Does pioglitazone improve depression through insulin-sensitization? Results of a randomized double-blind metformin-controlled trial in patients with polycystic ovarian syndrome and comorbid depression.

Thiazolidinediones have shown beneficial effects in short-term treatment of depression. However, it is unclear whether the antidepressant efficacy of these agents is related to their insulin-sensitizing action. We conducted the present study to compare the antidepressant efficacy of pioglitazone with another insulin-sensitizer, metformin, in obese patients with concomitant polycystic ovarian syndrome (PCOS) and major depressive disorder (MDD). In a six-week double-blind study, 50 patients with PCOS and MDD (DSM-IV-TR criteria) with Hamilton depression rating scale (HDRS) score of <20, randomly received pioglitazone (15 mg twice daily; PO) or metformin (750 mg twice daily; PO). Assessment was done using HDRS (weeks 0, 3, 6) together with fasting Insulin, glucose, and lipid profile, liver enzymes, homeostatic model assessment of insulin resistance (HOMA-IR), anthropometric measures, and serum androgens (weeks 0 and 6). Pioglitazone was superior to metformin in reducing HDRS scores at the end of the study [38.3% versus 8.3% reduction from baseline scores, F(1, 37) = 73.513, P<0.001]. Changes from baseline in HOMA-IR values at week 6 were not significantly different between the two groups (P = 0.888). Baseline (but not follow-up) HDRS and HOMA-IR values were significantly correlated (r = 0.393, P = 0.012). In multiple regression analysis, treatment with pioglitazone independent of HOMA-IR values predicted greater score reduction on HDRS at week 6 (standardized beta = 0.801, P<0.001). Biochemical and hormonal profile did not differ between the two groups at week 6. Metformin was associated with higher frequency of gastrointestinal side effects (P = 0.014). In summary, we showed that pioglitazone improved depression with mechanisms largely unrelated to its insulin-sensitizing action (registration number: IRCT201106081556N23).

Simvastatin effects on androgens, inflammatory mediators, and endogenous pituitary gonadotropins among patients with PCOS undergoing IVF: results from a prospective, randomized, placebo-controlled clinical trial.

OBJECTIVE: To evaluate effects of simvastatin on selected biochemical parameters and reproductive outcome among patients with polycystic ovary syndrome (PCOS) who undergo in vitro fertilization (IVF). METHODS: Patients with PCOS were randomized to receive either oral simvastatin, 20 mg/d (n = 32), or placebo (n = 32) in a prospective, double-blind, randomized clinical trial (NCT 005-75601) in parallel with controlled ovarian hyperstimulation for IVF. All patients were determined to be at average risk for cardiovascular disease, based on high-sensitivity C-reactive protein (hsCRP) measurement at entry. After an 8-week treatment interval concluding at periovulatory human chorionic gonadotropin administration, selected clinical and laboratory parameters were measured. RESULTS: Mean serum total testosterone level decreased by 25% in the simvastatin group, compared to a 10% reduction in the placebo group (P < 0.001). A trend of lower serum luteinizing hormone levels was noted in experimental and control groups (29% vs 22%, respectively), although this difference was not significant (P > 0.05). Neither fasting insulin nor quantitative insulin sensitivity check index were significantly impacted by simvastatin (P > 0.05). As expected, total cholesterol was not modified among placebo patients but was significantly reduced after simvastatin (P = 0.001). In addition, hsCRP and vascular cell adhesion protein-1 were both significantly lower after simvastatin therapy compared to controls (P ≤ 0.005 for both). At study completion, no important change in body mass index was observed in either group (P ≥ 0.60). Although oocyte maturation, fertilization, and clinical pregnancy rates were all higher after simvastatin, none of these improvements were statistically significant. CONCLUSIONS: This report presents data from the first prospective, randomized, placebo-controlled clinical investigation of simvastatin in the setting of PCOS and IVF. Simvastatin seems to be compatible with gonadotropin therapy for IVF and can offer beneficial endocrine and cardiovascular effects for patients with PCOS who undergo embryo transfer. Although the observed improvements in reproductive function were mild, the reductions in hsCRP and vascular cell adhesion protein-1 after simvastatin treatment were significant, suggesting the need for further clinical trials to clarify simvastatin's impact on reproductive physiology.

Menstrual cycle length in relation to antimüllerian hormone and follicle-stimulating hormone.

OBJECTIVE: To find a relationship between serum antimüllerian hormone (AMH) and follicle-stimulating hormone (FSH) levels in women with regular menstruation. STUDY DESIGN: A cross-sectional study was conducted on 71 women with male factor infertility. Serum level of AMH and FSH and mean menstrual cycle length (MCL) were measured. The study aimed to find the correlation between serum AMH and FSH levels in normal menstrual cycles. RESULTS: Our study included 71 women. Of them, 53 had an MCL of 25-35 days (group A) and 18 women had an MCL > 35 days (group B). The mean AMH in group A and group B differed significantly (4.11 +/- 3.4 ng/L, 7.42 +/- 4.34 ng/L, respectively; p < 0.008). In group A, reverse correlation between FSH and AMH was found (r = -0.32, p < 0.03). CONCLUSION: AMH level had significant difference with FSH in patients of group A who had FSH > or = 12 IU/L or FSH < 12 IU/L (1.02 +/- 0.7, 4.8 +/- 3.5 ng/L, respectively; p < 0.02). Serum AMH level with threshold of 2.2 ng/L had sensitivity of 75% and specificity of 82% in predicting FSH > or = 12 IU/L on the third day of menstrual cycle.

Testosterone and dehydroepiandrosterone sulphate levels and IVF/ICSI results.

OBJECTIVE: To determine the effect of serum androgens [testosterone and dehydroepiandrosterone sulphate (DHEAS)] on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes. STUDY DESIGN: This observational (cross sectional) study was conducted on 53 consecutive infertile women undergoing IVF cycles in an academic infertility clinic between September 2006 and August 2007. Basal testosterone and DHEAS were measured and on third day of IVF cycle and on 14th day of embryo transfer these values were re-checked. Serum beta-hCG analysis was done 12 days after embryo transfer and ultrasound scan was scheduled 2 weeks later. RESULTS: Testosterone level was significantly elevated in pregnant women on 14th day of embryo transfer (p < 0.001). Testosterone and DHEAS concentrations on third day of IVF cycle and DHEAS concentration 2 weeks after embryo transfer had not significant correlation with IVF success, but mean androgens concentrations were higher in pregnant group. CONCLUSION: Serum testosterone concentration on 14th day of embryo transfer can predict successful IVF cycles, so with regulating androgen levels, improved pregnancy rates can be expected.