Levels of lipoprotein and homocysteine in non-obese and obese patients with polycystic ovary syndrome

Aim.?This study was designed to examine the relationship between homocysteine (Hcy), lipoprotein levels and insulin resistance in obese and non-obese patients with polycystic ovary syndrome (PCOS).

Materials and methods.?Eighty-five patients (38 obese, 47 non-obese) with PCOS and 50 healthy subjects (25 obese, 25 non-obese) were included in the study. PCOS was defined according to the Homburg criterion. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEA-S), insulin, 17-hydroxyprogesterone, free testosterone, androstenedione, vitamin B₁₂ and folate were measured. Also, serum concentrations of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), lipoprotein (a) (Lp(a)), apoprotein B (Apo B) and apoprotein A (Apo A) were determined. Plasma Hcy levels were measured. Insulin resistance was evaluated by homeostasis model assessment (HOMA).

Results.?Plasma Hcy levels were significantly higher in women with PCOS than in healthy women. HOMA-R (insulin resistance) was significantly higher in women with PCOS compared with healthy women. Serum fasting TC, LDL-C, TG, Apo B, vitamin B₁₂ and folate levels were similar between PCOS and control groups. Lp(a) levels were higher in PCOS patients than in control subjects, whereas HDL-C and Apo A levels were lower. Compared with obese PCOS subjects, non-obese PCOS subjects had low HOMA-R, TC, LDL-C, TG, Apo B, Lp(a) and androgen levels. Plasma Hcy levels, serum HDL-C and Apo A levels were similar between obese and non-obese women with PCOS. Levels of HDL-C and Apo A were lower in both obese and non-obese PCOS patients than in obese and non-obese control subjects, whereas Lp(a) levels were higher. No correlation was observed between plasma Hcy, body mass index, HOMA-R, serum androgen levels, TC, LDL-C, HDL-C, Apo A, Apo B and Lp(a) levels.

Conclusion.?These results showed that elevated insulin resistance and plasma Hcy levels, and changes in serum lipid profile, which are possible risk factors for cardiovascular disorders, play important roles in the development of cardiovascular disease in both obese and non-obese patients with PCOS.     

Plasma beta-endorphin levels in obese and non-obese patients with polycystic ovary disease.

The aim of this study was to determine the influence of body weight on circulating plasma levels of beta-endorphin and insulin in women with polycystic ovary disease (PCOD), as well as the correlation between the plasma levels of beta-endorphin and insulin. One-hundred and sixty-seven consecutive subjects with PCOD were recruited, 117 of whom had normal weight (body mass index (BMI) < 25) while 50 were obese (BMI > 25). A venous blood sample was taken and plasma concentrations of beta-endorphin, insulin, gonadotropins, prolactin, progesterone, 17 beta-estradiol, estrone, androgens, dehydroepiandrosterone sulfate and sex hormone-binding globulin (SHBG) were measured. Mean beta-endorphin and insulin plasma levels were significantly higher (p < 0.05) in obese PCOD women than in non-obese ones. Correlation analysis showed a positive association between insulin and beta-endorphin, beta-endorphin and BMI (and weight), insulin and BMI (and weight), and a negative correlation was found between insulin and SHBG. A weak association was found between beta-endorphin and luteinizing hormone (LH) in peripheral plasma. Stratified and linear regression analysis showed that plasma beta-endorphin concentrations correlate more with BMI than with insulinemia.     

Serum 25-hydroxyvitamin D concentrations in obese and non-obese women with polycystic ovary syndrome

Purpose  To investigate the correlation between serum 25-hydroxyvitamin D (25-OH-VD) concentrations and metabolic parameters in obese and non-obese women with polycystic ovary syndrome (PCOS). Methods  One hundred women with PCOS were divided into two groups, obese and non-obese, according to their body mass index (BMI). Waist-to-hip ratio (WHR), Ferriman–Gallwey score, homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol, triglycerides, calcium, 25-OH-VD, LH/FSH, total testosterone, and DHEAS were measured. Results  The serum 25-OH-VD mean levels were 56.31% lower in the obese PCOS patients. There was an association of increased HOMA-IR, BMI, WHR, triglycerides, total testosterone, and DHEAS with decreased 25-OH-VD concentrations in the obese PCOS patients. Conclusion  Low serum 25-OH-VD concentrations result from the presence of obesity and insulin resistance. However, the dependency between PCOS and hypovitaminosis D is questionable. Hypovitaminosis D should be kept in mind while managing obese women with PCOS.     

