-paramétricos de Mann-Whitney e de Wilcoxon, com nível de significância de alfa= 5 por cento. RESULTADOS: Na comparação intergrupo, as mulheres apresentaram maiores valores da banda AFun e menores valores da banda BFun e da razão BF/AF em relação aos homens, diferenças essas significativas (p<0,05). Na comparação intragrupo, não foram observadas diferenças significativas nos índices de VFC entre as posições supina e sentada para os 2 grupos estudados. CONCLUSÃO: Nossos resultados mostram uma maior modulação vagal e menor simpática no controle autonômico da FC para as mulheres em comparação aos homens de mesma idade, o que sugere que as diferenças autonômicas relacionadas ao gênero não se devem unicamente aos níveis hormonais de estrogênio, uma vez que as mulheres estudadas já se encontravam na fase pós-menopausa. Outros fatores podem estar contribuindo para essas diferenças.

OBJECTIVE: To analyze and compare heart rate variability (HRV) in middle-aged men and women under resting conditions. METHOD: Ten men (54 ± 3.2 years) and fourteen postmenopausal women (56 ± 2.6 years) who were not using hormonal therapy were studied. Heart rates (HR) and R-R intervals (iR-R) on a beat-to-beat basis were obtained from electrocardiograms over an eight-minute period under resting conditions, in the supine and sitting positions. The HRV was analyzed in the frequency domain by means of fast Fourier transforms and the low (LF) and high (HF) frequency bands were obtained and presented as normalized units (LFnu and HFnu) and the LF/HF ratio. Wilcoxon and Mann-Whitney non-parametric statistical tests were used, with the significance level set at 5 percent. RESULTS: Comparing between the groups, the women presented significantly higher HFnu and lower LFnu and LF/HF ratios than did the men (p<0.05). Comparing within the groups, no significant differences (p>0.05) were found in the HRV indexes between the supine and sitting positions for either study group. CONCLUSION: Our results show greater vagal modulation and lower sympathetic activity in autonomic heart rate control among women than among men of similar age. This suggests that the gender-related autonomic differences are not solely dependent on estrogen levels, since the women studied were already postmenopausal. Other factors may be contributing towards these differences.

Acarbose in obese patients with polycystic ovarian syndrome: a double-blind, randomized, placebo-controlled study.

BACKGROUND: The present study assessed the effects of low-dose acarbose on obese patients with polycystic ovarian syndrome (PCOS). METHODS: A double-blind placebo-controlled study was conducted on 30 obese hyperinsulinaemic women with PCOS treated with 150 mg/day acarbose or placebo for 6 months. The women were evaluated for hirsutism, menstrual regularity, body mass index (BMI), insulin resistance and glucose tolerance, sex hormone-binding globulin (SHBG), LH, FSH, testosterone and androstenedione, and side-effects. RESULTS: The patients in the acarbose group showed a reduction in BMI (35.87 +/- 2.60 versus 33.10 +/- 2.94 kg/m(2)) and in the Ferriman-Gallwey index (8.85 +/- 2.31 versus 8 +/- 1.82), and an increased chance of menstrual regularity (rate = 2.67). SHBG concentration increased (21.01 +/- 7.9 versus 23.85 +/- 7.77 nmol/l) and the free androgen index was reduced (14.81 +/- 9.06 versus 11.48 +/- 6.18). None of these parameters were modified in the placebo group. Mild side-effects occurred in 84% of the patients in the acarbose group and disappeared after the first 3 months. CONCLUSION: A low dose of acarbose administered to obese patients with PCOS promotes a reduction in free androgen index and BMI and an increase in SHBG, with improvement of hirsutism and of the menstrual pattern, and is well tolerated by patients.

Estradiol and testosterone concentrations in follicular fluid as criteria to discriminate between mature and immature oocytes.

