PCOS高雄激素血症的特征及鉴别诊断

经过几十年的研究,尽管对多囊卵巢综合征(poly cysticovariansyndrome,PCOS)病因及发病机制目前尚不清楚,但雄激素过多作为PCOS的基本特征得到广泛认可,有报道约50%以上的中国PCOS患者有高雄激素血症。因此,有必要对PCOS患者高雄激素血症的特征进行深入探讨。1PCOS高雄激素血症的病因女性体内的雄激素主要有雄烯二酮(androstenedi one,A2)、睾酮(testosterone,T)、脱氢表雄酮(dehydroepi androsterone,DHEA)、硫酸脱氢表雄酮(sulfal dehydroepi androsterone,DHEA S)以及双氢睾酮(dihydrotestosterone,DHT)等,雄激素产生部位…     

生殖内分泌的动力学试验(二)

高雄激素血症妇女的雄性激素一般来自肾上腺皮质或卵巢,诊断目的是确定产生过多雄激素的主要器官及是否有肿瘤或自主性分泌源存在。筛选试验通常除测睾酮(T)外,还测定脱氢表雄酮(DHEA)或其硫酸盐的代谢物(DHEA—S)和雄烯二酮(Δ~4A)。DHEA     

不同高雄激素血症表型多囊卵巢综合征患者临床特征分析

目的:探讨不同高雄激素血症表型多囊卵巢综合征(PCOS)患者的临床、代谢特征及其意义。方法:回顾性分析2013年4月至2017年7月在黑龙江中医药大学附属第一医院门诊就诊的683例PCOS患者,根据血清雄烯二酮(AND)和睾酮(T)水平分为4个亚组:高AND伴高T组(A组);单纯高AND组(B组);单纯高T组(C组);非高T组(D组)。另选取50例健康体检女性作为对照组(NC组)。对5组受试者临床和生化指标进行特征性分析。结果:PCOS患者4个亚组的黑棘皮、痤疮和溢脂发生率、多毛评分、黄体生成激素(LH)、LH/血清卵泡刺激素(FSH)显著高于对照组(P0.05),伴高AND水平(A组和B组)的PCOS患者的游离雄激素指数(FAI)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、低密度脂蛋白(LDL)、总胆固醇(TC)较对照组明显升高(P0.05),且伴高AND水平(A组和B组)的PCOS患者与非高T的PCOS患者(D组)相比LH、LH/FSH、性激素结合球蛋白(SHBG)、硫酸脱氢表雄酮(DHEAS)、FAI差异有统计学意义(P0.05)。结论:PCOS患者合并高雄激素血症更易出现性激素异常、高胰岛素血症(HI)、胰岛素抵抗(IR)和脂代谢紊乱,且伴有高AND的患者激素水平异常和代谢紊乱更为严重,临床对血清AND的检测应予以重视。     

黄体生成素受体及类固醇激素合成急性调节蛋白在大鼠多囊卵巢综合征模型中的表达

目的:探讨黄体生成素受体(LHR)及类固醇激素合成急性调节蛋白(StAR)在大鼠多囊卵巢综合征(PCOS)模型中的表达及作用。方法:将50只21日龄SD大鼠随机分为模型组(PCOS组,n=35)和对照组(NC组,n=15)。通过注射脱氢表雄酮(DHEA)建立PCOS大鼠模型,放射免疫法和酶联免疫法分别检测血清孕酮(P)和雌二醇(E_2)水平及睾酮(T)水平;免疫组织化学法对LHR及StAR进行细胞定位分析,RT-PCR和Western blotting分别检测LHR及StAR mRNA和蛋白表达变化。结果:与NC组相比,血清E_2和T水平显著升高,P水平无显著变化;LHR和StAR mRNA和蛋白表达水平均显著升高。结论:PCOS高雄激素血症可能与LHR和StAR表达调控有关;两者与E_2水平升高之间的关系仍有待阐明。     

