Polycystic Ovary Syndrome Abstracts 1

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Effect of spearmint (Mentha spicata Labiatae) teas on androgen levels in women with hirsutism
            (Akdogan et al., 2007) Download
Mentha spicata Labiatae, known as spearmint and Mentha piperita Labiatae, known as peppermint can be used for various kinds of illnesses in herbal medicine and flavoring in industry. M. spicata Labiatae grows on the Anamas plateau of Yenithornarbademli town of Isparta, located in southwest part of Turkey. In this town, clinicians thought that consumption of tea steeped with M. spicata or M. piperita caused a diminished libido. Because antiandrogenic effects of spearmint and peppermint were found previously in rats, it was decided to observe the effect of this herbal tea on the androgen levels in hirsute women.Twenty-one female hirsute patients, 12 with polycystic ovary syndrome and 9 with idiopathic hirsutism were included to the study. They were took a cup of herbal tea which was steeped with M. spicata for 5 days twice a day in the follicular phase of their menstrual cycles. After treatment with spearmint teas, there was a significant decrease in free testosterone and increase in luteinizing hormone, follicle-stimulating hormone and estradiol. There were no significant decreases in total testosterone or dehydroepiandrostenedione sulphate levels. Spearmint can be an alternative to antiandrogenic treatment for mild hirsutism. Further studies are needed to test the reliability of these results and the availability of spearmint as a drug for hirsutism.

Metformin versus chromium picolinate in clomiphene citrate-resistant patients with PCOs: A double-blind randomized clinical trial.
            (Amooee et al., 2013) Download
BACKGROUND: Chromium picolinate could be effective in clomiphen citrate resistant PCOS patients. OBJECTIVE: To compare the effects of chromium picolinate vs. metformin in clomiphen citrate resistant PCOS patients. MATERIALS AND METHODS: The present randomized clinical trial was performed on 92 women with clomiphen citrate-resistant PCOS at the clinics which were affiliated to Shiraz University of Medical Sciences, Shiraz, Iran. The subjects were randomly assigned to two groups receiving either chromium picolinate (200microg daily) or metformin (1500mg daily) for 3 months. Anthropometric and hormonal profile were measured and compared both before and after the treatment. Ovulation and pregnancy rate was measured in the two study groups, as well. RESULTS: Chromium picolinate significantly decreased fasting blood sugar (FBS) after 3 months of treatment (p=0.042). In the same way, the serum levels of fasting insulin had significantly decreased leading to an increase in insulin sensitivity as measured by QUICKI index (p=0.014). In comparison to the patients who received chromium picolinate, those who received metformin had significantly lower levels of testosterone (p=0.001) and free testosterone (p=0.001) after 3 months of treatment. Nevertheless, no significant difference was found between the two study groups regarding ovulation (p=0.417) and pregnancy rates (p=0.500). CONCLUSION: Chromium picolinate decreased FBS and insulin levels and, thus, increased insulin sensitivity in clomiphene citrate-resistance PCOS women. These effects were comparable with metformin; however, metformin treatment was associated with decreased hyperandrogenism. Overall, chromium picolinate was better tolerated compared to metformin; nonetheless, the two study groups were not significantly different regarding ovulation and pregnancy rates. Registration ID in IRCT: IRCT201203139281N1.

Endocrine and clinical effects of myo-inositol administration in polycystic ovary syndrome. A randomized study.
            (Artini et al., 2013) Download
OBJECTIVE:  To evaluate the effects the administration of myo-inositol (MYO) on hormonal parameters in a group of polycystic ovary syndrome (PCOS) patients. DESIGN:  Controlled clinical study. SETTING:  PCOS patients in a clinical research environment. PATIENTS:  50 overweight PCOS patients were enrolled after informed consent. INTERVENTIONS:  All patients underwent hormonal evaluations and an oral glucose tolerance test (OGTT) before and after 12 weeks of therapy (Group A (n¼10): MYO 2 g plus folic acid 200 mg every day; Group B (n¼10): folic acid 200 mg every day). Ultrasound examinations and Ferriman-Gallwey score were also performed. MAIN OUTCOME MEASURES:  Plasma LH, FSH, PRL, E2, 17OHP, A, T, glucose, insulin, C peptide concentrations, BMI, HOMA index and glucose-to-insulin ratio. RESULTS:  After 12 weeks of MYO administration plasma LH, PRL, T, insulin levels and LH/FSH resulted significantly reduced. Insulin sensitivity, expressed as glucose-to-insulin ratio and HOMA index resulted significantly improved after 12 weeks of treatment. Menstrual cyclicity was restored in all amenorrheic and oligomenorrheic subjects. No changes occurred in the patients treated with folic acid. CONCLUSIONS:  MYO administration improves reproductive axis functioning in PCOS patients reducing the hyperinsulinemic state that affects LH secretion.