The objective of the present study was to examine the association between follicular fluid (FF) steroid concentration and oocyte maturity and fertilization rates. Seventeen infertile patients were submitted to ovulation induction with urinary human follicle-stimulating hormone, human menopausal gonadotropin and human chorionic gonadotropin (hCG). A total of 107 follicles were aspirated after hCG administration, the oocytes were analyzed for maturity and 81 of them were incubated and inseminated in vitro. Progesterone, estradiol (E2), estrone, androstenedione, and testosterone were measured in the FF. E2 and testosterone levels were significantly higher in FF containing immature oocytes (median = 618.2 and 16 ng/ml, respectively) than in FF containing mature oocytes (median = 368 and 5.7 ng/ml, respectively; P < 0.05). Progesterone, androstenedione and estrone levels were not significantly different between mature and immature oocytes. The application of the receiver-operating characteristic curve statistical approach to determine the best cut-off point for the discrimination between mature and immature oocytes indicated levels of 505.8 ng/ml for E2 (81.0% sensitivity and 81.8% specificity) and of 10.4 ng/ml for testosterone (90.9% sensitivity and 82.4% specificity). Follicular diameter was associated negatively with E2 and testosterone levels in FF. There was a significant increase in progesterone/testosterone, progesterone/E2 and E2/testosterone ratios in FF containing mature oocytes, suggesting a reduction in conversion of C21 to C19, but not in aromatase activity. The overall fertility rate was 61% but there was no correlation between the steroid levels or their ratios and the fertilization rates. E2 and testosterone levels in FF may be used as a predictive parameter of oocyte maturity, but not for the in vitro fertilization rate.

Estradiol and testosterone concentrations in follicular fluid as criteria to discriminate between mature and immature oocytes

The objective of the present study was to examine the association between follicular fluid (FF) steroid concentration and oocyte maturity and fertilization rates. Seventeen infertile patients were submitted to ovulation induction with urinary human follicle-stimulating hormone, human menopausal gonadotropin and human chorionic gonadotropin (hCG). A total of 107 follicles were aspirated after hCG administration, the oocytes were analyzed for maturity and 81 of them were incubated and inseminated in vitro. Progesterone, estradiol (E2), estrone, androstenedione, and testosterone were measured in the FF. E2 and testosterone levels were significantly higher in FF containing immature oocytes (median = 618.2 and 16 ng/ml, respectively) than in FF containing mature oocytes (median = 368 and 5.7 ng/ml, respectively; P < 0.05). Progesterone, androstenedione and estrone levels were not significantly different between mature and immature oocytes. The application of the receiver-operating characteristic curve statistical approach to determine the best cut-off point for the discrimination between mature and immature oocytes indicated levels of 505.8 ng/ml for E2 (81.0 percent sensitivity and 81.8 percent specificity) and of 10.4 ng/ml for testosterone (90.9 percent sensitivity and 82.4 percent specificity). Follicular diameter was associated negatively with E2 and testosterone levels in FF. There was a significant increase in progesterone/testosterone, progesterone/E2 and E2/testosterone ratios in FF containing mature oocytes, suggesting a reduction in conversion of C21 to C19, but not in aromatase activity. The overall fertility rate was 61 percent but there was no correlation between the steroid levels or their ratios and the fertilization rates. E2 and testosterone levels in FF may be used as a predictive parameter of oocyte maturity, but not for the in vitro fertilization rate.

Positive correlation of serum leptin with estradiol levels in patients with polycystic ovary syndrome

Patients with polycystic ovary syndrome (PCOS) usually are obese, insulin resistant and hyperinsulinemic. The known association between leptin, obesity andinsulin action suggests that leptin may have a role in PCOS but this has only been addressed peripherally. This study was designed to assess the relationship between serum leptin and the anthropometric, metabolic and endocrine variables of obese (body mass index, BMI > or = 30 kg/mý) and non-obese (BMI <30 kg/mý) PCOS patients. Twenty-eight PCOS patients and 24 control women subdivided into obese and non-obese groups were evaluated. Leptin, androgens, lipids, gonadotrophins and insulin-glucose response to the oral glucose tolerance test were measured by radioimmunoassay in all participants. The assays were done all in one time. The areas under the insulin curve (AUC-I) and the glycemia curve were calculated to identify patients with insulin resistance. Mean leptin levels were not significantly higher in patients with PCOS compared to the control group (21.2 ñ 10.2 vs 27.3 ñ 12.4 ng/ml). Leptin levels were found to be significantly higher in the obese subgroups both in patients with PCOS (26.9 ñ 9.3 vs 14.1 ñ 7.0 ng/ml) and in the control group (37.3 ñ 15.5 vs 12.9 ñ 5.8 ng/ml). The leptin of the PCOS group was correlated with BMI (r = 0.74; P < 0.0001) and estradiol (r = 0.48; P < 0.008) and tended to be correlated with the AUC-I (r = 0.36; P = 0.05). Of the parameters which showed a correlation with leptin in PCOS, only estradiol and probably insulinemia (AUC-I) did not show a significant correlation with BMI, suggesting that the other parameters were correlated with leptin due to their correlation with BMI. Estradiol correlated with leptin in PCOS patients regardless of their weight.

