The contributions of oestrogen and growth factors to increased adrenal androgen secretion in polycystic ovary syndrome

Adrenal hyperandrogenism is prevalent in many women with polycystic ovary syndrome (PCOS), although the expression of this enhanced secretion may be heterogeneous. Since no single factor acts in isolation, this study was performed to assess the influence of oestradiol (total and unbound), insulin, insulin-like growth factor (IGF)-I, IGF-II and the binding proteins IGFBP-I, and IGFBP-3, on basal and adrenocorticotrophic hormone (ACTH) stimulated adrenal androgen secretion in 25 women with PCOS and 10 matched ovulatory controls. Women with PCOS exhibited elevations of all androgens as well as unbound oestradiol, insulin and non-IGFBP-1 bound IGF-I. Positive correlations were noted between oestrogen and basal and ACTH stimulated delta 5 adrenal androgens. Serum IGF-I was only correlated with basal dehydroepiandrosterone sulphate (DHEA-S), while insulin exhibited a strong correlation with the delta 4 pathway and androstenedione formation in particular. This correlation was also confirmed by dividing the PCOS group into those women with and without hyperinsulinaemia. The activity of 17,20 lyase favouring androstenedione was increased in the hyperinsulinaemic women. By multivariate analyses, body mass index did not influence these findings. Although there are inherent difficulties in making major conclusions based on correlative analyses, it is suggested that oestrogen may have a greater influence on enhancing delta 5 adrenal androgen secretion, and insulin a greater effect on the delta 4 pathway. In turn, the relative importance of these influences may contribute to the heterogeneous nature of adrenal hyperandrogenism in PCOS.     

Hyperinsulinemia in polycystic ovary syndrome: relationship to clinical and hormonal factors

We analyzed the association between hyperandrogenism and hyperinsulinemia, and their relationship to body mass index, in a large series of patients with polycystic ovary syndrome (PCOS). A characteristic hormonal profile was sought in women with marked hyperinsulinemia. The patient group consisted of 73 women with PCOS, ranging in age from 16 to 29 years. The control group consisted of 34 healthy women with no evidence of hyperandrogenism, aged 19–30 years. None of the patients or control women had a body mass index above 27 kg/m². Follicle-stimulating hormone, luteinizing hormone, prolactin, testosterone, estradiol, androstenedione, dehydroepiandrosterone sulfate, sex hormone binding globulin, 17-hydroxyprogesterone, and free cortisol were determined by radioimmunoassay. The free testosterone index was calculated. The oral glucose tolerance test was used to analyze basal insulinemia, maximum insulin peak, and the insulinemia/glycemia index. In the group with PCOS body mass index was greater, free testosterone index was higher, and levels of dehydroepiandrosterone sulfate, testosterone, 17-hydroxyprogesterone (P < 0.001) and androstenedione (P < 0.05) were higher than in the control group. Of the insulin parameters, basal insulinemia, maximum insulin peak, and insulinemia/glycemia index were higher in the patient group (P < 0.001). In patients with marked insulinemia, free testosterone index was more markedly elevated, and gonadotrophin levels were normal. Our data confirm that a characteristic pattern of hyperinsulinemia is associated with PCOS. We found no causal relationship between hyperinsulinemia and androgen levels. A characteristic hormonal pattern was found in patients with marked hyperinsulinemia.Abbreviations BMI body mass index - 17OHP 17-hydroxyprogesterone - DHEAS dehydroepiandrosterone sulfate - FTI free testosterone index - I/G insulin/glucose ratio - OGTT oral glucose tolerance test - PCOS polycystic ovary syndrome - P_max maximun peak of insulin - SHBG sex hormone binding globulin - LH luteinizing hormone - FSH follicle-stimulating hormone     

Patterns of hormonal response to the GnRH agonist leuprolide in brothers of women with polycystic ovary syndrome: a pilot study