Metformin administration modulates neurosteroids secretion in non-obese amenorrhoic patients with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disease that is observed frequently to be related to increased insulin resistance. The use of insulin-sensitizer compounds, such as metformin, permits great improvement of such metabolic abnormality and the restoration of normal ovarian function. Metformin administration reduces insulin resistance and androgen production both from the ovary and adrenal gland. AIM: On this basis we aimed to evaluate a group of non-obese amenorrheic PCOS patients before and after 6 months of metformin administration (500 mg per os twice daily) to better understand what changes might be induced by metformin on adrenal and ovarian function and in terms of temporal coupling of the pulsatile profiles of luteinizing hormone (LH), cortisol and allopregnanolone, the latter representative of the neurosteroid family. METHOD: A group of non-obese PCOS patients (n = 8) was enrolled after informed consent and underwent to a pulsatility study for LH, cortisol and allopregnanolone, and an oral glucose tolerance test before and on day 7 of the first menstrual cycle occurring after the 5th month of treatment. RESULTS: Plasma androgen levels were decreased significantly by metformin treatment, as were plasma LH and allopregnanolone levels and insulin resistance. Metformin administration decreased LH pulse amplitude but not pulse frequency. On the contrary, cortisol and allopregnanolone showed a significant change in pulse frequency. When temporal coupling was tested between pulsatile profiles of LH or cortisol with allopregnanolone, cortisol pulses were temporally coupled to allopreganolone peaks both before and under metformin administration while LH pulses were temporally coupled to allopreganolone secretory peaks only under metformin treatment. CONCLUSIONS: Our data demonstrate that metformin administration modulates LH secretion as well as cortisol and allopregnanolone pulsatile release. In addition, the results demonstrate that adrenal and ovarian steroidogenic activity is greatly modulated by any change in insulin sensitivity.     

多囊卵巢综合征伴肥胖者助孕前处理

多囊卵巢综合征（PCOS）是育龄期女性常见的内分泌紊乱综合征,通常表现为持续性无排卵、高雄激素血症、胰岛素抵抗等。内分泌紊乱状态使PCOS患者容易伴肥胖,肥胖又可与PCOS内分泌紊乱发生相互作用,共同增加患者不孕不育的风险,影响助孕结局,并增加妊娠合并症及远期并发症的风险。故对此类患者行助孕前需要详细评估身心健康状态,调整生活方式,必要时辅以药物甚至手术,以达到改善助孕结局、降低妊娠合并症及远期并发症风险的目的。     

Relationships between circulating leptin concentrations and other hormonal parameters in obese and non-obese women with polycystic ovary syndrome

Aim: To clarify the role of leptin in women with polycystic ovary syndrome (PCOS), we analyzed whether serum leptin levels correlate with other hormonal parameters in obese and non-obese women with PCOS.
Methods: We studied 20 obese (body mass index, BM ≥25 kg/m²) and 20 non-obese (BMI <25 kg/m²) women with PCOS diagnosed by the existence of menstrual disturbance, elevated serum level of luteinizing hormone (LH) with normal follicle-stimulating hormone (FSH) and the characteristic polycystic appearance of the ovaries on transvaginal ultrasound images. Blood samples for LH, FSH, estradiol, testosterone (T), androstenedione (Δ₄) and leptin were obtained, and the relationships between variables were examined by calculating Spearman correlation coefficients.
Results: Mean levels of leptin, T and Δ₄ in obese PCOS women were significantly higher than those in non-obese PCOS women, but this was not the case for BMI, bodyweight and waist to hip ratio. In all the 40 PCOS women considered together, there were significant positive correlations of leptin with BMI, waist to hip ratio, and Δ₄ levels. However, in each group separately, serum leptin levels in obese PCOS women correlated only with BMI and bodyweight, whereas serum leptin levels in non-obese PCOS women correlated with serum A4 levels.
Conclusion: Although further study is needed to assess the role of leptin on ovarian function in non-obese women with PCOS, present findings do not support the fact that leptin is involved in the development of hormonal abnormalities in obese women with PCOS. (Reprod Med Biol 2002; 1 : 49–54)     

Endocrine-metabolic effects of the treatment with pioglitazone in obese patients with polycystic ovary syndrome.