复方醋酸环丙孕酮与螺内酯干预对非肥胖型多囊卵巢综合征(PCOS)内分泌代谢的影响

目的:比较复方醋酸环丙孕酮和螺内酯治疗以高雄激素血症为主要表现的非肥胖型多囊卵巢综合征(PCOS)的临床疗效和对内分泌代谢的影响。方法:按前瞻性随机对照研究方法选择以高雄激素血症为主要表现的非肥胖型PCOS患者80例,按随机化分组方案分为复方醋酸环丙孕酮(EE-CA)组和螺内酯(Sp)组,每组40例,分别口服相应的药物6个月,比较治疗前、后的体质量指数(BMI)、腰臀比(WHR)、多毛体征、痤疮程度以及卵巢体积,并测定血清卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇(E2)、泌乳素(PRL)、总睾酮(T)、性激素结合球蛋白(SHBG)、硫酸脱氢表雄酮(DHEAS)、空腹血糖(FPG)、空腹胰岛素(FINS)和血脂的水平,记录服药后不良反应。结果:治疗多毛EE-CA和Sp疗效接近(P>0.05);EE-CA组治疗6个月后痤疮评分下降较Sp组作用明显(P<0.05),在缩小卵巢体积方面显著优于Sp(P<0.05),降低血LH、LH/FSH、T、游离雄激素指数(FAI)、DHEAS和升高SHBG的作用较Sp组显著(P<0.05,P<0.01);EE-CA组FINS、甘油三酯(TG)和高密度脂蛋白(HDL)高于Sp组(P<0.05)。结论:本研究用于治疗以高雄激素血症为主要表现的非肥胖型PCOS的药物都是有效的;EE-CA降低高雄激素血症的效果优于Sp,但对高甘油三酯的患者使用要慎重;Sp亦有较好的降雄激素作用,且对糖、脂代谢没有显著影响。     

汉族多囊卵巢综合征患者各雄激素指标的临床意义分析

目的:探讨多囊卵巢综合征(PCOS)患者的雄激素表现及其与内分泌和代谢改变之间的关系。方法:分析100例PCOS患者及100例对照女性的临床和生化雄激素(A)指标及其与内分泌和代谢参数间的关系。结果:PCOS患者多毛评分高于对照组,但症状程度较轻(中位数=2)。生化雄激素指标中,硫酸脱氢表雄酮(DHEAS)和双氢睾酮(DHT)在组间无统计学差异(P0.05),而PCOS组患者睾酮(T,1.46 nmol/L vs 0.90 nmol/L)、雄烯二酮(A4,8.24 nmol/L vs 4.96 nmol/L)和游离雄激素指数(FAI,3.70 vs 1.54)显著高于对照组(P0.05),性激素结合球蛋白(SHBG,35.84 nmol/L vs56.08 nmol/L)则明显低于对照组(P0.05)。相关分析表明,与对照组相比PCOS组各雄激素指标间相关性明显减低。雄激素指标与内分泌和代谢参数的相关性在组间也存在统计学差异(P0.05)。对照组中FAI、A4、T、DHEAS与FSH呈负相关,而在PCOS组中FSH相关性消失,而是与LH呈正相关;对照组雄激素指标与糖脂代谢参数的相关性不明显,但在PCOS组中FAI、A4、T均与代谢指标明显呈正相关。结论:对于中国PCOS患者来说,生化雄激素指标较临床指标更为显著;FAI和A4在评价生化高雄激素时更有意义。PCOS中特异存在的雄激素代谢和作用过程改变可能是疾病病因机制的关键。     

