Smoking is associated with increased free testosterone and fasting insulin levels in women with polycystic ovary syndrome, resulting in aggravated insulin resistance

2010 ◽  
Vol 94 (2) ◽  
pp. 673-677 ◽  
Author(s):  
Susanne Cupisti ◽  
Lothar Häberle ◽  
Ralf Dittrich ◽  
Patricia G. Oppelt ◽  
Christine Reissmann ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Free Testosterone ◽  
Fasting Insulin ◽  
Ovary Syndrome ◽  
Insulin Levels

scholarly journals Metformin improves polycystic ovary syndrome symptoms irrespective of pre-treatment insulin resistance

2007 ◽  
Vol 157 (5) ◽  
pp. 669-676 ◽  
Author(s):  
Susanne Tan ◽  
Susanne Hahn ◽  
Sven Benson ◽  
Tiina Dietz ◽  
Harald Lahner ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Fasting Glucose ◽  
Polycystic Ovary ◽  
Model Assessment ◽  
Fasting Insulin ◽  
Ovary Syndrome ◽  
Insulin Levels ◽  
Outcome Parameters ◽  
Pre Treatment

AbstractObjectiveInsulin resistance (IR) and obesity are common features of the polycystic ovary syndrome (PCOS). Insulin-sensitizing agents have been shown to improve both reproductive and metabolic aspects of PCOS, but it remains unclear whether it is also beneficial in lean patients without pre-treatment IR. The aim of this study was to determine the influence of metformin on the clinical and biochemical parameters of PCOS irrespective of the presence of basal obesity and IR.DesignThe effect of 6 months of metformin treatment was prospectively assessed in 188 PCOS patients, divided into three groups according to body mass index (BMI; lean: BMI<25 kg/m2, overweight: BMI 25–29 kg/m2, and obese: BMI≥30 kg/m2). Outcome parameters, which were also assessed in 102 healthy controls, included body weight, homeostasis model assessment for IR (HOMA-IR), fasting glucose and insulin levels, area under the curve of insulin response (AUCI), hyperandrogenism, and menstrual irregularities.ResultsIn comparison with the respective BMI-appropriate control groups, only obese but not lean and overweight PCOS patients showed differences in fasting insulin and HOMA-IR. Metformin therapy significantly improved all outcome parameters except fasting glucose levels. Subgroup analyses revealed that in the group of lean PCOS patients without pre-treatment IR, metformin significantly improved HOMA-IR (1.7±1.0 vs 1.1±0.7 μmol/l×mmol/l2) and fasting insulin levels (7.7±4.2 vs 5.4±3.9 mU/l), in addition to testosterone levels (2.6±0.9 vs 1.8±0.7 nmol/l), anovulation rate (2.3 vs 59.5%), and acne (31.8 vs 11.6%; all P<0.017). In the overweight and obese PCOS groups, metformin also showed the expected beneficial effects.ConclusionMetformin improves parameters of IR, hyperandrogenemia, anovulation, and acne in PCOS irrespective of pre-treatment IR or obesity.

scholarly journals Leptin levels in women with polycystic ovary syndrome before and after treatment with diazoxide

1998 ◽  
pp. 184-189 ◽  
Author(s):  
GE Krassas ◽  
TT Kaltsas ◽  
N Pontikides ◽  
H Jacobs ◽  
W Blum ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Free Testosterone ◽  
Common Finding ◽  
Oral Glucose ◽  
Ovary Syndrome ◽  
Insulin Levels ◽  
Igf I ◽  
Before And After ◽  
Igfbp 3

