Plasma cytokines in obese women with polycystic ovary syndrome, before and after metformin treatment

Abstract Background: Whether treatment with oral contraceptives (OC) and metformin can reduce anti-Müllerian hormone (AMH) levels in PCOS remains controversial. This study aims to investigate the effects of OC and metformin on serum AMH concentrations in women with polycystic ovary syndrome (PCOS). Methods: This prospective study included 120 women with PCOS. Patients were treated with OC (35 μg of ethinyl estradiol plus 2 mg of cyproterone acetate), metformin, or OC plus metformin for 3 months according to their different endocrine/metabolic disturbances. Forty-eight patients with hyperandrogenism (HA) were treated with OC, 32 patients with insulin resistance (IR) were treated with metformin, and 40 patients with HA and IR were treated with a combination of OC and metformin. Serum AMH levels were compared before and after treatment within each group.Results: AMH levels decreased significantly in both OC groups (from 12.54 ± 5.59 ng/mL before treatment to 9.03 ± 4.49 ng/mL after treatment, P < 0.01) as well as in the OC + metformin group (from 10.62 ± 4.57 ng/mL to 7.74 ± 3.19 ng/mL, P < 0.01). However, AMH concentrations remained unchanged in the metformin group, although insulin sensitivity was improved. Conclusion: Treatment with OC alone or OC plus metformin led to a significant reduction of serum AMH in PCOS patients with HA, while metformin treatment alone did not affect AMH levels in patients with IR.

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Effects of metformin and ethinyl estradiol–cyproterone acetate on lipid levels in obese and non-obese women with polycystic ovary syndrome

Acta Endocrinologica ◽

10.1530/eje.1.01840 ◽

2005 ◽

Vol 152 (2) ◽

pp. 269-275 ◽

Cited By ~ 44

Author(s):

K Rautio ◽

J S Tapanainen ◽

A Ruokonen ◽

L C Morin-Papunen

Keyword(s):

Polycystic Ovary Syndrome ◽

Ethinyl Estradiol ◽

Polycystic Ovary ◽

Density Lipoprotein ◽

Serum Levels ◽

Lipoprotein Cholesterol ◽

Metformin Treatment ◽

Obese Women ◽

Ovary Syndrome ◽

Cholesterol Ratio

Objective: Women with polycystic ovary syndrome (PCOS) exhibit risk factors for cardiovascular diseases such as abdominal obesity, insulin resistance and dyslipidemia. Insulin sensitizers, especially metformin, have been shown to improve these metabolic disturbances, but there are only a few studies on their effects on serum lipids in polycystic ovary syndrome. Methods: Thirty-five women with PCOS (18 obese and 17 non-obese) were randomized to 6-month treatments with metformin or ethinyl estradiol–cyproterone acetate oral contraceptive pills. Results: In the whole-study population (non-obese and obese women) serum levels of high-density lipoprotein cholesterol increased from 1.4±0.2 to 1.6±0.1 mmol/l (means ±s.e. throughout) at 3 and 6 months (P < 0.001), the total cholesterol:high-density lipoprotein cholesterol ratio decreased significantly from 3.8±0.3 to 3.3±0.2 at 6 months (P < 0.001) and a similar trend was observed in serum triglyceride levels during metformin treatment. In the oral contraceptive group, serum levels of total cholesterol increased from 4.9±0.3 to 5.4±0.3 mmol/l (P < 0.05), high-density lipoprotein cholesterol increased from 1.2±0.1 to 1.5±0.1 mmol/l (P < 0.001), the total cholesterol:high-density lipoprotein cholesterol ratio decreased from 4.6±0.4 to 3.7±0.2 (P < 0.001) and triglycerides increased from 1.3±0.1 to 1.9±0.2 mmol/l at 6 months of treatment (P < 0.001). Serum low-density lipoprotein cholesterol levels remained unchanged during both treatments. Milder but similar changes in the subgroups of obese and non-obese women were observed during both treatments. Moreover, in the whole-study population both systolic (P = 0.02) and diastolic (P = 0.05) blood pressures decreased over the 6 months of metformin treatment. Conclusion: In women with PCOS, metformin treatment had beneficial effects on lipid profile and blood pressure, and therefore it could be useful in the prevention of cardiovascular complications in these women.