高雄激素和非高雄激素型多囊卵巢综合征患者血清抗苗勒管激素分泌特点及诊断效能比较

目的:比较抗苗勒管激素(AMH)在高雄激素和非高雄激素型多囊卵巢综合征(PCOS)患者的分泌特点和诊断效能,对发病机制进行探讨。方法:纳入具有排卵障碍的PCOS患者131例(高雄组62例,非高雄组69例),另外纳入61例输卵管或男方因素不孕的患者为对照组。采用酶联免疫吸附法和化学发光法检测并比较3组患者血清中AMH、性激素、糖脂代谢等生化指标,采用ROC曲线评估AMH对PCOS患者的诊断效能;采用Pearman's相关法分析高雄和非高雄型PCOS患者血清AMH水平与其他各参数间的关系。结果:①PCOS患者血清AMH水平显著高于对照组(P0.05),高雄组又显著高于非高雄组(P0.05)。②AMH诊断高雄组PCOS患者的AUC为0.82,敏感性为82%,特异性为64%。AMH诊断非高雄组PCOS患者的AUC为0.66,敏感性为64%,特异性为62%。③高雄组PCOS患者AMH与FSH呈负相关(r=-0.42,P=0.05),与LH呈正相关(r=0.46,P0.05)。非高雄组PCOS患者AMH与HDL呈负相关(r=-0.28,P0.05),与BMI、空腹血糖和LDL呈正相关(r=0.26;r=0.27;r=0.29,P0.05)。结论:AMH适合于诊断某种特定亚型如高雄激素型PCOS,对非高雄激素型PCOS的诊断准确性较低,由此也反映出两种亚型患者发病机制可能存在差异。     

达因-35对不同类型多囊卵巢综合征的疗效分析

目的:探讨达因-35对不同类型多囊卵巢综合征(PCOS)血清激素及窦卵泡数等的影响。方法:将138例PCOS患者按鹿特丹标准进行分型,选择同期无高雄激素血症及月经紊乱的输卵管性不孕患者78例作为对照组。测定血清生殖激素及空腹胰岛素(FINS)等水平,盆腔超声检测卵巢体积及窦卵泡计数,经达因-35治疗3个周期后观察上述指标变化,评价达因-35对不同类型PCOS的治疗效果。结果:A型[无排卵(O/A)+高雄激素(HA)+卵巢多囊(PCO)]、B型(O/A+PCO)、C型(HA+O/A)和D型(HA+PCO)分别为43例、73例、15例和7例。A型、C型和D型总睾酮(TT)和硫酸脱氢表雄酮(DHEAS)水平高于对照组,各型LH、LH/FSH、FINS及胰岛素评价指数(HOMA-IR)高于对照组,差异均有统计学意义(P0.05)。A型、B型和D型窦卵泡数多于C型及对照组,差异有统计学意义(P0.05)。达因-35治疗3个周期后:A型、C型和D型血清TT降低,差异有统计学意义(P0.05);DHEAS水平有所降低,但差异无统计学意义(P0.05);各型PCOS血清LH和LH/FSH下降,窦卵泡数减少,差异均有统计学意义(P0.01)。结论:华中地区PCOS临床表现以A型和B型多见,达因-35治疗3个周期可明显降低不同类型血清雄激素水平、血清LH水平和LH/FSH比值,减少窦卵泡数。     

地塞米松对伴有肾上腺雄激素分泌过多的PCOS患者的疗效观察

目的:探讨地塞米松对伴肾上腺雄激素分泌过多PCOS患者的疗效。方法:采用前瞻、随机、对照的研究方法,将60例经达英-35治疗后高雄激素和临床表现仍然未能明显改善且伴有肾上腺雄激素分泌过多的PCOS不孕患者作为研究对象,将患者随机分成对照组(达英-35+安慰剂)和实验组(达英-35+地塞米松),所有患者治疗3个月,比较2组患者性激素水平、临床表现。随后给予氯米芬(CC)及人绝经期促性腺激素(hMG)促排卵治疗,比较分析临床结局。结果:所有患者治疗后雄烯二酮(A2)均降低,下降率组间无差异(P>0.05),实验组硫酸脱氢表雄酮(DHEAS)降低率、性结合球蛋白(SHBG)提高率明显好于对照组(P<0.05);实验组较对照组的痤疮及多毛症状改善明显(P<0.05),而体质量指数(BMI)及腰臀比(WHR)的改变不明显(P>0.05)。实验组比对照组的成熟卵泡率、排卵率及妊娠率效果更好(P<0.05)。结论:经用达英-35治疗后高雄激素血症和临床表现仍然未能明显改善,并伴肾上腺雄激素分泌过多的PCOS不孕患者,加用地塞米松,较单纯应用达英-35更能有效抑制高雄激素血症,提高SHBG,改善临床表现,提高成熟卵泡率、排卵率及妊娠率。     

