Search

This study aimed to evaluate the efficacy and adverse effects of dienogest for the treatment of endometriomas. Dienogest (2 mg/day) was administered to patients with endometrioma continuously through the 6-month study period. The patients were prospectively examined on the efficacy and side effects at baseline, at third months, and sixth months of the treatment. Twenty-four out of 30 patients were able to complete the study. The mean volume of the endometrioma decreased significantly from 112.63 ± 161.31 cm³ at baseline to 65.47 ± 95.69 cm³ at a 6-month follow-up (-41%) (

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.

Aim The aim of this study was to assess the results of conservative treatment of cervical ectopic pregnancy (CEP). Methods We retrospectively reviewed all cervical ectopic pregnancies diagnosed at the present department between January 2010 and July 2015. Patients with CEP who were treated with either systemic or intra-amniotic methotrexate (MTX) injection were included in the study. Results Ten CEP patients were identified. Median maternal age was 33 years (range, 23–40 years). Median gestational age at diagnosis was 47 days (range, 44–58 days). Before treatment, overall mean serum beta-human chorionic gonadotrophin (β-hCG) was 29 706.9 ± 19 695.2 mIU/mL. Mean gestational sac size was 29.0 ± 6.24 mm. Eight patients had viable fetuses with detected cardiac activity. Six patients were treated primarily with systemic MTX, and four were treated with local MTX injection. One patient in the systemic MTX injection group was switched to local MTX treatment due to severe oral ulceration and increasing β-hCG titers after the fourth dose. One patient in the local treatment group had severe hemorrhage 7 days after local MTX. Three of six women achieved spontaneous pregnancy and gave birth to term, healthy infants after treatment. Conclusion Conservative treatment of CEP with both systemic and local MTX is generally successful with regard to maternal morbidity and reproductive function, but these patients must be closely followed due to the small but real risk of late hemorrhage.

Objective Acne is not solely a cosmetic problem. The clinical importance of acne in the estimation of androgen excess disorders is controversial. Recently, the Amsterdam ESHRE/ASRM-sponsored third PCOS Consensus Workshop Group suggested that acne is not commonly associated with hyperandrogenemia and therefore should not be regarded as evidence of hyperandrogenemia. Our aim was to investigate whether acne is a sign of androgen excess disorder or not. Study design This is a cross sectional study that was performed in a university hospital involving 207 women, aged between 18 and 45 years, suffering mainly from acne. The women were assigned as polycystic ovary syndrome (PCOS), idiopathic hirsutism (IH), idiopathic hyperandrogenemia (IHA). Women with acne associated with any of the androgen excess disorders mentioned above were named as hyperandrogenemia associated acne (HAA). Women with acne but without hirsutism and hyperandrogenemia and having ovulatory cycles were named as “isolated acne”. Serum luteinizing hormone, follicle stimulating hormone, estradiol, progesterone, 17-hydroxyprogesterone, dehydroepiandrosterone-sulfate (DHEAS), androstenedione, total testosterone and lipid levels were measured. Results Acne score was similar between the women with isolated acne and HAA. The most common cause for acne was PCOS and only 28% of the women had isolated acne. 114 (55%) women had at least one raised serum androgen level. Conclusions In this study, 72% of acneic women had clinical and/or biochemical hyperandrogenemia. In contrast to the suggestion of ESHRE/ASRM-sponsored third PCOS Consensus Workshop Group, our data indicate that the presence of androgen excess disorders should be evaluated in women presenting with acne.

