α-葡萄糖苷酶抑制剂
一些小型研究显示,阿卡波糖可能会降低雄激素水平,改善多毛症,改善 PCOS 患者的月经不规律,同时可以改善心血管危险因素。[121]Kircher C, Smith KP. Acarbose for polycystic ovary syndrome. Ann Pharmacother. 2008 Jun;42(6):847-51.http://www.ncbi.nlm.nih.gov/pubmed/18460589?tool=bestpractice.com 胃肠道副作用限制了该药使用。
芳香化酶抑制剂
芳香化酶抑制剂可降低雄激素向雌激素的转换。雌激素合成的降低减少了雌激素对于下丘脑或者垂体的负反馈,使 FSH 增加,刺激卵泡生长和排卵。[122]Casper RF, Mitwally MF. Review: aromatase inhibitors for ovulation induction. J Clin Endocrinol Metab. 2006;91:760-771.http://jcem.endojournals.org/cgi/content/full/91/3/760http://www.ncbi.nlm.nih.gov/pubmed/16384846?tool=bestpractice.com 针对少量临床试验的 meta 分析显示:芳香化酶抑制剂(例如来曲唑)和氯米芬会产生近似的排卵率、活产率和多胎妊娠率。[123]Requena A, Herrero J, Landeras J, et al. Use of letrozole in assisted reproduction: a systematic review and meta-analysis. Hum Reprod Update. 2008 Nov-Dec;14(6):571-82.http://humupd.oxfordjournals.org/cgi/content/full/14/6/571http://www.ncbi.nlm.nih.gov/pubmed/18812422?tool=bestpractice.com[124]He D, Jiang F. Meta-analysis of letrozole versus clomiphene citrate in polycystic ovary syndrome. Reprod Biomed Online. 2011 Jul;23(1):91-6.http://www.ncbi.nlm.nih.gov/pubmed/21550852?tool=bestpractice.com[125]Liu Z, Tang HL, Zhai SD. Letrozole for ovulation induction in women with polycystic ovarian syndrome: a systematic analysis. Chin Pharm J. 2011;46(22):1762-7.[126]Misso ML, Wong JL, Teede HJ, et al. Aromatase inhibitors for PCOS: a systematic review and meta-analysis. Hum Reprod Update. 2012 May-Jun;18(3):301-12.http://www.ncbi.nlm.nih.gov/pubmed/22431566?tool=bestpractice.com 后期的 meta 分析提示来曲唑优于氯米芬,并且对于妊娠和活产率效果和腹腔镜卵巢打孔相似,但是证据级别很低或者质量参差不齐。[127]Franik S, Kremer JA, Nelen WL, et al. Aromatase inhibitors for subfertile women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2014 Feb 24;(2):CD010287.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD010287.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/24563180?tool=bestpractice.com[128]Roque M, Tostes AC, Valle M, et al. Letrozole versus clomiphene citrate in polycystic ovary syndrome: systematic review and meta-analysis. Gynecol Endocrinol. 2015;31(12):917-21.http://www.ncbi.nlm.nih.gov/pubmed/26479460?tool=bestpractice.com来曲唑和氯米芬治疗所造成的流产和妊娠丢失率近似。[124]He D, Jiang F. Meta-analysis of letrozole versus clomiphene citrate in polycystic ovary syndrome. Reprod Biomed Online. 2011 Jul;23(1):91-6.http://www.ncbi.nlm.nih.gov/pubmed/21550852?tool=bestpractice.com[125]Liu Z, Tang HL, Zhai SD. Letrozole for ovulation induction in women with polycystic ovarian syndrome: a systematic analysis. Chin Pharm J. 2011;46(22):1762-7.[126]Misso ML, Wong JL, Teede HJ, et al. Aromatase inhibitors for PCOS: a systematic review and meta-analysis. Hum Reprod Update. 2012 May-Jun;18(3):301-12.http://www.ncbi.nlm.nih.gov/pubmed/22431566?tool=bestpractice.com[127]Franik S, Kremer JA, Nelen WL, et al. Aromatase inhibitors for subfertile women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2014 Feb 24;(2):CD010287.