多囊卵巢综合征妇女内源性胰岛素释放与睾酮反应的相关性研究

本研究以36例PCOS妇女和20例正常月经周期妇女为研究对象。通过测定激素基础水平,观察在糖耐量试验中胰岛素对糖负荷的反应和睾酮的变化以及分析体脂与胰岛素的关系。发现PCOS妇女有较高的空腹血糖水平、空腹血清胰岛素与空腹血清睾酮呈显著正相关(r=0.65,P<0.01)。在糖负荷期PCOS组血清胰岛素释放显著高于对照组(P<0.01),同时,总睾酮与总胰岛素呈正相关(r=0.69,P<0.01)。PCOS肥胖者总胰岛素对糖负荷的反应最大,对照非肥胖者反应最小(F=3.02,P<0.01)。PCOS妇女体脂百分率与空腹血清胰岛素呈正相关(r=0.523,P<0.05)。由此提示(1)PCOS妇女内源性胰岛素释放是PCOS雄激素增高的原因之一;(2)PCOS妇女体脂过多可能在PCOS的高胰岛素血症和胰岛素抵抗中起有部分作用。     

多囊卵巢综合征IGF-Ⅰ、IGFBP-1相关因素探讨

目的探讨多囊卵巢综合征(PCOS)患者胰岛素生长因子-Ⅰ(IGF-Ⅰ)、胰岛素生长因子结合球蛋白-1(IGFBP-1)水平与肥胖、性激素、糖代谢各项指标之间的关系。方法测定31例PCOS研究组和29例健康对照组IGF-Ⅰ、IGFBP-1水平及肥胖、性激素、糖代谢各项指标,比较两组间差异;分析研究组IGF-Ⅰ、IGFBP-1水平与其他各项指标之间相关性。结果研究组IGFBP-1,性激素结合球蛋白(SHBG)低于对照组,体重指数(BMI),臀围比值(WHR),多毛评分(F-G评分),黄体生成素(LH),黄体生成素/卵泡刺激素(LH/FSH),总睾酮(T),游离睾酮(FT),雄烯二酮(A2),硫酸脱氢表雄酮(DHEAS),空腹胰岛素(FINS),胰岛素抵抗指数(HomaIR)高于对照组,差异均有显著性(P0.001～0.05),IGF-Ⅰ,FSH,雌二醇(E2),17羟孕酮(17-OHP),泌乳素(PRL),空腹血糖(FBG)差别无显著性(P0.05)。研究组中IGFBP-1与BMI呈负相关(r=-0.372,P0.05),与FINS呈负相关(r=-0.481,P0.01),与SHBG呈正相关(r=0.504,P0.01),IGF-Ⅰ与各指标之间无明显相关性。结论 IGFBP-1与PCOS患者肥胖、空腹胰岛素水平密切相关。     

Polycystic ovary syndrome patients with high BMI tend to have functional disorders of androgen excess: a prospective study

Biochemical or clinical changes of hyperandrogenism are important elements of polycystic ovary syndrome (PCOS). There is currently no consensus on the definition and diagnostic criteria of hyperandrogenism in PCOS. The aim of this study was to investigate the complex symptoms of hyperandrogenic disorders and the correlations between metabolism and hyperandrogenism in patients with PCOS from an outpatient reproductive medicine clinic in China. We conducted a case control study of 125 PCOS patients and 130 controls to evaluate differences in body mass index (BMI), total testosterone (TT), modified Ferriman–Gallwey hirsutism score, sex hormone binding globulin (SHBG), homeostasis model assessment-estimated insulin resistance (HOMA-IR) and free androgen index (FAI) between PCOS patients and controls and subgroups of PCOS. The prevalence of acne and hirsutism did not differ significantly between the hyperandrogenic and non-hyperandrogenic subgroup. Patients with signs of hyperandrogenism had significantly higher BMI (P < 0.05), but differences in TT, SHBG, FAI and waist/hip ratio were insignificant. The odds ratio of overweight was calculated for all PCOS patients. Our results suggest that PCOS patients with high BMI tend to have functional disorders of androgen excess; therefore, BMI may be a strong predictor of hyperandrogenism in 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.     