Leptin, a product of the ob gene, is a 16 kDa protein which is produced by adipocytes. In humans, obesity is a common finding in women with polycystic ovary syndrome (PCOS). The role, however, of leptin in PCOS is not clear. Some studies have reported increased levels of leptin in PCOS, while others report that they are normal. Also, insulin resistance is a common finding in PCOS. The aim of this study was to investigate further the role of insulin in leptin secretion in patients with PCOS by treating them for 10 days with diazoxide, an insulin-reducing compound. Eight women with PCOS, mean age 22.1 +/- 2.7 years, with mean body mass index (BMI) 28.4 +/- 5.7kg/m2, were studied. An oral glucose tolerance test (OGTT) was performed in all women and blood samples were taken before and at 30, 60, 90, 120 and 150 min after the administration of glucose. Glucose, insulin, leptin, free testosterone, delta4 androstenedione, sex hormone binding globulin (SHBG), LH, FSH, IGF-I and insulin-like growth factor-binding protein-3 (IGFBP-3) were measured in the sera taken before the administration of glucose, while glucose and insulin levels were measured in all samples which were collected after the administration of glucose. Diazoxide 300 mg daily was given to all women starting after the end of the OGTT for 10 days. A second OGTT was performed the day after the discontinuation of the diazoxide treatment. The same hormonal and biochemical parameters were also measured in all patients during the second OGTT. After the administration of diazoxide a reduction in sum insulin (262 +/- 147 vs 679 +/- 341 microU/ml. P<().01), leptin (18.5 +/- 10.6 vs 24.2 +/- 10.2 ng/ml, P<0.01), free testosterone (3.0 +/- 1.9 vs 5.1 +/- 1.9 pg/ml, P<0.01), delta4 androstenedione (3.8 +/- 1.9 vs 5.7 +/- 2.0 ng/ml, P<0.01) and IGF-I (219.5 +/- 69.2 vs 314.5 +/- 82.3 ng/ml, P<0.01) levels was observed. Serum SHBG (38.8 +/- 16.8 vs 27.8 +/- 12.1 nmol/l, P<0.01) and sum glucose levels (994.1 +/- 252.7 vs 711.1 +/- 166.1 mg/dl, P<0.05) were increased while IGFBP-3 (3.96 +/- 2.49 vs 3.75 +/- 2.24mg/l), FSH (6.2 +/- 1.8 vs 6.0 +/- 2.5 mU/l) and LH (18.9 +/- 6.7 vs 21.4 +/- 6.7 mU/l) concentrations did not change significantly. A significant positive correlation was found between serum leptin and BMI values before and after administration of diazoxide as well as between leptin, insulin and IGFBP-3 values. Also, sum insulin values correlated significantly with BMI. However, when multiple regression analysis was used this correlation was eliminated except that between leptin and BMI. This was most probably due to the small number of cases. The mechanism of the reduction of leptin levels is unclear. However, it is suggested that the concomitant decrease of insulin levels may play a role.

scholarly journals The treatment of insulin resistance does not improve adrenal cytochrome P450c17alpha enzyme dysregulation in polycystic ovary syndrome

1999 ◽  
pp. 56-61 ◽  
Author(s):  
K Unluhizarci ◽  
F Kelestimur ◽  
Y Sahin ◽  
F Bayram
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Tolerance Test ◽  
Glucose Disposal ◽  
Ovary Syndrome ◽  
Metformin Therapy ◽  
Insulin Levels ◽  
Healthy Women

OBJECTIVE: To determine whether metformin. when given to non-diabetic women with polycystic ovary syndrome (PCOS), results in a reduction of insulin resistance and hyperinsulinemia while body weight is maintained. Also we aimed to see whether the reduction in insulin levels attenuates the activity of adrenal P450c17alpha enzyme in patients with PCOS. DESIGN: We investigated the 17-hydroxyprogesterone (17-OHP) and androstenedione responses to ACTH, insulin responses to an oral glucose tolerance test (OGTT) and glucose disposal rate in an insulin tolerance test before and after metformin therapy (500 mg, orally, twice daily, for 12 weeks). METHODS: The presence of hyperinsulinemia in 15 women with PCOS was demonstrated by an OGTT and results were compared with those of 10 healthy women. Insulin sensitivity was measured by the rate of endogenous glucose disposal after i.v. bolus injection of insulin. 17-OHP and androstenedione responses to ACTH were measured in all the women with PCOS and the normal women. RESULTS: Women with PCOS were hyperinsulinemic (102.0+/-13.0 (S.E.M.) VS 46.2+/-4.4 pmol/l) and hyperandrogenemic (free testosterone 15.3+/-1.7 vs 7.9+/-0.6 nmol/l; androstenedione 11.8+/-0.8 vs 8.2+/-0.6 nmol/l) and more hirsute (modified Ferriman-Gallwey score, 17.7+/-1.6 vs 3.0+/-0.3) than healthy women. In addition, women with PCOS had higher 17-OHP and androstenedione responses to ACTH when compared with healthy women. Metformin therapy resulted in some improvement in insulin sensitivity and reduced the basal and post-glucose load insulin levels. But 17-OHP and androstenedione responses to ACTH were unaltered in response to metformin. CONCLUSIONS: PCOS is characterized by hyperactivity of the adrenal P450c17alpha enzyme and insulin resistance. It seems that there is no direct relationship between insulin resistance and adrenal P450c17alpha enzyme dysregulation.

scholarly journals Serum Leptin Levels in Women with Polycystic Ovary Syndrome: The Role of Insulin Resistance/ Hyperinsulinemia1