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD010287.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/24563180?tool=bestpractice.com[128]Roque M, Tostes AC, Valle M, et al. Letrozole versus clomiphene citrate in polycystic ovary syndrome: systematic review and meta-analysis. Gynecol Endocrinol. 2015;31(12):917-21.http://www.ncbi.nlm.nih.gov/pubmed/26479460?tool=bestpractice.com关于使用曲唑所致的多胎妊娠率是否低于氯米芬,meta 分析产生了不一致的结果。[127]Franik S, Kremer JA, Nelen WL, et al. Aromatase inhibitors for subfertile women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2014 Feb 24;(2):CD010287.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD010287.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/24563180?tool=bestpractice.com[128]Roque M, Tostes AC, Valle M, et al. Letrozole versus clomiphene citrate in polycystic ovary syndrome: systematic review and meta-analysis. Gynecol Endocrinol. 2015;31(12):917-21.http://www.ncbi.nlm.nih.gov/pubmed/26479460?tool=bestpractice.com曾经希望芳香化酶抑制剂会对效氯米芬耐药的患者有效;然而,meta 分析显示来曲唑的结果并非如此。[126]Misso ML, Wong JL, Teede HJ, et al. Aromatase inhibitors for PCOS: a systematic review and meta-analysis. Hum Reprod Update. 2012 May-Jun;18(3):301-12.http://www.ncbi.nlm.nih.gov/pubmed/22431566?tool=bestpractice.com 目前需要更多的试验直接比较芳香化酶抑制剂和氯米芬的效果。关于多囊卵巢综合征中妊娠的 II 期临床试验(PPCOS II,样本量 750)发现来曲唑在提高活产率方面优于氯米芬。[129]Legro RS, Brzyski RG, Diamond MP, et al. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med. 2014 Jul 10;371(2):119-29.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175743/http://www.ncbi.nlm.nih.gov/pubmed/25006718?tool=bestpractice.com 一项针对氯米芬抵抗的 PCOS 患者的随机对照试验显示,在排卵和妊娠方面,来曲唑和腹腔镜卵巢打孔的效果类似。[130]Abu Hashim H, Mashaly AM, Badawy A. Letrozole versus laparoscopic ovarian diathermy for ovulation induction in clomiphene-resistant women with polycystic ovary syndrome: a randomized controlled trial. Arch Gynecol Obstet. 2010 Nov;282(5):567-71.http://www.ncbi.nlm.nih.gov/pubmed/20577748?tool=bestpractice.com 另一项针对克罗米芬耐药的 PCOS 患者的随机对照临床试验显示,来曲唑与二甲双胍联合克罗米芬在排卵和妊娠率方面效果类似。[131]Abu Hashim H, Shokeir T, Badawy A. Letrozole versus combined metformin and clomiphene citrate for ovulation induction in clomiphene-resistant women with polycystic ovary syndrome: a randomized controlled trial. Fertil Steril. 2010 Sep;94(4):1405-9.http://www.ncbi.nlm.nih.gov/pubmed/19732888?tool=bestpractice.com 对于 BMI<30 kg/m² 的女性,来曲唑在妊娠率方面可能优于氯米芬。[125]Liu Z, Tang HL, Zhai SD. Letrozole for ovulation induction in women with polycystic ovarian syndrome: a systematic analysis. Chin Pharm J. 2011;46(22):1762-7. 其他的随机临床试验显示,来曲唑可能最终会成为 PCOS 的不孕症的一线治疗。
他汀类药物