Vitamin D improves endometrial thickness in PCOS women who need intrauterine insemination: a randomized double-blind placebo-controlled trial.
            (Asadi et al., 2014) Download
PURPOSE:  To determine whether administration of vitamin D affects the success rates of intra uterine insemination (IUI) in infertile polycystic ovarian syndrome (PCOS) women and their endometrial thickness. METHODS:  This randomized, double-blind, placebo-controlled trial was conducted in an infertility clinic of Women's Hospital, and 110 infertile PCOS patients undergoing IUI were randomly divided to receive vitamin D or placebo. Endometrial thickness, IUI results, number of dominant follicles, duration of IUI cycle, and dose of HMG used in IUI were determined. RESULTS:  The endometrial thickness was significantly different in the group treated with vitamin D versus the placebo group (p = 0.003). There was no statistical difference in pregnancy out come between the two groups (RR = 1.167, CI 95 % 0.70-1.93). No statistical difference was found in number of dominant follicles (p = 0.96), duration of IUI cycles (p = 0.70) and dose of HMG used for IUI (p = 0.95). CONCLUSIONS:  It seems that administration of vitamin D induces endometrial proliferation in PCOS women during IUI cycle. The study was recorded in Iranian Registry of Clinical Trials(IRCT201104216246N1).

Calcium plus vitamin D supplementation affects glucose metabolism and lipid concentrations in overweight and obese vitamin D deficient women with polycystic ovary syndrome.
            (Asemi et al., 2015) Download
BACKGROUND & AIMS:  Few studies have examined the effects of calcium plus vitamin D supplementation on glucose metabolism and lipid concentrations in overweight and obese vitamin D deficient women with polycystic ovary syndrome (PCOS). This study was conducted to determine the effects of calcium plus vitamin D supplementation on glucose metabolism and lipid concentrations among overweight and obese vitamin D deficient women with PCOS. METHODS:  This randomized double-blind placebo-controlled clinical trial was conducted among 104 overweight and obese vitamin D deficient women diagnosed with PCOS. Participants were randomly assigned into four groups to receive: 1) 1000 mg/d calcium + vitamin D placebo (n = 26); 2) 50,000 IU/wk vitamin D + calcium placebo (n = 26); 3) 1000 mg calcium/d + 50,000 IU/wk vitamin D (n = 26) and 4) calcium placebo + vitamin D placebo (n = 26) for 8 weeks. Fasting blood samples were taken at baseline and after 8 weeks' intervention to measure glucose metabolism and lipid concentrations. RESULTS:  Calcium-vitamin D co-supplementation resulted in higher levels of serum calcium (P = 0.002) and vitamin D (P < 0.001) compared with other groups. Co-supplementation, compared with other groups, led to decreased serum insulin levels (P = 0.03), homeostasis model of assessment-insulin resistance (HOMA-IR) score (P = 0.04) and a significant rise in quantitative insulin sensitivity check index (QUICKI) (P = 0.001). Furthermore, a significant decrease in serum triglycerides (P = 0.02) and VLDL-cholesterol levels (P = 0.02) was seen following the administration of calcium plus vitamin D supplements compared with the other groups. Co-supplementation with calcium and vitamin D had no significant effects on FPG, total-, LDL-, HDL-, and non-HDL-cholesterol levels. CONCLUSIONS:  In conclusion, calcium plus vitamin D supplementation for eight weeks among vitamin D deficient women with PCOS had beneficial effects on serum insulin levels, HOMA-IR, QUICKI, serum triglycerides and VLDL-cholesterol levels, but it did not affect FPG and other lipid profiles. Clinical registration numberwww.irct.ir: IRCT201309275623N10.