A pilot study of the human chorionic gonadotrophin test for ovarian hyperandrogenism

A controlled clinical study was designed to investigate the value of human chorionic gonadotrophin (HCG) challenge as a test for functional ovarian hyperandrogenism. Dexamethasone administration was followed by 5000 IU HCG and blood samples for steroid hormone assay were obtained 0, 8, 16, and 24 h thereafter. Study subjects were normal women (n = 13); women with functional ovarian hyperandrogenism, defined by androgen excess, amenorrhoea and an increased 17-hydroxyprogesterone response to nafarelin (n = 6); and normal men (n = 4). The responses of 17-hydroxyprogesterone, androstenedione and testosterone to HCG in women with functional ovarian hyperandrogenism were significantly greater than in normal women. However, the 17-hydroxyprogesterone response to HCG in functional ovarian hyperandrogenism was significantly lower after HCG than after nafarelin. The oestradiol response was also significantly lower after HCG than nafarelin, although oestradiol concentration more than doubled in normal women as well as in women with functional ovarian hyperandrogenism. The responses to HCG confirm that functional ovarian hyperandrogenism abnormalities are luteinizing hormone (LH)-dependent. Therefore, the 17- hydroxyprogesterone response to HCG could represent a useful test for the diagnosis of ovarian hyperandrogenism. The lower 17- hydroxyprogesterone response to HCG than to nafarelin in functional ovarian hyperandrogenism suggests that a follicle-stimulating hormone (FSH)-responsive factor modulates thecal 17-hydroxyprogesterone secretion. The oestradiol response to HCG is consistent with HCG directly stimulating the oestradiol secretion by thecal cells.      

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.     

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   

Six-month treatment with low-dose dexamethasone further reduces androgen levels in PCOS women treated with diet and lifestyle advice, and metformin

BACKGROUND: The purpose of this study was to investigate the effect of low-dose dexamethasone on androgen levels in women with polycystic ovary syndrome (PCOS) treated with diet and lifestyle counselling, and metformin. METHODS: A prospective, randomized, double blind, placebo-controlled study was carried out. Thirty-eight women with PCOS were randomized to either dexamethasone 0.25 mg daily or placebo for 26 weeks. All received diet and lifestyle counselling at inclusion and metformin 850 mg three times daily during the whole study. Main outcome measures were: androgen levels, body mass index (BMI), insulin c-peptide, fasting glucose and serum lipids. Two-tailed t-tests and Pearson's statistics were used. RESULTS: Compared with the placebo, dexamethasone reduced testosterone by 27%, androstenedione by 21%, dehydroepiandrosterone sulphate by 46% and free testosterone index by 50% in women with PCOS treated with diet and lifestyle advice, and metformin. BMI, fasting glucose, insulin c-peptide and serum lipid levels were unaffected. CONCLUSIONS: Six-month, low-dose dexamethasone treatment further reduces androgen levels in metformin-treated PCOS women.     

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.     

多囊卵巢综合征女性一级亲属胰岛素抵抗及高雄激素血症的临床分析

目的检测多囊卵巢综合征（PCOS）一级亲属的胰岛素及雄激素水平,进一步分析其胰岛素抵抗或高雄激素血症的发病情况。方法选择50例PCOS一级亲属为实验组,50例无PCOS家族史的正常健康者作为对照组,检测两组胰岛素、血脂、血糖、瘦素以及生殖激素睾酮、雄烯二酮水平情况。结果与正常对照组相比,PCOS一级亲属血脂、血糖明显高于对照组,胰岛素敏感性指数降低,胰岛素抵抗指数显著升高（P〈0．05）;游离睾酮、雄烯二酮与对照组差异明显,明显高于正常水平（P〈0．05）,血清瘦素水平与正常组间无明显差异。结论PCOS女性一级亲属较正常健康者更易诱发胰岛素抵抗及高雄激素血症,更容易并发PCOS。     