BACKGROUND: The aim of this study was to evaluate the effect of a single dose of leuprolide acetate on gonadotrophin and gonadal steroid secretion in brothers of women with polycystic ovary syndrome (PCOS), in order to assess P450c17alpha activity. An oral glucose tolerance test (OGTT) and a lipid profile were also performed. METHODS: Twenty-two unrelated brothers of women with PCOS (PCOS(b)) and 14 brothers of normal cycling women (C(b)), matched for age, underwent a leuprolide acetate test (10 microg/kg s.c.) and an OGTT with measurement of circulating concentrations of gonadotrophins, steroid hormones, glucose, insulin and lipids. RESULTS: Clinical and basal hormonal parameters were similar in both groups. After leuprolide administration, PCOS(b) exhibited a significant increase of 17alpha-hydroxyprogesterone (17-OHP) compared to C(b) (P<0.05). However, only 45% of PCOS(b) showed a supranormal increase of 17-OHP (2 SD above the respective control group mean values, P<0.003) with a normal gonadotrophin response (group 1). The other 55% of the PCOS(b) exhibited a normal 17-OHP response to the analogue (group 2). However, in group 2, basal steroid concentrations did not show a uniform pattern: six of the PCOS(b) exhibited high basal androstenedione (2 SD above the respective control group mean values), three were very similar to C(b), and the other three presented lower basal testosterone concentrations (2 SD below the respective control group mean values) than those observed in C(b). CONCLUSIONS: This study shows that different responses to leuprolide in PCOS brothers make evident the heterogeneity of this syndrome in which P450c17alpha activity could be involved.     

17-Hydroxyprogesterone responses to gonadotrophin-releasing hormone agonist buserelin and adrenocorticotrophin in polycystic ovary syndrome: investigation of adrenal and ovarian cytochrome P450c17alpha dysregulation

Abnormal regulation of cytochrome P450c17alpha causes the exaggerated secretion of ovarian androgens in polycystic ovary syndrome (PCOS). This enzyme is active in both the ovaries and adrenal glands. We examined whether there is an abnormal regulation of cytochrome P450c17alpha in the adrenal gland by investigating the relationship of 17-hydroxyprogesterone (17-OH progesterone) hyperresponsiveness to the gonadotrophin releasing hormone (GnRH) agonist, buserelin, testing with 17-OH progesterone response to adrenocorticotrophic hormone (ACTH) in PCOS. In all, 68 women with PCOS and 24 normal women were included in the study. Ultrasound, clinical and hormonal parameters were used to define PCOS. 17-OH progesterone response to ACTH was measured in all the women. In 52 of the 68 women with PCOS, 17-OH progesterone response to buserelin was measured. The mean basal 17-OH progesterone concentrations were similar in both PCOS and control groups. PCOS women had significantly higher net increment in 17-OH progesterone after ACTH administration (P<0.02). No significant correlations were found between the peak 17-OH progesterone values, the net increments in 17-OH progesterone and the area under the 17-OH progesterone-response curves after ACTH stimulation and buserelin test. Although 17-OH progesterone response to ACTH was significantly higher in the patients with PCOS than in the control subjects, the lack of relationship between 17-OH progesterone response to GnRH agonist buserelin and 17-OH progesterone response to ACTH stimulation suggests that the dysregulation of the cytochrome P450c17alpha enzyme may not play a role in adrenal androgen excess seen in PCOS.      

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

BACKGROUND: To investigate the effectiveness and safety of pioglitazone (45 mg/day) on clinical and endocrine-metabolic features of polycystic ovary syndrome (PCOS), we studied 18 obese PCOS patients, classified 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 profile 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 significantly 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 significance in H-PCOS. A significant 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.     

Endocrine and metabolic effects of rosiglitazone in overweight women with PCOS: a randomized placebo-controlled study