To compare the surgical outcomes of vaginal hysterectomy and prophylactic oophorectomy in women with a uterine size12 weeks' gestation and 12-20 weeks' gestation, without decensus.In this prospective comparative study, 241 consecutive vaginal hysterectomies were planned for women with benign disease of the uterus. All hysterectomies were performed by the same surgeon (author), and divided into 2 groups: a uterine weight280 g (n=83, 280-1150 g) and a uterine weight280 g (n=158). The 2 groups were compared for success rates of hysterectomy and bilateral oophorectomy vaginally, operative time, change in haemoglobin, haemorrhage, length of hospital stay, operative complications, and febrile morbidity.All 241 hysterectomies were completed successfully vaginally, and no patients required laparotomy or additional procedures in both groups. No significant intra- and post-operative complications requiring admission to the hospital were encountered in either group. Mean operating time was significantly longer in the uteri/=280-g group than in the280-g group (69.4+/-24.4 versus 108.2+/-41.2 min, p0.0001). The rate of intraoperative haemorrhage (8.43 versus 1.2%) and the change in haemoglobin were significantly higher in the/=280-g group compared with the280-g group (p0.01). Significant positive linear correlation between uterine weight and operative time was seen in all 241 hysterectomies (p0.001). The rate of bilateral oophorectomy was similar between the uteri/=280-g group (89.8%) and the280-g group (92.9%). The main intraoperative complication of the 241 vaginal hysterectomies was bladder injury that occurred in 1 case (0.4%) in the280-g group. There were no statistically significant differences in intra- and post-operative complications, febrile morbidity, and postoperative hospital stay between the groups.Our findings demonstrate that despite the prolonged operating time and increased intraoperative blood loss, vaginal hysterectomy can be safely performed on a large uterus. Routine bilateral prophylactic oophorectomy can be performed in all patients who have sufficiently long infundibulopelvic ligaments to permit removal of the entire ovary.

Objecti{dotless}ve: To investigate the prevalence of polycystic ovary syndrome (PCOS) and polycystic ovary (PCO) among premenopausal women with type 2 diabetes mellitus (DM). Desi{dotless}gn: Case-control study of women with type 2 DM. Setti{dotless}ng: Tertiary referral university hospital. Pati{dotless}ent(s): Ninety-two premenopausal women with DM, ?30 years of age, and 20 age- and body mass index-matched healthy premenapousal eumenorrheic women were recruited into the study. Interventi{dotless}on(s): An oral glucose tolerance test was performed according to the American Diabetes Association criteria for each healthy woman. After an overnight fasting, blood samples were obtained for the determination of fasting blood glucose, LH, FSH, free T, androstenedione (A4), 17-hydroxyprogesterone (17-OHP), DHEAS, PRL, free T4, TSH, E2, and sex hormone-binding globulin (SHBG) levels. A GnRH analog (buserelin) test was carried out in 36 patients with DM and PCO (including PCOS subjects), 20 patients with DM without PCO or PCOS, and 20 healthy subjects. Mai{dotless}n Outcome Measure(s): The prevalence of PCO and PCOS in women with type 2 DM. Result(s): Fifty-seven (62%) of diabetic patients had normal ovaries, 31 (33.7%) had PCO, and 4 (4.3%) had PCOS. The women with DM (n = 92) and healthy women (n = 20) had similar basal A4, FSH, E2, 17-OHP, free T, and DHEAS levels. The LH and SHBG levels were lower and the hirsutism score higher in diabetic patients than in healthy women (P

OBJECTIVE: To compare the clinical efficacy and safety of the combination of spironolactone (100 mg/day) plus finasteride (5 mg/day) and spironolactone (100 mg/day) alone in the treatment of hirsutism. PATIENTS AND MEASUREMENTS: Sixty-five hirsute women were randomly assigned to one of these two treatment groups. Hirsutism score was measured according to the modified Ferriman-Gallwey scoring system. Baseline and post-treatment assessments were carried out in each subject by an investigator blinded to the therapy. Both groups had similar demographic properties at baseline. The serum levels of total and free testosterone, dehydroepiandrosterone sulphate and sex hormone-binding globulin were measured at the beginning and after 1 year of therapy. Blood chemistry and side-effects were evaluated during the study. Hirsutism scores were decreased significantly in both groups at the end of the year. RESULTS: The mean percentage change in hirsutism scores from baseline in the spironolactone plus finasteride-treated group (51.3%) was significantly (P

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)

