scholarly journals Therapeutic effects of metformin on insulin resistance and hyperandrogenism in polycystic ovary syndrome

1998 ◽  
pp. 269-274 ◽  
Author(s):  
E Diamanti-Kandarakis ◽  
C Kouli ◽  
T Tsianateli ◽  
A Bergiele

Evidence suggests that insulin resistance and hyperinsulinaemia are associated with ovarian hyperandrogenism and menstrual irregularities in polycystic ovary syndrome (PCOS). Sixteen obese women with PCOS on a weight-maintaining diet were studied before and after 6 months of therapy with the insulin-sensitizing antidiabetic agent metformin at a dose of 1700 mg per day. Compared with baseline values, glucose utilization was markedly enhanced at 6 months using the two-step euglycaemic-hyperinsulinaemic clamp to measure changes in insulin sensitivity (2.56 +/- 0.32 vs 4.68 +/- 0.49 mg/kg per min, P = 0.0001, when 40 mU insulin/m2 per min was infused, and 6.48 +/- 0.58 vs 9.84 +/- 0.72 mg/kg per min, P = 0.0002, when 400 mU insulin insulin/m2 per min was infused). The improvement in insulin action was accompanied by significant increases in the levels of sex hormone-binding globulin (24.5 +/- 7.2 vs 39.8 +/- 16.2 nmol/l, P = 0.003) and decreases in free testosterone (12.8 +/- 5.8 vs 9.0 +/- 3.0 pmol/l, P = 0.03) and androstenedione (12.9 +/- 5.6 vs 7.3 +/- 1.7 nmol/l, P = 0.003). No significant changes were recorded in body weight. Seven subjects resumed normal menstruation and two cases of spontaneous pregnancy occurred during treatment. Metformin was well tolerated except for one case of flatulence. These results confirm that metformin treatment can lead to improvements in insulin resistance and ovarian hyperandrogenism.

Author(s):  
Sujana Thalamati

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.


2006 ◽  
Vol 155 (6) ◽  
pp. 859-865 ◽  
Author(s):  
Marco C Amato ◽  
Aldo Galluzzo ◽  
Simona Merlino ◽  
Antonina Mattina ◽  
Pierina Richiusa ◽  
...  

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.


1997 ◽  
pp. 670-674 ◽  
Author(s):  
Y Sahin ◽  
F Kelestimur

OBJECTIVE: To determine the frequency of late-onset adrenal hyperplasia (LOCAH) due to 21-hydroxylase (21-OH) and 11 beta-hydroxylase (11 beta-OH) deficiency in women with clinical and biochemical features of polycystic ovary syndrome (PCOS). DESIGN: Eighty-three consecutively selected women with PCOS and eighteen normal women were included in the study. METHODS: Ultrasound, clinical and hormonal parameters were used to define PCOS. Basal FSH, LH, testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEA-S), sex hormone-binding globulin (SHBG) and cortisol levels were measured. Serum 17-hydroxyprogesterone (17-OHP) and 11-deoxycortisol (11-DOC) levels were also measured before, 30 and 60 min after a single bolus injection of 0.25 mg ACTH (1-24) at 0900 h during the mid-follicular phase of the cycle. ACTH-stimulated 17-OHP levels > 30 nmol/l were considered as the criteria of 21-OH deficiency. The diagnosis 11 beta-OH deficiency was made if the adrenal 11-DOC response to ACTH stimulation exceeded threefold the 95th percentile of controls. RESULTS: Basal serum testosterone, free testosterone, androstenedione, DHEA-S, cortisol and 11-DOC levels were significantly higher in PCOS than in control subjects. ACTH-stimulated 17-OHP (P < 0.05) and 11-DOC (P < 0.0005) levels were found to be significantly higher in patients with PCOS than in controls. Seven (8.4%) patients had an 11-DOC response to ACTH higher than threefold the 95th percentile of controls, while no patients showed evidence of 21-OH deficiency. CONCLUSIONS: We have found that 8.4% of the women with clinical and biochemical features of PCOS could be presumed to have 11 beta-OH deficiency. No patients among the women with PCOS showed evidence of 21-OH deficiency. 11 beta-OH deficiency is unexpectedly more common than 21-OH deficiency in women with PCOS.