BACKGROUND: The objective of the study was to assess the therapeutic effects of rosiglitazone in overweight women with polycystic ovary syndrome (PCOS). METHODS: A double-blind, placebo-controlled study was conducted on 30 (BMI > 25 kg/m2, mean age 29.1 +/- 1.2 years) overweight women with PCOS treated with rosiglitazone or placebo for 4 months. Waist-to-hip ratios (WHRs), serum concentrations of sex hormones and binding proteins, blood glucose, serum insulin and serum C-peptide during a 75-g oral glucose tolerance test (OGTT), first-phase insulin secretion as determined by an intravenous glucose tolerance test (IVGTT), M values (expressing insulin sensitivity using a euglycaemic clamp) and calorimetric data were assessed at 0 and 4 months of treatment. RESULTS: Rosiglitazone improved menstrual cyclicity, increased serum sex hormone-binding globulin (SHBG) levels and decreased serum levels of androstenedione, 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEA-S). Glucose tolerance [expressed as AUC(glucose) during the OGTT] improved (P = 0.002) and peripheral insulin response (expressed as AUC(insulin)) decreased (P = 0.004) in the rosiglitazone group (ROSI group). M value improved in the ROSI group from 33.4 +/- 3.27 to 40.0 +/- 5.51 micromol/kg min (P = 0.04). CONCLUSION: Rosiglitazone, by improving menstrual cyclicity, hyperandrogenism, insulin resistance and hyperinsulinaemia, represents an alternative treatment for overweight anovulatory women with PCOS and no pregnancy desire.     

ACTH stimulation tests and plasma dehydroepiandrosterone sulfate levels in women with hirsutism

BACKGROUND. Hirsutism in women is a clinical manifestation of excessive production of androgens. The source of the excess androgen may be either the ovaries or the adrenal glands, and distinguishing between these sources may be difficult. METHODS. To determine whether measurements of plasma dehydroepiandrosterone (DHEA) sulfate and ACTH stimulation tests, both widely used in the evaluation of hirsutism in women, provide useful information, we performed both tests in 22 normal women and 31 female patients with hirsutism. The hormones measured in plasma during the ACTH stimulation tests were progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, DHEA, androstenedione, 11-deoxycortisol, and cortisol. RESULTS. The women with hirsutism were divided into four groups based on their individual responses to ACTH stimulation: patients with a possible 3 beta-hydroxy-delta 5-steroid dehydrogenase deficiency, those with a possible 21-hydroxylase deficiency, those with a possible 11 beta-hydroxylase deficiency, and those with no apparent defect in steroidogenesis. The results in 19 patients (61 percent) suggested subtle defects in adrenal steroidogenesis. There was no significant correlation between the basal plasma DHEA sulfate levels and the hormonal response to ACTH, nor were the basal levels of hormones predictive of the levels after ACTH stimulation. Eleven patients had significantly elevated basal levels of plasma DHEA sulfate; only 5 of these 11 had responses to ACTH suggestive of compromised steroidogenesis. Thirteen patients who had responses suggestive of defective steroidogenesis had DHEA sulfate levels within the normal range. CONCLUSIONS. A substantial proportion of women with hirsutism have mild defects in adrenal steroidogenesis, revealed by an ACTH stimulation test, that are indicative of late-onset (nonclassic) congenital adrenal hyperplasia. Measurements of basal steroid levels are not helpful in differentiating among the causes of increased androgen production in such patients and may be misleading.     

Insulin sensitivity in non-obese women with polycystic ovary syndrome during treatment with oral contraceptives containing low-androgenic progestin.

BACKGROUND: Combined oral contraceptives (COC) effectively suppress hyperandrogenism in women with polycystic ovary syndrome (PCOS), though deterioration of insulin sensitivity during treatment is assumed. The study aim was to investigate insulin action and androgen production during treatment with COC containing low-androgenic progestin. METHODS: A total of 13 PCOS women and nine controls was enrolled into the study. Only non-obese women with a body mass index (BMI) 相似文献   

Impact of overnight dexamethasone suppression on the adrenal androgen response to an oral glucose tolerance test in women with and without polycystic ovary syndrome