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The effects of long-term metformin treatment on adrenal and ovarian steroidogenesis in women with polycystic ovary syndrome

Acta Endocrinologica ◽

10.1530/eje.0.1440619 ◽

2001 ◽

Vol 144 (6) ◽

pp. 619-628 ◽

Cited By ~ 47

Author(s):

J Vrbikova ◽

M Hill ◽

L Starka ◽

D Cibula ◽

B Bendlova ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Hydroxysteroid Dehydrogenase ◽

Gnrh Analogue ◽

Metformin Treatment ◽

Ovary Syndrome ◽

Ovarian Steroidogenesis ◽

Long Term Treatment ◽

Before And After

OBJECTIVE: To evaluate adrenal and ovarian steroidogenesis before and after long-term treatment with metformin in women with polycystic ovary syndrome (PCOS). DESIGN AND METHODS: Twenty-four women with PCOS were evaluated before and after treatment (27+/-4 weeks) with metformin (1000 mg/day) using adrenocorticotrophin (ACTH), GnRH analogue and oral glucose tolerance (oGTT) tests. For statistical evaluation, ANOVA and Wilcoxon's test were used. RESULTS: In 58% of the women a significant improvement in menstrual cyclicity was observed. No significant change in basal steroid levels was found. After ACTH stimulation, a significant decrease in the activity of 3 beta-hydroxysteroid dehydrogenase in C(21) steroids (P<0.05) and in 17 beta-hydroxysteroid dehydrogenase (P<0.01) was observed, as was an increase in the activity of C17,20-lyase in the Delta(4) pathway (P<0.01). A significant growth in the dehydroepiandrosterone (DHEA)/DHEA-sulfate ratio (P<0.05) was detected. With regard to ovarian steroidogenesis, a significant decrease in the stimulated levels of testosterone (P<0.05), index of free testosterone (P<0.01), LH (P<0.05) and oestradiol (P<0.01), and an increase in the levels of 17-hydroxypregnenolone (P<0.05) were detected. In the indices of ovarian enzyme activities, we observed a significant decrease in 3 beta-hydroxysteroid dehydrogenase in C21 steroids (P<0.01), in C17,20-lyase in the Delta 5 pathway (P<0.01), in 17 beta-hydroxysteroid dehydrogenase (P<0.05) and in aromatase. In glucose metabolism, a tendency towards reduction in the homeostasis model assessment (HOMA)-R (for insulin resistance) and HOMA-F (for beta cell function) was detected. In addition, an increase in the levels of C peptide during oGTT was observed (P<0.01). CONCLUSIONS: Long-term metformin treatment reduced various steroid enzymatic activities both in the ovary and the adrenal glands, without apparent changes in basal steroid levels and in insulin sensitivity.

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Asymmetrical Dimethylarginine, Inflammatory and Metabolic Parameters in Women with Polycystic Ovary Syndrome before and after Metformin Treatment

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2007-0842 ◽

2008 ◽

Vol 93 (1) ◽

pp. 82-90 ◽

Cited By ~ 74

Author(s):

Dennis Heutling ◽

Hasmik Schulz ◽

Ingrid Nickel ◽

Juergen Kleinstein ◽

Petra Kaltwasser ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Metabolic Parameters ◽

Metformin Treatment ◽

Ovary Syndrome ◽

Asymmetrical Dimethylarginine ◽

Before And After

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

Acta Endocrinologica ◽

10.1530/eje.0.1380269 ◽

1998 ◽

pp. 269-274 ◽

Cited By ~ 190

Author(s):

E Diamanti-Kandarakis ◽

C Kouli ◽

T Tsianateli ◽

A Bergiele

Keyword(s):

Insulin Resistance ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Free Testosterone ◽

Sex Hormone Binding Globulin ◽

Therapeutic Effects ◽

Obese Women ◽

Ovary Syndrome ◽

Before And After ◽

Ovarian Hyperandrogenism

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.

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