Effectiveness of Chinese herbal medicine granules and traditional Chinese medicine-based psychotherapy for perimenopausal depression in Chinese women: a randomized controlled trial.

OBJECTIVE: The aim of the study was to assess the effectiveness of Chinese herbal medicine combined with traditional Chinese medicine (TCM)-based psychotherapy (TBP) on perimenopausal depression (PMD). METHODS: This multicenter, randomized, placebo-controlled clinical trial was conducted in nine hospitals in China between August 2015 and June 2017. The study included 307 women with PMD who were divided randomly into two treatment groups: the Bushen Tiaogan formula (BSTG) plus TBP (n = 156) and placebo plus TBP (n = 151). All participants underwent treatment for 8 weeks and were followed up for 4 weeks. The primary outcome measures included scores of the Greene Climacteric Scale (GCS), Self-Rating Depression Scale (SDS), and Self-Rating Anxiety Scale (SAS). Secondary outcomes included serum levels of sex hormones and lipids, as well as adverse events. RESULTS: The average GCS, SDS, and SAS scores after treatment were significantly lower in the BSTG-plus-TBP group than those in the placebo-plus-TBP group, and the differences were greatest at the end of the 12th week: the average GCS scores were 10.8 in the BSTG-plus-TBP group versus 18.5 in the placebo-plus-TBP group (P < 0.001); the average SDS scores were 30.7 in the BSTG-plus-TBP group versus 45.4 in the placebo-plus-TBP group (P < 0.001); the SAS scores were 28.6 in the BSTG-plus-TBP group versus 42.6 in the placebo-plus-TBP group (P < 0.001). In addition, treatments with BSTG plus TBP significantly reduced the levels of basal follicle-stimulating hormone (P = 0.045) and triglycerides (P = 0.039) and increased the level of high-density lipoprotein cholesterol (P < 0.001) compared to placebo treatments with TBP. No serious adverse events occurred, and the safety indices of complete blood counts, renal function, and liver function were within normal ranges, before and after treatments. CONCLUSIONS: Treatment with BSTG formula plus TBP was more effective than TBP alone for improving PMD symptoms, sexual hormone levels, and blood lipid conditions in women with mild PMD.

American ginseng regulates gene expression to protect against premature ovarian failure in rats.

Premature ovarian failure (POF) is defined as lost ovarian functions before the age of 40. Three possible molecular markers (PLA2G4A, miR-29a, and miR-144) have been identified in our previous study by integrated analysis of mRNA and miRNA expression profiles. The present study aimed to evaluate American ginseng root's protective potential against POF by studying transcriptional and protein variations between American ginseng treatments and controls in rats. 4-Vinylcyclohexene diepoxide (VCD) was administered to rats for 14 days to induce POF. Additionally, American ginseng was administered to POF rats for one month, and PLA2G4A, miR-29a, and miR-144 expressions were measured in rat ovaries by qRT-PCR. PLA2G4A protein expression was examined by Western Blot, and PGE2, LH, FSH, and E2 serum levels were detected by ELISA. PLA2G4A mRNA and protein were downregulated in American ginseng-treated rats, miR-29a and miR-144 levels increased, and PGE2 serum levels decreased, while LH, FSH, and E2 increased compared to POF induction alone. Analysis of transcriptional and protein variations suggested that American ginseng protects the ovary against POF by regulating prostaglandin biosynthesis, ovulation, and preventing ovarian aging. High hormone levels (PGE2, FSH, and LH) were reduced, and E2 secretion approached normal levels, leading to improved POF symptoms and abnormal ovulation.

A randomized, controlled, pilot trial on the effect of dehydroepiandrosterone on ovarian response markers, ovarian response, and in vitro fertilization outcomes in poor responders.