Postprandial effects of long-term niacin/laropiprant use on glucose and lipid metabolism and on cardiovascular risk in patients with polycystic ovary syndrome.
            (Aye et al., 2014) Download
AIM:  This study investigated the effect of long-term niacin/laropiprant therapy on CV risk and IR in obese women with PCOS. METHODS:  In this double-blind randomized placebo-controlled trial, 13 and 12 PCOS women completed a 12 week course of niacin/laropiprant or placebo, respectively. Fasted subjects had an endothelial function test (EndoPat2000) and then consumed a mixed meal with blood sampled postprandially for 6 h before and after intervention. RESULTS:  By 12 weeks, niacin/laropiprant lowered low-density lipoprotein cholesterol (LDL-c) (13%) and increased HDL-c (17%). Despite a reduction in fasting triglycerides (21%), the drug had no effect on their postprandial rise (2.69 ± 1.44 vs. 2.49 ± 1.14 mmol/l, p = 0.72). However, following the mixed meal, plasma glucose area under the response curve increased from 13.1 ± 2.9 to 14.0 ± 2.8 mmol/l, p = 0.05, as a consequence of both increased insulin resistance [HOMA-IR: 2.2 (1.2, 4.2) vs. 3.8(1.3, 5.5), p = 0.02] and a reduced acute insulin response to glucose [424 (211, 975) vs. 257(122, 418) pmol/mmol, p = 0.04]. Niacin/laropiprant did not improve RHI (1.97 ± 0.40 vs. 2.05 ± 0.58, p = 0.33) or hsCRP. CONCLUSIONS:  In PCOS, niacin/laropiprant had a significant negative impact on postprandial glucose and no improvement in postprandial hypertriglyceridaemia, with at least the former mediated through increased IR and reduced β-cell function. This data may help explain why the improvement in fasting lipids has not translated into improved CV risk markers in PCOS.

Inositol: effects on oocyte quality in patients undergoing ICSI. An open study.
            (Brusco and Mariani, 2013) Download
OBJECTIVES:  Nuclear and cytoplasmic competence of human oocyte is critical for future competence of the embryo upon which ultimately depends the outcome of an ART (Assisted Reproductive Technology) treatment. Follicular microenvironment in which the oocyte develops is crucial, and this must be taken into account particularly with the use of hormonal ovarian stimulation protocols. Inositol is an important element of the follicular environment and data support that its higher level in follicular fluid correlates with the development of a good oocyte. Aim of this study is to understand the effects of treatment with inositol on oocyte quality in a sample of patients undergoing ICSI (Intracytoplasmic Sperm Injection). PATIENTS AND METHODS:  Assessment of oocyte/embryo quality and pregnancy rates in 149 patients divided, according to a controlled randomized pattern, into two groups: study group 1 treated with folic acid and inositol and control group 2 treated with folic acid alone. RESULTS:  The number of patients with excellent and good oocyte quality appears to be significantly higher in group 1 (p = 0.02), as shown, they significantly increased the number of embryos of grade A transferred in the group 1 (p = 0.02) compared to group 2, despite being completely similar averages of total embryos transferred (total mean ± SD = 2.4 ± 0.8, group 1 mean ± SD = 2.4 ± 0.8, group 2 mean ± SD = 2.4 ± 0.8). There is not any significant difference between groups 1 and 2 in the number of positivity to β-hCG and in the number of biochemical pregnancies detected although it has a tendency to increase in the first and to decrease in the second for group 1. The increase in percentage of clinical pregnancies in group 1 was statistically significant (p = 0.02), whereas there was no apparent significance in the difference between the biochemical and clinical pregnancies in the two groups despite the positive trend in the study group. CONCLUSIONS:  Relying on "inositol help" to solidify our efforts, seems to be an easy path to help to deepen the effectiveness of its use in all patients still under 40 but with prior failed attempts at ICSI or diagnosed with PCOS or as "poor responders".

The combined therapy myo-inositol plus D-chiro-inositol, rather than D-chiro-inositol, is able to improve IVF outcomes: results from a randomized controlled trial.
            (Colazingari et al., 2013) Download
PURPOSE: The present study aims to investigate the effects of the combined therapy myo-inositol (MI) plus D-chiro-inositol (DCI) or D-chiro-inositol treatment in oocyte quality. METHODS: Polycystic ovary syndrome (PCOS) women undergoing IVF-ET were treated with myo-inositol combined with D-chiro-inositol in the physiological ratio (1.1 g myo-inositol plus 27.6 mg of D-chiro-inositol; INOFOLIC combi Lo.Li.pharma) or D-chiro-inositol alone (500 mg; Interquim, s.a., Barcelona, Spain) to evaluate the umber of morphological mature oocytes, total International Units (IU) of recombinant FSH administered and the number of grade 1 embryos. RESULTS: The data clearly showed that only the combined therapy was able to improve oocyte and embryo quality, as well as pregnancy rates, in PCOS women undergoing IVF-ET. CONCLUSION: The present paper further supports the hypothesis that MI plays a crucial role in the ovary in PCOS women. In particular, due to the physiological role played by MI and DCI, the combined therapy should represent a better choice.