HMG-CoA-还原酶抑制剂(他汀类药物),结合 OCP 时能进一步降低循环雄激素水平,改善血脂,减少多毛症,改善 PCOS 的炎症标志物。[132]Banaszewska B, Pawelczyk L, Spaczynski RZ, et al. Effects of simvastatin and oral contraceptive agent on polycystic ovary syndrome: prospective, randomized, crossover trial. J Clin Endocrinol Metab. 2007 Feb;92(2):456-61.http://jcem.endojournals.org/cgi/content/full/92/2/456http://www.ncbi.nlm.nih.gov/pubmed/17105841?tool=bestpractice.com 一项 meta 分析发现他汀类药物在 PCOS 中能降低睾酮水平,改善血脂,而对胰岛素抵抗和排卵没有影响。[133]Raval AD, Hunter T, Stuckey B, et al. Statins for women with polycystic ovary syndrome not actively trying to conceive. Cochrane Database Syst Rev. 2011 Oct 5;(10):CD008565.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008565.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/21975784?tool=bestpractice.com 然而,至少一项研究显示他汀类药物可能会减少 PCOS 患者的胰岛素抵抗。[134]Puurunen J, Piltonen T, Puukka K, et al. Statin therapy worsens insulin sensitivity in women with polycystic ovary syndrome (PCOS): a prospective, randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab. 2013 Dec;98(12):4798-807.http://www.ncbi.nlm.nih.gov/pubmed/24152688?tool=bestpractice.com 一般说来,他汀类药物与新发糖尿病的风险相关,女性尤其敏感。[135]Goodarzi MO, Li X, Krauss RM, et al. Relationship of sex to diabetes risk in statin trials. Diabetes Care. 2013 Jul;36(7):e100-1.http://care.diabetesjournals.org/content/36/7/e100.longhttp://www.ncbi.nlm.nih.gov/pubmed/23801803?tool=bestpractice.com 尽管目前仍处于试验阶段,还需要进一步的研究来确定他汀类药物在 PCOS 中的作用。尽管在 PCOS 中,他汀类药物并不推荐于单独治疗高雄激素,但对于满足现阶段心血管风险标准的女性可使用他汀类药物治疗。[44]Legro RS, Arslanian SA, Ehrmann DA, et al; Endocrine Society. Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2013 Dec;98(12):4565-92.http://www.endocrine.org/~/media/endosociety/Files/Publications/Clinical%20Practice%20Guidelines/120513_PCOS_FinalA_2013.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/24151290?tool=bestpractice.com
减肥药
在几项临床试验中,对多囊卵巢综合征患者给予了奥利司他和利莫那班 (rimonabant) 等减肥药物。这些药物似乎促进减肥,并带来代谢和激素方面的效果。[136]Moran JL, Brinkworth GD, Norman RJ. Dietary therapy in polycystic ovary syndrome. Semin Reprod Med. 2008 Jan;26(1):85-92.http://www.ncbi.nlm.nih.gov/pubmed/18181086?tool=bestpractice.com[137]Tziomalos K, Krassas GE, Tzotzas T. The use of sibutramine in the management of obesity and related disorders: an update. Vasc Health Risk Manag. 2009;5(1):441-52.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2686261/http://www.ncbi.nlm.nih.gov/pubmed/19475780?tool=bestpractice.com
减重手术
一些小型临床试验,随访了 PCOS 肥胖女性,在减肥手术后的情况。大部分受试者恢复了规律的月经周期,并伴随高雄激素的症状和体征减轻,有些女性甚至能够妊娠。[136]Moran JL, Brinkworth GD, Norman RJ. Dietary therapy in polycystic ovary syndrome. Semin Reprod Med. 2008 Jan;26(1):85-92.http://www.ncbi.nlm.nih.gov/pubmed/18181086?tool=bestpractice.com一项 meta 分析表明,肥胖症手术后 PCOS 的患病率从 46% 下降到 7%,月经不规律和多毛症得到改善。[138]Skubleny D, Switzer NJ, Gill RS, et al. The impact of bariatric surgery on polycystic ovary syndrome: a systematic review and meta-analysis. Obes Surg. 2016 Jan;26(1):169-76.http://www.ncbi.nlm.nih.gov/pubmed/26431698?tool=bestpractice.com
促性腺激素释放激素 (GnRH) 脉冲治疗
通过自动化静脉输液或者皮下输液泵给予促性腺激素释放激素脉冲治疗可以诱导排卵。这种治疗风险最小,排卵率为 50%。主要优点是没有多胎妊娠和卵巢过度刺激的风险。然而,在活产率方面的有效性还没有充分证实。[139]Bayram N, van Wely M, van der Veen F. Pulsatile gonadotrophin releasing hormone for ovulation induction in subfertility associated with polycystic ovary syndrome. Cochrane Database Syst Rev. 2004;(1):CD000412.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD000412.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/14973957?tool=bestpractice.com 因此这项治疗可能最适合那些具有卵巢过度刺激综合征风险或者经历过严重的过度刺激综合征的女性。