The hyperandrogenism found in polycystic ovary syndrome (PCOS) can be a consequence of hyperinsulinemia as a result of peripheral insulin resistance. Metformin and insulin sensitizers have become a potential therapeutic tool for treating these patients; however, there are few studies with pioglitazone in PCOS. Elevated luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratios and LH hyper-responsivity to stimulation with gonadotropin-releasing hormone (GnRH) are common findings in PCOS. The reason why hyperinsulinemia produces hyperandrogenism and whether insulin action on the pituitary alters gonadotropin liberation remain unknown. In the present study, we evaluated the effect of pioglitazone (30 mg/day for 2 months) on insulin response to an oral glucose tolerance test (OGTT), serum levels of androgens and sex hormone-binding globulin (SHBG), and pituitary gonadotropin response to GnRH stimulation in 15 obese PCOS women. We found a significant decrease in insulin response to the OGTT and also in total and free testosterone levels, an increase in SHBG and a reduction in the LH response to GnRH stimulation after pioglitazone treatment. In conclusion, this short-term treatment with pioglitazone decreased hyperinsulinemia and hyperandrogenemia in obese PCOS patients, and there was a significant reduction in LH response to GnRH stimulation. Further research should be carried out to establish the risks and benefits of pioglitazone, which would assist in the physiopathologic comprehension of PCOS.     

非肥胖型多囊卵巢综合征患者体脂分布与胰岛素抵抗的研究

目的:研究非肥胖型多囊卵巢综合征(non-obese polycystic ovary syndrome,Nob-PCOS)患者体脂分布与胰岛素抵抗的关系。方法:非肥胖型多囊卵巢综合征(Nob-P-COS组)40例,以年龄、体重指数相匹配健康育龄妇女45例为对照组,采用双能X线吸收仪(DXA)测量全身和局部身体脂肪含量,化学发光法检测生殖内分泌,全自动生化分析仪检测糖、脂代谢指标。结果:Nob-PCOS组空腹胰岛素(INS)、胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、睾酮(T)分别为9.90±4.40μIU/ml、4.62±0.65mmol/L、2.98±1.02mmol/L、1.72±0.81nmol/L,均显著高于对照组的7.39±4.45μIU/ml、4.37±0.73mmol/L、2.63±0.65mmol/L、1.20±0.62nmol/L,差异均有统计学意义(P<0.05);Nob-PCOS组胰岛素敏感指数(ISI)为0.026±0.016,低于对照组的0.050±0.034,差异有统计学意义(P<0.01);Nob-PCOS组躯干脂肪量9081.38±2726.81g,高于对照组的7878.69±1187.41g,差异有统计学意义(P<0.01);Nob-PCOS组躯干/大腿脂肪比为1.51±0.31,高于对照组的1.33±0.24,差异有统计学意义(P<0.01)。躯干/大腿脂肪比与ISI呈负相关(r=-0.307,P<0.05)。结论:Nob-PCOS患者糖、脂代谢存在异常和胰岛素抵抗;Nob-PCOS组脂肪分布呈男性脂肪分布模式,向心性脂肪分布与胰岛素抵抗呈正相关。     