OBJECTIVE: To evaluate whether pretreatment dehydroepiandrosterone (DHEA) supplementation improves ovarian response markers, ovarian response to standard low-dose gonadotropin stimulation, and in vitro fertilization (IVF) outcomes in poor responders. DESIGN: Randomized, double-blind, placebo-controlled pilot study. SETTING: Tertiary reproductive medicine unit. PATIENT(S): Thirty-two women with anticipated poor ovarian response. INTERVENTION(S): Randomization into DHEA group (n=16) receiving GNC (25 mg three times a day) or placebo (n=16) starting from at least 12 weeks before the scheduled IVF treatment according to a computer-generated randomization list. MAIN OUTCOME MEASURE(S): Measurement of monthly ovarian response markers, including antral follicle count (AFC), serum antimüllerian hormone (AMH), and follicle-stimulating hormone (FSH) levels; comparison of ovarian response to a standard dose of gonadotropin stimulation at week 8 and IVF outcomes; and AFC after 12 weeks (primary outcome). RESULT(S): The DHEA supplementation resulted in statistically significantly higher serum DHEA-S, free androgen index, and follicular DHEA-S levels. No statistically significant differences in the ovarian response markers (AFC, AMH, or FSH), the ovarian response to standard-dose gonadotropin stimulation, or IVF outcomes were found between the two groups. CONCLUSION(S): No statistically significant improvement in ovarian response markers, ovarian response to standard dose gonadotropin stimulation, or IVF outcomes was found in poor responders receiving pretreatment DHEA. CLINICAL TRIAL REGISTRATION NUMBER: HKCTR-1149 (www.hkclinicaltrials.com) and NCT01915186 (www.ClinicalTrials.org).

A prospective study on role of dehydroepiandrosterone (DHEA) on improving the ovarian reserve markers in infertile patients with poor ovarian reserve.

AIM: The aim of this study was to evaluate the role of dehydroepiandrosterone (DHEA) supplementation on the ovarian reserve markers in infertile patients who were poor responders in previous in vitro fertilization (IVF) cycles. STUDY DESIGN: A prospective clinical trial was conducted on 30 patients with history of poor response in previous IVF cycles. These patients were treated with DHEA, (Tab Eema-D, Corona Remedies Pvt Ltd., Ahmedabad, Gujurat, India) 25 mg thrice a day for four months. Ovarian stimulation was done using the previous protocol. Clinical parameters were measured before and treatment with DHEA. Results were analysed using Student's "t" paired test. RESULTS: DHEA resulted in a significant increase (p < 0.05) in the serum Antimullerian hormone in all age groups (35, 36-38 and >38 years). Peak estradiol level on the day of human chorionic gonadotrophin administration also increased significantly (p < 0.05). A significant decrease (p < 0.05) was noted in Day 2 follicle-stimulating hormone (FSH) in all age groups. There was no statistically significant difference in the antral follicle count (AFC). Pregnancy rate was 16.7% after treatment. Thus, DHEA has a significant effect in improving the ovarian reserve in poor responders with previously failed IVF cycles. It can help in enhancing clinical pregnancy rate in these patients.

Plasma selenium levels in Turkish women with polycystic ovary syndrome.

OBJECTIVE(S): To evaluate selenium (Se) levels in serum and their relation with hyperandrogenism and insulin resistance (IR) in women with polycystic ovary syndrome (PCOS) and in control subjects. STUDY DESIGN: Women with any gynecological problem who presented to the Kahramanmaras Sutcuimam University Medical Faculty Gynecology and Obstetric Outpatient Clinic were invited to participate. Group 1 consisted of 36 cases with a diagnosis of PCOS according to the 2003 Rotterdam Consensus Criteria, and Group 2 (control group) consisted of 33 age- and BMI-matched healthy women. In all cases, serum total testosterone (tT), dihydroepiandrostenedione-sulfate (DHEAS), follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), insulin, glucose (mg/dL), total cholesterol (TC) (mg/dL), high density lipoprotein-cholesterol (HDL-C) (mg/dL), low density lipoprotein-cholesterol (LDL-C) (mg/dL), triglyceride (TG) (mg/dL) and Se levels were measured. RESULTS: The level of FSH was significantly lower, and the levels of LH, E2, tT, and DHEAS were significantly higher in group 1 than in group 2 (p<0.05). The hirsutism score was significantly higher among PCOS women compared to the control group (p<0.05). Although insulin levels and HOMA-IR were markedly increased in the PCOS group compared to the control group, the differences were not significant (p>0.05). The plasma Se level was significantly lower in PCOS women compared to the control group (p<0.05). When we combined the all women in two groups, regarding them as one group (combined group, n=69), a negative correlation between Se and LH and tT was present (p<0.05). CONCLUSION(S): Our results show decreased plasma concentrations of Se and a negative correlation between Se and LH, tT in women with PCOS. These results indicate that Se may play a role in the pathogenesis of PCOS related with hyperandrogenism.

