With infertility populations rapidly aging, treatments improving pregnancy chances assume increasing clinical importance. Dehydroepiandrosterone (DHEA) has been reported to improve pregnancy rates and lower miscarriage rates in women with diminished ovarian function. This study was planned to evaluate whether pretreatment with DHEA may improve in vitro fertilization (IVF) parameters and pregnancy outcomes in infertile women with advanced reproductive age and normal ovarian reserve. Methods: In this double-blind, randomized, placebo-controlled study, 109 infertile patients aging 36-40 years old were selected to undergo the long protocol IVF. Eight weeks before starting the IVF cycle and during treatment, patients in Group 1 received 75 mg of DHEA once a day; patients in control group (Group 2) received placebo. The primary endpoint of the study was number of clinical pregnancy, live birth and miscarriage rates; secondary endpoint was modification of standard IVF parameters, including stimulation duration (days of rhFSH administration), E2 on HCG-day, endometrial thickness, number of retrieved oocytes, metaphase II oocytes, number of transferred embryos and score of leading embryos transferred. Results: Patients in the DHEA group had a significantly higher live birth rate compared with controls (P < 0.05). Conversely, miscarriage rate was higher for patients in the control group (P < 0.05). Conclusions: DHEA supplementation may significantly improve IVF outcomes in infertile women with advanced reproductive age and normal ovarian reserve. © Tartagni et al.; licensee BioMed Central.

Objective: To evaluate whether the addition of finasteride (a 5 <-reductase inhibitor) to conventional protocol of ovarian stimulation with gonadotropin can improve ovarian follicular growth in polycystic ovary syndrome (PCOS) women who did not respond to previous stimulation with gonadotropin alone. Design: Double-blind randomized study. Setting: Outpatient in an academic research environment. Patient(s): Thirty-six PCOS patients in whom the previous multifollicular stimulation protocols with gonadotropin failed. Intervention(s): The patients were randomly assigned to two treatment groups: group 1 underwent ovarian stimulation with recombinant FSH (rFSH) plus finasteride, and group 2 received rFSH alone. When the dominant follicle reached a mean diameter of 18 mm, hCG was administered and finasteride withdrawn. Main Outcome Measure(s): Ovulation rate in women with PCOS. Result(s): Follicular growth and ovulation occurred in eight patients in group 1, whereas no cases were detected in group 2. Conclusion(s): This study confirms that hyperandrogenism interferes with follicular growth and suggests that administration of finasteride during ovarian stimulation with rFSH improves ovulation rate in selected hyperandrogenic anovulatory women. (Fertil Steril (R) 2010; 94: 247-9. (C) 2010 by American Society for Reproductive Medicine.)

STUDY OBJECTIVE: Hirsutism has negative impact on adolescent psychosocial development for both cosmetic and endocrine reasons. This study evaluated the effectiveness of a new intermittent, low-dose finasteride regimen consisting of 2.5 mg of drug given every 3 days (1 day of treatment, 2 days of drug withdrawal) for 6 months in girls with hirsutism by polycystic ovarian syndrome (PCOS) or idiopathic hirsutism (IH). DESIGN AND PARTICIPANTS: Twenty-eight girls (15-19 y old) with hirsutism were randomly assigned to 2 treatment groups and treated for 6 months. Fourteen patients (7 with IH, 7 with PCOS) received finasteride; fourteen patients (7 with IH, 7 with PCOS) received placebo. Hirsutism score (HS), clinical, and hormonal effects were compared between the 2 groups. RESULTS: In patients treated with finasteride, the HS value at 6 months was 52.9% lower than that observed at baseline in girls with IH, and 52.8% lower in girls with PCOS (P < .0001 for both). Similarly, the 3α-17 β-androstenediol glucuronide serum levels were decreased by 34.8% in patients with IH, and by 47.5% in patients with PCOS (P < .0001, respectively). Finasteride treatment was well tolerated and did not alter values of BMI, serum levels of sexual hormones, metabolic parameters related to liver and kidney function as well as glycemic and lipidic asset. CONCLUSIONS: A low-dose of finasteride, given every 3 days, reduces the HS in young patients affected by PCOS or IH. Compared with conventional continuous finasteride administration, the intermittent low-dose regimen has similar efficacy with the advantage to be safer and less expensive