Subclinical inflammation in obese women with polycystic ovary syndrome

ObjectiveTo study the relation between subclinical inflammation and metabolic disorders in obese women with polycystic ovary syndrome (PCOS).DesignA cross sectional case controlled study.Main outcome measureAnti-inflammatory and pro-inflammatory biomarkers.Materials and methodsSixty-three obese women, body mass index (BMI) ?30 with PCOS and 45 obese women without PCOS, BMI ? 30 with normal menstrual pattern and normal morphology of the ovaries as controls. All cases were submitted to the estimation of waist circumference (WC), waist/hip ratio (WHR) and sagittal abdominal diameter (SAD) as well as fasting plasma glucose and fasting serum insulin and quantitative insulin sensitivity check index (QUICKI) to estimate the insulin sensitivity. For all subjects anti-inflammatory biomarkers acting as insulin sensitizers as interleukin (IL)-10, adiponectin, and pro-inflammatory biomarkers that depress insulin sensitivity as high sensitivity C-reactive protein (hsCRP), prothrombin activator inhibitor-1 (PAI-1), IL-6, together with, total testosterone (TT), free androgen index (FAI), sex hormone binding globulin (SHBG) together with LH and FSH as well as total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-c) and low density lipoprotein cholesterol (LDL-c) were estimated.ResultsThirty-three cases (52.38%) of PCOS and 23 cases (51.11%) of controls had android obesity and insulin resistance (IR): QUIKI < 0.330 and compensatory hyperinsulinemia (HI) and 30 cases (47.61%) of PCOS and 22 cases (48.88%) of controls had gluteofemoral (gynoid) obesity and normal insulin sensitivity (NIS). PCOS and controls with IR/HI and android obesity had significantly (P < 0.05) higher levels of pro-inflammatory biomarkers (PAI-1, IL-6 and hsCRP) and FFAs while anti-inflammatory biomarkers (IL-10 and adiponectin) were significantly (P < 0.05) lower than PCOS and controls with NIS and gynoid obesity. TT, FAI and LH were significantly (P < 0.05) higher in the two groups of PCOS than the two groups of controls. But TT and FAI were significantly (P < 0.05) higher in PCOS + IR/HI and android obesity than PCOS + NIS and gynoid obesity.ConclusionPCOS and controls with andriod obesity had higher levels of pro-inflammatory biomarkers and lower levels of anti-inflammatory biomarkers than PCOS and controls with gynoid obesity. The former groups had IR/HI and metabolic disorders of carbohydrate and lipid metabolism while the latter groups had NIS and normal metabolism. It seems that these metabolic disorders are induced by android obesity with subclinical inflammation of the expanded visceral adipose tissue rather than PCOS per se. The PCOS per se is not associated with subclinical inflammation.     

Endometrial thickness measurement throughout a menstrual cycle in non-obese infertile patients with polycystic ovary syndrome

Purpose

To analyze the changes in the endometrial thickness in infertile polycystic ovary syndrome (PCOS) patients throughout an entire menstrual cycle and compare the changes to those seen in infertile patients without PCOS.

Methods

This prospective, cross-sectional study was conducted in a total of 58 non-obese, infertile women with PCOS. The endometrial thickness was measured at three different times throughout the menstrual cycle by ultrasound. Age- and body mass index (BMI)-matched control group consisted of 62 non-obese infertile patients without PCOS. Demographic, hormonal and the ultrasonographic measurements of the two groups were compared.

Results

Day 3 levels of LH were significantly different between the groups (p?=?0.013). Ovarian volume measurement was significant between the groups (p?=?0001). All the endometrial thickness measurements in the early, mid-cycle and late luteal phases were also significantly different; p?=?0.001 for all.

Conclusion

The study demonstrated an increased endometrial stripe measurements throughout a menstrual cycle in infertile patients with PCOS, when compared to infertile patients without PCOS.     