 

Combined coenzyme Q10 and clomiphene citrate for ovulation induction in clomiphene-citrate-resistant polycystic ovary syndrome.
            (El Refaeey et al., 2014) Download
This prospective randomized controlled trial evaluated the effect of combined oral coenzyme Q10 (CoQ10) and clomiphene citrate for ovulation induction in clomiphene-citrate-resistant polycystic ovary syndrome (PCOS). A total of 101 infertile women with PCOS resistant to clomiphene citrate were randomized either to combined CoQ10 and clomiphene citrate (51 patients, 82 cycles) or to clomiphene citrate alone (50 patients, 71 cycles). The outcome measures were number of follicles, serum oestradiol, serum progesterone, endometrial thickness and ovulation, clinical pregnancy and miscarriage rates. Numbers of follicles >14 mm and >/=18 mm were significantly higher in the CoQ10 group. Endometrial thickness on the day of human chorionic gonadotrophin was significantly greater in the CoQ10 group (8.82 +/- 0.27 mm versus 7.03 +/- 0.74 mm). Ovulation occurred in 54/82 cycles (65.9%) in the CoQ10 group and 11/71 cycles (15.5%) in the control group. Clinical pregnancy rate was significantly higher in the CoQ10 group (19/51, 37.3%) versus the control group (3/50, 6.0%). Combination of CoQ10 and clomiphene citrate in the treatment of clomiphene-citrate-resistant PCOS patients improves ovulation and clinical pregnancy rates. It is an effective and safe option and can be considered before gonadotrophin therapy or laparoscopic ovarian drilling.

Spearmint herbal tea has significant anti-androgen effects in polycystic ovarian syndrome. a randomized controlled trial
            (Grant, 2009) Download
Hirsutism in polycystic ovarian syndrome (PCOS), consequent to elevated androgen levels leads to significant cosmetic and psychological problems. Recent research in Turkey has shown that spearmint tea has antiandrogenic properties in females with hirsutism. No research has yet been undertaken to assess whether a reduction in androgen levels brought about by spearmint tea, translates to a clinical improvement in the degree of hirsutism.This study was a two centre, 30 day randomized controlled trial. Forty two volunteers were randomized to take spearmint tea twice a day for a 1 month period and compared with a placebo herbal tea. At 0, 15 and 30 days of the study serum androgen hormone levels and gonadotrophins were checked, the degree of hirsutism was clinically rated using the Ferriman-Galwey score and a questionnaire (the modified DQLI = Dermatology Quality of Life Index) was used to assess improvements in the level of self-reported hirsutism.Forty one of 42 patients completed the study. Free and total testosterone levels were significantly reduced over the 30 day period in the spearmint tea group (p < 0.05). LH and FSH also increased (p < 0.05). Patient's subjective assessments of their degree of hirsutism scored by the modified DQLI were significantly reduced in the spearmint tea group (p < 0.05). There was, however, no significant reduction in the objective Ferriman-Galwey ratings of hirsutism between the two trial groups over the trial duration (p = 0.12). There was a clear and significant alteration in the relevant hormone levels. This is associated clinically with a reduction in the self-reported degree of hirsutism but unfortunately not with the objectively rated score.It was demonstrated and confirmed that spearmint has antiandrogen properties, the simple fact that this does not clearly translate into clinical practice is due to the relationship between androgen hormones and follicular hair growth and cell turnover time. Simply put, the study duration was not long enough. The original studies from Turkey were in fact only 5 days long. The time taken for hirsutism to resolve is significant and a much longer future study is proposed as the preliminary findings are encouraging that spearmint has the potential for use as a helpful and natural treatment for hirsutism in PCOS. Copyright (c) 2009 John Wiley & Sons, Ltd.

Metformin lowers serum cobalamin without changing other markers of cobalamin status: a study on women with polycystic ovary syndrome
            (Greibe et al., 2013) Download
Treatment with the anti-diabetic drug metformin is followed by a decline in plasma cobalamin, but it is unsettled whether this denotes an impaired cobalamin status. This study has explored changes in the markers of cobalamin status in women with Polycystic Ovary Syndrome treated with metformin (1.5-2.5 g per day) (n = 29) or placebo (n = 23) for six months. Serum samples were collected before and after two, four, and six months of treatment. We found serum cobalamin to decline and reach significant lower levels after six months of treatment (p = 0.003). Despite the decline in serum cobalamin, we observed no reductions in the physiological active part of cobalamin bound to transcobalamin (holotranscobalamin), or increase in the metabolic marker of cobalamin status, methylmalonic acid. Instead, the non-functional part of circulating cobalamin bound to haptocorrin declined (p = 0.0009). Our results have two implications: The data questions whether metformin treatment induces an impaired cobalamin status in PCOS patients, and further suggests that serum cobalamin is a futile marker for judging cobalamin status in metformin-treated patients.