我院育龄妇女血清睾酮水平正常值范围的修正及其对PCOS诊断的影响

目的:修正高雄激素血症的诊断标准,并分析其对PCOS诊断标准的影响。方法:以3 545例无排卵障碍和无内分泌疾病的育龄妇女为正常排卵组,测定其睾酮(T)水平,并根据测定值修正T水平的正常值范围,按修正的正常值范围通过1 248例PCOS患者分析其对PCOS诊断标准及分型的影响。结果:①正常排卵组和PCOS组的年龄、FSH、E2组间比较差异无统计学意义(P0.05),而BMI、LH、T组间比较差异有统计学意义(P0.05)。根据正常排卵组的T水平确定其正常值范围为0.27±0.23(0.04~0.50)ng/ml,修正后T0.65 ng/ml即可诊断为生化高雄激素血症。②修正雄激素的正常值范围后,PCOS组高雄激素血症的比例有明显提高,PCOS 4个亚型构成比有变化,有359例Ⅱ型PCOS患者转为Ⅰ型PCOS。结论:我院育龄女性雄激素水平的正常值范围需要修正,修正的雄激素正常值范围对PCOS的诊断及分型有影响。     

Adrenocortical steroid response to ACTH in different phenotypes of non-obese polycystic ovary syndrome

Background

Adrenal androgen excess is frequently observed in PCOS. The aim of the study was to determine whether adrenal gland function varies among PCOS phenotypes, women with hyperandrogenism (H) only and healthy women.

Methods

The study included 119 non-obese patients with PCOS (age: 22.2?±?4.1y, BMI:22.5?±?3.1?kg/m²), 24 women with H only and 39 age and BMI- matched controls. Among women with PCOS, 50 had H, oligo-anovulation (O), and polycystic ovaries (P) (PHO), 32 had O and H (OH), 23 had P and H (PH), and 14 had P and O (PO). Total testosterone (T), SHBG and DHEAS levels at basal and serum 17-hydroxprogesterone (17-OHP), androstenedione (A4), DHEA and cortisol levels after ACTH stimulation were measured.

Results

T, FAI and DHEAS, and basal and AUC values for 17-OHP and A4 were significantly and similarly higher in PCOS and H groups than controls (p?<?0.05 for all) whereas three groups did not differ for basal or AUC values of DHEA and cortisol. Three hyperandrogenic subphenotypes (PHO, OH, and PH) compared to non-hyperandrogenic subphenotype (PO) had significantly and similarly higher T, FAI, DHEAS and AUC values for 17-OHP, A4 and DHEA (p?<?0.05). All subphenotypes had similar basal and AUC values for cortisol.

Conclusion

PCOS patients and women with H only have similar and higher basal and stimulated adrenal androgen levels than controls. All three hyperandrogenic subphenotypes of PCOS exhibit similar and higher basal and stimulated adrenal androgen secretion patterns compared to non-hyperandrogenic subphenotype.

     

