围绝经期应用不同剂量绝经激素治疗的临床观察

doi:10.6040/j.issn.1671-7554.0.2018.1490

摘要/Abstract

摘要： 目的比较不同剂量绝经激素治疗(MHT)对缓解患者绝经相关症状的有效性和安全性。方法回顾分析2012年至2017年就诊浙江大学医学院附属妇产科医院妇科内分泌门诊的围绝经期综合征患者450例,根据MHT方案中雌激素剂量分为3组,A组:标准剂量组(n=62),B组:低剂量组(n=322)及C组:超低剂量组(n=66)。以28 d为1个治疗周期,连续序贯给药。分别于治疗前后进行改良Kupperman问卷评分、生殖激素及糖脂代谢指标测定、乳腺超声检查。结果治疗前3组患者在一般资料及各临床观察指标上差异均无统计学意义(P均>0.05)。与治疗前相比,治疗1、3、6个周期后,3组改良Kupperman评分、血清卵泡刺激素(FSH)均下降,雌二醇(E2)均上升,差异有统计学意义(P均<0.001)。B组与C组高密度脂蛋白胆固醇在治疗6周期后均较治疗前升高,A组与B组低密度脂蛋白胆固醇在治疗6周期后均较治疗前下降,差异有统计学意义(P均<0.01); A组与B组空腹血糖、空腹胰岛素在治疗6周期后均较治疗前下降,差异有统计学意义(P均<0.01)。治疗前后3组乳腺腺体厚度、结节大小、导管扩张程度均无明显变化(P均>0.05);A组7例(11.3%)、B组14例(4.3%)、C组1例(1.5%)出现乳房胀痛,发生率在A、C组间差异有统计学意义(P<0.05)。结论标准剂量、低剂量、超低剂量MHT均有效缓解围绝经期患者的绝经症状。其中,标准剂量、低剂量MHT在改善糖脂代谢方面优于超低剂量MHT,超低剂量MHT在耐受方面具有一定优势,观察期内不同剂量MHT均对乳腺无影响。

关键词: 绝经激素治疗, 围绝经期, 低剂量, 超低剂量, 绝经相关症状

Abstract: Objective To compare the effectiveness and safety of different doses of menopause hormone therapies(MHT)in the remission of menopausal symptoms. Methods The clinical data of 450 perimenopausal women who received MHT during 2012 and 2017 were retrospectively analyzed. According to the doses of estradiol valerate, the pa- 山东大学学报 (医学版)57卷2期 -徐文娴,等.围绝经期应用不同剂量绝经激素治疗的临床观察 \=-tients were divided into 3 groups:group A(standard dose, n=62), group B(low dose, n=322)and group C(ultralow dose, n=66). One treatment cycle lasted for 28 days, during which the continuous sequential regimen was adopted. Before and after treatment, modified Kupperman menopausal index(mKMI)were surveyed, reproductive hormones and glucolipid metabolic indexes were detected, and breast ultrasound was performed. Results Before treatment, there were no significant differences in the general characters and clinical indexes among the 3 groups(all P>0.05). Compared to baseline, the mKMI scores and follicle stimulating hormone(FSH)level significantly decreased, while estradiol level significantly increased after 1, 3 and 6 treatment cycles in all 3 groups(all P<0.001). After 6 treatment cycles, the level of high-density lipoprotein cholesterol(HDL-C)markedly increased in groups B and C, and the levels of low-density lipoprotein cholesterol(LDL-C), fasting blood glucose and fasting insulin significantly decreased in groups A and B(all P<0.01). There were no statistical changes in the thickness of mammary glands, size of mammary nodules and dilatation of ducts in the 3 groups before and after treatment(all P>0.05). Breast distention occurred in 7 cases(11.3%)in group A, 14 cases in group B(4.3%)and 1 case in group C(1.5%), the difference in incidence between groups A and C was significant(P<0.05). Conclusion The standard, low and ultra-low doses of MHT can effectively relieve the menopausal symptoms in perimenopausal women. The standard and low dose are superior to the ultra-low dose in improving glucolipid metabolism. The ultra-low dose has advantages in tolerance. The different doses of MHT has no effects on the mammary glands during the observation period.