Tumor necrosis factor alpha (TNF-alpha) and other cytokines have been implicated in the pathogenesis of ovarian hyperstimulation syndrome (OHSS). Pentoxifylline, a methylxanthine derivative, was found to inhibit TNF-alpha synthesis. The aim of this study was to evaluate whether the use of pentoxifylline would prevent the occurrence of OHSS in a rabbit model. Thirteen rabbits were divided into two groups. The first group (n = 6) were given pentoxifylline 15 mg/kg intravenously and the second group (n = 7) were given physiological serum 15 mg/kg before ovulation induction. Ovarian hyperstimulation was induced in rabbits by 200 IU equine chorionic gonadotropin on day 1 and 100 IU human chorionic gonadotropin on day 3. Blood samples were analyzed for TNF-alpha on days 1, 3 and 5. All animals were autopsied on day 6 to evaluate the ovarian weight, ascites formation and histopathological changes. There was no difference between groups regarding weight gain, ascites formation and plasma TNF-alpha levels (p0.05). Ovarian weight and number of ovulations were significantly lower in the pentoxifylline group than the control group (p0.05). Pentoxifylline did not prevent ascites formation despite the observed decrease in ovarian weight and number of ovulations in OHSS in a rabbit model.

Objective Polycystic ovary syndrome (PCOS) is a form of functional ovarian hyperandrogenism and affects approximately 5-10% of women of reproductive age. Insulin resistance and hyperinsulinaemia appear to be almost universal feature of the polycystic ovary syndrome. Abnormal regulation of cytochrome P450c17alpha causes the exaggerated secretion of ovarian androgens in PCOS. The aim of the present study was to determine whether reduction of insulin levels by metformin would attenuate FSH, LH, 17-Hydroxyprogesterone (17-OHP) and androstenedione hyperresponsiveness to buserelin testing in PCOS women. Design The presence of hyperinsulinaemia in 16 women with PCOS was demonstrated by an oral glucose tolerance test (OGTT) and results were compared with 13 healthy women. PCOS women were also evaluated with insulin tolerance test (ITT) for the assessment of insulin sensitivity. FSH, LH, 17-OHP and androstenedione responses to buserelin testing were measured in all the women with PCOS. PCOS patients were given metformin (500 mg, orally, two times daily) for 12 weeks and re-evaluated at the end of the treatment period. Results Women with PCOS were hyperinsulinaemic (basal insulin 92.1+/-14.3 vs. 44.0+/-4.0 pmol/l; AUCinsulin 68087.4+/-8862.3 vs. 13075.5+/-1327.6 pmol/lx120 min) compared with healthy women. Metformin therapy improved menstrual disturbances in 25% of the women with PCOS and also resulted in some improvement in insulin sensitivity and reduced basal and post glucose load insulin levels. However, FSH, LH, 17-OHP and androstenedione responses to buserelin testing were unaltered in response to metformin. Conclusion It is clear that PCOS is often associated with profound insulin resistance and hyperinsulinaemia. These abnormalities explain the increased prevalence of glucose intolerance in women with PCOS and metformin has beneficial effects on insulin sensitivity in women with PCOS. Amelioration of hyperinsulinaemia has no significant effect on ovarian cytochrome P450c17alpha enzyme activity. However, it can be used in obese women with PCOS as an adjuvant therapy and long term studies should be performed to evaluate the endocrine effects of metformin in women with PCOS.