1997 ◽  
Vol 82 (6) ◽  
pp. 1692-1696
Author(s):  
G. A. Laughlin ◽  
A. J. Morales ◽  
S. S. C. Yen
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Body Fat ◽  
Polycystic Ovary ◽  
Pulse Amplitude ◽  
Percent Body Fat ◽  
Ovary Syndrome ◽  
Serum Leptin ◽  
Insulin Levels

Abstract Polycystic ovary syndrome (PCOS) is associated with chronic anovulation, hyperandrogenemia, insulin resistance (IR)/hyperinsulinemia, and a high incidence of obesity. Thus, PCOS serves as a useful model to assess the role of IR and chronic endogenous insulin excess on leptin levels. Thirty-three PCOS and 32 normally cycling (NC) women of similar body mass index (BMI) were studied. Insulin sensitivity (SI) was assessed by rapid ivGTT in a subset of 28 PCOS and 29 NC subjects; percent body fat was determined by dual-energy x-ray absorptiometry (DEXA) in 14 PCOS and 17 NC. Fasting (0800 h) and 24-h mean hourly insulin levels were 2-fold higher (P &lt; 0.0001), and SI was 50% lower (P = 0.005) in PCOS than in NC, while serum androstenedione (A), testosterone (T), 17-α hydroxyprogesterone (17OHP), and estrone (E1) levels were elevated (P &lt; 0.0001), and sex hormone-binding globulin (SHBG) levels were decreased (P &lt; 0.01). Twenty-four hour LH pulse frequency, mean pulse amplitude, and mean LH levels were elevated in PCOS (P &lt; 0.001) as compared with NC. Serum leptin levels for PCOS (24.1 ± 2.6 ng/mL) did not differ from NC (21.5 ± 3.5 ng/mL) and were positively correlated with BMI (r = 0.81) and percent body fat (r = 0.91) for the two groups (both P &lt; 0.0001). Leptin levels for PCOS and NC correlated positively with fasting and 24-h mean insulin levels (r = 0.81, P &lt; 0.0001 for both PCOS and NC) and negatively with SI and SHBG levels. Leptin concentrations for PCOS, but not NC, correlated positively with 24-h mean glucose levels and inversely with 24-h mean LH levels and 24-h mean LH pulse amplitude. Leptin levels were not correlated with estrogen or androgen levels for either PCOS or NC, although leptin levels were positively related to the ratios of E1/SHBG and E2/SHBG for both PCOS and NC and to the ratio of T/SHBG for PCOS only. In stepwise multivariate regression with forward selection, only 24-h mean insulin levels contributed significantly (P &lt; 0.01) to leptin levels independent of BMI and percent body fat for both PCOS and NC. Given this relationship and the presence of 2-fold higher 24-h mean insulin levels in PCOS, the expected elevation of leptin levels in PCOS was not found. This paradox may be explained by the presence of adipocyte IR specific to PCOS, which may negate the stimulatory impact of hyperinsulinemia on leptin secretion, a proposition requiring further study.

scholarly journals A comparative study of combination of Myo-inositol and D-chiro-inositol versus Metformin in the management of polycystic ovary syndrome in obese women with infertility

2019 ◽  
Vol 8 (3) ◽  
pp. 825
Author(s):  
Sujana Thalamati
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Comparative Study ◽  
Polycystic Ovary ◽  
Free Testosterone ◽  
Obese Women ◽  
Ovary Syndrome ◽  
Serum Lh ◽  
Symptom Complex ◽  
Group B

Background: Polycystic ovary syndrome (PCOS) is a symptom complex associated with increased amounts of circulating androgens in females, increased insulin resistance and obesity. The drugs, Myo-inositol, D-chiro-inositol and Metformin, which are insulin sensitizers, are very helpful in taking care of one of the key components of PCOS that is insulin resistance. This study was done to compare the effects of combination of Myo-inositol and D-chiro-inositol with the use of metformin on clinical and biochemical profile in PCOS.Methods: A prospective, randomized, comparative study was conducted on 200 patients. The patients were randomly assigned into the two groups of 100 each. Group A receiving Tab. Myoinositol 550mg twice daily and Tab. D-chiro-inositol 13.8mg twice daily and Group B receiving Tab. Metformin 500mg thrice daily. The patients were assessed by menstrual cycle regulation, hirsutism score (Ferriman Gallwey), fasting and post prandial glucose and insulin levels, serum DHEA levels, serum free testosterone levels and fasting day 3 serum LH and FSH ratio.Results: In both the groups there was significant improvement in all the above mentioned parameters, however the group with Combination of Myo-inositol and D-chiro-inositol had statistically significant improvement over the Metformin group.Conclusions: Combination of Myo-inositol and D-chiro-inositol and use of metformin, significantly improved insulin sensitivity in PCOS women. But combination of Myo-inositol and D-chiro-inositol was effective in controlling the hormonal profiles (LH/FSH ration and free testosterone) when compared to Metformin.

