The effect of probiotics, prebiotics, and synbiotics on hormonal and inflammatory indices in women with polycystic ovary syndrome: a systematic review and meta-analysis.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is among the most prevalent endocrine disorders in women and can lead to many other disorders and chronic diseases. Thus, early diagnosis and treatment of this syndrome is important. Using probiotics, prebiotics, and synbiotics supplementations to treat PCOS seems appropriate because of their useful effects and low complications. AIMS: To assess the effects of probiotics, prebiotics, and synbiotics on hormonal indices such as testosterone, dehydroepiandrosterone sulfate (DHEA-S), sex hormone binding globulin, Free Androgen Index (FAI), and inflammatory indices, such as high sensitive C reactive protein (hsCRP), malondialdehyde (MDA), total glutathione (GSH), nitric oxide (NO), and total antioxidant capacity (TAC) as the primary outcomes and the hirsutism score as the secondary outcome. METHODS: All published articles from the beginning until 10 November 2018 in English (Cochrane Library, Web of Sciences, Google Scholar, PubMed, Scopus, and ProQuest) and Persian (SID and Magiran) databases were searched. The effect of interventions on the outcomes was reported with a standard mean difference (SMD) and confidence interval of 95%. In case of high heterogeneity, the random effect model was used instead of the fixed effect model. The statistical heterogeneity of the included clinical trials was tested using the Chi square test and I2. RESULTS: Thirteen studies with 855 participants with PCOS(438 women in the intervention group and 417 women in the control group) were included in the meta-analysis. Results of the meta-analysis showed that the SHBG (SMD: 0.56; 95% CI 0.26-0.86; P = 0.0002) and NO (SMD: 0.38; 95% CI 0.09-0.68; P = 0.01) concentration increased significantly in the probiotics and synbiotics groups compared to the placebo group. FAI (SMD: - 0.58; 95% CI - 0.95 to - 0.21; P = 0.002) and MDA (SMD: - 0.76; 95% CI - 1.46 to - 0.05; P = 0.03) concentration in the probiotics and synbiotics groups reduced significantly compared to the placebo group. The results of meta-analyses on other hormonal and inflammatory indices such as testosterone, DHEAS, GSH, hsCRP, TAC, and hirsutism score showed that there were no significant differences between the intervention and control groups. CONCLUSION: Using synbiotics and probiotics in women with polycystic ovary syndrome improve hormonal (FAI, SHBG) and inflammatory (NO, MDA) indices in these patients.

Cross-sectional association of coffee and caffeine consumption with sex hormone-binding globulin in healthy nondiabetic women.

OBJECTIVE: Low sex hormone-binding globulin (SHBG) is a consistent risk factor for type 2 diabetes, particularly in women. Coffee consumption has been associated with a lower risk of type 2 diabetes, but its effects on SHBG are less known. DESIGN AND METHODS: This was a cross-sectional study of 2377 nondiabetic pre- and postmenopausal women from the E3N cohort study whose baseline SHBG was measured. Information on diet (including coffee and caffeine consumption), lifestyle and medical conditions was collected through questionnaires. The relationship between coffee and caffeine consumption and SHBG was modelled, with adjustment for covariates and stratification by body mass index (BMI) categories (< or ≥25 kg/m2 ) and menopausal status. RESULTS: The mean age was 57.2±6.4 years and 61% of the 2377 women were postmenopausal. High coffee (≥3 cups/day) and caffeine (≥265 mg/day) intakes were associated with a reduced risk of being in the 1st quartile of the SHBG level distribution (<46.3 nmol/L) in a multivariate adjusted model (OR: 0.72 [95% CI: 0.52-1.01] and OR: 0.71 [95% CI: 0.53-0.95], respectively). No association was found between tea consumption and SHBG levels. In multivariate models stratified on BMI categories and menopausal status, associations were restricted to women with a BMI ≥25 kg/m2 or being postmenopausal. The association with SHBG was consistently noted with consumption of both caffeinated coffee and caffeine, but not decaffeinated coffee. CONCLUSIONS: Consumption of high coffee and caffeine is associated with a reduced risk of low SHBG, an established risk marker for T2DM, which might contribute to the protective effects of coffee for type 2 diabetes.

No interacting influence of lavender oil preparation silexan on oral contraception using an ethinyl estradiol/levonorgestrel combination.