OBJECTIVE: To determine whether metformin. when given to non-diabetic women with polycystic ovary syndrome (PCOS), results in a reduction of insulin resistance and hyperinsulinemia while body weight is maintained. Also we aimed to see whether the reduction in insulin levels attenuates the activity of adrenal P450c17alpha enzyme in patients with PCOS. DESIGN: We investigated the 17-hydroxyprogesterone (17-OHP) and androstenedione responses to ACTH, insulin responses to an oral glucose tolerance test (OGTT) and glucose disposal rate in an insulin tolerance test before and after metformin therapy (500 mg, orally, twice daily, for 12 weeks). METHODS: The presence of hyperinsulinemia in 15 women with PCOS was demonstrated by an OGTT and results were compared with those of 10 healthy women. Insulin sensitivity was measured by the rate of endogenous glucose disposal after i.v. bolus injection of insulin. 17-OHP and androstenedione responses to ACTH were measured in all the women with PCOS and the normal women. RESULTS: Women with PCOS were hyperinsulinemic (102.0+/-13.0 (S.E.M.) VS 46.2+/-4.4 pmol/l) and hyperandrogenemic (free testosterone 15.3+/-1.7 vs 7.9+/-0.6 nmol/l; androstenedione 11.8+/-0.8 vs 8.2+/-0.6 nmol/l) and more hirsute (modified Ferriman-Gallwey score, 17.7+/-1.6 vs 3.0+/-0.3) than healthy women. In addition, women with PCOS had higher 17-OHP and androstenedione responses to ACTH when compared with healthy women. Metformin therapy resulted in some improvement in insulin sensitivity and reduced the basal and post-glucose load insulin levels. But 17-OHP and androstenedione responses to ACTH were unaltered in response to metformin. CONCLUSIONS: PCOS is characterized by hyperactivity of the adrenal P450c17alpha enzyme and insulin resistance. It seems that there is no direct relationship between insulin resistance and adrenal P450c17alpha enzyme dysregulation.

The aim of this study was to compare the clinical efficacy and safety of low dose cyproterone acetate-estrogen combination (Diane(R)) and the 5 alpha-reductase inhibitor finasteride in the treatment of hirsutism. Fourty-two women with hirsutism were included in the study. Twenty-one patients treated with cyproterone acetate (CPA) 2 mg and ethinyl estradiol (E) 35 mu g daily on days 5-25 of the menstrual cycle, 21 with finasteride 5 mg daily. Hirsutism score, hormone levels, multiscreen blood chemistry and side effects were evaluated at three-monthly intervals for 9 months. A significant decrease in hirsutism score as compared to baseline was observed after 9 months with either CPA+E (Diane(R)) (mean +/- SE, 15.81+/-1.19 vs 8.38+/-1.21) or finasteride treatment (17.81+/-1.05 vs 10.86+/-0.91) (p

We investigated the possible effects of the angiotensin converting enzyme (A CE) inhibitor cilazapril and angiotensin II antagonist saralasin on ovulation, ovarian steroidogenesis and ascites formation in the ovarian hyperstimulation syndrome (OHSS) in the rabbit model. OHSS was induced in rabbits by human menopausal gonadotropin (hMG) and intermittent human chorionic gonadotropin (hCG). In the cilazapril group (n = 10), animals also received cilazapril 2 mg/kg intraperitoneally daily for 7 days. In the saralasin group (n = 8), animals received saralasin intraperitoneally 1 h before or 1 h after hCG administration. Control animals (n = 8) received intraperitoneal saline solution. Serial blood samples were drawn on days 1, 5, 7 and 9 to measure serum estradiol and progesterone levels. On day 9, all rabbits underwent surgical exploration. Peritoneal and pleural fluid formation, ovarian weights and number of ovulations were determined. The volume of the ascitic and pleural fluids after hyperstimulation were not statistically different between the control, cilazapril and saralasin groups. The weight gains and ovarian weights of animals were similar between treatment and control groups. Saralasin significantly (p < 0.05) inhibited ovulation, but cilazapril did not. Cilazapril and saralasin did not affect progesterone production. Only cilazapril significantly decreased estradiol production (p < 0.05). In conclusion, the ACE inhibitor cilazapril and angiotensin II antagonist saralasin did not prevent ascites formation in OHSS. The ovarian renin-angiotensin system may not be the only factor acting in ascites formation in the OHSS.