A prospective pilot study of the effect of acupuncture on insulin sensitivity in women with polycystic ovary syndrome and insulin resistance

2020 ◽  
Vol 38 (5) ◽  
pp. 310-318
Author(s):  
Juan Li ◽  
Wanting Wu ◽  
Elisabet Stener-Victorin ◽  
Ernest Hung Yu Ng ◽  
Raymond Hang Wun Li ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Pilot Study ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Secondary Outcome ◽  
Ovary Syndrome ◽  
Insulin Levels ◽  
Prospective Pilot Study

Objective: To test the hypothesis that acupuncture improves insulin sensitivity in women with polycystic ovary syndrome (PCOS) and insulin resistance (IR). Design: Prospective pilot study. Setting: Guangzhou, China, 2014–2016. Participants: Eighty women with PCOS aged 18–40 years with body mass index (BMI) above 18.5 kg/m2 and with homeostatic model assessment for insulin resistance (HOMA-IR) index ⩾2.14. Interventions: Subjects received acupuncture with combined manual and low-frequency electrical stimulation of the needles three times per week for 6 months. Primary and secondary outcome measures: The primary outcome was the change in HOMA-IR after 6 months of acupuncture relative to baseline. Secondary outcomes included changes after 6 months of acupuncture and at 3 months of follow-up (both relative to baseline) in oral glucose tolerance test (OGTT) parameters (glucose and insulin levels), anthropometric measurements, and circulating metabolic and endocrine variables. Results: HOMA-IR and fasting plasma glucose and insulin levels were significantly decreased after 6 months of acupuncture, and both HOMA-IR and fasting insulin remained significantly decreased at 3 months of follow-up. In a subgroup analysis of normal-weight and overweight/obese women, HOMA-IR was reduced after 6 months of acupuncture in both subgroups, but there was no significant difference between the two groups. Conclusions: Acupuncture treatment in Chinese women with PCOS and IR was associated with an encouraging improvement in insulin sensitivity. Further randomized controlled studies are required to confirm the efficacy of acupuncture for this indication.

Insulin levels, insulin resistance and the use of metformin in polycystic ovary syndrome

2007 ◽  
Vol 186 (5) ◽  
pp. 268-269 ◽  
Author(s):  
Samantha K Hutchison ◽  
Sophia Zoungas ◽  
Helena J Teede
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Insulin Levels

scholarly journals The androgen receptor CAG repeat modifies the impact of testosterone on insulin resistance in women with polycystic ovary syndrome

2006 ◽  
Vol 155 (1) ◽  
pp. 127-130 ◽  
Author(s):  
Matthias Möhlig ◽  
Annette Jürgens ◽  
Joachim Spranger ◽  
Kurt Hoffmann ◽  
Martin O Weickert ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Androgen Receptor ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Free Testosterone ◽  
Cag Repeat ◽  
Repeat Polymorphism ◽  
Ovary Syndrome ◽  
Interaction Term ◽  
The Impact

Objective: Hyperandrogenism is a central feature of the polycystic ovary syndrome (PCOS) and might worsen insulin resistance (IR) often seen in PCOS. Androgens act through the androgen receptor (AR). A polymorphic CAG repeat sequence within the AR gene was reported to modulate its transactivation activity. Therefore, we investigated a putative interaction between testosterone and the CAG repeat length polymorphism with respect to IR. Design: In 63 PCOS women with normal glucose tolerance free testosterone, the biallelic CAG repeat length and a multiplicative interaction term were investigated by multiple linear regression analysis for an association with IR as indicated by the homeostasis model assessment of IR (HOMA-IR). Results: Free testosterone was correlated with HOMA-IR. The impact of testosterone on HOMA-IR was modified by the AR CAG length as indicated by an interaction term. This interaction remained significant after adjustment for smoking, age and body mass index. While there was a positive association of free testosterone with HOMA-IR, the interaction term was inversely associated. The model, which explained 42.5% of the variation of HOMA-IR predicted that in carriers of short CAG lengths, an increase in testosterone increased IR. This effect attenuated with rising biallelic CAG length until it turns into the opposite at a CAG length longer than 23. The results were confirmed by using CIGMA as another measure of IR. Conclusions: The association between testosterone and IR is modified by the CAG repeat polymorphism within the AR. Therefore, the evaluation of testosterone effects on IR seems to require consideration of the AR CAG repeat polymorphism in PCOS women.