Androgen excess in cystic acne

We measured hormone levels in 59 women and 32 men with longstanding cystic acne resistant to conventional therapy. Affected women had higher serum levels of dehydroepiandrosterone sulfate, testosterone, and luteinizing hormone and lower levels of sex-hormone-binding globulin than controls. Affected men had higher levels of serum dehydroepiandrosterone sulfate and 17-hydroxyprogesterone and lower levels of sex-hormone-binding globulin than controls. To lower dehydroepiandrosterone sulfate, dexamethasone was given to men, and dexamethasone or an oral contraceptive pill, Demulen (or both), was given to women. Of the patients treated for six months, 97 per cent of the women and 81 per cent of the men had resolution or marked improvement in their acne. The dose of dexamethasone required to reduce dehydroepiandrosterone sulfate levels was low, rarely exceeding the equivalent of 20 mg of hydrocortisone per day. We conclude that most patients with therapeutically resistant cystic acne have androgen excess and that lowering elevated dehydroepiandrosterone sulfate results in improvement or remission of acne in most instances.     

Serum visfatin in relation to insulin resistance and markers of hyperandrogenism in lean and obese women with polycystic ovary syndrome

BACKGROUND: Visfatin, a protein secreted by adipose tissue, is suggested to play a role in pathogenesis of insulin resistance. In polycystic ovary syndrome (PCOS), insulin resistance might be involved in the development of endocrine and metabolic abnormalities. The aim of the study was to asses the relation between serum visfatin concentration and insulin sensitivity and markers of hyperandrogenism in lean and obese PCOS patients. METHODS: The study group consisted of 70 women with PCOS (23 lean and 47 obese) and 45 healthy women (25 lean and 20 obese). Euglycemic hyperinsulinemic clamp and the measurements of serum visfatin, sex hormones were performed. RESULTS: The PCOS group had lower insulin sensitivity (P=0.00049) and higher serum visfatin (P=0.047) in comparison to the control group. The decrease in insulin sensitivity was present in both the lean (P=0.019) and obese (P=0.0077) PCOS subjects, whereas increase in serum visfatin was observed only in lean PCOS subjects (P=0.012). In the whole group, serum visfatin was negatively correlated with insulin sensitivity (r=-0.27, P=0.004). This relationship was also observed in the subgroup of lean (r=-0.30, P=0.038), but not obese women. Additionally, in lean women, visfatin was associated with serum testosterone (r=0.47, P=0.002) and free androgen index (r=0.48, P=0.002), independently of other potential confounding factors. CONCLUSIONS: Visfatin is associated with insulin resistance and markers of hyperandrogenism in lean PCOS patients.     

二甲双胍和罗格列酮对肥胖型PCOS治疗作用的对照性研究

目的观察罗格列酮和二甲双胍联合氯米芬治疗肥胖型多囊卵巢综合征患者的内分泌改善及生殖功能的临床疗效。方法50例肥胖型PCOS患者分别给予罗格列酮4mg/d和二甲双胍1500mg/d联合氯米芬100mg/d,治疗3个月,比较治疗前后体重指数、内分泌参数、腰臀比和Hom a IR的变化。结果用罗格列酮治疗后排卵率为88%,周期排卵率为64.29%,优势卵泡平均个数为1.8±0.8个,妊娠率为56%,而用二甲双胍治疗后分别为72%、54.84%、1.1±0.6个、48%。两者治疗后能使LH、LH/FSH、T的血清浓度明显下降,SHBG的浓度明显上升,Hom a IR明显改善。结论罗格列酮和二甲双胍联合氯米芬治疗肥胖型多囊卵巢综合征疗效可靠。二甲双胍有降低体重作用、价格便宜,适用于肥胖型P-COS伴胰岛素抵抗不严重者;罗格列酮在胰岛素增敏作用优于二甲双胍,适用于胰岛素抵抗较严重的PCOS患者。     

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.     

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.     