In order to test the hypothesis that adrenocortical overactivity, possibly related to the stress of testing, may impact on the measurement of circulating androgen concentrations during glucose- induced hyperinsulinaemia, we prospectively screened 10 patients with the polycystic ovary syndrome (PCOS) and nine healthy control women with an oral glucose tolerance test (OGTT), before and after the administration of dexamethasone. Blood sampling was performed at 0, 30, 60, 90, and 120 min following the oral ingestion of 75 g of glucose, before and after the administration of 1.0 mg dexamethasone on the evening prior to testing. Total and free testosterone, androstenedione, dehydroepiandrosterone (DHEA), DHEA sulphate (DHEAS), cortisol, glucose and insulin were assessed during the 2 h OGTT. Women with PCOS had increased basal concentrations of free testosterone, total testosterone, androstenedione, and insulin compared to control women. In women with PCOS an acute decline in circulating concentrations of DHEAS occurred during the OGTT. In PCOS women there were no changes in other ovarian or adrenal androgens during OGTT before or following dexamethasone administration. In control women DHEA concentrations declined during the OGTT. Following overnight dexamethasone suppression in control women, circulating concentrations of DHEAS and testosterone also declined. It is concluded that: (i) in PCOS women only the concentration of circulating DHEAS decreased during glucose-induced hyperinsulinaemia and dexamethasone administration did not further alter androgen responses to an OGTT; (ii) it is possible that, in these hyperandrogenic patients, the insulin-related suppression of adrenocortical testosterone and DHEA is negated by their much greater ovarian secretion of these androgens; (iii) in control women DHEA concentrations acutely declined during the OGTT and the administration of dexamethasone resulted in the acute decline of DHEA, DHEAS, and testosterone; (iv) it appears that the stress related to testing impacts on the androgen response to OGTT, at least in healthy women.      

Relationships of basal level of serum 17-hydroxyprogesterone with that of serum androstenedione and their stimulated responses to a low dose of ACTH in young adult patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

A single measurement of serum 17α-hydroxyprogesterone (17OHP) level can be unreliable because of its marked diurnal variation. We investigated the relationship of serum level of 17OHP with that of androstenedione (AD), which shows a smaller diurnal variation. And we tested whether the responses of these two hormones to low-dose ACTH stimulation are correlated in patients with 21-hydroxylase deficiency. Baseline serum 17OHP and AD levels were measured in 87 patients and a low-dose ACTH stimulation test was performed in 41 patients. The basal 17OHP level correlated positively with the basal AD level independently of sex, type of 21-hydroxylase deficiency, and the time of day of blood sampling (n = 87, R(2) = 0.75, P < 0.001). The area under the curve of 17OHP and AD correlated positively with their respective basal levels. The fold-change increase in 17OHP after ACTH injection correlated negatively with the basal 17OHP level, but that of AD did not correlate with the basal AD level. The random serum 17OHP level, used in the clinic, is a reliable guide and a low-dose ACTH stimulation test provides no extra benefit for assessing the treatment adequacy in patients with 21-hydroxylase deficiency.     

Ovarian steroidogenic response to human chorionic gonadotrophin in obese women with polycystic ovary syndrome: effect of metformin.

BACKGROUND: The aim of the present study was to investigate the steroidogenic response pattern to HCG in obese women with polycystic ovary syndrome (PCOS) and the possible effects of metformin treatment on it. METHODS: A single injection of human chorionic gonadotrophin (HCG, 5000 IU) was given to 12 obese [body mass index (BMI) > or = 27 kg/m2] women with PCOS and to 27 control women. Blood samples for assays of 17alpha-hydroxyprogesterone (17-OHP), androstenedione, testosterone and oestradiol were collected at baseline and 1, 2 and 4 days after the injection. Responses to HCG were also assessed in the PCOS women after 2-month treatment with metformin (500 mg x 3 daily). RESULTS: Serum 17-OHP and oestradiol concentrations peaked at 24 h in the PCOS women and preceded the maximum testosterone concentration, which was seen at 48 h. In the control women the maximum concentrations of all these steroids were reached 96 h after HCG. After metformin treatment, the basal serum testosterone concentration and the areas under the androstenedione (AUC(A)) and testosterone (AUC(T)) response curves after HCG decreased significantly. CONCLUSIONS: The results demonstrate that obese PCOS women have a male-type steroidogenic response pattern to a single injection of HCG and a higher androgen secretory capacity than control women, which may be explained by the increased thecal cell activity in the polycystic ovary. The slight alleviation of hyperandrogenism brought about by metformin therapy appears to be due to its effect on ovarian steroidogenesis possibly mediated by decreased insulin action.     

Follistatin and activin A serum concentrations in obese and non-obese patients with polycystic ovary syndrome.

