二甲雙胍對多囊卵巢綜合征不孕癥患者的治療及臨床觀察

潘 利，黎會麗，劉 潔，李 睿

(陜西省咸陽市中心醫(yī)院，陜西 咸陽 712000)

二甲雙胍對多囊卵巢綜合征不孕癥患者的治療及臨床觀察

潘 利，黎會麗，劉 潔，李 睿

(陜西省咸陽市中心醫(yī)院，陜西 咸陽 712000)

目的觀察二甲雙胍治療多囊卵巢綜合癥不孕癥患者的療效，探討其臨床價值。方法選擇陜西省咸陽市中心醫(yī)院于2014年1月至2015年6月收治的多囊卵巢綜合征不孕癥患者100例作為研究對象，按照配對分組法分為對照組和觀察組，每組50例，對照組給予口服達英-35治療，觀察組于對照組基礎(chǔ)上聯(lián)合應(yīng)用二甲雙胍治療，兩組均連續(xù)服藥3個月，比較兩組療效。結(jié)果兩組患者治療前體質(zhì)量指數(shù)、黃體生成素、睪酮水平比較均無統(tǒng)計學(xué)差異(t值分別為0.869、1.534、1.153，均Pgt;0.05)；治療后觀察組體質(zhì)量指數(shù)、黃體生成素、睪酮水平均低于對照組，且兩組治療后水平均低于治療前(t=7.889～25.876，均Plt;0.05)。兩組患者治療前、治療后空腹血糖及2h血糖水平比較均無顯著統(tǒng)計學(xué)差異(t值分別為0.665、0.905、0.766、0.665，均Pgt;0.05)；觀察組治療后空腹胰島素及2h胰島素水平均顯著低于對照組，且均低于術(shù)前(t值分別為37.915，18.404，均Plt;0.05)。觀察組治療后排卵率及妊娠率分別為72.0%(36例)、42.0%(21例)，均顯著高于對照組52.0%(26例)、20.0%(10例)，差異有統(tǒng)計學(xué)意義(χ2值分別為4.244、5.657，均Plt;0.05)。觀察組治療期間不良反應(yīng)發(fā)生率34.0%(17例)，與對照組32.0%(16例)比較，無顯著統(tǒng)計學(xué)差異(χ2=0.045，Pgt;0.05)。結(jié)論二甲雙胍用于多囊卵巢綜合征不孕癥患者治療可取得較佳療效，胰島素水平顯著降低，有助于排卵，且不良反應(yīng)發(fā)生率低，具有重要臨床價值。

二甲雙胍；多囊卵巢綜合征；胰島素；排卵；不良反應(yīng)

多囊卵巢綜合征患者臨床并不少見，調(diào)查研究表明，其發(fā)病率高達5%～10%，約占不排卵不孕癥患者的70%[1-2]。該病為機體生殖內(nèi)分泌及代謝功能紊亂所引起的排卵障礙性疾病，具有高度異質(zhì)性及復(fù)雜性，遠期并發(fā)癥發(fā)生率較高，嚴重影響著患者的生活質(zhì)量。目前，臨床極為重視多囊卵巢綜合癥不孕癥患者的治療，隨著臨床研究不斷深入，已有較多藥物及干預(yù)措施廣泛應(yīng)用于臨床治療。多囊卵巢綜合癥以胰島素抵抗及高胰島素血癥為主要病理變化，二甲雙胍為治療糖尿病及增加胰島素敏感性藥物之一，其改善胰島素抵抗效果較佳，但其應(yīng)用于多囊卵巢綜合癥患者治療較少見于文獻報道[3-4]，本研究旨在探討其療效，現(xiàn)報道如下。

1資料與方法

1.1研究對象

本研究選擇陜西省咸陽市中心醫(yī)院于2014年1月至2015年6月收治的多囊卵巢綜合癥不孕癥患者100例作為研究對象，按照配對分組法分為對照組和觀察組，每組50例。所有患者均經(jīng)患者及家屬知情同意，且符合倫理委員會基本要求。100例患者均符合多囊卵巢綜合癥診斷標準，均無對本研究所應(yīng)用藥物過敏史，且均為已婚不孕患者，均排除輸卵管性不孕。對照組年齡為25～36歲，平均(29.6±4.3)歲，不孕年限2～5年，平均(3.3±0.5)年，體質(zhì)指數(shù)(body mass index，BMI)為22.5～27.5kg/m2，平均24.5±1.8kg/m2。觀察組年齡為24～35歲,平均(29.1±4.1)歲，不孕年限2～6年，平均(3.5±0.3)年，BMI為22.5～27.2 kg/m2，平均23.3±1.2kg/m2。兩組患者的年齡、不孕年限、BMI等一般資料比較均無顯著統(tǒng)計學(xué)差異(均Pgt;0.05)。

1.2診斷標準

多囊卵巢綜合征診斷標準采取2003年鹿特丹會議修正標準：①患者稀發(fā)排卵或者無排卵；②具有雄激素分泌過多的臨床表現(xiàn)；③超聲檢查結(jié)果表明卵巢多囊改變；④以上3項具備兩項，且排除其他病因所致的高雄激素血癥；無胰島素抵抗及糖耐量受損(impaired glucose tolerance，IGT)者，或者BMI超過30 kg/m2患者[5-6]。