肥胖与非肥胖型多囊卵巢综合征患者糖代谢特征

目的 探讨肥胖和非肥胖型多囊卵巢综合征(PCOS)患者的糖代谢特征.方法 回顾性分析2006年5月至2009年4月在山东大学附属省立医院生殖医学中心就诊的1928例PCOS患者的临床资料和糖耐量、胰岛素释放试验结果,按体质指数(BMI)分为肥胖组(BMI≥25 kg/m2)901例和非肥胖组(BMI<25 kg/m2)1027例,比较两组患者口服糖耐量试验(OGTT)结果、空腹血糖受损(IFG)、糖耐量受损(IGT)和2型糖尿病(T2DM)的发生率.结果 (1)血糖水平:空腹及服糖后30、60、120、180 min,肥胖组血糖水平分别为(5.3±1.1)、(9.0±2.4)、(9.3±4.4)、(7.5±2.8)、(5.3±1.8)mmol/L,非肥胖组分别为(5.0±0.8)、(8.4±3.5)、(8.0±4.2)、(6.5±3.2)、(4.9±1.6)mmol/L,两组各时间点血糖水平比较,差异均有统计学意义(P<0.01).(2)胰岛素水平:空腹及服糖后30、60、120 min,肥胖组胰岛素水平分别为(13±7)、(81±51)、(102±65)、(83±63)mU/L,非肥胖组胰岛素水平分别为(8±5)、(57±35)、(62±44)、(46±39)mU/L,两组各时间点比较,差异均有统计学意义(P<0.01);但服糖后180 min两组胰岛素水平比较,差异无统计学意义(P>0.05).(3)糖代谢异常发生率:IFG总发生率为4.98%(96/1928);糖耐量异常总发生率为23.08%(445/1928);肥胖组和非肥胖组IGT发生率分别为24.20%(218/901)和13.05%(134/1027),两组比较,差异有统计学意义(P<0.01);肥胖组和非肥胖组T2DM发生率分别为7.44%(67/901)和2.53%(26/1027),两组比较,差异也有统计学意义(P<0.01).结论 肥胖型较非肥胖型PCOS患者更易发生糖代谢紊乱.     

Plasma beta-endorphin levels in obese and non-obese patients with polycystic ovarian disease

Several reports have shown elevated circulating beta-endorphin (beta-EP) levels in patients with polycystic ovarian disease (PCOD). However, it is not yet clear whether these high beta-EP levels are linked to the etiopathogenesis of PCOD or are secondary to the obesity. In the present study we measured beta-EP plasma concentrations in 19 PCOD patients, 10 with normal weight (Group A) and 9 with excessive weight (Group B), and in 18 normally ovulating women, 10 with normal weight (Group C) and 9 with excessive weight (Group D). beta-EP values were similar in the two groups of non-obese patients and controls. beta-EP concentrations were also similar in the two groups of obese patients and controls, and they were significantly higher (p less than 0.05) than in non-obese patients. Our data indicate that in PCOD, elevated beta-EP values are related to obesity, suggesting that they are not linked to the pathogenesis of PCOD.     

Metformin administration is more effective when non-obese patients with polycystic ovary syndrome show both hyperandrogenism and hyperinsulinemia.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disease that is frequently observed to be related to increased insulin resistance independent of body weight. The use of insulin-sensitizer compounds, such as metformin, permits great improvement of such metabolic abnormality, restoring ovarian function and gonadal steroid synthesis and reducing insulin resistance. AIM: On this basis we aimed to evaluate a group of non-obese amenorrheic PCOS patients before and after 6 months of metformin administration (500 mg orally twice daily) to better understand upon which basis of clinical and endocrine parameters metformin administration might be chosen as a putative therapeutic tool. METHOD: A group of non-obese PCOS patients (n = 42) was enrolled after informed consent. They underwent an oral glucose tolerance test for insulin, glucose and C-peptide levels and provided blood samples for determination of plasma levels of luteinizing hormone (LH), follicle-stimulating hormone, prolactin, estradiol, androstenedione, 17-hydroxyprogesterone, insulin, cortisol and testosterone levels on two occasions: before and on day 7 of the first menstrual cycle occurring after the 5th month of treatment. RESULTS: Plasma LH, estradiol, insulin and C-peptide were decreased significantly by metformin treatment in the entire group of PCOS patients. When subdividing PCOS patients according to insulin sensitivity (i.e. hyper- and normoinsulinemic subjects), a greater rate of positive endocrine changes was observed in hyperinsulinemic patients and the highest rate was observed in hyperinsulinemic hyperandrogenic subjects. Menstrual cyclicity was recovered in all patients under treatment. CONCLUSIONS: Our data show that metformin modulates ovarian function and greatly affects LH secretion through reduction of the hyperandrogenic condition. The highest rate of endocrine changes was observed in the hyperinsulinemic hyperandrogenic non-obese PCOS patients. Our study demonstrates that metformin administration is more appropriate in hyperinsulinemic hyperandrogenic non-obese PCOS patients.     