Body weight reduction and metformin: Roles in polycystic ovary syndrome

Background and objectives: Polycystic ovary syndrome (PCOS) is a common problem in women at fertile age. A prospective study was conducted to clarify the pathophysiological responses during an application of insulin sensitizer, metformin and weight reduction therapy at the Gynecology Center in Ohud hospital, in AL-Madinah AL-Munawarah, Kingdom of Saudi Arabia. Methodology: Twenty healthy women served as controls and 180 PCOS women divided into three groups participated in the study. First group was treated with Clomid citrate 100 mg/day from the 2nd day of menses to the 6th day plus gonadotrophin from day three to the 13th. Group II was treated as group I plus 850 mg metformin twice a day and group III was treated as group I plus weight reduction. Clinical symptoms, menstrual pattern, hirsutism, blood glucose, body mass index, waist-to-hip ratio, insulin, hormonal, and lipid profiles were assessed pre- and post treatment. Insulin resistance was calculated. Results: PCOS women had significantly higher values than the healthy women in most of the measurements. Metformin and weight reduction therapy resulted in a significant decrease in the fasting insulin, glucose/insulin ratio and HOMA-IR. Metformin and weight reduction therapy resulted in a significant decrease in the lipid parameters, testosterone, LH/FSH ratio, SHBG, and prolactin levels. HOMA-IR was significantly higher in women with PCOS. HOMA-IR was positively correlated with testosterone, estradiol, TG, total cholesterol and LDL-cholesterol parameters, and negatively correlated with HDL-cholesterol and FSH levels. Conclusion: Metformin therapy and weight reduction had favorable influences on the basic metabolic and hormonal profiles in women with PCOS and that metformin and lifestyle modification (weight reduction via diet restriction or exercise) resulted in a significantly greater weight loss than hormonal therapy alone. Metformin and weight reduction therapy decreased also hyperandrogenism and insulin resistance.     

The effect of combination therapy with metformin and combined oral contraceptives (COC) versus COC alone on insulin sensitivity, hyperandrogenaemia, SHBG and lipids in PCOS patients

BACKGROUND: Neither oral contraceptives (COC) nor metformin are an optimal modality for the long-term treatment of polycystic ovary syndrome (PCOS). The aim of this study was to evaluate whether a combination of both is beneficial over COC monotherapy. METHODS: Altogether, 30 women were included in the study and 28 finished the protocol. The patients were randomly assigned to two groups treated with either COC (COC group) or COC and metformin (1500 mg/day) (METOC group) for 6 months. Anthropometric parameters, androgens, lipids, fasting insulin, glucose and sex hormone binding globulin (SHBG) concentrations were measured before and at the end of the sixth cycle of treatment. The insulin sensitivity index was evaluated using the euglycaemic clamp. RESULTS: There were no significant changes in anthropometric parameters, fasting glucose or insulin sensitivity in either group. Total testosterone, free androgen index, androstenedione and dehydroepiandrosterone decreased and SHBG increased significantly in both groups. When comparing the effect of both treatments, only a more pronounced decrease in free androgen index was found in the METOC group. CONCLUSIONS: Adding metformin slightly modified the treatment effect of COC, causing a more significant decrease in the free androgen index but having no additional positive impact on lipids, insulin sensitivity, SHBG or testosterone. The available data do not offer enough evidence to advocate the standard use of combined treatment in PCOS. Whether the combination might be beneficial for specific subgroups of patients is of further interest.     

The relationship between anti-Mullerian hormone, androgen and insulin resistance on the number of antral follicles in women with polycystic ovary syndrome