Evaluation of the efficacy of flaxseed meal and flaxseed extract in reducing menopausal symptoms.

The objective of this study was to evaluate the efficacy of flaxseed meal and flaxseed extract in reducing climacteric symptoms of menopausal women. Ninety menopausal women were randomly distributed into three study groups: group I received 1 g per day of flaxseed extract containing at least 100 mg of secoisolariciresinol diglucoside (SDG), group II received 90 g per day of flaxseed meal containing at least 270 mg of SDG, and group III received 1 g per day of collagen (placebo group). Subjects were assessed for menopausal symptoms by the Kupperman index at the beginning and at the end of the 6 months of treatment. Subjects were also assessed for endometrial thickness and vaginal cytology. The Kupperman index values at the beginning and end of the treatments were analyzed using the paired t-test. Both the flaxseed extract (P=.007) and the flaxseed meal (P=.005) were effective in reducing the menopausal symptoms when compared with the placebo control (P=.082). Alternatively, the changes in Kupperman index were also computed and submitted to analysis of variance. In this case, no significant differences were found (P=.084) although the data indicate a decreasing tendency for the Kupperman index by both the flaxseed extract and the flaxseed meal groups. Neither the flaxseed extract nor the flaxseed meal exerted clinically important estrogenic effects on the vaginal epithelium or endometrium as revealed by the absence of changes in the blood levels of follicle stimulating hormone and estradiol, as well as in the endometrial thickness, and vaginal epithelial maturation value. No serious adverse events related to the treatments were reported. Although the results of the present study do not allow an unequivocal conclusion about the action of flaxseed on the menopausal symptoms, they suggest that it could be premature to conclude that no such action exists. Clearly the matter still deserves further experimental attention.

Maternal folic acid supplement intake and semen quality in Danish sons: a follow-up study.

OBJECTIVE: To examine whether maternal folic acid supplement intake during pregnancy is related to better semen quality in male offspring. DESIGN: A follow-up study. SETTING: Two major Danish municipalities, Aalborg and Odense. PATIENT(S): The study population included 347 singleton sons of mothers enrolled into the Healthy Habits for Two cohort when pregnant in 1984-87. INTERVENTION(S): Information on maternal folic acid supplement intake during pregnancy was provided by self-administered questionnaire in the 36th week of gestation. MAIN OUTCOME MEASURE(S): Semen characteristics and serum concentrations of sex hormones. RESULT(S): The distribution of semen characteristics among sons whose mothers took folic acid supplement during pregnancy (n = 88, 25%) did not differ from the distributions among those without (n = 75, 22%) or with unknown folic acid supplement intake (n = 84, 53%). On the contrary, serum levels of FSH and LH were significantly higher in the folic acid supplement group. CONCLUSION(S): The hypothesis that folic acid supplement intake during pregnancy will improve semen quality in male offspring was not corroborated by a follow-up study in young Danish men.

Treatment options for sexual dysfunction in patients with chronic kidney disease: a systematic review of randomized controlled trials.

BACKGROUND AND OBJECTIVES: Sexual dysfunction is very common in patients with chronic kidney disease (CKD), but treatment options are limited. The benefits and harms of existing interventions for treatment of sexual dysfunction were assessed in patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: MEDLINE (1966 to December 2008), EMBASE (1980 to December 2008), and the Cochrane Trial Registry (Issue 4 2008) were searched for parallel and crossover randomized and quasi-randomized trials. Treatment effects were summarized as mean differences (MD) or standardized mean difference (SMD) with 95% confidence intervals (CI) using a random effects model. RESULTS: Fourteen trials (328 patients) were included. Phosphodiesterase-5 inhibitors (PDE5i) compared with placebo significantly increased the overall International Index of Erectile Function-5 (IIEF-5) score (three trials, 101 patients, MD 1.81, 95% CI 1.51 to 2.10), all of its individual domains, and the complete 15-item IIEF-5 (two trials, 80 patients, MD 10.64, 95% CI 5.32 to 15.96). End-of-treatment testosterone levels were not significantly increased by addition of zinc to dialysate (two trials, 22 patients, SMD 0.19 ng/dl, 95% CI -2.12 to 2.50), but oral zinc improved end-of-treatment testosterone levels. There was no difference in plasma luteinizing and follicle-stimulating hormone level at the end of the study period with zinc therapy. CONCLUSIONS: PDE5i and zinc are promising interventions for treating sexual dysfunction in CKD. Evidence supporting their routine use in CKD patients is limited. There is an unmet need for studying interventions for male and female sexual dysfunction in CKD considering the significant disease burden.