体外促性腺激素
在体外受精中,一项高度实验性的措施显示,在受精和移植前获取未成熟的卵母细胞,并通过在体外给予未成熟卵母细胞促性腺激素促使其成熟,可以避免卵巢过度刺激综合征。[140]Chian RC, Buckett WM, Abdul Jalil AK, et al. Natural-cycle in vitro fertilization combined with in vitro maturation of immature oocytes is a potential approach in infertility treatment. Fertil Steril. 2004 Dec;82(6):1675-8.http://www.ncbi.nlm.nih.gov/pubmed/15589878?tool=bestpractice.com 需要随机对照实验来确定这项技术在 PCOS 中的作用。[141]Siristatidis CS, Vrachnis N, Creatsa M, et al. In vitro maturation in subfertile women with polycystic ovarian syndrome undergoing assisted reproduction. Cochrane Database Syst Rev. 2013 Oct 8;(10):CD006606.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006606.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/24101529?tool=bestpractice.com 没有随机试验的情况下,一项对现有证据的 meta 分析表示,使用此技术,临床妊娠率和着床率更高,但活产率是否增加尚无结论。[142]Siristatidis C, Sergentanis TN, Vogiatzi P, et al. In vitro maturation in women with vs. without polycystic ovarian syndrome: a systematic review and meta-analysis. PLoS One. 2015 Aug 4;10(8):e0134696.http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0134696http://www.ncbi.nlm.nih.gov/pubmed/26241855?tool=bestpractice.com
针灸
少数研究推荐针灸作为 PCOS 患者的生育能力治疗方式;然而考虑到目前已进行的数量有限的随机对照试验中没有决定性的证据表明针灸对生育治疗有益,这种治疗仍然是被认为经验性的。[143]Lim CE, Ng RW, Xu K, Cheng NC, et al. Acupuncture for polycystic ovarian syndrome. Cochrane Database Syst Rev. 2016 May 3;(5):CD007689.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007689.pub3/abstracthttp://www.ncbi.nlm.nih.gov/pubmed/27136291?tool=bestpractice.com
噻唑烷二酮
目前已经有噻唑烷二酮类胰岛素增敏剂(TZD,例如罗格列酮、吡格列酮)用于治疗 PCOS 的相关研究,但与二甲双胍相比,研究的数量少得多。因为会导致体重增加,因此此类药物 PCOS 中并不常用。在美国,从 2010 年到 2013 年,罗格列酮由于会导致心肌梗死的风险增加,而限制其使用。并且已不在欧盟市场销售。吡格列酮的长期使用与膀胱癌的风险相关。动物研究显示噻唑烷二酮类可能会导致胎儿丢失。[44]Legro RS, Arslanian SA, Ehrmann DA, et al; Endocrine Society. Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2013 Dec;98(12):4565-92.http://www.endocrine.org/~/media/endosociety/Files/Publications/Clinical%20Practice%20Guidelines/120513_PCOS_FinalA_2013.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/24151290?tool=bestpractice.com 对于 PCOS 患者,噻唑烷二酮类药物 (TZDs) 在排卵和妊娠方面与二甲双胍有类似的效果。[144]Li XJ, Yu YX, Liu CQ, et al. Metformin vs thiazolidinediones for treatment of clinical, hormonal and metabolic characteristics of polycystic ovary syndrome: a meta-analysis. Clin Endocrinol (Oxf). 2011 Mar;74(3):332-9.http://www.ncbi.nlm.nih.gov/pubmed/21050251?tool=bestpractice.com
胰高血糖素样肽-1 受体激动剂
一项 meta 分析表明,艾塞那肽和利拉鲁肽可增加 PCOS 女性患者的体重和血糖水平;少数研究表明,这些药物轻微提高了雄激素水平并改善了经期频率。[145]Lamos EM, Malek R, Davis SN. GLP-1 receptor agonists in the treatment of polycystic ovary syndrome. Expert Rev Clin Pharmacol. 2017 Apr;10(4):401-8.http://www.ncbi.nlm.nih.gov/pubmed/28276778?tool=bestpractice.com 最显著的副作用是恶心。