BACKGROUND: Anti-Müllerian hormone (AMH) is a biomarker that predicts the number of antral follicles and is involved in follicle arrest for women with polycystic ovary syndrome (PCOS). We investigated the association between the characteristic hyperandrogenemia, insulin resistance (IR), AMH, and the morphology and size of ovaries for women with PCOS. METHODS: A total of 99 Taiwanese women with PCOS who were willing to undergo vaginal ultrasonography were enrolled in this cross-sectional study. RESULTS: The number of antral follicles and the ovarian volume showed a significant correlation with AMH, total testosterone and the free androgen index, but not with age, body mass index (BMI) or the homeostasis model assessment of insulin resistance (HOMA-IR). AMH had a significant negative association with both BMI and HOMA-IR. Multiple stepwise regression analysis demonstrated that AMH, BMI and total testosterone were independently related to the number of antral follicles. AMH and total testosterone were the main determinants for ovarian volume in a stepwise regression model. CONCLUSIONS: Our results suggest that not only the AMH level, but also obesity, IR and elevated androgen levels may relate to the development of the large size of antral follicle pool and ovarian volume in women with PCOS. Obesity and IR may enhance the follicular excess through the dysregulation of AMH or through the pathway of hyperandrogenemia. These findings might partly explain why adequate body weight management and improvement in IR can improve the ovulatory function for women with PCOS.     

Detection of functional ovarian hyperandrogenism in women with androgen excess.

BACKGROUND. Distinguishing between ovarian and adrenal causes of androgen excess may be difficult. We have found that women with the polycystic ovary syndrome have supranormal plasma 17-hydroxyprogesterone responses to the gonadotropin-releasing hormone agonist nafarelin. We determined the usefulness of testing with nafarelin to distinguish ovarian causes of hyperandrogenism in women. METHODS. We studied 40 consecutive women with hyperandrogenism who had oligomenorrhea, hirsutism, or acne. All 40 underwent testing with nafarelin, dexamethasone, and corticotropin with measurement of circulating concentrations of gonadotropins and steroid hormones, and 19 underwent ovarian ultrasonography. RESULTS. The plasma 17-hydroxyprogesterone response to nafarelin was supranormal in 23 of the 40 women (58 percent), and the plasma androgen response to corticotropin was elevated in 23; 13 women had both abnormalities. Only one woman had conclusive evidence of a steroidogenic block; she had nonclassic adrenal 21-hydroxylase deficiency. Of the 23 women with abnormal responses to nafarelin, only 11 (48 percent) had elevated base-line serum luteinizing hormone concentrations. Of the 13 women with abnormal responses to nafarelin who underwent ultrasonography, 7 (54 percent) had polycystic ovaries. Peak plasma 17-hydroxyprogesterone concentrations after nafarelin administration correlated closely with plasma free testosterone concentrations after dexamethasone administration (r = 0.75, P less than 0.001). CONCLUSIONS. Approximately half of women with oligomenorrhea, hirsutism, or acne have an abnormal response to the gonadotropin-releasing hormone agonist nafarelin, suggesting an ovarian cause of their androgen excess.     

Metformin treatment reduces ovarian cytochrome P-450c17alpha response to human chorionic gonadotrophin in women with insulin resistance-related polycystic ovary syndrome

It has recently been proposed that hyperinsulinaemic insulin resistance and increased ovarian cytochrome P-450c17alpha activity, two features of the polycystic ovary syndrome (PCOS), are pathogenetically linked. The aim of the present study was to test the hypothesis of the linkage between hyperinsulinaemia and supranormal activity of cytochrome P-450c17alpha using the human chorionic gonadotrophin (HCG) challenge, which is a more direct ovarian stimulus than gonadotrophin-releasing hormone (GnRH) in detecting modifications in ovarian steroidogenesis. Eleven women with insulin resistance-related PCOS were studied. HCG (10 000 IU) was given i.m., and blood samples were obtained 0, 8, 12, 16 and 24 h thereafter. Next day, metformin was given at a dose of 500 mg three times a day for 30-32 days, at which time the pretreatment study was repeated. Two women ovulated after metformin treatment. The administration of metformin was associated with a decrease in area under the curve for insulin during a 2h, 75g oral glucose tolerance test, in plasma free testosterone concentrations and an increase in plasma sex hormone binding globulin concentration. The plasma 17-hydroxyprogesterone response to HCG was significantly lower after metformin treatment. The present study gives a direct demonstration that metformin leads to a reduction in stimulated ovarian cytochrome P-450c17alpha activity in women with polycystic ovary syndrome.