Altered vascular endothelial growth factor expression during GnRH antagonist protocol in women of reproductive age with normal baseline hormone profiles.

OBJECTIVE: To explain the unexpected low response to GnRH antagonist protocol in reproductive women with normal baseline hormone profiles. DESIGN: Retrospective study. SETTING: University hospital. PATIENT(S): Twenty-five women undergoing their first IVF cycle. INTERVENTION(S): Follicular fluid (FF) from large follicles (>15 mm) was obtained during oocyte retrieval from unexpected low responders (n = 13, group A) and 12 age-matched normal responders (n = 12, group B). MAIN OUTCOME MEASURE(S): The FF markers known to reflect follicle environment (insulin-like growth factor [IGF] II, IGF-binding protein 4, müllerian-inhibiting substance, pregnancy-associated plasma protein A, soluble Fas, and vascular endothelial growth factor [VEGF]) were analyzed by ELISA. RESULT(S): The baseline characteristics (age, day 3 serum LH, FSH, E(2), duration and dose of r-FSH, GnRH antagonist) were not different between the two groups. The number of large follicles, oocytes retrieved, and serum E(2) levels on the day of hCG injection were significantly higher in group B. Whereas the other follicular markers did not differ between the two groups, VEGF was significantly higher in group A. In addition, the VEGF concentration showed an inverse correlation with the total number of oocytes retrieved. CONCLUSION(S): The unexpected low response in women with normal basal hormone profiles, during GnRH antagonist protocol, was associated with altered follicular VEGF expression.

Pharmacodynamics of a single low dose of long-acting recombinant follicle-stimulating hormone (FSH-carboxy terminal peptide, corifollitropin alfa) in women with World Health Organization group II anovulatory infertility.

In a double-blind, placebo-controlled, randomized study, 55 anovulatory subjects received a single s.c. injection of placebo (n = 10) or recombinant long-acting FSH [FSH-carboxy terminal peptide (CTP), ORG 36286, corifollitropin alfa; NV Organon, The Netherlands] in doses of 7.5 (n = 13), 15 (n = 10), 30 (n = 11), or 60 microg (n = 11). The injection was given 2 or 3 d after the onset of a spontaneous or progestagen-induced withdrawal bleed. After drug administration, the induced follicular response varied widely among subjects in each dose group. The percentage of subjects with a follicular response (at least one follicle > or = 10.0 mm) increased with the dose (P < 0.01) and was 10, 31, 70, 73, and 82% in the placebo and 7.5-, 15-, 30-, and 60-microg treatment groups, respectively. In responding subjects, the average maximum number of follicles was 4.0, 7.6, 13.4, and 20.0, respectively, which was reached at 6.5, 6.9, 6.6, and 8.2 d after a single dose of 7.5, 15, 30, and 60 microg FSH-CTP, respectively. The dose-response for the number of follicles was statistically significant within the dose range tested (P < 0.01). Peak serum inhibin-B levels were significantly correlated with serum estradiol (E2) levels (r = 0.84, P < 0.01), and peak concentrations of inhibin-B and E2 correlated with the number of follicles observed at the same time point (for both hormones; r = 0.47, P < 0.01). Overall per treatment group, serum E2 and inhibin B concentrations significantly increased only in the two highest FSH-CTP dose groups, reaching peak concentrations at d 3 in the 30-microg group and at d 5 in the 60-microg group. Thereafter these hormone values declined rapidly, returning to baseline within 1 wk after FSH-CTP administration. In total, nine of the 55 treated subjects (16.4%) ovulated after drug administration: one subject in the placebo group, two subjects in the 7.5-microg group, three subjects in the 15-microg group, two in the 30-microg group, and one in the 60-microg group. Three subjects had monofollicular ovulation after placebo (n = 1) and a single dose of 15 microg FSH-CTP (n = 2). In two subjects with too many preovulatory follicles, (multiple) ovulation was prevented by GnRH antagonist administration. Thus, a single low dose of long-acting FSH-CTP was able to induce one or more follicles to grow up to ovulatory sizes, but the anovulatory status was not reversed because the incidence of subsequent (mono)ovulations was low.