抗苗勒管激素与不同表型多囊卵巢综合征发病特征的相关性分析

目的探讨不同表型多囊卵巢综合征(polycystic ovary syndrome,PCOS)患者血清抗苗勒管激素(AMH)及性激素指标水平,并评估AMH与这些指标的相关性。方法应用UNION免疫分析仪和Uni Cel Dx I800免疫分析系统检测702例PCOS患者和118例健康女性(对照组)AMH和其他性激素水平,并进行超声下窦卵泡计数(AFC)和卵巢体积测量。应用Pearson分析进行双变量相关分析。结果 PCOS患者的卵泡刺激素(FSH)低于对照组,其中无排卵或稀发排卵(OA)+高雄激素血症(HA)+多囊卵巢(PCO)组与对照组间的差异具有统计学意义(P0.05)。黄体生成素(LH)、L H/F S H、AMH均显著高于对照组。血清睾酮(T)水平在O A+H A组和O A+H A+P C O组显著升高。各组间泌乳素(P R L)、雌二醇(E2)水平无明显差异。A M H与F S H呈负相关,与L H、L H/F S H、T、A F C、左卵巢体积和右卵巢体积呈正相关。结论血清AMH浓度可以反映窦卵泡的数目和血清T的浓度高低,可作为PCOS诊断与监测指标之一,提高PCOS诊断的简便性,在临床上有广泛的应用前景。     

青春期不同月经方式的多囊卵巢综合征120例育龄期内分泌状态的研究

目的　探讨青春期不同月经方式的多囊卵巢综合征 (PCOS)患者在育龄期内分泌状态。方法　选择12 0例PCOS育龄妇女 ,按青春期月经方式分为三组。测定其血清性激素、胰岛素、血糖 ,并进行分析对比。结果　原发不孕的PCOS患者青春期月经异常的发生率明显高于继发不孕的PCOS患者 (P <0 0 5 )。青春期月经稀发组T及E2 显著高于继发闭经组 ,A显著高于月经规律组 (P <0 0 5 )。继发闭经组胰岛素拮抗指数和BMI显著高于月经规律组 (P <0 0 5 )。结论　在青春期表现有月经稀发和继发闭经的PCOS患者在育龄期有更严重的分泌代谢失调、并伴有较低的妊娠率。     

Effects of metformin therapy on hyperandrogenism in women with polycystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS) is one of the most common endocrine diseases in women. This syndrome is characterized by hyperandrogenism, chronic anovulation, infertility and obesity. The association between PCOS-related hyperandrogenemia and insulin resistance is well documented in the literature. Insulin resistance and the resulting raised plasma levels of insulin are reported to be responsible for the high androgen concentration observed in patients with PCOS. In this prospective study, blood samples for levels of testosterone (T), dehydroepiandrosterone sulfate (DHEAS), luteinizing hormone (LH), follicle-stimulating hormone (FSH), LH/FSH, prolactin and fasting blood sugar (FBS) before starting metformin administration were obtained randomly from 40 women who were apparently obese, had PCOS and had been referred to a university hospital. Metformin was then given at a dose of 500 mg three times a day for 8 weeks, after which time the pretreatment study was repeated. Clinical symptoms of PCOS, including acne and hirsutism score and body mass index (BMI), were assessed before and after the treatment cycle. Metformin therapy resulted in a significant decrease in total testosterone levels and FBS. There was also a significant decline in BMI, length of the menstrual cycle, acne and hirsutism score. There were no significant changes in the levels of DHEAS, prolactin, FSH or LH, or in LH/FSH. The effect of metformin on subjects with elevated DHEAS levels was different to that on individuals with normal DHEAS levels. In the latter group there were only significant improvements in the length of the menstrual cycle, BMI and testosterone and DHEAS levels. It is concluded that metformin therapy in subjects with PCOS results in a decrease in fasting blood sugar and testosterone levels, and leads to a significant improvement in the clinical manifestation of hyperandrogenism. These responses also related to the level of adrenal function.     

Influence of insulin and testosterone on adrenocortical steroidogenesis in vitro: preliminary studies