OBJECTIVE The present study was designed to determine the prevalence of 11 beta-hydroxylase deficiency in adult women with hirsutism in a Turkish population. DESIGN AND PATIENTS One hundred and twenty-four consecutive unselected hirsute patients were studied. An ACTH stimulation test was performed in the midfollicular phase of the cycle on the patients and 20 age-matched controls by administration of a single bolus of 0.25 mg ACTH (1-24) at 0900 h. MEASUREMENTS Serum 11-deoxycortisol levels were measured before, 30 and 60 minutes after ACTH injection. Basal free testosterone (fT), SHBG, cortisol and androstenedione (A) were also measured. The diagnosis of 11 beta-hydroxylase deficiency has been presumed when the serum 11-deoxycortisol response to ACTH stimulation exceeded three times the 95th percentile of controls. RESULTS Basal hormone levels including fT and A were significantly higher in the hirsute women than in the healthy women. SHBG was significantly lower in the hirsute patients. Basal and ACTH stimulated 11-deoxycortisol levels were found to be significantly increased in the patients compared with the controls. Eight patients (6.5%) had an 11-deoxycortisol response higher than three times the upper normal limit. CONCLUSIONS Using stringent diagnostic criteria, we have found that 6.5% of the hirsute women in a Turkish population could be presumed to have 11 beta-hydroxylase deficiency.

ContextPrevalence of Cushing's syndrome (CS) in patients presenting with hirsutism is not well known.ObjectiveScreening of CS in patients with hirsutism.SettingReferral hospital.Patients and other participantsThis study was carried out on 105 patients who were admitted to the Endocrinology Department with the complaint of hirsutism.InterventionAll the patients were evaluated with low-dose dexamethasone suppression test (LDDST) for CS.Main outcome measureResponse to LDDST in patients presenting with hirsutism.ResultsAll the patients had suppressed cortisol levels following low-dose dexamethasone administration excluding CS. The etiology of hirsutism was polycystic ovary syndrome in 79%, idiopathic hirsutism in 13%, idiopathic hyperandrogenemia in 6%, and nonclassical congenital hyperplasia in 2% of the patients.ConclusionRoutine screening for CS in patients with a referral diagnosis of hirsutism is not required. For the time being, diagnostic tests for CS in hirsute patients should be limited to patients who have accompanying clinical stigmata of hypercortisolism.

To investigate the effect of sodium carboxymethylcellulose (SCMC) and the combination of low molecular weight heparin (LMWH) with SCMC in the prevention of intraperitoneal adhesion.Thirty-eight rats underwent bilateral surgical injury to the uterine horn and the parietal peritoneum. In 13 rats, a solution of SCMC was instilled at laparotomy. In 11 rats, LMWH was delivered on to serosal and peritoneal defects, and SCMC was instilled. As a control group 14 rats were included in the study.Surgical Research Laboratory, Erciyes University.Female Wistar-Albino rats, weighing 200 to 250 g each.Adhesions between the uterine horn and the abdominal sidewall were scored for extent and severity two weeks after the initial surgery.Although the mean adhesion score both in the SCMC group (2.8, s.d. 1.15) and in the SCMC with LMWH group (1.6, s.d 1.18) was found to be significantly lower than in the control group (3.4, s.d. 0.89) (p0.05 and p0.001, respectively), more favorable adhesion prophylaxis was achieved in the SCMC with LMWH group in comparison with the SCMC treatment group without any hemorrhagic complications (p0.001).We conclude that SCMC with LMWH are highly effective in reducing postoperative adhesions in this animal model. SCMC with LMWH appears promising in adhesion prophylaxis.

The objective of the study was to compare intracytoplasmic sperm injection (ICSI) outcome and gonadotropin doses between obese women with PCOS and non-obese patients with PCOS. This follow-up study represents ICSI outcomes in obese women with PCOS (BMI ≥ 30 kg/m(2)) compared with non-obese women with PCOS (BMI 30 kg/m(2)). Obese (n = 18) and non-obese (n = 26) women with PCOS underwent long protocol pituitary suppression, ovarian stimulation and ICSI with fresh embryo transfer. Obese patients with PCOS required higher doses of gonadotropin (2994 IU vs 1719 IU; p 0.001). Miscarriage rate was significantly higher in obese women compared with the non-obese women with PCOS (60% vs 6.7%, p = 0.002). Our results are valuable for counselling couples before initiation of assisted reproduction techniques (ART).

