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.

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.

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.

The effects of thymus-derived peptides on hypothalamic LRF and pituitary gonadotropin content in prepubertal congenitally athymic nude mice and their normal heterozygous littermates.

Congenitally athymic nude mice have recognized reproductive defects, accompanied by decreased pituitary gonadotropin and hypothalamic LRF concentrations at 3 weeks of age, compared to their normal heterozygous littermates. To determine if these hormonal changes are due to decreased secretion of thymic peptides, we measured pituitary concentrations of LH and FSH and hypothalamic LRF content at 21 days of age in 122 congenitally athymic nude (nu/nu) mice and in 190 heterozygous (nu/+) littermates administered daily injections of a crude thymic extract, semipurified thymosin fraction 5, or a synthetic thymic protein preparation. All animals receiving crude thymic protein extract, and some receiving either thymosin or synthetic thymic factor, had reduced levels of hypothalamic LRF. The changes in concentrations of gonadotropins were more variable. All mice receiving crude thymic extract (with reduced hypothalamic LRF content) appeared to have increased pituitary concentrations of LH, FSH, or both when compared to control animals, although statistical significance was not achieved in all groups. A similar but less marked trend toward increased pituitary gonadotropins was also noted in mice receiving thymic factor. These preliminary results suggest that thymus-derived peptides can affect hypothalamic-pituitary function and support our hypothesis that thymic hormones may play a role in programming the hypothalamic-pituitary axis in the prepubertal period in rodents.

Effect of estradiol on the pituitary response to intravenous stimulation with luteinizing hormone-releasing hormone in menopausal women.

Five menopausal patients were submitted to stimulation with 100-micrograms doses of luteinizing hormone-releasing hormone (LH-RH) administered 120 minutes apart under three different types of conditions: (1) in a hypoestrogenic state (test 1); (2) in a hyperestrogenic state after acute intravenous bolus injection of 400 micrograms 17 beta-estradiol (E2) (test 2); (3) in a hyperestrogenic state after daily oral administration of 50 micrograms ethinyl E2 for 3 to 4 weeks (test 3). The results of the three tests showed that (1) the time needed to reach maximum LH values after LH-RH injection was longest in test 3; (2) the hormonal production rate (HPR) in test 1 was greatest after the first stimulus with LH-RH. In test 2, the two stimulations with LH-RH induced an equivalent HPR, whereas in test 3, the HPR was greatest after the second stimulation; (3) the correlation between basal LH values before LH-RH injection and the maximal values of the responses obtained after each injection changed throughout the experiment. In all three tests, the slope of the line (significant positive correlation) was always greater after the second stimulation. When the three tests were compared, the slope in test 3 was greater than in test 2, and the slope in test 2 greater than in test 1. These results clearly suggest the important role of estrogens in the regulation of LH release in women by acting not only at the hypothalamus but also at the pituitary level, and demonstrate a correlation between basal LH levels and the maximum response to LH-RH stimulation. This correlation is more marked during estrogen treatment and depends on the time of exposure to estrogen.

A comparative study of longitudinal and cross-sectional changes in plasma levels of prolactin and estriol during normal pregnancy.

Plasma prolactin (PRL) and total estriol levels were measured in normal pregnant women using blood samples collected from different patients at different gestational ages (cross-sectional study) and samples collected from the same patient at different gestational ages (longitudinal study). The cross-sectional study showed that PRL exhibited an ascending curve, with a tendency towards increased sample variability as pregnancy progressed. The longitudinal study showed that the slopes of the curves for the isolated cases differed according to the phase of gestation, in contrast to what was suggested by the cross-sectional study. A positive relationship between estriol and PRL was observed.

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.

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.

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.

Differences between serum and urinary LH in hypergonadotropic states.

In an attempt to investigate the relationship between molecular configuration, immunoreactivity, radioligand binding, and biological activity, we compared the elution profiles of immunoreactive and radioligand receptor-active LH following gel filtration over Sephadex G-100 (1.6 X 100 cm column). Samples of sera and urinary acetone-insoluble material from normal cycling women during the LH surge (n = 4) and postmenopausal (n = 2) and castrate women (n = 2) were examined. One major peak of LH immunoreactivity was present in the sera and the urinary samples from all subjects. However, this peak of immunoreactive LH in the urinary precipitate consistently occurred 8-10 fractions later than the peak activity observed in the sera. Despite the differences in the profiles of immunoreactivity between sera and urinary precipitates, the major peak of radioligand receptor activity for LH was observed in the same fractions in all samples and corresponded to the major peak of immunoreactivity observed in the sera. Thus, binding activity was sometimes observed in urinary fractions containing little immunoreactivity for LH. Bioassay of selected fractions using the rat interstitial cell-testosterone assay revealed good agreement between receptor activity and bioactivity but not between immunoreactivity and bioactivity. The ratios of total radioreceptor-active to total immunoreactive LH were consistently higher in the sera than in the urinary precipitates. These data suggest alterations in molecular form during metabolism and/or excretion of LH. Whether these alterations represent differences in peptide structure or merely carbohydrate moieties remains to be determined.

Molecular forms of LH subunits in hypergonadotropic states.

To determine whether differences in subunits of LH exist in various hypergonadotropic states, we compared the elution profiles of immunoreactive alpha LH and beta LH following gel filtration over Sephadex G-100 (1.6 X 100 cm column) of sera and urinary acetone-insoluble precipitates from normal cycling women during the LH surge and untreated agonadal women and those receiving estrogen replacement. The elution profiles for the alpha subunit were similar in all subjects in both sera and urinary precipitates. In contrast, the elution profiles of beta LH varied between sera and urinary extracts among the 3 groups of subjects. Sera and urinary precipitates from the individual agonadal women eluted identically, but the profiles were distinct from those in samples from each of the cycling women. Exogenous estrogen therapy had no effect on the elution profiles of immunoreactive urinary beta LH in agonadal women but altered the ratios of beta LH/alpha LH excreted to those observed in normal cycling women. These data document the existence of immunoreactive subunits of LH in sera and urinary acetone-insoluble precipitates and confirm the existence of multiple forms of immunoreactive beta LH. The data further suggest that gonadal steroids may modulate the metabolism and/or excretion of beta LH in various hypergonadotropic states.

Effect of venipuncture stress on plasma prolactin levels.

Venipuncture for blood collection is postulated to be a stress factor that can increase circulating prolactin (PRL) and therefore produce false results. Seven normal non-pregnant women and 44 gravidae were submitted to venipuncture with a butterfly needle connected to a syringe for vein maintenance. Blood was collected immediately (zero time) and 15 and 30 min after venipuncture. After the last collection, a vein in the contralateral arm was punctured in the non-pregnant women only and a new blood sample was collected. PRL, measured by immunoassay, varied from 7 to 13.2 ng/ml in the non-pregnant women and from 7 to 300 ng/ml in the gravidae. No significant difference in PRL values was detected at any of the collection times. It is concluded that the stress or pain caused by venipuncture is not sufficient to alter plasma PRL levels in normal (non-pregnant) or hyperprolactinemic (gravidae) 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.

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.

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.

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.