OBJECTIVE: The mechanisms underlying the adrenal androgen (AA) excess of polycystic ovary syndrome (PCOS) remain unclear, although it is possible that the adrenocortical dysfunction may be a response to other, extraadrenal factors. Consistent with the pathophysiology of PCOS and with in vivo data in normal and PCOS women, we have hypothesized that insulin inhibits and that T stimulates AA secretion in vitro. DESIGN: In vitro experimental study. SETTING: University medical center. PATIENT(S): Normal human adrenals (n = 4 women, ages 25-57 years) were obtained with consent at the time of organ donation. INTERVENTION(S): Fresh adrenal tissue minces were incubated in serum-free medium with 10-microM pregnenolone substrate and 1-microM ACTH-(1-24). Challenge doses of 0.2, 1, 5, 20, and 100 nM of insulin and 1, 10, 100, 1,000, and 10,000 nM of T were added, and the media were sampled after 8 hours of incubation at 37 degrees C, 4% CO2. Dehydroepiandrosterone (DHEA), DHEA-sulfate (DHEAS), and cortisol (F) were measured by radioimmunoassay (significant effects compared with the case of zero-dose control). MAIN OUTCOME MEASURE(S): The production of DHEA, DHEAS, and F in the media of the adrenal minces was compared between different subjects and at different concentrations of T and insulin. RESULT(S): Analysis of the combined data from all donors indicated that insulin stimulated DHEAS and suppressed DHEA production but had no consistent effect on F. Similar analyses of the combined data indicated that T had no significant predictable effect on the production of DHEAS, DHEA, or F. When examining donor data individually, insulin and T did elicit significant increases and/or decreases in steroid production within subjects, although no consistent trends were observed. CONCLUSION(S): On the basis of these data, it is clear that extra-adrenal factors such as insulin and T have some adrenal regulatory capacity. In general, insulin stimulated DHEAS and decreased DHEA production, suggesting that it increases adrenocortical sulfotransferase activity. However, although in the individual subjects studied, both insulin and T frequently altered the production of DHEAS, DHEA or F, these effects did not appear to be uniform or consistent from subject to subject. Expanded studies are required to confirm these results.     

Heterogenous origins of hyperandrogenism in the polycystic ovary syndrome in relation to body mass index and insulin resistance

Background: Insulin resistance and obesity are not universal features of polycystic ovary syndrome (PCOS). We planned to assess the differences between patients with nonobese /insulin-sensitive phenotype vs. obese/ insulin-resistant phenotype in terms of the potential mechanisms underlying their hyperandrogenism.

Materials and methods: A total of 52 women satisfying Androgen Excess Society (AES) criteria were included. Hormonal and metabolic profile including prolactin, dehydroepiandrosterone sulfate (DHEAS), free testosterone, sex hormone binding globulin (SHBG), fasting plasma glucose and insulin were measured in follicular phase.

Results: DHEAS was found to be higher in the nonobese patients as compared to the obese (p?=?0.01). There was also a strong trend for a higher DHEAS among patients with lower insulin resistance by homeostatic model assessment (HOMA-IRp?=?.06).While the total testosterone (p?=?.044) and SHBG (p?=?.007) were found to be lower in the more insulin-resistant group (HOMA-IR ≥ 2.3), the free testosterone levels were similar. However, the percentage of free testosterone was higher in the more insulin-resistant group (p?=?.005).

Conclusions: The hyperandrogenic state in PCOS appears to have heterogenous origins. Nonobese patients with PCOS have adrenal hyperandrogenism as the underlying mechanism while their obese/ insulin-resistant counterparts have low SHBG and hence an increased fraction of free testosterone.     

Adrenocortical hyperresponsiveness to corticotropin in polycystic ovary syndrome patients with adrenal androgen excess