scholarly journals Lower insulin sensitivity differentiates hirsute from non-hirsute Sicilian women with polycystic ovary syndrome

2006 ◽  
Vol 155 (6) ◽  
pp. 859-865 ◽  
Author(s):  
Marco C Amato ◽  
Aldo Galluzzo ◽  
Simona Merlino ◽  
Antonina Mattina ◽  
Pierina Richiusa ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Free Testosterone ◽  
Total Testosterone ◽  
Obese Women ◽  
Ovary Syndrome ◽  
The Metabolic Syndrome ◽  
Matsuda Index

Objective: It is well known that hyperandrogenism and insulin-resistance with or without compensatory hyperinsulinism are closely associated, but the Rotterdam Consensus has concluded that principally obese women with polycystic ovary syndrome (PCOS) should be evaluated for the metabolic syndrome. Our aim was to study insulin sensitivity in PCOS women with hirsutism regardless of obesity. Methods: Clinical characteristics, sex hormones and fasting- and after OGTT-glycemia and insulinemia, homeostatic model of insulin resistance (HOMA IR), and Matsuda index of insulin sensitivity were analyzed in 130 women with PCOS. Hirsutism has been evaluated through the Ferriman–Gallwey (FG) map scoring system. Results: PCOS women with hirsutism (57.7% of participants) showed significant higher values of total testosterone levels (P = 0.016), free testosterone (P = 0.027), DHEA sulfate (P = 0.017), and Δ4androstenedione (P = 0.018). They had similar body mass index (BMI) (P = 0.073) and were significantly less insulin sensitive (P = 0.002) than those without hirsutism (42.3% of participants). In women with PCOS and hirsutism, there was a significant correlation between FG score and insulin-sensitivity indexes (HOMA IR, ρ = 0.33, P = 0.005; Matsuda index, ρ = −0.34, P = 0.003) but not with the androgen levels. Moreover, women with hirsutism showed a significantly greater insulin (P = 0.019), C-peptide (P = 0.002), and glucose (P = 0.024) areas under the curve (auc2h). Conclusions: Our study suggests that the increased responsiveness of the pilo-sebaceous unit to androgens seems to be influenced by insulin sensitivity and that insulin resistance should be assessed in all hirsute women with PCOS regardless of their BMI, as insulin resistance was found in hirsute women irrespective of whether they were overweight or obese.

scholarly journals Association between the serum estrone-to-estradiol ratio and parameters related to glucose metabolism and insulin resistance in women with polycystic ovary syndrome

2021 ◽  
Vol 48 (4) ◽  
pp. 374-379
Author(s):  
Nayoung Kim ◽  
Sungwook Chun
Keyword(s):  
Insulin Resistance ◽  
Glucose Metabolism ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Postprandial Glucose ◽  
Serum Glucose ◽  
Clinical Variable ◽  
Fasting Insulin ◽  
Ovary Syndrome ◽  
Glucose Levels

Objective: We aimed to evaluate associations between the ratio of serum estrone (E1) to estradiol (E2) and parameters related to serum glucose metabolism and insulin resistance in women with polycystic ovary syndrome (PCOS). Methods: In total, 133 women between the ages of 18 and 33 diagnosed with PCOS were enrolled in this study. All participants with PCOS underwent blood tests to determine hormonal and biochemical metabolic parameters and a standard 2-hour 75-g oral glucose tolerance test. They were divided into two groups according to the serum E1-to-E2 ratio: group 1 (E1/E2 ratio <2.0) and group 2 (E1/E2 ratio ≥2.0). Results: In the comparative analysis, the waist-to-hip ratio (WHR) was the only clinical variable that was significantly different between the two groups. Patients with a higher E1/E2 ratio showed higher fasting insulin levels, homeostasis model for insulin resistance, and postprandial glucose levels at 2 hours (PPG2). In a correlation analysis, only PPG2 was significantly related to the serum E1/E2 ratio. However, after controlling for the confounding effects of body mass index (BMI) and WHR, fasting glucose was also significantly correlated with the serum E1/E2 ratio. Conclusion: Women with PCOS with a higher serum E1/E2 ratio were found to be more likely to show higher fasting insulin and postprandial glucose levels. Significant correlations were found between the serum E1/E2 ratio and both fasting and postprandial serum glucose levels after adjusting for BMI and WHR in women with PCOS.

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