To evaluate the hypothesis that pretreatment with dehydroepiandrosterone(DEHA) may improve the result on in vitro fertilization (IVF) and the pregnancy outcome among infertile women with normal ovarian reserve STUDY DESIGN: Double-blind, randomized, placebo-controlled study. 52 infertile patients received the long protocol IVF. Patients in Group 1, received 75 mg of DHEA once a day , 8 weeks before starting the IVF cycle and during treatment; control group (Group 2) received placebo. The primary endpoint was pregnancy, live birth and miscarriage rates, secondary endpoint was standard IVF parameters such us stimulation duration (hCG day ), E2 on HCGday, endometrial thickness, number of retrieved oocytes, metaphase II oocytes, embryos transferred and score of leading embryos transferred. RESULT(S): Patients in the DHEA group had a significantly higher live birth rate compared with controls ( P< 0.05). Miscarriage rate was higher in control group ( P< 0.05) CONCLUSION: DHEA supplementation could have a beneficial effect on IVF outcome in infertile women with normal ovarian reserve.

Background – Thiazolidinediones (TZDs) including rosiglitazone (ROSI) are insulin sensitizing agents with beneficial gastrointestinal effects. However, no studies are available on TZDs effect in gastrointestinal motility. We evaluated the effects of ROSI on gastrointestinal inhibitory neurotransmission focusing on the modulatory roles of nitric oxide synthase/nitric oxide (NOS/NO) and heme oxygenase/carbon monoxide (HO/CO) pathways. Methods – Spontaneously hypertensive rats (SHR) were used as model of insulin-resistance. Duodenal strips were obtained from vehicle-treated SHR, ROSI-treated SHR (5 mg/kg by gavage daily per 6 weeks), and Wistar Kyoto (WKY). Inhibitory responses to electrical field stimulation (EFS) were evaluated in the presence of HO inhibitor zinc protoporphyrin IX (ZnPPIX, 10 μM) or NOS inhibitor NG-nitro-L-arginine (L-NNA, 100 μM), alone and in combination. Protein levels of HO and NOS isoforms were evaluated by immunohistochemistry and western blot analysis. Key results – Basal responses to EFS were significantly increased in duodenum strips from vehicletreated SHR vs. WKY. This effect was reversed in ROSI-treated SHR. EFS-mediated relaxation was comparably reduced by ZnPPIX in WKY and SHR, but not in ROSI -treated SHR animals. LNNA reduced EFS response to a similar extent in WKY and ROSI -treated SHR, but its effect was significantly higher in vehicle-treated SHR. Expression of HO-1 protein was significantly lower, while HO-2 protein levels were unchanged in ROSI-treated SHR with respect to vehicle-treated SHR. Finally, increased levels of nNOS in vehicle-treated SHR were reduced in ROSI-treated SHR. Conclusions – Chronic ROSI treatment reverses increased SHR duodenal inhibitory response acting on CO and NO components.

The association of obesity and diabetes, termed "diabesity", defines a combination of primarily metabolic disorders with insulin resistance as the underlying common pathophysiology. Cardiovascular disorders associated with diabesity represent the leading cause of morbidity and mortality in the Western world. This makes diabesity, with its rising impacts on both health and economics, one of the most challenging biomedical and social threats of present century. The emerging comprehension of the genes whose alteration confers inter-individual differences on risk factors for diabetes or obesity, together with the potential role of genetically determined variants on mechanisms controlling responsiveness, effectiveness and safety of anti-diabetic therapy underlines the need of additional knowledge on molecular mechanisms involved in the pathophysiology of diabesity. Endothelial cell dysfunction, resulting from the unbalanced production of endothelial-derived vascular mediators, is known to be present at the earliest stages of insulin resistance and obesity, and may precede the clinical diagnosis of diabetes by several years. Once considered as a mere consequence of metabolic abnormalities, it is now clear that endothelial dysfunctional activity may play a pivotal role in the progression of diabesity. In the vicious circle where vascular defects and metabolic disturbances worsen and reinforce each other, a low-grade, chronic, and 'cold' inflammation (metaflammation) has been suggested to serve as the pathophysiological link that binds endothelial and metabolic dysfunctions. In this paradigm, it is important to consider how traditional antidiabetic treatments (specifically addressing metabolic dysregulation) may directly impact on inflammatory processes or cardiovascular function. Indeed, not all drugs currently available to treat diabetes possess the same anti-inflammatory potential, or target endothelial cell function equally. Perspective strategies pointing at reducing metaflammation or directly addressing endothelial dysfunction may disclose beneficial consequences on metabolic regulation. This review focuses on existing and potential new approaches ameliorating endothelial dysfunction and vascular inflammation in the context of diabesity.