OBJECTIVE: To test the hypothesis that adrenal androgen (AA) excess in the polycystic ovary syndrome (PCOS) is due to a generalized exaggeration in AA output in response to adrenocorticotropic hormone (ACTH), and that this abnormality is due to an identifiable alteration in the biosynthesis of AAs. DESIGN: Cross-sectional prospective controlled study. SETTING: Academic tertiary care medical center. PATIENT(S): Patients with PCOS (n = 9) and without (n = 9) AA excess and controls (n = 12) without hyperandrogenism, matched for age and body mass. INTERVENTION(S): Acute 60-minute ACTH test was performed on patients. MAIN OUTCOME MEASURE(S): Basal levels of dehydroepiandrosterone sulfate (DHEAS), total testosterone (T), free T, and basal (Steroid(0)) and the 60-minute ACTH-stimulated levels (Steroid(60)) of pregnenolone (PREG), progesterone (P4), 17-hydroxypregnenolone (17-HPREG), 17-hydroxyprogesterone (17-HP), dehydroepiandrosterone (DHEA), and androstenedione (A4) were measured. Adrenocortical activities of 17-hydroxylase (17-OH), 17,20-lyase, and 3beta-hydroxysteroid dehydrogenase were estimated from product to precursor ratio, using Steroid(60) values. RESULT(S): Compared with PCOS patients without AA excess, PCOS patients with AA excess demonstrated significantly greater levels of DHEA(0) and A4(60). PCOS patients with AA excess had significantly higher activity of delta(5)17-OH, compared with PCOS patients without AA excess. CONCLUSION(S): Adrenal androgen excess in PCOS is associated with a greater delta(5)17-OH activity in response to ACTH.     

Short-term metformin treatment for clomiphene citrate-resistant women with polycystic ovary syndrome

Objective

To evaluate the effect of a short-course pretreatment with metformin on hyperandrogenism, insulin resistance, cervical scores, and pregnancy rates in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS).

Methods

Thirty-seven women with CC-resistant PCOS were randomly assigned to be pretreated with 500 mg of metformin or placebo 3 times per day for 2 cycles, and 100 mg of CC was given on days 5 through 9 of the second cycle in both groups. Luteinizing hormone (LH), follicle stimulating hormone (FSH), dehydroepiandrostendione sulfate (DHEAS), total testosterone (T), glucose, and insulin levels were measured at baseline and after the first cycle, as well as body mass index (BMI), cervical score, and pregnancy rate.

Results

After 1 cycle, BMI, total T level, and percentage of participants with insulin resistance were significantly decreased in the metformin group, without any significant decrease in LH, FSH, and DHEAS levels; and in the second cycle, CC treatment resulted in a higher ovulation rate and a thicker endometrium in the metformin group. The pregnancy rate and cervical scores were also higher in that group.

Conclusion

The short-course pretreatment with metformin decreased hyperandrogenism and insulin resistance and improved cervical sores, ovulation rate, and pregnancy rate among women with CC-resistant PCOS.     

Metformin therapy decreases hyperandrogenism and hyperinsulinemia in women with polycystic ovary syndrome

Objective: To evaluate the effects of 12 weeks of metformin therapy on hormonal and clinical indices in polycystic ovary syndrome (PCOS).

Design: Prospective study.

Setting: University hospital.

Patient(s): Thirty-nine women with PCOS and fasting hyperinsulinemia.

Intervention(s): Twelve weeks of therapy with oral metformin (500 mg three times per day).

Main Outcome Measure(s): Levels of insulin, T, DHEAS, insulin-like growth factor-I (IGF-I), gonadotropins, and sex hormone-binding globulin (SHBG); and clinical symptoms including acne, hirsutism, and length of the menstrual cycle were assessed before and after treatment with metformin.

Result(s): Metformin therapy resulted in a significant decrease in fasting insulin and total T and an increase in SHBG, leading to a decrease in the free T index. In addition, there was a significant decline in mean body mass index, waist-hip ratio, hirsutism, and acne, as well as an improvement in the menstrual cycle. No changes in LH and LH-FSH ratio were observed. Multiple regression analysis demonstrated that the greatest decline of T and free T index in response to metformin was observed among patients with the most pronounced hyperandrogenemia. Subjects with elevated DHEAS differed from those with normal DHEAS in their responses to metformin treatment. Women with high DHEAS exhibited less improvement of menstrual cycle regularity, no change in hirsutism, and an increase in levels of IGF-I after treatment.

Conclusion(s): Metformin treatment of women with PCOS results in a decline of insulin as well as total and bioavailable T, leading to significant improvement of clinical manifestations of hyperandrogenism. Responses to metformin are related to the severity of hyperandrogenemia and to adrenal function.