1.3方法

兩組患者均于月經(jīng)第3天清晨禁食禁飲條件下測定身高、體重等，并測定黃體生成素、睪酮及空腹胰島素、血糖水平；然后測定口服72g葡萄糖2h后胰島素及血糖水平。對照組給予口服達英-35(國藥準字J20100003；規(guī)格:0.035mg)治療3個月，觀察組在對照組基礎(chǔ)上給予二甲雙胍治療500mg，3次/日，連續(xù)服用3個月。治療結(jié)束后兩組均于第4個月月經(jīng)來潮第3天測定身高、體重、黃體生成素、睪酮及空腹胰島素、血糖水平、口服葡萄糖2h血糖、胰島素水平。在月經(jīng)來潮第5天，開始服用克羅米芬(CC)(國藥準字H31021107；規(guī)格:50mg)，50～100mg/日，服用5日。于月經(jīng)第11天監(jiān)測子宮內(nèi)膜發(fā)育情況，觀察卵泡變化，處于成熟時則肌內(nèi)注射人體絨膜促性腺激素(human chorionic gonadotropin，hCG)5 000～10 000IU促進排卵，囑咐患者于24～48h內(nèi)性交兩次。治療周期中檢測卵泡數(shù)目和直徑，如有3個以上直徑大于14mm卵泡，立刻停止治療，定期B超檢測，預(yù)防卵巢過度刺激癥(ovarian hyper-stimulation syndrome，OHSS，發(fā)生。

1.4觀察指標

①比較兩組患者治療前后BMI、黃體生成素、睪酮水平；②比較兩組患者治療前后血糖、胰島素水平；③比較兩組患者排卵率及妊娠率；④比較兩組患者治療期間不良反應(yīng)發(fā)生率。

1.5統(tǒng)計學(xué)方法

2結(jié)果

2.1兩組患者治療前后BMI、黃體生成素、睪酮水平比較

兩組患者治療前體質(zhì)量指數(shù)、黃體生成素、睪酮水平比較均無統(tǒng)計學(xué)差異(均Pgt;0.05)；治療后觀察組體質(zhì)量指數(shù)、黃體生成素、睪酮水平均低于對照組，兩組治療后水平均低于治療前，差異均有統(tǒng)計學(xué)意義(均Plt;0.05)，見表1。

表1 兩組患者治療前后BMI、黃體生成素、睪酮水平比

2.2兩組患者治療前后血糖、胰島素水平比較

兩組患者治療前、治療后空腹血糖、2h血糖水平比較均無顯著統(tǒng)計學(xué)差異(均Pgt;0.05)；觀察組治療后空腹胰島素及2h胰島素水平均顯著低于對照組，且均低于術(shù)前，差異有統(tǒng)計學(xué)意義(均Plt;0.05)，見表2。

表2 兩組患者治療前后血糖、胰島素水平比較

2.3兩組患者排卵率及妊娠率比較

經(jīng)分析，觀察組治療后排卵率及妊娠率均顯著高于對照組，差異有統(tǒng)計學(xué)意義(均Plt;0.05)，見表3。

2.4兩組患者治療期間不良反應(yīng)發(fā)生率比較

觀察組治療期間不良反應(yīng)發(fā)生率17例(34.0%)，與對照組16例(32.0%)比較，無顯著統(tǒng)計學(xué)差異(Pgt;0.05)，見表4。

表3 兩組患者排卵率及妊娠率比較[n(%)]

表4 兩組患者治療期間不良反應(yīng)發(fā)生率比較[n(%)]

3討論

3.1多囊卵巢綜合征不孕癥及危害

多囊卵巢綜合癥不孕癥已成為女性常見生殖功能障礙及糖代謝異常關(guān)聯(lián)的特殊疾病，相關(guān)研究表明，該病不僅影響患者生育及家庭幸福，同時可引起心血管疾病、糖尿病等，嚴重影響患者生活質(zhì)量[7-9]。有文獻報道，多囊卵巢綜合征不孕癥患者合并2型糖尿病發(fā)生率遠高于健康人群，約82.0%患者合并2型糖尿病，約50%患者為肥胖人群[10-11]。多囊卵巢綜合征、糖尿病、肥胖相互影響，患者表現(xiàn)為月經(jīng)失調(diào)、排卵障礙及不孕等，給患者及家庭帶來極大心理負擔及壓力。