Key words: Menopause hormone therapy, Perimenopause period, Low dose, Ultra-low dose, Menopausal symptoms

中图分类号:

R711

徐文娴,王泉梅,马麟娟,黄艺舟,戚彤云,傅东霞,宋阳,兰义兵,李春明,陈沛琼,应倩,周坚红. 围绝经期应用不同剂量绝经激素治疗的临床观察[J]. 山东大学学报 (医学版), 2019, 57(2): 44-51.

XU Wenxian, WANG Quanmei, MA Linjuan, HUANG Yizhou, QI Tongyun, FU Dongxia, SONG Yang, LAN Yibing, LI Chunming, CHEN Peiqiong, YING Qian, ZHOU Jianhong. Effects of different doses of menopause hormone therapies in perimenopausal women[J]. Journal of Shandong University (Health Sciences), 2019, 57(2): 44-51.

参考文献

[1] 中华医学会妇产科学分会绝经学组. 中国绝经管理与绝经激素治疗指南(2018)[J]. 中华妇产科杂志, 2018, 53(11): 729-739.
[2] 郁琦. 绝经学[M]. 北京: 人民卫生出版社, 2013: 303-304.
[3] Liu M, Wang Y, Li X, et al. A health survey of Beijing middle-aged registered nurses during menopause [J]. Maturitas, 2013, 74(1): 84-88.
[4] Muhleisen AL, Herbst-Kralovetz MM. Menopause and the vaginal microbiome [J]. Maturitas, 2016, 91: 42-50. doi:10.1016/j.maturitas.2016.05.015.
[5] Lan Y, Huang Y, Song Y, et al. Prevalence, severity, and associated factors of menopausal symptoms in middle-aged Chinese women: a community-based cross-sectional study in southeast China [J]. Menopause, 2017, 24(10): 1200-1207.
[6] Huang Y, Chatooah N, Qi T, et al. Health-related quality of life and its associated factors in Chinese middle-aged women [J]. Climacteric, 2018, 21(5): 483-490.
[7] Baber RJ, Panay N, Fenton A, et al. 2016 IMS Recommendations on womens midlife health and menopause hormone therapy[J]. Climacteric, 2016, 19(2): 109-150.
[8] The NAMS Hormone Therapy Position Statement Advisory Panel. The 2017 hormone therapy position statement of the north american menopause society[J]. Menopause, 2017, 24(7): 728-753.
[9] 陈蓉, 魏代敏, 郁琦. 绝经后小剂量激素补充治疗的有效性和安全性[J]. 中国实用妇科与产科杂志, 2011, 27(9):709-712.
[10] Manson JE, Kaunitz AM. Menopause management: getting clinical care back on track[J]. N Engl J Med, 2016, 374(9): 803-806.
[11] Ku SY, Kang JW, Kim H, et al. Regional differences in age at menopause between Korean-Korean and Korean-Chinese[J]. Menopause, 2004, 11(5): 569-574.
[12] 周小丹. 国内外不同种族/民族妇女围绝经期现况研究进展[J]. 中国妇幼保健, 2012, 27(14): 2227-2229.
[13] Haines CJ, Xing SM, Park KH, et al. Prevalence of menopausal symptoms in different ethnic groups of Asian women and responsiveness to therapy with three doses of conjugated estrogens/medroxyprogesterone acetate: the Pan-Asia Menopause(PAM)study[J]. Maturitas, 2005, 52(3-4): 264-276.
[14] Honjo H, Taketani Y. Low-dose estradiol for climacteric symptoms in Japanese women: a randomized, controlled trial[J]. Climacteric, 2009, 12(4): 319-328.
[15] Stevenson JC, Durand G, Kahler E, et al. Oral ultra-low dose continuous combined hormone replacement therapy with 0.5 mg 17β-oestradiol and 2.5 mg dydrogesterone for the treatment of vasomotor symptoms: Results from a double-blind, controlled study [J]. Maturitas, 2010, 67(3): 227-232.
