Insulin secretion in polycystic ovarian disease: effect of ovarian suppression by GnRH agonist

Lanzone, Antonio; Fulghesu, Anna Maria; Andreani, Cristiana Laura; Apa, Rosanna; Fortini, Antonio; Caruso, Alessandro; Mancuso, Stefano

doi:10.1093/oxfordjournals.humrep.a137058

Cited by 51 publications

(31 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To our knowledge, this speci®c aspect was not considered in previous studies in which troglitazone and metformin were administered to PCOS patients, probably because of the assumption that all obese PCOS subjects are hyperinsulinaemic and insulin resistant. However, several reports have clearly demonstrated the heterogeneity of insulin secretion also in this speci®c subset of patients (Dunaif et al, 1989;Lanzone et al, 1990;Ciampelli et al, 1997).…”

Section: Discussionmentioning

confidence: 92%

Selective effects of pioglitazone on insulin and androgen abnormalities in normo- and hyperinsulinaemic obese patients with polycystic ovary syndrome

Romualdi¹

2003

Human Reproduction

130

View full text Add to dashboard Cite

BACKGROUND: To investigate the effectiveness and safety of pioglitazone (45 mg/day) on clinical and endocrinemetabolic features of polycystic ovary syndrome (PCOS), we studied 18 obese PCOS patients, classi®ed as normoinsulinaemic (N-PCOS, n = 6) and hyperinsulinaemic (H-PCOS, n = 12) according to their insulin secretion. METHODS: Evaluation of clinical signs, hormonal and lipid pro®le assays, oral glucose tolerance tests and euglycaemic hyperinsulinaemic clamps were performed at baseline and after 2 (visit 2), 4 (visit 3) and 6 (visit 4) months of treatment. RESULTS: Body weight, body fat distribution and blood pressure remained stable throughout the treatment; hirsutism and acne signi®cantly improved (P < 0.001 for visits 3 and 4 versus baseline) in both groups. A restoration of menstrual cyclicity was observed at visit 4 in 83% (P < 0.001) of H-PCOS and in 33% of N-PCOS. A decrease in LH, LH/FSH ratio, androstenedione and 17-hydroxy-progesterone was observed in both groups, attaining statistical signi®cance in H-PCOS. A signi®cant amelioration of insulin secretion, sensitivity and clearance was obtained in H-PCOS. A trend towards improvement was observed in lipid assessment of both groups. Therapy was well-tolerated. CONCLUSIONS: Present data suggest that there is a selective effect, partially independent of insulin secretion, of pioglitazone on the clinical and hormonal disturbances of PCOS.

show abstract

Section: Discussionmentioning

confidence: 92%

Selective effects of pioglitazone on insulin and androgen abnormalities in normo- and hyperinsulinaemic obese patients with polycystic ovary syndrome

Romualdi¹

2003

Human Reproduction

130

View full text Add to dashboard Cite

show abstract

“…Previously, we showed that despite a marked and prolonged decrease in androgen ovarian production obtained by GnRH agonist, insulin secretion in response to an oral glucose tolerance test (OGTT) did not change in PCOS patients, thus indicating that androgens do not cause hyperinsulinism (5).…”

mentioning

confidence: 93%

Involvement of Ovarian Steroids in the Opioid-Mediated Reduction of Insulin Secretion in Hyperinsulinemic Patients with Polycystic Ovary Syndrome

Guido

Pavone

Ciampelli

et al. 1998

The Journal of Clinical Endocrinology &Amp; Metabolism

Self Cite

View full text Add to dashboard Cite

To evaluate the possible involvement of ovarian steroids on the opioid-mediated disorders of insulin in patients affected by polycystic ovary syndrome (PCOS), we studied 40 PCOS women. All patients underwent an oral glucose tolerance test (OGTT; 75 g) and basal hormone assay; based on the insulin response to OGTT, 26 women were classified as hyperinsulinemic and continued the study protocol.Patients were randomly divided into three groups characterized by different treatments: group A (nine patients) was treated with GnRH analog (one ampule every 28 days for 2 months), group B (eight patients) was treated with naltrexone (an oral opioid antagonist, 50 mg/day, orally) for 8 weeks, and group C (nine patients) was treated with GnRH analog plus naltrexone for 2 months. After continuation of treatment, all patients repeated the basal study in a second hospitalization.Naltrexone treatment significantly reduced the insulin response to OGTT, whereas GnRH analogue administration did not significantly change the insulin secretion after the glucose load. The GnRH analog/ naltrexone cotreatment was not able to influence the insulin secretory pattern; in fact, the insulin area under the curve was superimposable before and after therapy. These data could lead to the hypothesis that the opioidergic regulation of insulin secretion requires a normal steroidogenic pattern, thus suggesting that ovarian steroids modulate opioid activity also at peripheric districts. (J Clin Endocrinol Metab 83: [1742][1743][1744][1745] 1998) T HE PATHOGENESIS of polycystic ovary syndrome (PCOS) is still controversal. Inappropriate gonadotropin secretion, elevated serum androgen concentrations, hyperinsulinism, and insulin resistance are the common features (1, 2).Many studies have found a relationship between hyperinsulinism and elevated circulating androgen levels in PCOS (2-4), suggesting that insulin may cooperate with LH in inducing chronic hyperandrogenemia in PCOS patients. Previously, we showed that despite a marked and prolonged decrease in androgen ovarian production obtained by GnRH agonist, insulin secretion in response to an oral glucose tolerance test (OGTT) did not change in PCOS patients, thus indicating that androgens do not cause hyperinsulinism (5).Our recent data demonstrated that treatment with naltrexone (a long acting opioid antagonist) is able to reduce the LH response to GnRH stimulus in PCOS patients (6).Moreover, increasing evidence indicates that endogenous opiates are involved not only in the mechanism of gonadotropin release, but also in the regulation of many other compartments such as pancreatic islet function and thus in the pathogenesis of hyperinsulinemia and insulin resistance in subjects suffering from PCOS (7). Both acute (naloxone) and chronic (naltrexone) inhibition of opioidergic system significantly decreased the insulinemic response to an OGTT in a group of hyperinsulinemic PCOS patients without any change of plasma androgen levels (8, 9).Several in vivo and in vitro studies suggested that the ef...