BACKGROUND: Activin promotes ovarian follicular development, inhibits androgen production and increases FSH and insulin secretion. Follistatin, an activin-binding protein, neutralizes activin bioactivity. Therefore, a decrease in the ratio of activin/follistatin might encourage characteristic features of polycystic ovary syndrome (PCOS). We investigated whether women with PCOS showed disordered follistatin and/or activin serum concentrations. METHODS: The study group included 24 obese and 20 non-obese (body mass index vertical line and <27 kg/m2 respectively) clomiphene-failure PCOS patients. The control group included 16 obese and 46 non-obese patients with normal ovulatory cycles. Blood samples were obtained from the patients on day 3-5 of a progesterone-induced or spontaneous cycle and were assayed for LH, FSH, testosterone, 17-hydroxy-progesterone, androstenedione, follistatin, activin A, fasting glucose and insulin. RESULTS: Follistatin concentrations were comparable between obese and non-obese PCOS patients (mean +/- SE; 1171 +/- 103 and 1045 +/- 159 pg/ml respectively) and significantly higher than their respective controls (628 +/- 61 and 592 +/- 49 pg/ml, P < 0.0001 and P < 0.02 respectively). Activin A concentrations were comparable between the four groups (590 +/- 35, 513 +/- 74, 661 +/- 87 and 595 +/- 43 pg/ml in obese and non-obese PCOS and controls respectively). Stepwise regression analyses for relationships between follistatin or activin A levels and all other variables indicated that follistatin was significantly and independently positively affected by PCOS (P < 0.0001), age (P < 0.02), androstenedione (P < 0.03) and weight (P < 0.05). Activin A was significantly and independently negatively affected by PCOS (P < 0.003) and FSH (P < 0.03), and positively affected by weight (P < 0.009) and androstenedione (P < 0.02). CONCLUSIONS: Serum follistatin is increased in PCOS patients, regardless of obesity. PCOS is the most significant variable that relates to high follistatin and low activin A serum concentration. A high follistatin/activin ratio could well contribute to the pathophysiology of PCOS.     

Effect of ovarian suppression on glucose metabolism of young lean women with and without ovarian hyperandrogenism

Gonadal steroids are believed to influence glucose metabolism, oestrogens inducing an improvement and androgens or progestins a deterioration. At baseline and after 3 months of ovarian suppression with a gonadotrophin-releasing hormone analogue (GnRHa: goserelin depot 3.75 mg/28 days), glucose metabolism was evaluated in eight lean women affected by ovarian hyperandrogenism (PCOS) and six age-weight-matched non-hyperandrogenic women (controls) by using both an oral glucose tolerance test (75 g; OGTT) and the minimal model method. The latter method allows calculation of peripheral insulin sensitivity (Si) and glucose dependent glucose utilization (Sg). In PCOS, higher fasting concentrations (P < 0.05) of insulin and C-peptide, and lower Sg (P < 0.05) and Si (P < 0.01) were found. GnRHa did not significantly modify glucose metabolism of controls, while in women with PCOS it decreased fasting glucose (P < 0.05) and significantly increased Si (P < 0.03) up to control values. The present data indicate that strong suppression of ovarian activity improves Si in lean women with PCOS, while it is without relevant effects on glucose metabolism of non-hyperandrogenic women.     

Androgen excess is associated with the increased carotid intima-media thickness observed in young women with polycystic ovary syndrome

BACKGROUND: We evaluated carotid intima-media thickness (CIMT) as an early marker of atherosclerosis, as well as its main determinants among androgen excess, obesity and insulin resistance, in patients with polycystic ovary syndrome (PCOS). METHODS: We selected 40 PCOS patients and 20 non-hyperandrogenic women who were similar in terms of age and grade of obesity. Complete clinical, metabolic and hormonal profiles and left common CIMT measurements were obtained. RESULTS: Patients with PCOS presented with increased mean CIMT values when compared with controls (F = 8.575; P = 0.005), and this was independent of obesity. Five PCOS patients but no controls had increased CIMT values. CIMT correlated directly with serum total and free testosterone, androstenedione and dehydroepiandrosterone-sulfate levels and mean 24-h heart rate (HR), and inversely with the insulin sensitivity index (ISI), but no correlation was observed with the body mass index (BMI). Multiple stepwise linear regression models showed that in PCOS patients, the main determinants of CIMT were serum total testosterone or androstenedione concentrations, with no influence of ISI or the mean 24-h HR. CONCLUSIONS: Compared with control women, PCOS patients present with an increased CIMT, independent of obesity and related directly to androgen excess; this suggests that hyperandrogenism is associated with atherosclerosis and cardiovascular risk in these women.     