We describe a woman with acromegaly who had acanthosis nigricans and hirsutism. Serum growth hormone (GH) and testosterone levels were markedly elevated. Standard oral glucose tolerance test (OGTT) showed a diabetic curve and no suppressed GH levels. Fasting insulin levels were very high while plasma glucose levels were not hypoglycemic. Insulin tolerance test revealed blunted hypoglycemic response. Acanthosis nigricans was present in the right axilla and face. Ultrasonogram demonstrated bilateral polycystic changes in the ovaries. From the above findings this patient's condition is characteristic of a very rare syndrome consisting of acromegaly, polycystic ovaries (PCO), hyperandrogenism, hirsutism, insulin resistance and acanthosis nigricans.

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.

Objective To compare the effectiveness of oral and vaginal misoprostol for preoperative cervical ripening in premenopausal women before hysteroscopic surgery. Design Placebo-controlled, double blind, randomized trial. Setting University hospital. Patient(s) Eighty-six premenopausal women eligible for operative hysteroscopy were recruited. Nine women were excluded from the study. Intervention(s) Patients were randomly assigned to receive 400 μg of misoprostol orally (n = 39) or vaginally (n = 38), 10–12 hours before operative hysteroscopy. Main Outcome Measure(s) Extent of initial cervical width, percentage of patients requiring cervical dilatation, duration of cervical dilatation and surgical procedure, complications during procedure, and associated side effects. Result(s) Mean cervical widths in the vaginal and oral misoprostol groups after treatment were 7.3 ± 1.6 mm and 6.0 ± 1.5 mm, respectively, which was a statistically significant difference. Time required for cervical dilatation (98.6 ± 88.7 s vs. 49.1 ± 34.9 s) and duration of surgery (14.5 ± 6 vs. 7.7 ± 4.0 min) was statistically significantly shorter in the vaginal misoprostol group. The percentage of women with an initial cervical width of 9 mm was statistically significantly higher in the vaginal misoprostol group (36.8% vs. 5.1%). Uterine perforation occurred in two patients in the oral misoprostol group and in none in the vaginal misoprostol group. Side effects were comparable between the two treatment groups. Conclusion(s) Vaginal administration of misoprostol is more effective than the oral route for preoperative cervical ripening in premenopausal women.

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 compare the clinical efficacy and safety of the combination of Diane 35 (2 mg of cyproterone acetate, and 35 μg of ethinyl estradiol) plus finasteride (5 mg), and Diane 35 alone in the treatment of hirsutism. Design: Prospective randomized clinical study. Setting: Outpatients in Erciyes University Medical School. Patient(s): Forty women with hirsutism were selected. Intervention(s): For 1 year, group 1 patients (n = 20) were treated with Diane 35 alone (2 mg of cyproterone acetate and 35 μg of ethinyl estradiol) daily on days 5 to 25 of the menstrual cycle and group 2 patients (n = 20) with Diane 35 plus finasteride (5 mg daily). Main Outcome Measure(s): Hirsutism was graded at 6-month intervals using the Ferriman-Gallwey method. The basal hormone levels of total and free testosterone (T), androstenedione, DHEAS, and sex-hormone-binding globulin (SHBG) were measured by radioimmunoassay before the study. Total T, free T, SHBG, and DHEAS were also measured at 6-month intervals for 1 year. Multiscreen blood chemistry and side effects were evaluated during the treatment. Result(s): Thirty-four patients completed the 12-month study period. A significant decrease in the hirsutism score as compared to baseline was observed after 12 months with both Diane 35 treatment (mean ± SD, 15.62 ± 4.89 vs. 9.75 ± 3.97) and Diane 35 plus finasteride treatment (16.27 ± 6.90 vs. 8.38 ± 4.44). The percentage decreases in the hirsutism score (mean percent ± SD) were 30.26 ± 14.56 vs. 34.70 ± 11.60 at 6 months, 38.09 ± 11.46 vs. 48.14 ± 14.27 at 12 months in the Diane 35 and the Diane 35 plus finasteride groups, respectively. The percentage reduction in the hirsutism score in the Diane 35 plus finasteride group at 12 months was greater than in the Diane 35 group ( P Conclusion(s): The percentage decrease in the hirsutism score at 12 months was higher in the Diane 35 plus finasteride group than in the Diane 35 group. We believe that Diane 35 plus finasteride is an effective and safe combination for the treatment of hirsutism.