2013 ◽  
Vol 125 (9) ◽  
pp. 423-432 ◽  
Author(s):  
Daniela Jakubowicz ◽  
Maayan Barnea ◽  
Julio Wainstein ◽  
Oren Froy

In women with PCOS (polycystic ovary syndrome), hyperinsulinaemia stimulates ovarian cytochrome P450c17α activity that, in turn, stimulates ovarian androgen production. Our objective was to compare whether timed caloric intake differentially influences insulin resistance and hyperandrogenism in lean PCOS women. A total of 60 lean PCOS women [BMI (body mass index), 23.7±0.2 kg/m2] were randomized into two isocaloric (~1800 kcal; where 1 kcal≈4.184 J) maintenance diets with different meal timing distribution: a BF (breakfast diet) (980 kcal breakfast, 640 kcal lunch and 190 kcal dinner) or a D (dinner diet) group (190 kcal breakfast, 640 kcal lunch and 980 kcal dinner) for 90 days. In the BF group, a significant decrease was observed in both AUCglucose (glucose area under the curve) and AUCinsulin (insulin area under the curve) by 7 and 54% respectively. In the BF group, free testosterone decreased by 50% and SHBG (sex hormone-binding globulin) increased by 105%. GnRH (gonadotropin-releasing hormone)-stimulated peak serum 17OHP (17α-hydroxyprogesterone) decreased by 39%. No change in these parameters was observed in the D group. In addition, women in the BF group had an increased ovulation rate. In lean PCOS women, a high caloric intake at breakfast with reduced intake at dinner results in improved insulin sensitivity indices and reduced cytochrome P450c17α activity, which ameliorates hyperandrogenism and improves ovulation rate. Meal timing and distribution should be considered as a therapeutic option for women with PCOS.


Diabetes Care ◽  
2007 ◽  
Vol 30 (9) ◽  
pp. 2309-2313 ◽  
Author(s):  
M. Luque-Ramirez ◽  
F. Alvarez-Blasco ◽  
J. I. Botella-Carretero ◽  
R. Sanchon ◽  
J. L. San Millan ◽  
...  

2020 ◽  
Vol 11 ◽  
pp. 204201882093830 ◽  
Author(s):  
Mohammed Altigani Abdalla ◽  
Harshal Deshmukh ◽  
Stephen Atkin ◽  
Thozhukat Sathyapalan

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. Metabolic sequelae associated with PCOS range from insulin resistance to type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Insulin resistance plays a significant role in the pathophysiology of PCOS and it is a reliable marker for cardiometabolic risk. Although insulin sensitising agents such as metformin have been traditionally used for managing metabolic aspects of PCOS, their efficacy is low in terms of weight reduction and cardiovascular risk reduction compared with newer agents such as incretin mimetics and SGLT2 inhibitors. With current pharmaceutical advances, potential therapeutic options have increased, giving patients and clinicians more choices. Incretin mimetics are a promising therapy with a unique metabolic target that could be used widely in the management of PCOS. Likewise, bariatric procedures have become less invasive and result in effective weight loss and the reversal of metabolic morbidities in some patients. Therefore, surgical treatment targeting weight loss becomes increasingly common in the management of obese women with PCOS. Newer emerging therapies, including twincretins, triple GLP-1 agonists, glucagon receptor antagonists and imeglemin, are promising therapeutic options for treating T2DM. Given the similarity of metabolic and pathological features between PCOS and T2DM and the variety of therapeutic options, there is the potential to widen our strategy for treating metabolic disorders in PCOS in parallel with current therapeutic advances. The review was conducted in line with the recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome 2018.


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