show abstract

“…2,3 Obesity in women with PCOS is rather high, ranging from 30% to 60%, whereas hyperinsulinemia is present in more than 50% of patients with PCOS. 4,5 Furthermore, although about 70% of obese women with PCOS exhibit an exaggerated insulin secretion, this feature is also present in 20%-40% of lean PCOS. [6][7][8] Chronic hyperinsulinemia results in different pathologies such as diabetes mellitus type 2, hypertension, cardiovascular diseases and metabolic syndrome.…”

mentioning

confidence: 99%

Comparison of metformin and N-acetylcysteine on metabolic parameters in women with polycystic ovarian syndrome

Ali

Radhakrishnan

Singh

2017

Int J Reprod Contracept Obstet Gynecol

View full text Add to dashboard Cite

INTRODUCTIONPolycystic ovary syndrome (PCOS) is a common disease that affects up to 10% of women of reproductive age, in which hyperandrogenism (HA), enlarged cystic ovaries, and chronic anovulation often coexist with obesity, dyslipidemia and insulin resistance (IR).1 The etiology of the syndrome has remained unknown although it has been revealed that IR lies at the core of its pathophysiology. 2,3 Obesity in women with PCOS is rather high, ranging from 30% to 60%, whereas hyperinsulinemia is present in more than 50% of patients with PCOS. 4,5 Furthermore, although about 70% of obese women with PCOS exhibit an exaggerated insulin secretion, this feature is also present in 20%-40% of lean PCOS. [6][7][8] Chronic hyperinsulinemia results in different pathologies such as diabetes mellitus type 2, hypertension, cardiovascular diseases and metabolic syndrome.1,9 Risk factors of cardiovascular diseases tend to accumulate in these women even at their young age and dyslipidemia in these patients is correlated with IR. [10][11][12] It has been proven ABSTRACT Background: Polycystic ovary syndrome (PCOS) is a common disease that affects up to 10% of women of reproductive age, in which hyperandrogenism (HA), enlarged cystic ovaries, and chronic anovulation often co-exist with obesity, dyslipidemia and insulin resistance (IR). There is a need for an alternative to metformin with minimal side effects to improve insulin sensitivity and correct dyslipidemia in PCOS patients. Methods: It was a prospective, Randomized controlled clinical trial. 116 PCOS patients, 58 each in two groups received either Metformin 500 mg TDS or N-acetylcysteine (NAC) 600 mg TDS for 3 months. Clinical and biochemical parameters contributing to metabolic syndrome (MS) and insulin resistance (fasting blood sugar (FBS), fasting insulin (FI), FBS:FI, HOMA-IR and QUICKI) were assessed at the start and end of the study. Results were compared between the two groups. Results: Both treatment modalities resulted in a significant reduction in number of cases with IR (p=0.001) and MS. Fasting hyperinsulinemia improved in 15 % (p=0.12) and 30% (p=0.001) of patients while 12% (p=0.23) and 18% (p=0.049) improvement was seen in FBS:FI in MET and NAC group respectively. Similarly, improvement in HOMA-IR was 12% (p=0.30) and 32% (p=0.001) in MET and NAC group which is significant with NAC. QUICKI and impaired glucose tolerance showed significant improvement in both the groups with a p-value of 0.04 and 0.006, 0.035 and 0.046 respectively. Significant reduction was seen in triglycerides (p=0.048) in NAC group. Conclusions: NAC is equally efficacious as metformin in improving parameters of insulin resistance and metabolic syndrome with minimal occasional side effects ensuring better compliance for a long-term therapy.

show abstract

Insulin secretion in polycystic ovarian disease: effect of ovarian suppression by GnRH agonist

Cited by 51 publications

References 11 publications

Selective effects of pioglitazone on insulin and androgen abnormalities in normo- and hyperinsulinaemic obese patients with polycystic ovary syndrome

Selective effects of pioglitazone on insulin and androgen abnormalities in normo- and hyperinsulinaemic obese patients with polycystic ovary syndrome

Involvement of Ovarian Steroids in the Opioid-Mediated Reduction of Insulin Secretion in Hyperinsulinemic Patients with Polycystic Ovary Syndrome

Comparison of metformin and N-acetylcysteine on metabolic parameters in women with polycystic ovarian syndrome

Contact Info

Product

Resources

About