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Amaç:Bu çalışmada letrozol ve gonadotropinlerin evre 1-2 endometriozisli infertilhastalarda ovülasyon indüksiyonu üzerine etkilerinin karşılaştırılmasıamaçlanmıştır.Gereçve yöntem: Prospektif randomize olarak dizayn edilençalışmaya tanısal laparoskopi yapılan ve histolojik olarak tanı konulan evre1-2 endometriozisli 20 hasta dahil edildi. Zamanlanmış cinsel ilişki ile devametmeyi planlayan hastalar, en az üç en fazla beş ovulasyon indüksiyonu döngüsüiçin letrozol (n=10) veya gonadotropinler (n=10) olmak üzere iki tedavi grubunaardışık olarak randomize edildi.Bulgular:Ovulasyon, letrozol grubunda %82,2 (37/45 siklus) ve gonadotropin grubunda%86,4 (32/37 siklus) oranlarında gerçekleşti. İki grup arasında ovulasyonoranları istatistiksel olarak benzerdi (p=0,590). hCG uygulamasınınyapıldığı gün gonadotropin grubunda toplam folikül sayısı anlamlı olarakyüksekti (2,33±0,71 ve 3,05±0,91, p, Purpose: This study aimed to compare theeffects of letrozole and gonadotropins for ovulation induction in infertilepatients with stage 1-2 endometriosis. Materials and methods: Twenty patients who underwentdiagnostic laparoscopy and histologically diagnosed stage 1-2 endometriosiswere included in this prospective randomized study. Patients whoplanned to continue with timed sexual intercourse were randomized into twotreatment groups including letrozole (n=10) or gonadotropins (n=10) for minimumthree and maximum five treatment cycles. Results: Ovulation occurred in 37/45cycles (82.2%) in the letrozole group and 32/37 cycles (86.4%) in thegonadotropin group, without statistically significant difference (p=0.590).Total number of follicles was significantly higher in gonadotropin group on theday of hCG administration (2.33±0.71 vs. 3.05±0.91, p

BACKGROUND Polycystic ovary syndrome (PCOS) is the most frequent cause of anovulatory infertility. In women with PCOS, effective ovulation induction serves as an important first-line treatment for anovulatory infertility. Individual participant data (IPD) meta-analysis is considered as the gold standard for evidence synthesis which provides accurate assessments of outcomes from primary randomised controlled trials (RCTs) and allows additional analyses for time-to-event outcomes. It also facilitates treatment–covariate interaction analyses and therefore offers an opportunity for personalised medicine. OBJECTIVE AND RATIONALE We aimed to evaluate the effectiveness of different ovulation induction agents, in particular letrozole alone and clomiphene citrate (CC) plus metformin, as compared to CC alone, as the first-line choice for ovulation induction in women with PCOS and infertility, and to explore interactions between treatment and participant-level baseline characteristics. SEARCH METHODS We searched electronic databases including MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials up to 20 December 2018. We included RCTs comparing the following interventions with each other or placebo/no treatment in women with PCOS and infertility: CC, metformin, CC plus metformin, letrozole, gonadotrophin and tamoxifen. We excluded studies on treatment-resistant women. The primary outcome was live birth. We contacted the investigators of eligible RCTs to share the IPD and performed IPD meta-analyses. We assessed the risk of bias by using the Cochrane risk of bias tool for RCTs. OUTCOMES IPD of 20 RCTs including 3962 women with PCOS were obtained. Six RCTs compared letrozole and CC in 1284 women. Compared with CC, letrozole improved live birth rates (3 RCTs, 1043 women, risk ratio [RR] 1.43, 95% confidence interval [CI] 1.17–1.75, moderate-certainty evidence) and clinical pregnancy rates (6 RCTs, 1284 women, RR 1.45, 95% CI 1.23–1.70, moderate-certainty evidence) and reduced time-to-pregnancy (6 RCTs, 1235 women, hazard ratio [HR] 1.72, 95% CI 1.38–2.15, moderate-certainty evidence). Meta-analyses of effect modifications showed a positive interaction between baseline serum total testosterone levels and treatment effects on live birth (interaction RR 1.29, 95% CI 1.01–1.65). Eight RCTs compared CC plus metformin to CC alone in 1039 women. Compared with CC alone, CC plus metformin might improve clinical pregnancy rates (8 RCTs, 1039 women, RR 1.18, 95% CI 1.00–1.39, low-certainty evidence) and might reduce time-to-pregnancy (7 RCTs, 898 women, HR 1.25, 95% CI 1.00–1.57, low-certainty evidence), but there was insufficient evidence of a difference on live birth rates (5 RCTs, 907 women, RR 1.08, 95% CI 0.87–1.35, low-certainty evidence). Meta-analyses of effect modifications showed a positive interaction between baseline insulin levels and treatment effects on live birth in the comparison between CC plus metformin and CC (interaction RR 1.03, 95% CI 1.01–1.06). WIDER IMPLICATIONS In women with PCOS, letrozole improves live birth and clinical pregnancy rates and reduces time-to-pregnancy compared to CC and therefore can be recommended as the preferred first-line treatment for women with PCOS and infertility. CC plus metformin may increase clinical pregnancy and may reduce time-to-pregnancy compared to CC alone, while there is insufficient evidence of a difference on live birth. Treatment effects of letrozole are influenced by baseline serum levels of total testosterone, while those of CC plus metformin are affected by baseline serum levels of insulin. These interactions between treatments and biomarkers on hyperandrogenaemia and insulin resistance provide further insights into a personalised approach for the management of anovulatory infertility related to PCOS.