Vitamin D Supplementation Decreases TGF-β1 Bioavailability in PCOS: A Randomized Placebo-Controlled Trial.
            (Irani et al., 2015) Download
CONTEXT:  There is an abnormal increase in TGF-β1 bioavailability in women with polycystic ovary syndrome (PCOS), which might play a role in the pathophysiology of this syndrome. Vitamin D (VD) supplementation improves various clinical manifestations of PCOS and decreases TGF-β1 levels in several diseases including myelofibrosis. OBJECTIVE:  The objective of the study was to determine the effect of VD supplementation on TGF-β1 bioavailability in VD-deficient women with PCOS and assess whether changes in TGF-β1/soluble endoglin (sENG) levels correlate with an improvement in PCOS clinical manifestations. DESIGN:  This was a prospective, randomized, placebo-controlled trial. SETTING:  The study was conducted at an academic-affiliated medical center. PARTICIPANTS:  Sixty-eight VD-deficient women with PCOS who were not pregnant or taking any exogenous hormones were recruited between October 2013 and January 2015. INTERVENTIONS:  Forty-five women received 50 000 IU of oral vitamin D3 and 23 women received oral placebo once weekly for 8 weeks. MAIN OUTCOMES MEASURES:  Serum TGF-β1, sENG, lipid profile, testosterone, dehydroepiandrosterone sulfate, and insulin resistance were measured. The clinical parameters were evaluated before and 2 months after treatment. RESULTS:  The VD level significantly increased and normalized after VD supplementation (16.3 ± 0.9 [SEM] to 43.2 ± 2.4 ng/mL; P < .01), whereas it did not significantly change after placebo. After the VD supplementation, there was a significant decrease in the following: the interval between menstrual periods (80 ± 9 to 60 ± 6 d; P = .04), Ferriman-Gallwey score (9.8 ± 1.5 to 8.1 ± 1.5; P < .01), triglycerides (138 ± 22 to 117 ± 20 mg/dL; P = .03), and TGF-β1 to sENG ratio (6.7 ± 0.4 to 5.9 ± 0.4; P = .04). In addition, the ΔTGF-β1 to sENG ratio was positively correlated with Δtriglycerides (r = 0.59; P = .03). CONCLUSIONS:  VD supplementation in VD-deficient women with PCOS significantly decreases the bioavailability of TGF-β1, which correlates with an improvement in some abnormal clinical parameters associated with PCOS. This is a novel mechanism that could explain the beneficial effects of VD supplementation in women with PCOS. These findings may support new treatment modalities for PCOS, such as the development of anti-TGF-β drugs.

Phytotherapeutic management of polycystic ovary syndrome: role of aerial parts of wood betony (Stachys lavandulifolia).
            (Jalilian et al., 2013) Download
Pharmacological treatments of polycystic ovary syndrome (PCOS) have side effects. We compared the efficacy and safety of the aerial parts of wood botany (AWB) with those of Medroxyprogesterone acetate (MPA) in the management of abnormal uterine bleeding (AUB) due to PCOS. We conducted a randomized clinical trial of 66 women aged 15-45 years, with AUB. Participants were randomly assigned to either cyclical 10-mg BD MPA for three cycles or 5 g ABW TDS for three months. Clinical symptoms and paraclinical parameters were recorded before and 3 months after initiation of the treatment. Comparisons were made using generalized linear models. Age-adjusted prevalence rate of different patterns of AUB, decreased from 2.7 (95%CIs: 0.6-48.0) to 1.1 (95%CIs: 0.1-18.3) for patients taking MPA, and from 2.5 (95% CIs: 0.2-40.2) to 0.7 (95%CIs: 0.0-12.1). Decrease in prevalence rate was similar across two arms of the study (P value = 0.248). Adverse effects were observed less frequently (24.2%) among participants on MPA than among those on AWB (45.5%). The multivariate-adjusted odds for developing adverse reaction of MPA was 0.40 (95%CIs: 0.14-1.19, P value = 0.099) time odds of AWB. In conclusion, AWB may be used as an alternative for MPA in the treatment of AUB caused by PCOS.