Positive correlation of serum leptin with estradiol levels in patients with polycystic ovary syndrome.

Patients with polycystic ovary syndrome (PCOS) usually are obese, insulin resistant and hyperinsulinemic. The known association between leptin, obesity and insulin action suggests that leptin may have a role in PCOS but this has only been addressed peripherally. This study was designed to assess the relationship between serum leptin and the anthropometric, metabolic and endocrine variables of obese (body mass index, BMI (3)30 kg/m(2)) and non-obese (BMI <30 kg/m(2)) PCOS patients. Twenty-eight PCOS patients and 24 control women subdivided into obese and non-obese groups were evaluated. Leptin, androgens, lipids, gonadotrophins and insulin-glucose response to the oral glucose tolerance test were measured by radioimmunoassay in all participants. The assays were done all in one time. The areas under the insulin curve (AUC-I) and the glycemia curve were calculated to identify patients with insulin resistance. Mean leptin levels were not significantly higher in patients with PCOS compared to the control group (21.2 +/- 10.2 vs 27.3 +/- 12.4 ng/ml). Leptin levels were found to be significantly higher in the obese subgroups both in patients with PCOS (26.9 +/- 9.3 vs 14.1 +/- 7.0 ng/ml) and in the control group (37.3 +/- 15.5 vs 12.9 +/- 5.8 ng/ml). The leptin of the PCOS group was correlated with BMI (r = 0.74; P < 0.0001) and estradiol (r = 0.48; P < 0.008) and tended to be correlated with the AUC-I (r = 0.36; P = 0.05). Of the parameters which showed a correlation with leptin in PCOS, only estradiol and probably insulinemia (AUC-I) did not show a significant correlation with BMI, suggesting that the other parameters were correlated with leptin due to their correlation with BMI. Estradiol correlated with leptin in PCOS patients regardless of their weight.

Analise da modulacao autonomica do coracao durante condicoes de repouso em homens de meia idade e mulheres pos-menopausa / Analysis of heart autonomic modulation during resting conditions in middle-aged men and postmenopausal women

O controle autonomico do coracao pode ser investigado a partir da analise da variabilidade da requencia cardiaca (VFC). Sabe-se que o aparecimento de doencas cardiovasculares (DCV) em mulheres aumenta com a idade, principalmente apos a menopausa, quando o risco torna-se similar ao observado em homens. Assim, o objetivo deste trabalho e analisar e comparar a VFC de homens de meia-idade e de mulheres pos-menopausa em condicoes de repouso. Foram estudados dois grupos saudaveis e sedentarios, sendo 10 homens de meia-idade (52,6 +- 2,63 anos) e 10 mulheres pos-menopausa (56,8+-5,09 anos) que nao faziam uso de terapia de reposicao hormonal. A frequencia cardiaca e os intervalos R-R (iR-R) foram obtidos a partir de eletrocardiograma em tempo real, batimento a batimento, durante 6 minutos em condicoes de repouso, nas posicoes supina(S) e sentada(SE). Para analise da VFC foram calculados os indices RMSM e RMSSD dos iR-R em milissegundo(ms). Nao foram observadas diferencas estatisticamente significativas nos valores dos indices RMSM e RMSSD entre os homens e as mulheres e entre as posicoes supina e sentada de ambos os grupos. A reducao da VFC observada em ambos os grupos estudados sugere similar decrescimo da modulacao parasimpatica sobre o coracao, fato que pode contribuir para o aumento do risco de DCV observado nessa faixa etaria em ambos os sexos

Effects of raloxifene therapy on the anticoagulant system in postmenopausal women.

BACKGROUND: Raloxifene therapy is associated with a three-fold increase in the risk for venous thromboembolism; however, its effects on the hemostatic system in postmenopausal women have not been well defined. OBJECTIVE: To determine the effects of raloxifene therapy on the levels of natural anticoagulant proteins in postmenopausal women. METHODS: Sixteen healthy postmenopausal women were enrolled in this prospective longitudinal study. The patients were treated with raloxifene hydrochloride (60 mg/day) for a period of 6 months. Antithrombin and protein C activities and protein S antigen levels were measured in all users at baseline, and after 1, 3 and 6 months of treatment. Statistical analysis included one-way analysis of variance (ANOVA) and the Bonferroni test for multiple comparisons among the study periods. RESULTS: Statistically significant 5.1% and 6.5% reductions of plasma antithrombin activity were observed at 3 and 6 months of therapy, respectively (p < 0.05). Compared with baseline, raloxifene did not significantly affect protein C activity or protein S level. CONCLUSIONS: The results of this prospective study show for the first time that raloxifene use is associated with a significant reduction in plasma antithrombin activity. This effect may contribute to a procoagulant state and partly explain the increased risk of venous thromboembolism in raloxifene users.