Objectives: The aim of the study was to compare the effects of uterine size and surgeon experience on the surgical out­comes of laparoscopically-assisted vaginal hysterectomy (LAVH) for benign gynecological conditions. Material and methods: This was a retrospective analysis of 184 LAVH cases. All hysterectomies were performed by the same surgeon and divided into two groups, with uterine weight of 280 g (group 2). The groups were compared in terms of the effects of the uterine size and surgeon experience vs. the operative outcomes (operative time, change in hemoglobin levels, hospital stay, and perioperative complications). Results: No significant differences in mean age, parity, history of chronic systemic diseases and previous surgery history were observed between the two groups. However, operative time was significantly greater in group 2 as compared to group 1 (132.1 ± 42.7 minutes vs. 111.5 ± 30.4 minutes, p < 0.05). There were no differences in the hospital stay and perioperative complications between the two groups. One case of bladder injury occurred in each group and one patient underwent a second laparoscopic surgery for postoperative bleeding in group 2. Greater surgeon experience was demonstrated to be associated with decreased operative bleeding and, consequently, smaller differences between preoperative and postop­erative hemoglobin levels. Operative time was also reduced as the surgeon was getting more experienced but the effect did not reach statistical significance. Conclusions: Our study supports the thesis that LAVH is a safe and effective procedure for managing benign gynecologi­cal conditions. Despite increased operative time, LAVH can be safely performed for enlarged uterus in conjunction with increased surgeon experience.

Dexketoprofen trometamol (DT), a nonsteroidal anti-inflammatory drug, is a highly water-soluble salt and active enantiomer of rac-ketoprofen. Its parenteral form is commonly used for acute pain management in emergency departments of our country. Side effects such as diarrhea, indigestion, nausea, stomach pain, and vomiting may be seen after the use of DT. Anaphylactic shock (AS) secondary to infusion of DT is very rare and, to our knowledge, it is the first case report describing this side effect. This case report was presented to emphasize that AS may be seen after the use of DT. Keywords: Anaphylactic shock, Dexketoprofen trometamol, Intravenous infusion (MeSH database)

Summary Objective There are conflicting data regarding the effects of metformin in lean women with polycystic ovary syndrome (PCOS). Thus, our aim was to evaluate the effects of 6 months of metformin therapy on various metabolic and cardiovascular risk factors in lean women with PCOS. Design This was a prospective clinical study performed in a University hospital. Patients Twenty nonobese PCOS women and 20 age- and BMI-matched healthy women were included in the study. Metformin (2550 mg/day) was administered for 6 months in women with PCOS. The hormonal and metabolic parameters were evaluated before and after metformin treatment. Measurements The main outcome measures were serum androgens, FSH, LH, oestradiol, 17-hydroxyprogesterone, glucose, insulin, lipid profile, lipoprotein(a) [Lp(a)] and homocysteine levels. In addition 24-h ambulatory blood pressure monitoring (ABPM) and carotid intima-media thickness (IMT) were taken. Results After 6 months of metformin therapy, women with PCOS had decreased LH, total testosterone, free androgen index and slightly increased SHBG levels. Metformin treatment resulted in resumption of regular menses in 12 (60%) patients, and in 8 (40%) of them serum progesterone level was compatible with ovulation. Glucose and insulin responses to oral glucose tolerance test (OGTT) and homeostasis model assessment of insulin resistance (HOMA-IR) did not improve after the metformin therapy. There were no significant changes in terms of cardiovascular risk factors such as lipids and homocysteine, IMT and ABPM. Conclusion Metformin may have beneficial effects in lean PCOS women in terms of resumption of menses without any remarkable effect on metabolic and cardiovascular risk factors.