Metabolic response to selenium supplementation in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial.
            (Jamilian et al., 2015) Download
OBJECTIVE:  We are aware of no study examining the effects of selenium supplementation on metabolic profiles of patients with polycystic ovary syndrome (PCOS). This study was conducted to evaluate the effects of selenium supplementation on glucose homeostasis parameters and lipid concentrations in women with PCOS. DESIGN, PATIENTS AND MEASUREMENTS:  This randomized, double-blind, placebo-controlled trial was conducted among 70 women diagnosed with PCOS and aged 18-40 years old. Participants were randomly divided into two groups to receive 200 μg per day selenium supplements (N = 35) or placebo (N = 35) for 8 weeks. Fasting blood samples were taken at baseline and after 8 weeks intervention to quantify glucose, insulin and lipid concentrations. RESULTS:  After 8 weeks of intervention, subjects who received selenium supplements had significantly decreased serum insulin levels (-29·83 ± 47·29 vs +9·07 ± 77·12 pmol/l, P = 0·013), homeostasis model of assessment-insulin resistance (HOMA-IR) (-1·15 ± 1·81 vs +0·42 ± 3·09, P = 0·011), homeostatic model assessment-beta-cell function (HOMA-B) (-19·06 ± 30·95 vs +4·55 ± 47·99, P = 0·017) and increased quantitative insulin sensitivity check index (QUICKI) (+0·03 ± 0·04 vs +0·0009 ± 0·05, P = 0·032) compared with placebo. In addition, supplementation with selenium resulted in a significant reduction in serum triglycerides (-0·14 ± 0·55 vs +0·11 ± 0·30 mmol/l, P = 0·025) and VLDL-C concentrations (-0·03 ± 0·11 vs +0·02 ± 0·06 mmol/l, P = 0·025) compared with placebo. CONCLUSIONS:  In conclusion, 200 microgram per day selenium supplementation for 8 weeks among PCOS women had beneficial effects on insulin metabolism parameters, triglycerides and VLDL-C levels; however, it did not affect FPG and other lipid profiles.

Effect of folic acid in women with and without insulin resistance who have hyperhomocysteinemic polycystic ovary syndrome
            (Kazerooni et al., 2008) Download
OBJECTIVE: To study the effect of folic acid on homocysteine (Hcy) levels in women with insulin resistance and polycystic ovary syndrome (PCOS) in a prospective clinical trial. METHOD: Of 210 women with PCOS, 70 were hyperhomocysteinemic; and of these, 32 were insulin resistant and 38 were not. The 70 women were treated with folic acid for 3 months. Baseline and serum levels of Hcy and insulin were measured in both groups. RESULTS: In both groups Hcy concentrations were significantly decreased following folic acid supplementation. The mean+/-SD levels before and after treatment were 14.03+/-1.5 micromol/L and 12.53+/-1.72 micromol/L in group 1 (P<0.001), and they were 12.07+/-0.87 micromol/L and 8.83+/-0.78 micromol/L in group 2 (P<0.001). CONCLUSION: The Hcy levels of hyperhomocysteinemic women with PCOS were reduced after 3 months of folic acid supplementation, and the rate of reduction was higher among women without insulin resistance. No change was found in fasting insulin levels.

Hormonal and metabolic effects of polyunsaturated fatty acids in young women with polycystic ovary syndrome: results from a cross-sectional analysis and a randomized, placebo-controlled, crossover trial.
            (Phelan et al., 2011) Download
BACKGROUND:  Polycystic ovary syndrome (PCOS) is characterized by an adverse metabolic profile. Although dietary changes are advocated, optimal nutritional management remains uncertain. Polyunsaturated fatty acids (PUFAs), particularly long-chain (LC) n-3 (omega-3) PUFAs, improve metabolic health, but their therapeutic potential in PCOS is unknown. OBJECTIVES:  We aimed to determine the associations between plasma PUFAs and metabolic and hormonal aspects of PCOS to investigate the efficacy of LC n-3 PUFA supplementation and to support the findings with mechanistic cellular studies. DESIGN:  We selected a cross-sectional PCOS cohort (n = 104) and conducted a principal component analysis on plasma fatty acid profiles. Effects of LC n-3 PUFA supplementation on fasting and postprandial metabolic and hormonal markers were determined in PCOS subjects (n = 22) by a randomized, crossover, placebo-controlled intervention. Direct effects of n-6 (omega-6) compared with n-3 PUFAs on steroidogenesis were investigated in primary bovine theca cells. RESULTS:  Cross-sectional data showed that a greater plasma n-6 PUFA concentration and n-6:n-3 PUFA ratio were associated with higher circulating androgens and that plasma LC n-3 PUFA status was associated with a less atherogenic lipid profile. LC n-3 PUFA supplementation reduced plasma bioavailable testosterone concentrations (P < 0.05), with the greatest reductions in subjects who exhibited greater reductions in plasma n-6:n-3 PUFA ratios. The treatment of bovine theca cells with n-6 rather than with n-3 PUFAs up-regulated androstenedione secretion (P < 0.05). CONCLUSIONS:  Cross-sectional data suggest that PUFAs modulated hormonal and lipid profiles and that supplementation with LC n-3 PUFAs improves androgenic profiles in PCOS. In bovine theca cells, arachidonic acid modulated androstenedione secretion, which suggests an indirect effect of n-3 PUFAs through the displacement of or increased competition with n-6 PUFAs. This trial was registered at clinicaltrials.gov as NCT01189669.