Flow-mediated dilatation in overweight and obese women with polycystic ovary syndrome

OBJECTIVE: There remains a large degree of disagreement about the association of polycystic ovary syndrome (PCOS) with impaired endothelial dysfunction and cardiovascular disease (CVD) risk. The purpose of this study was to determine whether overweight and obese women with PCOS have impaired endothelial function compared with weight-matched controls without PCOS and whether endothelial function is associated with cardiovascular risk markers and hormonal parameters. DESIGN: Cross-sectional analysis. SETTING: An outpatient trial at the Commonwealth Scientific Industrial Research Organisation Clinical Research Unit. POPULATION: Overweight and obese women with PCOS (n= 12) and weight-matched controls without PCOS (n= 10). METHODS: Endothelial function, cardiovascular risk markers and hormonal parameters were assessed in the patients. MAIN OUTCOME MEASURES: Endothelial function was assessed by flow-mediated dilatation (FMD) of the brachial artery using high-resolution ultrasound. Lipid profile, fasting insulin level, glucose level, insulin resistance, C-reactive protein level, folate level, Vitamin B(12) level and hormonal parameters. RESULTS: Women with PCOS had significantly higher testosterone levels (P < 0.001) and free androgen index (P= 0.006) compared with the controls without PCOS. Both groups were normoinsulinaemic, and there were no significant differences in any of the markers of CVD between women with and without PCOS. Furthermore, FMD was similar in both groups (PCOS 6.1 +/- 1.2% versus control 5.6 +/- 1.0%, P= 0.77). CONCLUSIONS: Compared with a group of weight-matched women with similar metabolic profiles, normoinsulinemic, overweight and obese women with PCOS did not show any greater impairment in endothelial function assessed by FMD. A normoinsulinemic phenotype of PCOS with low metabolic risk factors may reduce the risk of endothelial dysfunction in overweight and obese women with this syndrome. Further studies are required that directly compare FMD in normoinsulinemic and hyperinsulinaemic women with PCOS.     

The influence of body weight on lipoprotein lipids in patients with polycystic ovary syndrome

Lipoprotein lipid and androgen profiles were compared after a 12-hour fast that involved 13 women with polycystic ovary syndrome and 13 who did not have the syndrome. All women were matched for percent ideal body weight. As expected, patients with polycystic ovary syndrome had significantly higher luteinizing hormone--to--follicle-stimulating hormone ratios, higher testosterone levels, higher free testosterone levels, higher dehydroepiandrosterone sulfate levels, and lower testosterone-estradiol-binding globulin binding capacity than the other women. Patients with polycystic ovary syndrome had significantly higher mean serum triglyceride levels, very-low-density lipoprotein cholesterol levels, and lower high-density lipoprotein cholesterol levels. Differences in body weight do not explain the male pattern of lipoprotein lipid concentrations in women with polycystic ovary syndrome. The association of hyperandrogenism with lipoprotein lipid abnormalities should be evaluated in regard to the influence of endogenous sex steroids on differences between the sexes in incidence of cardiovascular disease.     

The correlation of plasma homocysteine with insulin resistance in polycystic ovary syndrome

AIM: This study aims to investigate the existence of any relationship between homocysteine levels and insulin resistance in Turkish women with polycystic ovary syndrome. METHODS: A case-controlled, cross-sectional, observational study was undertaken in a total of 94 infertile Turkish women who required professional help in the Department of Infertility of Dr Zekai Tahir Burak Women's Health Research and Education Hospital. The correlation between serum homocysteine with age, body mass index, hormone profile, fasting insulin and glucose concentrations and insulin resistance were examined in patients with polycystic ovary syndrome and the results were compared to those of women with normal ovaries, who served as a control group. RESULTS: The mean serum fasting glucose and insulin levels, thus insulin resistance index of women with polycystic ovary syndrome, were significantly higher than those of the control subjects. The mean serum homocysteine levels were significantly higher in women with polycystic ovary syndrome than those in the control group. A positive correlation was detected between the mean homocysteine, the insulin resistance index determined by homeostasis model assessment and the fasting insulin levels in polycystic ovary syndrome patients. CONCLUSIONS: Serum homocysteine levels are elevated in women with polycystic ovary syndrome, and this elevation is associated with the serum insulin level rather than androgen excess. The intense treatment of hyperhomocysteinemia in women with polycystic ovary syndrome might improve reproductive outcome and contribute to protection from cardiovascular risks.     