Hirsutism, which is a common clinical problem in women of reproductive age, is characterized by excessive growth of terminal hair in the androgen-sensitive skin regions. It is the result of either androgen excess or increased sensitivity of the hair follicles to normal levels of androgens. The management, which includes cosmetic measures and medical treatment, is far from satisfactory. Anti-androgen drugs play a key role in the treatment of hirsutism, but they have some side-effects which may result in cessation of the drug. On the other hand, anti-androgen treatment often needs to be continued for a long time. So, safe, inexpensive, and effective anti-androgen drugs are needed. Recently low-dose anti-androgen drugs have been shown to be effective in the maintenance of treatment. On the other hand, cyproterone acetate plus ethyniloestradiol and spironolactone, cyproterone acetate plus ethyniloestradiol and finasteride, and spironolactone and finasteride combinations have been used successfully in decreasing the hirsutism score. There are also some promising data regarding the effects of insulin sensitizers in the treatment of hirsutism, particularly in patients with polycystic ovarian syndrome. In the present review, the main features of anti-androgen drugs, new combined treatments, and insulin sensitizers in the treatment of hirsutism are discussed.

Objective(s): To evaluate the effects of metformin on insulin resistance, ovarian androgen production, and clomiphene-induced ovulation and pregnancy rates in infertile women with polycystic ovary syndrome (PCOS). Study design: Twenty-one infertile women with PCOS were selected in this prospective randomized clinical study. Basal steroid and gonadotropin levels were measured, and oral glucose tolerance test (OGTT) was performed. The patients were divided randomly into group 1 (n = 11) and group 2 (n = 10). Group 1 patients were treated with 1700 mg per day of metformin for 3 months. The basal tests and OGTT were repeated after metformin therapy. Group 2 patients did not receive metformin. The patients in both groups received 100 mg of clomiphene citrate (CC) daily for 5 days until either a pregnancy occurred, or six CC cycles were reached. Metformin administration continued during CC therapy until the day of hCG in group 1. Serum progesterone (P) level greater than or equal to5 ng/ml was considered as confirmatory of ovulation. Ovulation and pregnancy rates after six cycles were determined. Results: Serum androgens and insulin response to OGTT decreased significantly after metformin therapy. Midluteal serum P level was significantly higher in cycles treated with metformin plus CC (P < 0.05). The ovulation (38 of 51 cycles, 74.4% versus 34 of 55 cycles, 61.8%) and pregnancy rates (5 of 11 women, 45.5% versus 3 of 10 women, 30%) were higher, but not significantly, in the metformin plus CC group than in the CC alone group. All the patients who conceived had insulin resistance in group 1 whereas non-insulin resistance in group 2. Conclusion(s): Metformin improves insulin resistance and reduces androgen levels. Metformin did not increase significantly the ovulation and pregnancy rates. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

OBJECTIVE: To determine the frequency of late-onset adrenal hyperplasia (LOCAH) due to 21-hydroxylase (21-OH) and 11 beta-hydroxylase (11 beta-OH) deficiency in women with clinical and biochemical features of polycystic ovary syndrome (PCOS). DESIGN: Eighty-three consecutively selected women with PCOS and eighteen normal women were included in the study. METHODS: Ultrasound, clinical and hormonal parameters were used to define PCOS. Basal FSH, LH, testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEA-S), sex hormone-binding globulin (SHBG) and cortisol levels were measured. Serum 17-hydroxyprogesterone (17-OHP) and 11-deoxycortisol (11-DOC) levels were also measured before, 30 and 60 min after a single bolus injection of 0.25 mg ACTH (1-24) at 0900 h during the mid-follicular phase of the cycle. ACTH-stimulated 17-OHP levels > 30 nmol/l were considered as the criteria of 21-OH deficiency. The diagnosis 11 beta-OH deficiency was made if the adrenal 11-DOC response to ACTH stimulation exceeded threefold the 95th percentile of controls. RESULTS: Basal serum testosterone, free testosterone, androstenedione, DHEA-S, cortisol and 11-DOC levels were significantly higher in PCOS than in control subjects. ACTH-stimulated 17-OHP (P < 0.05) and 11-DOC (P < 0.0005) levels were found to be significantly higher in patients with PCOS than in controls. Seven (8.4%) patients had an 11-DOC response to ACTH higher than threefold the 95th percentile of controls, while no patients showed evidence of 21-OH deficiency. CONCLUSIONS: We have found that 8.4% of the women with clinical and biochemical features of PCOS could be presumed to have 11 beta-OH deficiency. No patients among the women with PCOS showed evidence of 21-OH deficiency. 11 beta-OH deficiency is unexpectedly more common than 21-OH deficiency in women with PCOS.