Developmental changes in rabbit and dog adrenal function: a possible homologue of adrenarche in the dog

Histologic, hormonal, and enzymatic studies were performed in the rabbit and dog to identify maturational changes similar to human adrenarche. Development of an adrenal reticular zone was observed in both the rabbit and dog, analogous to the change in the man. Plasma dehydroepiandrosterone (DHA) and androstenedione (delta 4-A) increased significantly in postpubertal compared to prepubertal male rabbits and dogs, but the increases were much smaller than those reported in man. Orchiectomy reduced plasma DHA and delta 4-A of adult rabbit and dog to near undetectable levels, suggesting a primarily testicular origin. The activities of adrenal microsomal 17-hydroxylase and 17,20-desmolase in the orchiectomized rabbit and dog were subsequently measured to explain this apparent low adrenal contribution to DHA and delta 4-A. Adrenal 17-hydroxylase activity in the rabbit ad 17,20-desmolase activity in both the rabbit and dog were significantly lower than in an adrenal androgen-secreting primate (cynomolgus macaque). Adrenal 17-hydroxylase activity in the dog, measured 1 wk after castration, doubled after sexual maturation (P less than 0.001). This change was paralleled by a significant rise in basal and ACTH-stimulated plasma 17-hydroxyprogesterone in the intact dog (P less than 0.05). Because adrenal 17-hydroxylase activity has been shown to increase during adrenarche in man, this change may be homologous to human adrenarche.     

Maternal serum androgens in pregnant women with polycystic ovarian syndrome: possible implications in prenatal androgenization

BACKGROUND: The aim of this study was to evaluate the peripheral serum androgen concentrations in normal and polycystic ovarian syndrome (PCOS) women during pregnancy, in order to establish if PCOS may induce gestational hyperandrogenism and therefore constitute a potential source of androgen excess for the fetus. METHODS: Twenty pregnant PCOS (PPCOS) women and 26 normal pregnant (NP) women of similar age with singleton pregnancies were selected for the study. During gestational weeks 10-16 and 22-28, a 2 h, 75 g oral glucose tolerance test (OGTT) was performed. For the OGTT, glucose and insulin were measured in each sample and testosterone, androstenedione, dehydroepiandrosterone sulphate (DHEAS), estradiol, progesterone and sex hormone-binding globulin were determined in the fasting sample. RESULTS: In the first study period (gestational weeks 10-16), the levels of androstenedione, testosterone and DHEAS and the free androgen index tended to be higher in the PCOS group. These differences became significant in the second study period (gestational weeks 22-28). In this second period, 2 h insulin concentrations were also significantly higher in PPCOS than in NP women. CONCLUSIONS: The present study demonstrates a significant increase in androgen concentrations during pregnancy in PCOS women. We propose that these androgen concentrations could provide a potential source of androgen excess for the fetus, without leading to fetal virilization.     

Structured exercise training programme versus hypocaloric hyperproteic diet in obese polycystic ovary syndrome patients with anovulatory infertility: a 24-week pilot study

