Effects of Synbiotic Supplementation and Lifestyle Modifications on Women With Polycystic Ovary Syndrome

Izabela Chudzicka-Strugała; Anna Kubiak; Beata Banaszewska; Barbara Zwozdziak; Martyna Siakowska; Leszek Pawelczyk; Antoni J. Duleba

Disclosures

J Clin Endocrinol Metab. 2021;106(9):2566-2573. 

In This Article

Materials and Methods

Subjects

Sixty-five women diagnosed with PCOS and body mass index (BMI) > 25 were recruited to the study carried out at Reproductive Endocrinology & Infertility Clinical Services at Poznan University of Medical Sciences. All subjects fulfilled PCOS criteria as defined by the Rotterdam consensus and had at least 2 of the following: (1) clinical or chemical hyperandrogenism; (2) oligo- or amenorrhea; and/or (3) polycystic ovaries as determined by transvaginal ultrasound.[19] Congenital adrenal hyperplasia, hyperprolactinemia, thyroid disease, Cushing disease, and diabetes mellitus were excluded. During the 2 months before the study, none of the study subjects used any form of hormonal therapy, antibiotics, laxatives, dietary supplements for weight loss, probiotics, or synbiotics. Written informed consent was obtained from all participants. Approval of the study was obtained from the institutional review board at the Poznan University of Medical Sciences. The study was registered at www.clinicaltrials.gov with the identifier NCT03325023.

Procedures

The flowchart of this study is summarized in Figure 1. Randomization was performed using a 1:1 allocation ratio with blocks of 4. Patient allocation was obtained using GraphPad QuickCalcs (GraphPad Software Inc., La Jolla, CA). Investigators and patients were blinded to treatment and could not identify the actual treatment throughout the study. Primary endpoints were changes in BMI and body fat percentage. Change of testosterone level was a secondary outcome measure. Randomization allocated the subjects to 2 groups: placebo group and synbiotic group. Both groups received identical lifestyle modifications consisting of closely monitored diet and exercise regimen. Diet included restriction of caloric intake to 1400 to 1800 kcal/day based on body composition analysis, as well as individualized advice regarding selection of food composition and exclusion of alcohol. The exercise regimen consisted of daily walking for 30 to 40 minutes. Subjects were followed up in person by dietician every 2 to 3 weeks.

Figure 1.

CONSORT flow diagram of the study.

Subjects in the placebo group received four capsules of placebo daily. Subjects in the synbiotic group received synbiotic supplement (SANPROBI Super Formula; 4 capsules per day). This supplement contains following probiotics: 2 strains of Bifidobacterium lactis (W51 and W52), Lactobacillus acidophilus (W22), Lactobacillus paracasei (W20), Lactobacillus plantarum (W21), Lactobacillus salivarius (W24), and Lactobacillus lactis (W19) as well as the prebiotics fructooligosaccharides and inulin.

All participants were evaluated at baseline during the follicular phase of a natural cycle or after medroxyprogesterone-induced menses and after 3 months of treatment. Clinical assessments included determinations of BMI, hirsutism (using the Ferriman and Gallwey score), and acne score. Percentage of body fat was evaluated by body impedance analysis (Tanita MC 980 Body Analyzer; Tokyo, Japan) Acne was scored using a 4-point scale described Previously.[20] Transvaginal ultrasound evaluations were performed using Aloka ProSound α7 (Aloka Co, Ltd, Tokyo, Japan). Ovarian volume was calculated using the prolate ellipsoid formula.

Venous blood was collected after an overnight fast. Serum specimens were stored at -70°C until analysis was performed. A 2-hour oral glucose tolerance test was performed with determinations of glucose and insulin in the fasting state as well as after a 75-g glucose load at 30, 60, 90, and 120 minutes. Glucose was determined using the enzymatic reference method with hexokinase using Roche Cobas e6001 immunoanalyzer (Roche Polska Sp z o.o., Warsaw, Poland). Insulin, total testosterone, LH, FSH, SHBG, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate, were determined using specific electrochemiluminescence assays (Roche Cobas e6001 immunoanalyzer; Roche Polska Sp z o.o.). The insulin sensitivity index was calculated using glucose and insulin levels obtained during an oral glucose tolerance test as described by Matsuda and DeFronzo: Insulin sensitivity index = (10 000/square root of [(fasting glucose × fasting insulin) × (mean glucose × mean insulin during oral glucose tolerance test)].[21] Total cholesterol and triglycerides were determined by enzymatic colorimetric assays (Roche Cobas e6001 immunoanalyzer; Roche Polska Sp z o.o.). High-density lipoprotein was separated by precipitating apolipoprotein-B (Roche Polska Sp z o.o.). Low-density lipoprotein was calculated using the Friedwald formula.

Statistical Analysis

Analysis was carried out using JMP pro 15 statistical software (SAS Institute, Cary, NC). P values < 0.05 were considered significant. Comparisons between groups were performed using an unpaired t test or, when appropriate, the Mann-Whitney U test. Comparisons of baseline and follow-up values were performed using paired t test. In the absence of a normal distribution (using the Anderson- Darling test), Box-Cox transformations or nonparametric testing (Wilcoxon signed rank) was carried out.

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