Differential insulin response to myo-inositol administration in obese polycystic ovary syndrome patients

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, chronic anovulation, polycystic ovaries at ultrasound evaluation, and quite frequently by insulin resistance or compensatory hyperinsulinemia. Attention has been given to the role of inositol-phosphoglycan (IPG) mediators of insulin action and growing evidences suggest that a deficiency of d-chiro-inositol (DCI) containing IPG might be at the basis of insulin resistance, frequent in PCOS patients. On such basis, we investigated the efficacy on insulin sensitivity and hormonal parameters of 8 weeks treatment with myo-inositol (MYO) (Inofert, ItalPharmaco, Milano, Italy) at the dosage of 2 g day in a group (n = 42) of obese PCOS patients,. After the treatment interval body mass index (BMI) and insulin resistance decreased together with luteinizing hormone (LH), LH/FSH and insulin. When subdividing the patients according to their fasting insulin levels, Group A (n = 15) insulin below 12 µU/ml and Group B (n = 27) insulin above 12 µU/ml, MYO treatment induced similar changes in both groups but only patients of Group B showed the significant decrease of both fasting insulin plasma levels (from 20.3 ± 1.8 to 12.9 ± 1.8 µU/ml, p < 0.00001) and of area under the curve (AUC) of insulin under oral glucose tolerance test (OGTT). In conclusion, our study supports the hypothesis that MYO administration is more effective in obese patients with high fasting insulin plasma levels.     

Metformin administration is more effective when non-obese patients with polycystic ovary syndrome show both hyperandrogenism and hyperinsulinemia

Background. Polycystic ovary syndrome (PCOS) is a common endocrine disease that is frequently observed to be related to increased insulin resistance independent of body weight. The use of insulin-sensitizer compounds, such as metformin, permits great improvement of such metabolic abnormality, restoring ovarian function and gonadal steroid synthesis and reducing insulin resistance.

Aim. On this basis we aimed to evaluate a group of non-obese amenorrheic PCOS patients before and after 6 months of metformin administration (500 mg orally twice daily) to better understand upon which basis of clinical and endocrine parameters metformin administration might be chosen as a putative therapeutic tool.

Method. A group of non-obese PCOS patients (n = 42) was enrolled after informed consent. They underwent an oral glucose tolerance test for insulin, glucose and C-peptide levels and provided blood samples for determination of plasma levels of luteinizing hormone (LH), follicle-stimulating hormone, prolactin, estradiol, androstenedione, 17-hydroxyprogesterone, insulin, cortisol and testosterone levels on two occasions: before and on day 7 of the first menstrual cycle occurring after the 5th month of treatment.

Results. Plasma LH, estradiol, insulin and C-peptide were decreased significantly by metformin treatment in the entire group of PCOS patients. When subdividing PCOS patients according to insulin sensitivity (i.e. hyper- and normoinsulinemic subjects), a greater rate of positive endocrine changes was observed in hyperinsulinemic patients and the highest rate was observed in hyperinsulinemic hyperandrogenic subjects. Menstrual cyclicity was recovered in all patients under treatment.

Conclusions. Our data show that metformin modulates ovarian function and greatly affects LH secretion through reduction of the hyperandrogenic condition. The highest rate of endocrine changes was observed in the hyperinsulinemic hyperandrogenic non-obese PCOS patients. Our study demonstrates that metformin administration is more appropriate in hyperinsulinemic hyperandrogenic non-obese PCOS patients.