BACKGROUND: Lifestyle modifications are successfully employed to treat obese and overweight women with polycystic ovary syndrome (PCOS). The aims of the current pilot study were (i) to compare the efficacy on reproductive functions of a structured exercise training (SET) programme with a diet programme in obese PCOS patients and (ii) to study their clinical, hormonal and metabolic effects to elucidate potentially different mechanisms of action. METHODS: Forty obese PCOS patients with anovulatory infertility underwent a SET programme (SET group, n = 20) and a hypocaloric hyperproteic diet (diet group, n = 20). Clinical, hormonal and metabolic data were assessed at baseline, and at 12- and 24-week follow-ups. Primary endpoint was cumulative pregnancy rate. RESULTS: The two groups had similar demographic, anthropometric and biochemical parameters. After intervention, a significant improvement in menstrual cycles and fertility was noted in both groups, with no differences between groups. The frequency of menses and the ovulation rate were significantly (P < 0.05) higher in the SET group than in diet group but the increased cumulative pregnancy rate was not significant. Body weight, body mass index, waist circumference, insulin resistance indexes and serum levels of sex hormone-binding globulin, androstenedione and dehydroepiandrosterone sulphate changed significantly (P < 0.05) from baseline and were significantly different (P < 0.05) between the two groups. CONCLUSIONS: Both SET and diet interventions improve fertility in obese PCOS patients with anovulatory infertility. We hypothesize that in both interventions an improvement in insulin sensitivity is the pivotal factor involved in the restoration of ovarian function but potentially acting through different mechanisms.     

Clinical, endocrine and metabolic effects of acarbose, an alpha-glucosidase inhibitor, in PCOS patients with increased insulin response and normal glucose tolerance

BACKGROUND: The aim of this study was to evaluate whether treatment with acarbose, an alpha-glucosidase inhibitor, improved hyperandrogenic symptoms, insulin and androgen serum concentrations in hyperinsulinaemic patients with polycystic ovary syndrome (PCOS). METHODS: 30 hyperinsulinaemic women with PCOS and 15 controls were evaluated. Patients were randomized, using a computer-generated randomization list, into two groups of 15 each and treated with placebo or 300 mg/day of acarbose for three months. Hirsutism and acne/seborrhoea scores, hormonal and sex hormone binding globulin serum concentrations, glycaemia and insulin responses to a standard oral glucose load (75g) were measured in all patients before and after three months of treatment. RESULTS: A significant reduction of the acne/seborrhoea score was observed in patients treated with acarbose and eight of them resumed a regular menstrual rhythm. These clinical improvements were associated with a significant reduction of the insulin response to glucose load, a significant decrease of LH, total testosterone and androstenedione and with a significant increase of sex hormone binding globulin serum concentrations. The serum concentrations of FSH, dehydroepiandrosterone sulphate, prolactin and 17alpha-hydroxyprogesterone did not change significantly. No clinical, metabolic and hormonal modifications were observed in PCOS patients treated with placebo. CONCLUSIONS: This is the first report showing a reduction of the acne/seborrhoea score in hyperinsulinaemic patients with PCOS treated with acarbose. This improvement was associated with a significant decrease of the insulin response to oral glucose load and of LH and androgen serum concentrations and with a significant rise of sex hormone binding globulin concentration.     

Endocrine and metabolic effects of octreotide, a somatostatin analogue, in lean PCOS patients with either hyperinsulinaemia or lean normoinsulinaemia

The effects on insulin secretion and on the glycaemic and androgen status before and after short-term treatment with octreotide were evaluated in 16 normal weight patients with polycystic ovarian syndrome (PCOS). Hyperinsulinaemia was determined by measuring the insulin response after oral glucose tolerance test (OGTT). Seven patients (group A) were classified as normoinsulinaemic, while nine patients (group B) were considered hyperinsulinaemic according to insulin response after OGTT. Octreotide treatment did not modify either glycaemic or insulinaemic response after OGTT, or androgen profile, in normoinsulinaemic patients. On the contrary, a significant decrease in the basal concentrations of luteinizing hormone (LH), testosterone and androstenedione, and a significant increase in serum concentrations of sex hormone-binding globulin (SHBG) were observed in the hyperinsulinaemic group of patients, in which we observed also a significant decrease of insulinaemic response and a decompensation of the glycaemic profile after OGTT. Our study is the first report showing that: (i) octreotide does not appear to significantly influence pituitary release of gonadotrophins in this group of PCOS patients; (ii) octreotide is able to reduce insulin release, LH and androgen concentrations in lean PCOS patients with hyperinsulinaemia. Due to the presence of a decompensation of glucose homeostasis during treatment, octreotide does not seem advisable for long-term therapy of hyperandrogenism in lean PCOS patients with hyperinsulinaemia.