3.2二甲雙胍治療機制

隨著臨床研究深入，對多囊卵巢綜合征不孕癥發(fā)病機制逐漸明確，其治療措施也應(yīng)用日益廣泛?？刂企w重、加強體育鍛煉及調(diào)整月經(jīng)周期、藥物干預(yù)等均具有一定療效，達英-35干預(yù)多囊卵巢綜合癥高雄激素可取得一定療效[12-13]。本研究選擇本院于2014年1月至2015年6月收治的多囊卵巢綜合癥不孕癥患者100例作為研究對象，將其分為對照組和觀察組，各50例，對照組給予口服達英-35治療，觀察組在對照組基礎(chǔ)上聯(lián)合應(yīng)用二甲雙胍治療，兩組均連續(xù)服藥3個月，比較兩組療效。結(jié)果顯示，治療后觀察組體質(zhì)量指數(shù)、黃體生成素、睪酮水平及空腹胰島素、2h胰島素水平均低于對照組，觀察組排卵率及妊娠率均顯著高于對照組，差異有統(tǒng)計學(xué)意義(Plt;0.05)。治療期間不良反應(yīng)發(fā)生率比較兩組差異無統(tǒng)計學(xué)意義(Pgt;0.05)。多囊卵巢綜合癥不孕癥常合并胰島素抵抗及高胰島素血癥，其病理變化為早期機體糖代謝異常，通過增加胰島素分泌維持血糖于正常水平，但長期胰島素分泌過量后，靶器官對胰島素敏感性降低，進展至胰島素抵抗，繼續(xù)發(fā)展胰島素抵抗無法代償時，則發(fā)生2型糖尿病[14-15]。研究表明，胰島素抵抗可引起高雄激素血癥，其機制為胰島素處于高水平時，可抑制肝臟性激素結(jié)合球蛋白合成，進而刺激腎上腺及卵巢分泌雄激素，導(dǎo)致游離雄激素水平升高，影響卵泡發(fā)育及成熟，導(dǎo)致不孕[16]。二甲雙胍為臨床常用胰島素增敏劑，具有加強外周組織對葡萄糖利用及加速無氧酵解，降低肝糖原異生，并對降低腸壁吸收葡萄糖具有重要作用。相關(guān)研究表明，二甲雙胍可改善機體胰島素抵抗，并增強機體對胰島素敏感性，且可降低細胞色素P450 C17α酶的活性，降低雄激素合成水平，增加排卵幾率[17-19]。

綜上所述：二甲雙胍用于多囊卵巢綜合癥不孕癥患者治療可取得較佳療效，胰島素水平顯著降低，有助于排卵，且不良反應(yīng)發(fā)生率低，具有重要臨床價值。

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[專業(yè)責(zé)任編輯：呂淑蘭]

Clinicalobservationofmetforminintreatmentofinfertilewomenwithpolycysticovarysyndrome

PAN Li, LI Hui-li, LIU Jie, LI Rui

(XianyangCentralHospitalofShaanxiProvince,ShaanxiXianyang712000,China)

ObjectiveTo observe the therapeutic effect of metformin on treatment of infertile patients with polycystic ovary syndrome and to evaluate its clinical value.MethodsAltogether 100 cases of infertile patients with polycystic ovary syndrome treated in Xianyang Central Hospital of Shaanxi Province from January 2014 to June 2015 were selected as study objects, and they were divided into control group and observation group in accordance with paired grouping method with 50 cases in each group. Patients in the control group were treated with oral Diane-35, while patients in the observation group accepted metformin treatment based on treatment

in the control group. Patients in both groups were treated for 3 months, and efficacy was compared between two groups.ResultsThere was no statistically significant difference in body mass index, luteinizing hormone and testosterone levels between two groups before treatment (tvalue was 0.869，1.534 and 1.153, respectively, allPgt;0.05). After treatment body mass index, luteinizing hormone and testosterone levels in the observation group were less than those in the control group, and indexes in two groups after treatment were lower than those before treatment (tvalue was 8.485, 7.889 and 16.745, respectively, allPlt;0.05). Fasting blood glucose and 2h blood glucose levels in two groups showed no significant difference before and after treatment (tvalue was 0.665 and 0.905, respectively, bothPgt;0.05). After treatment fasting insulin and 2h insulin levels in the observation group were significantly lower than those in the control group and the indexes were lower than those before treatment (tvalue was 37.915 and 18.404, respectively, bothPlt;0.05). After treatment ovulation and pregnancy were reported in 36 cases (72.0%) and 21 cases (42.0%), respectively in the observation group, which were significantly higher than in the control group (26 cases, 52.0%; 10 cases, 20.0%), and the differences were statistically significant (χ2value was 4.244 and 5.657, respectively, bothPlt;0.05). Incidence of adverse reactions during treatment was found in 17 cases (34.0%) in the observation group and in 16 cases (32.0%) in the control group, which showed no significant difference (χ2=0.045,Pgt;0.05).ConclusionMetformin used in treating women with polycystic ovary syndrome and infertility can get better curative effect with significantly decreased insulin level. It is helpful for ovulation with low incidence of adverse reactions, so it has important clinical value.

metformin; polycystic ovary syndrome; insulin; ovulation; adverse reactions

10.3969/j.issn.1673-5293.2017.11.033

R711.75

A

1673-5293(2017)11-1415-04

2016-11-01

潘 利(1980—)，女，主治醫(yī)師，主要從事婦產(chǎn)科臨床工作。

李 睿，主任醫(yī)師。