Objective: To determine whether hyperinsulinism affects cytochrome P450c 17α activity by investigating the correlation between 17–hydroxyprogesterone (17–OHP) hyper-responsiveness to the gonadotropin-releasing hormone (GnRH) agonist, buserelin, and the insulin response to oral glucose in polycystic ovary syndrome (PCOS). Design: Ultrasound, clinical and hormonal parameters were used to define PCOS in this prospective clinical study. We investigated the correlation between the 17–OHP response to buserelin testing and the insulin response to oral glucose in PCOS. Methods: Twenty-eight women with PCOS and eighteen normal women were included in the study. 17–OHP response to buserelin, and insulin and C–peptide responses to oral glucose were measured. Results: Twenty–live women with PCOS had an increased 17–OHP response. The PCOS patients showed significantly higher mean post–glucose load insulin and C–peptide levels than controls (PP >0·05). Conclusions: Lack of a relationship between the 17–OHP response to the GnRH agonist buserelin and hyperinsulinism suggests that hyperinsulinism may not play a role in the dysregulation of the cytochrome P450c17α enzyme seen in PCOS. European Journal of Endocrinology 136 410–415

Objective To investigate the effects of low dose flutamide (250mg/d) on hirsutism score and some hormone levels in women with hirsutism. Design Nonrandomized, prospective clinical trial. Patients Forty-one patients with moderate-severe hirsutism were included in the study. Intervention Hirsute patients received 250mg/d flutamide for a period of 6 months. Main Outcome Measures Hirsutism score, FSH, LH, E 2 , total T, free T, androstenedione, DHEAS, PRL, 17-hydroxyprogesterone, and sex hormone-binding globulin levels were detected in all the patients before treatment and every 3 months during treatment. Results Treatment with the antiandrogen flutamide resulted in a particularly rapid and marked decrease in the hirsutism score, which decreased from 17.48±5.35 to 5.07±2.89 after 6 months. No significant changes in the levels of hormone and no serious side effects were observed in the study. Conclusion The low-dose flutamide, 250mg/d, is a cost-effective drug in the treatment of hirsutism. Low-dose flutamide may be used in place of high-dose flutamide, 500 to 750mg/d.

Summary OBJECTIVE We determined the 17-hydroxyprogesterone (17-OH P) response to buserelin, a GnRH agonist, and its relation to ovarian volume in the patients with polycystic ovary syndrome (PCOS). DESIGN We compared 17-OH P response to buserelin in a large group of patients with that In a control group of healthy women. We also investigated whether there is any relation between LH-induced 17-OH P production in response to buserelin and ovarian volume. PATIENTS Ten normal women and 31 women with PCOS were included in the study. MEASUREMENT Pelvic ultrasound examination by abdominal or vaginal transducer was performed. Serum basal levels of LH, FSH, free testosterone and 17-OH P were measured by radioimmunoassay. 17-OH P responses to both ACTH and buserelin were detected. Cortisol levels were measured before and after dexamethasone suppression. RESULTS The subcutaneous administration of 1 mg buserelin produced an increase in serum 17-OH P, which peaked within 24 hours in all groups. The mean ±SEM level of 17-OH P, 24 hours after buserelin stimulation in the women with PCOS (15.94 ±1.31 nmol/l) was significantly higher (P

Purpose: The boron and fluoride mainly accumulate in the bones and teeth of the human body. The purpose of this study is to determine boron or fluoride levels in the whole tooth, to evaluate the correlation between their levels and to compare these levels in primary/permanent, carious, and non-carious groups. Materials and Methods: The boron and fluoride levels of thirty-six teeth, separated such as primary carious (n=9) and non-carious (n=9), permanent carious (n=9) and non-carious (n=9), were determined by ICP-MS and ion-selective electrode, respectively. Results: While boron levels were between 0.001 and 5.88 ppm, the fluoride levels were between 21.24 and 449.22 ppm. The boron level of non-carious teeth was higher than those of carious teeth in primary and permanent tooth groups. However, this difference was not statistically significant (p>0.05). The fluoride level of non-carious teeth was higher than those of carious teeth in primary (p=0.062) and permanent teeth groups (p=0.046). Negative correlation, found between boron and fluoride in all groups, was significant only in non-carious teeth group (r=-0.488, p=0.040). Conclusion: The results of our study proved the importance of fluoride as a protective factor for dental caries once more. The boron levels in non-carious teeth were also higher than carious teeth. However, it was not significant. Moreover, there was negative correlation between teeth boron and fluoride levels. Therefore, it is necessary to conduct more detailed studies on the tooth boron level and its relation with caries formation and with fluoride levels.