[16] Polisseni AF, Andrade AT, Ribeiro LC, et al. Effects of a continuous-combined regimen of low-dose hormone therapy(oestradiol and norethindrone acetate)and tibolone on the quality of life in symptomatic postmenopausal women: a double-blind, randomised study[J]. Maturitas, 2013, 74(2): 172-178.
[17] Janssen I, Powell LH, Crawford S, et al. Menopause and the metabolic syndrome: the Study of Womens Health Across the Nation[J]. Arch Intern Med, 2008, 168(14): 1568-1575.
[18] 何柳, 唐迅, 胡永华. 绝经与心血管疾病及相关代谢紊乱的关联[J]. 北京大学学报(医学版), 2016, 48(3): 448-453. HE Liu, TANG Xun, HU Yonghua. Relationship of menopause with cardiovascular disease and related metabolic disorders[J]. Journal of Peking University(Health Sciences), 2016, 48(3): 448-453.
[19] 陈建芳, 万惠卿, 黄艺舟, 等. 更年期女性胆固醇水平调查与影响因素分析[J]. 中华生殖与避孕杂志, 2017, 37(10): 831-836. CHEN Jianfang, WAN Huiqing, HUANG Yizhou, et al. Investigation of serum cholesterol level of women in different menopausal stages and its influencing factors[J]. Chinese Journal of Reproduction and Contraception, 2017, 37(10): 831-836.
[20] Lovre D, Lindsey SH, Mauvais-Jarvis F. Effect of menopausal hormone therapy on components of the metabolic syndrome[J]. Ther Adv Cardiovasc Dis, 2016.pii: 1753944716649358. doi:10.1177/17539447166-49358.
[21] Casanova G, Radavelli S, Lhullier F, et al. Effects of nonoral estradiol-micronized progesterone or low-dose oral estradiol-drospirenone therapy on metabolic variables and markers of endothelial function in early postmenopause[J]. Fertil Steril, 2009, 92(2): 605-612.
[22] Godsland IF, Manassiev NA, Felton CV, et al. Effects of low and high dose oestradiol and dydrogesterone therapy on insulin and lipoprotein metabolism in healthy postmenopausal women[J]. Clin Endocrinol, 2004, 60(5): 541-549.
[23] Matsui S, Yasui T, Tani A, et al. Effect of ultra-low-dose estradiol and dydrogesterone on arterial stiffness in postmenopausal women[J]. Climacteric, 2014, 17(2): 191-196.
[24] Mattsson LA, Ipsen HE, Granqvist CJ, et al. Ultra-low-dose estradiol and norethisterone acetate: bleeding patterns and other outcomes over 52 weeks of therapy [J]. Climacteric, 2015, 18(3): 419-425.
[25] Files JA, Miller VM, Cha SS, et al. Effects of different hormone therapies on breast pain in recently postmenopausal women: findings from the Mayo Clinic KEEPS breast pain ancillary study [J]. J Womens Health, 2014, 23(10): 801-805.
[26] Simionescu M. Implications of early structural-functional changes in the endothelium for vascular disease[J]. Arterioscler Thromb Vasc Biol, 2007, 27(2): 266-274.
[27] Stute P, Becker HG, Bitzer J, et al. Ultra-low dose- new approaches in menopausal hormone therapy[J]. Climacteric, 2015, 18(2): 182-186.
[28] Stuenkel CA, Davis SR, Gompel A, et al. Treatment of symptoms of the menopause: an endocrine society clinical practice guideline[J]. J Clin Endocrinol Metab, 2015, 100(11):3975-4011. doi:10.1210/jc.2015-2236.

多维度评价

Viewed

Full text

Abstract

Cited

Shared

Discussed