Objective: To compare the clinical efficacy and safety of Diane 35 (cyproterone acetate [2] mg and ethinyl estradiol [35μg]) plus spironolactone [100mg]combination and Diane 35 alone in the treatment of hirsutism. Design: Prospective clinical study. Setting: Outpatients in Erciyes University Medical School. Patient(s): Fifty women with hirsutism. Intervention(s): Group I patients ( n = 22) were treated with Diane 35 alone and group II patients ( n = 28) with Diane 35 plus spironolactone [100mg]. Main Outcome Measure(s): The basal hormone levels total and free T, androstenedione, DHEAS, sex hormone-binding globulin (SHBG), and prolactin (PRL) were measured by RIA before the study. Free T, SHBG, and DHEAS were also measured at 6-month intervals for 12 months. Hirsutism was graded at 6-month intervals. Result(s): The basal hormone levels were similar between the groups. Hirsutism score significantly decreased at the end of the therapy in both groups. The reduction in hirsutism score in group 11 at 12 months was greater than in group I. But the scores before the treatment, at 6 and 12 months were similar between the groups. Conclusion(s): Although the actual hirsutism score and free T concentration are not significantly different between the two groups at 12 months, percentage change in the hirsutism score at 12 months was higher in the Diane 35 plus spironolactone group. Therefore, the addition of spironolactone to Diane 35 may have a synergistic effect on hirsutism score.

To compare the effects of flutamide at 250 mg/d and 500 mg/d in the treatment of hirsutism.Randomized, prospective clinical study.Sixty-five patients with moderate to severe hirsutism.Group I (n = 35) patients were treated with flutamide, 250 mg/d, and group II (n = 30) patients were treated with flutamide, 500 mg/d, for 12 months. Baseline hormone levels, body mass index, and hirsutism scores were similar between the groups. Hirsutism score, hormone levels, and multiscreen blood chemistry were measured at 3-month intervals for 12 months.The modified Ferriman-Gallwey scores for hirsutism decreased significantly at months 6 and 12 from a mean +/- SEM of 17.8 +/- 0.9 to 6.0 +/- 0.6 (P0.001) and 17.8 +/- 0.9 to 4.8 +/- 0.7 (P0.001) in group I and from 17.0 +/- 0.9 to 6.6 +/- 0.7 and 17.0 +/- 0.9 to 5.2 +/- 0.7 (P0.001) in group II, respectively. The reductions in hirsutism scores (mean +/- SEM) were similar in group I at 6 months (64.6% +/- 2.5%) and at 12 months (71.2% +/- 2.2%) and in group II at 6 months (62.1% +/- 3.0%) and at 12 months (70.3% +/- 3.0%). The percent reductions in hirsutiam scores at 6 and at 12 months were similar within group I (64.6% +/- 2.5% and 71.2% +/- 2.2%) and group II (62.1% +/- 3.0% and 70.3% +/- 3.0%), respectively. The decreases in hirsutism scores in the first 6 months were more significant than in the last 6 months of treatment in both groups. There were no significant differences in any of the hormone levels during therapy in either group. One patient in group II was excluded from the study because of liver dysfunction.This study shows that two different doses of flutamide (250 mg/d and 500 mg/d) are similarly effective in reducing hair growth. Flutamide at a dose of either 250 mg/d or 500 mg/d has no further effect after 6 months. We conclude that if flutamide is administered at a dose of 250 mg/d it may represent an effective and well tolerated treatment with reduced cost for the patient.

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.