PURPOSE: Silexan is an oral Lavender oil preparation with proven anxiolytic efficacy. Given the high prevalence of anxiety and restlessness in younger women, oral contraceptives and Silexan will likely be co-administered. METHODS: A double-blind, randomised, 2-period crossover study was performed to investigate the effects of Silexan on the pharmacokinetics and pharmacodynamics of Microgynon(®), a combination oral contraceptive containing ethinyl estradiol 0.03 mg (EE) and levonorgestrel 0.15 mg (LNG) in healthy, fertile, adult females. During 2 consecutive cycles of 28 days, oral contraception was given for 21 days combined with 1 × 160 mg/day Silexan or placebo. Plasma concentration-time profiles of EE and LNG were obtained on day 18 ± 1 up to 24 h after dosing. The primary outcome measure was the area under the concentration-time curve over a dosing interval of τ = 24 h (AUCτ) for EE and LNG plasma levels. An interaction with Silexan was formally excluded if the 90 % confidence interval for the AUCτ ratio during co-administration with Silexan or placebo was included within the range of 0.80-1.25. Secondary outcomes included EE and LNG peak concentration (C max) and time to C max (t max), follicle size, endometrial thickness, the Hoogland score, and serum levels of estradiol, progesterone, and sex hormone-binding globulin. RESULTS: A total of 24 women (mean age 27.3 years; mean body mass index 22.2 kg/m(2)) participated. The confidence intervals for the EE and LNG AUCτ and C max ratios fell within the pre-specified limits, indicating no interaction (point estimates [Silexan/placebo] AUCτ EE 0.97, LNG 0.94; C max EE 0.99, LNG 0.96). For LNG, t max was slightly delayed. No secondary outcome indicated any impairment of contraceptive efficacy. CONCLUSIONS: Co-administration of Silexan did not affect the efficacy of a combination oral contraceptive containing EE and LNG and was well tolerated.

Coffee and caffeine consumption in relation to sex hormone-binding globulin and risk of type 2 diabetes in postmenopausal women.

OBJECTIVE: Coffee consumption has been inversely associated with type 2 diabetes risk, but its mechanisms are largely unknown. We aimed to examine whether plasma levels of sex hormones and sex hormone-binding globulin (SHBG) may account for the inverse association between coffee consumption and type 2 diabetes risk. RESEARCH DESIGN AND METHODS: We conducted a case-control study nested in the prospective Women's Health Study (WHS). During a median follow-up of 10 years, 359 postmenopausal women with newly diagnosed type 2 diabetes were matched with 359 control subjects by age, race, duration of follow-up, and time of blood draw. RESULTS: Caffeinated coffee was positively associated with SHBG but not with sex hormones. Multivariable-adjusted geometric mean levels of SHBG were 26.6 nmol/l among women consuming ≥4 cups/day of caffeinated coffee and 23.0 nmol/l among nondrinkers (P for trend = 0.01). In contrast, neither decaffeinated coffee nor tea was associated with SHBG or sex hormones. The multivariable-adjusted odds ratio (OR) of type 2 diabetes for women consuming ≥4 cups/day of caffeinated coffee compared with nondrinkers was 0.47 (95% CI 0.23-0.94; P for trend = 0.047). The association was largely attenuated after further adjusting for SHBG (OR 0.71 [95% CI 0.31-1.61]; P for trend = 0.47). In addition, carriers of rs6259 minor allele and noncarriers of rs6257 minor allele of SHBG gene consuming ≥2 cups/day of caffeinated coffee had lower risk of type 2 diabetes in directions corresponding to their associated SHBG. CONCLUSIONS: Our findings suggest that SHBG may account for the inverse association between coffee consumption and type 2 diabetes risk among postmenopausal women.

Effect of long-term treatment with raloxifene on mammary density in postmenopausal women.