 

Comparison between effects of myo-inositol and D-chiro-inositol on ovarian function and metabolic factors in women with PCOS.
            (Pizzo et al., 2014) Download
Myo-inositol and D-chiro-inositol are capable of improving the ovarian function and metabolism of polycystic ovary syndrome (PCOS) patients. The aim of this work is to compare the effects of myo-inositol and D-chiro-inositol in PCOS. We enrolled 50 patients, with homogeneous bio-physical features, affected by PCOS and menstrual irregularities, and we randomly divided them into two groups: 25 were treated with 4 g of myo-inositol/die plus 400 mcg of folic acid/die orally for six months, 25 with 1 g of D-chiro-inositol/die plus 400 mcg of folic acid/die orally for six months. We analyzed in both groups pre-treatment and post-treatment BMI, systolic and diastolic blood pressure, Ferriman-Gallwey score, Cremoncini score, serum LH, LH/FSH ratio, total and free testosterone, dehydroepiandrosterone sulfate (DHEA-S), Δ-4-androstenedione, SHBG, prolactin, glucose/immunoreactive insulin (IRI) ratio, homeostatic model assessment (HOMA) index, and the resumption of regular menstrual cycles. Both the isoforms of inositol were effective in improving ovarian function and metabolism in patients with PCOS, although myo-inositol showed the most marked effect on the metabolic profile, whereas D-chiro-inositol reduced hyperandrogenism better.

Insulin sensitiser agents alone and in co-treatment with r-FSH for ovulation induction in PCOS women
            (Raffone et al., 2010) Download
OBJECTIVE: The aim of this study was to compare the effectiveness of myo-inositol (MYO) and metformin, in monotherapy or in association with recombinant follicle stimulating hormone (r-FSH), in the treatment of menstrual irregularities, chronic anovulation, and female infertility in patients with polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: One hundred twenty patients were randomly treated with metformin 1500 mg/day orally (n = 60), or 4 g MYO plus 400 microg folic acid daily (n = 60), continuously. If no pregnancy occurred, r-FSH (37.5 units/day) was added to the treatment for a maximum of three attempts. RESULTS: Fifty percent of the patients who assumed metformin restored spontaneous ovulation, 18.3% of these obtained pregnancy. The remaining 42 patients were treated with metformin plus r-FSH. Pregnancy occurred in a total of 11 women (26.1%). The total pregnancy rate was 36.6%. Sixty-five percent of the patients treated with MYO plus folic acid restored spontaneous ovulation activity, 30% of these obtained pregnancy. The remaining 38 patients were treated with MYO, folic acid plus r-FSH. Pregnancy occurred in a total of 11 women (28.9%). The total pregnancy rate was 48.4%. CONCLUSIONS: Both metformin and MYO, can be considered as first line treatment for restoring normal menstrual cycles in most patients with PCOS, even if MYO treatment seems to be more effective than metformin.

High-dose vitamin D supplementation and measures of insulin sensitivity in polycystic ovary syndrome: a randomized, controlled pilot trial.
            (Raja-Khan et al., 2014) Download
OBJECTIVE:  To determine the effects of high-dose vitamin D on insulin sensitivity in polycystic ovary syndrome (PCOS). DESIGN:  Randomized, placebo-controlled trial. SETTING:  Academic medical center. PATIENT(S):  Twenty-eight women with PCOS. INTERVENTION(S):  Vitamin D3, 12,000 IU, or placebo daily for 12 weeks. MAIN OUTCOME MEASURE(S):  The primary outcome was quantitative insulin sensitivity check index. Secondary outcomes included glucose and insulin levels during a 75-g oral glucose tolerance test and blood pressure. RESULT(S):  Twenty-two women completed the study. Compared with placebo, vitamin D significantly increased 25-hydroxyvitamin D (mean [95% confidence interval] in vitamin D group 20.1 [15.7 to 24.5] ng/mL at baseline and 65.7 [52.3 to 79.2] ng/mL at 12 weeks; placebo 22.5 [18.1 to 26.8] ng/mL at baseline and 23.8 [10.4 to 37.2] ng/mL at 12 weeks). There were no significant differences in quantitative insulin sensitivity check index and other measures of insulin sensitivity; however, we observed trends toward lower 2-hour insulin and lower 2-hour glucose. We also observed a protective effect of vitamin D on blood pressure. CONCLUSION(S):  In women with PCOS, insulin sensitivity was unchanged with high-dose vitamin D, but there was a trend toward decreased 2-hour insulin and a protective effect on blood pressure. CLINICAL TRIAL REGISTRATION NUMBER:  NCT00907153.