Heart rate variability under resting conditions in postmenopausal and young women.

The aim of the present study was to compare the modulation of heart rate in a group of postmenopausal women to that of a group of young women under resting conditions on the basis of R-R interval variability. Ten healthy postmenopausal women (mean +/- SD, 58.3 +/- 6.8 years) and 10 healthy young women (mean +/- SD, 21.6 +/- 0.82 years) were submitted to a control resting electrocardiogram (ECG) in the supine and sitting positions over a period of 6 min. The ECG was obtained from a one-channel heart monitor at the CM5 lead and processed and stored using an analog to digital converter connected to a microcomputer. R-R intervals were calculated on a beat-to-beat basis from the ECG recording in real time using a signal-processing software. Heart rate variability (HRV) was expressed as standard deviation (RMSM) and mean square root (RMSSD). In the supine position, the postmenopausal group showed significantly lower (P<0.05) median values of RMSM (34.9) and RMSSD (22.32) than the young group (RMSM: 62.11 and RMSSD: 49.1). The same occurred in the sitting position (RMSM: 33.0 and RMSSD: 18.9 compared to RMSM: 57.6 and RMSSD: 42.8 for the young group). These results indicate a decrease in parasympathetic modulation in postmenopausal women compared to young women which was possibly due both to the influence of age and hormonal factors. Thus, time domain HRV proved to be a noninvasive and sensitive method for the identification of changes in autonomic modulation of the sinus node in postmenopausal women.

Heart rate variability under resting conditions in postmenopausal and young women

The aim of the present study was to compare the modulation of heart rate in a group of postmenopausal women to that of a group of young women under resting conditions on the basis of R-R interval variability. Ten healthy postmenopausal women (mean Ý SD, 58.3 Ý 6.8 years) and 10 healthy young women (mean Ý SD, 21.6 Ý 0.82 years) were submitted to a control resting electrocardiogram (ECG) in the supine and sitting positions over a period of 6 min. The ECG was obtained from a one-channel heart monitor at the CM5 lead and processed and stored using an analog to digital converter connected to a microcomputer. R-R intervals were calculated on a beat-to-beat basis from the ECG recording in real time using a signal-processing software. Heart rate variability (HRV) was expressed as standard deviation (RMSM) and mean square root (RMSSD). In the supine position, the postmenopausal group showed significantly lower (P<0.05) median values of RMSM (34.9) and RMSSD (22.32) than the young group (RMSM: 62.11 and RMSSD: 49.1). The same occurred in the sitting position (RMSM: 33.0 and RMSSD: 18.9 compared to RMSM: 57.6 and RMSSD: 42.8 for the young group). These results indicate a decrease in parasympathetic modulation in postmenopausal women compared to young women which was possibly due both to the influence of age and hormonal factors. Thus, time domain HRV proved to be a noninvasive and sensitive method for the identification of changes in autonomic modulation of the sinus node in postmenopausal women

Hypogonadotropic hypogonadism: retrospective analysis of 19 cases.

OBJECTIVES: To survey the clinical data of patients with isolated gonadotropin deficiency. METHODS: We retrospectively surveyed the medical records of 19 patients with isolated gonadotropin deficiency aged 16-31 years (mean: 20 years). The major complaint was primary amenorrhea in 100% of the patients, with 42.1% of them also reporting absence of secondary sex traits, and 10% reporting anosmia or hyposmia. Seventy-four percent of the patients had been submitted to hormonal replacement therapy. RESULTS: Bone densitometry was determined in 5 patients and revealed lumbar spine osteopenia in 3 patients and femoral osteopenia in 1. An association with urologic malformations was detected in 10.5% of cases and an association with gynecologic malformations was detected in 31.6%. CONCLUSIONS: Isolated gonadotropin deficiency can be easily diagnosed but requires early estrogen replacement therapy because of a higher risk of osteopenia and consequently of osteoporosis. Concomitant urogenital malformations are frequent and should be investigated.