OBJECTIVE: To evaluate in a group of postmenopausal women the effects of long-term raloxifene treatment on breast density using a digitized analysis of mammograms and on insulinlike growth factor-1 (IGF-1), insulinlike growth factor binding protein-3 (IGFBP-3), and sex hormone-binding globulin (SHBG) plasma levels. DESIGN: Seventy healthy postmenopausal women with normal body weight were enrolled in this study and were divided into two groups based on their bone status, evaluated by dual-energy x-ray at the lumbar spine (L2-4). Fifty women (chronological age 52.4 +/- 4.1 y, menopausal age 42.1 +/- 3.9 y), in whom the L2-4 T score was less than -2.5 SD, were treated with raloxifene HCl 60 mg/day orally for 2 years. The other 20 women (chronological age 53.6 +/- 3.5 y, age at menopause 43.1 +/- 3.6 y), in whom the L2-4 T score ranged between -1 and -2.5 SD, were enrolled as controls. All 70 women received calcium (1 g/d orally) and cholecalciferol (880 UI/d orally) supplementation. Moreover, all women followed a normocaloric and personalized diet. All women had mammography at baseline and after 2 years of therapy. The mammographic images on traditional support (radiography) were acquired by using a film scanner and were then elaborated by means of ad hoc software. Moreover, assessments of IGF-1, IGFBP-3, and SHBG plasma levels were obtained at baseline and after 24 months. RESULTS: After 24 months of therapy, there was a significant variation in the raloxifene-treated group with respect to baseline in the distribution of gray classes of radiographic images. In particular, an attenuation of graphic trace with a reduction of the areas with the lowest and most elevated gray classes was observed. In the control group, no significant variations of graphic traces were observed. Moreover, raloxifene treatment significantly reduced IGF-1 and increased IGFBP-3 and SHBG plasma levels at 24 months. During follow-up, IGF-1, IGFPB-3, and SHBG levels did not change significantly in the control group. CONCLUSIONS: Long-term treatment with raloxifene in a population of postmenopausal women is able to reduce breast density. Such an effect could perhaps explain the reduction in the incidence of mammary carcinoma observed in the Multiple Outcomes of Raloxifene Evaluation study probably due to the direct antiestrogenic activity of raloxifene on mammalian tissue and/or its indirect activity increasing SHBG levels or modifying the IGF-1/IGFBP-3 ratio.

Effects of St John's wort (Hypericum perforatum L.) extract on plasma androgen concentrations in healthy men and women: a pilot study.

St John's wort extract (SJW; Hypericum perforatum L.) is taken extensively as a putative herbal antidepressant. It has been shown to induce the activity of cytochrome P-450 3A4 (CYP3A4) and to increase the clearance of numerous drugs and steroids such as cortisol and ethinyl estradiol. This study was conducted to determine if SJW exposure also alters the concentrations of circulating androgenic steroid hormones. The study was conducted using healthy volunteers (6M, 6F) studied before and after a 14-day treatment period with a SJW preparation previously demonstrated to induce the activity of CYP3A4. Plasma concentrations of testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG) and the combined concentrations of androsterone sulfate (AoS) and epiandrosterone sulfate (epiAoS) were measured by immunoassay methods. The results of analysis demonstrated that SJW did not significantly alter the majority of the androgens studied (p > 0.05) although the combined concentrations of the 5alpha-reduced steroids, AoS and epiAoS, significantly declined following treatment in all subjects (p = 0.02), and in males (p = 0.04). Furthermore, the testosterone to DHT ratio was increased in both men and women. Although the latter increase did not reach statistical significance, it is also consistent with the possible inhibition of 5alpha-reductase by SJW. It is concluded that despite significant induction of CYP3A4, short term administration of SJW does not significantly alter the concentrations of most circulating androgens in men and women but may produce a dimunition in some of the circulating 5alpha-reduced androgens.

Isoflavone supplements exert hormonal and antioxidant effects in postmenopausal Korean women with diabetic retinopathy.

There is growing evidence that soy isoflavones exert hormonal and antioxidant effects in postmenopausal women. In the present study, 12 postmenopausal Korean women with diabetic retinopathy consumed 2 g of genistein combined polysaccharides (GCP), containing 120 mg of genistein and 57 mg of daidzein, daily for 12 weeks. Blood was collected prior to and after 12 weeks of GCP supplementation for analysis of fasting blood glucose, insulin, lipid profiles, sex hormone-binding globulin (SHBG), estradiol, testosterone, free testosterone, and osteocalcin and activities of glutathione peroxidase (GSH-Px), catalase, and paraoxonase. After GCP supplementation, blood glucose, insulin, total cholesterol, triglyceride, high-density lipoprotein, and low-density lipoprotein cholesterols did not change significantly. However, there were significant increases in SHBG (P < .05) and testosterone (P < .05) and a decrease in estradiol (P < .01). Free testosterone levels were not significantly affected by GCP supplementation. After supplementation, osteocalcin decreased, but the difference was not statistically significant. Although activities of catalase and paraoxonase were unchanged, GSH-Px activity (P < .01) was increased significantly. These findings suggest that GCP supplementation may change the levels of some hormones and improve antioxidant status in postmenopausal Korean women with diabetic retinopathy.