Adding the phytoestrogen Cimicifugae Racemosae to clomiphene induction cycles with timed intercourse in polycystic ovary syndrome improves cycle outcomes and pregnancy rates - a randomized trial.
            (Shahin and Mohammed, 2014) Download
BACKGROUND:  Owing to their potential to act as estrogen receptor modulators and interfere with aromatase enzyme in animal studies, phytoestrogens (PE) may be useful as part of ovulation induction for polycystic ovary syndrome (PCOS). PATIENTS AND METHODS:  Patients <35 years, presenting with infertility and PCOS, were included and randomly allocated to either group I (clomiphene citrate; CC) or group II (CC plus Cimicifugae racemosae; CR). Primary outcome was pregnancy rate. Secondary outcomes included ovulation, midcycle serum estradiol and luteinizing hormone (LH) as well as mid-luteal serum progesterone. RESULTS:  Analysis included 98 patients in group I versus 96 patients in group II. Both groups were matched regarding demographics and basic data. Significant differences were elicited when comparing days until HCG injection (15.0 ± 1.7 versus 12.0 ± 1.9, p=0.91), endometrial thickness (mm) (8.5 ± 1.9 versus 12.5 ± 1.9, p<0.001), serum levels of mid-luteal and midcycle estradiol (p<0.001; Figure 2), LH (IU/ml) (p<0.001) as well as mid-luteal progesterone (p<0.001). PE plus CC group had significantly higher clinical pregnancies per cycle (33/192 (17.2%) versus 71/204 (34.8%), p<0.01), compared to the CC only group. CONCLUSIONS:  Adding CR to clomiphene-induction cycles with timed intercourse in polycystic ovarian syndrome improves cycle outcomes and pregnancy rates.

Efficacy of a Novel Fenugreek Seed Extract (Trigonella foenum-graecum, Furocyst) in Polycystic Ovary Syndrome (PCOS).
            (Swaroop et al., 2015) Download
Polycystic ovary syndrome (PCOS) is one of the most prevalent hormonal disorders among women of reproductive age causing irregular menstrual cycles, excessive body or facial hair, miscarriage and infertility. The latter being a most common PCOS symptoms. Because the symptoms are seemingly unrelated to one another, PCOS is often overlooked and undiagnosed. The present study is an open label, one-arm, non-randomized, post-marketing surveillance study in 50 premenopausal women (18-45 years, BMI<42) diagnosed with PCOS using a novel Trigonella foenum-graecum seed extract (fenugreek seed extract, Furocyst, 2 capsules of 500 mg each/day) extract, enriched in approximately 40% furostanolic saponins, over a period of 90 consecutive days. The study was conducted to determine its efficacy on the reduction of ovarian volume and the number of ovarian cysts. Ethical committee approval was obtained for this study. Furocyst treatment caused significant reduction in ovary volume. Approximately 46% of study population showed reduction in cyst size, while 36% of subjects showed complete dissolution of cyst. It is important to mention that 71% of subjects reported the return of regular menstrual cycle on completion of the treatment and 12% of subjects subsequently became pregnant. Overall, 94% of patients benefitted from the regimen. Significant increases in luteinizing hormone (LH) and follicular stimulating hormone (FSH) levels were observed compared to the baseline values. Extensive blood chemistry, hematological and biochemical assays demonstrated the broad-spectrum safety. Furocyst caused significant decrease in both ovarian volume and the number of ovarian cysts. Serum ALT, BUN and CK were assessed to demonstrate the broad-spectrum safety of Furocyst. No significant adverse effects were observed. In summary, Furocyst was efficacious in ameliorating the symptoms of PCOS.

N-acetylcysteine for polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled clinical trials.
            (Thakker et al., 2015) Download
Objective. To review the benefits and harms of N-acetylcysteine (NAC) in women with polycystic ovary syndrome (PCOS). Method. Literature search was conducted using the bibliographic databases, MEDLINE (Ovid), CINAHL, EMBASE, Scopus, PsyInfo, and PROQUEST (from inception to September 2013) for the studies on women with PCOS receiving NAC. Results. Eight studies with a total of 910 women with PCOS were randomized to NAC or other treatments/placebo. There were high risk of selection, performance, and attrition bias in two studies and high risk of reporting bias in four studies. Women with NAC had higher odds of having a live birth, getting pregnant, and ovulation as compared to placebo. However, women with NAC were less likely to have pregnancy or ovulation as compared to metformin. There was no significant difference in rates of the miscarriage, menstrual regulation, acne, hirsutism, and adverse events, or change in body mass index, testosterone, and insulin levels with NAC as compared to placebo. Conclusions. NAC showed significant improvement in pregnancy and ovulation rate as compared to placebo. The findings need further confirmation in well-designed randomized controlled trials to examine clinical outcomes such as live birth rate in longer follow-up periods. Systematic review registration number is CRD42012001902.

 


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