Effect of flaxseed and wheat bran on serum hormones and lignan excretion in premenopausal women.

OBJECTIVE: To examine the effects of flaxseed consumption (a lignan-rich plant food) alone and in combination with wheat bran on serum hormones and urinary lignan excretion in premenopausal women. METHODS: Sixteen subjects were studied for four feeding treatments lasting two menstrual cycles each in a randomized, crossover design. During each treatment, subjects consumed their habitual diets supplemented with baked goods containing no flaxseed or wheat bran, 10 g of flaxseed, 28 g of wheat bran, or 10 g of flaxseed plus 28 g of wheat bran/day. Serum samples collected during the mid-luteal phase of the second menstrual cycle of each diet treatment were analyzed for serum hormones and sex hormone binding globulin. Urine samples collected during the same time period were analyzed for urinary lignan excretion. RESULTS: There were no changes in serum hormone concentrations or sex hormone binding globulin on any of the treatments. Urinary lignan excretion significantly increased on diet treatments that included flaxseed, but inclusion of wheat bran did not significantly alter lignan excretion. CONCLUSIONS: Urinary lignan excretion increased with flaxseed consumption, but serum hormones did not change in this group of premenopausal women. Consumption of wheat bran with flaxseed did not alter urinary lignan excretion associated with flaxseed consumption.

Neuroendocrine and behavioral effects of high-dose anabolic steroid administration in male normal volunteers.

OBJECTIVE: Despite widespread abuse of anabolic-androgenic steroids (AAS), the endocrine effects of supraphysiologic doses of these compounds remain unclear. We administered the AAS methyltestosterone (MT) to 20 normal volunteers in an in-patient setting, examined its effects on levels of pituitary-gonadal, -thyroid, and -adrenal hormones, and examined potential relationships between endocrine changes and MT-induced psychological symptoms. METHOD: Subjects received MT (three days of 40 mg/day, then three days of 240 mg/day) or placebo in a fixed sequence with neither subjects nor raters aware of order. Samples were obtained at the ends of the baseline, high-dose MT and withdrawal phases. Potential relationships between hormonal changes and visual analog scale measured mood changes were examined. RESULTS: Significant decreases in plasma levels of gonadotropins, gonadal steroids, sex hormone binding globulin, free T3 and T4, and thyroid binding globulin (Bonferroni t, p<0.01 for each) were seen during high-dose MT; free thyroxine and TSH increased during high-dose MT, with TSH increases reaching significance during withdrawal. No significant changes in pituitary-adrenal hormones were observed. Changes in free thyroxine significantly correlated with changes in aggressiveness (anger, violent feelings, irritability) (r=0.5,p=0.02) and changes in total testosterone correlated significantly with changes in cognitive cluster symptoms (forgetfulness, distractibility) (r=0.52,p=0.02). Hormonal changes did not correlate with plasma MT levels. CONCLUSIONS: Acute high-dose MT administration acutely suppresses the reproductive axis and significantly impacts thyroid axis balance without a consistent effect on pituitary-adrenal hormones. Mood and behavioral effects observed during AAS use may in part reflect secondary hormonal changes.

Hormonal effects of high dose medroxyprogesterone acetate treatment in males with renal or prostatic adenocarcinoma.

In 18 patients, 12 with renal and 6 with prostatic carcinoma, the gonadal, pituitary and adrenal functions were studied by measurements of steroid hormones and gonadotrophins, before and after six weeks treatment with medroxyprogesterone acetate (MPA), injected intramuscularly 500 mg per day for 5 days each week. The testosterone-oestradiol-binding globulin (TeBg) was measured and the amount of albumin and TeBg bound and unbound testosterone was calculated. Treatment with high doses of MPA caused a profound decrease in serum concentrations of testosterone, dehydroepiandrosterone sulphate (DHEAS), cortisol and TeBg. There were significant decreases in serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH) and oestradiol-17 beta. The serum concentration of prolactin was significantly elevated. The protein unbound testosterone fraction was lowered by MPA treatment but less than total testosterone. In conclusion, MPA therapy in high dose alters the gonadal, pituitary and adrenal functions suppressing serum concentrations of androgens, gonadotrophins, cortisol and TeBg but elevating prolactin concentration.