Uterine bleeding with hormone therapies in menopausal women: a systematic review

Abstract

Uterine bleeding is a common reason why women discontinue menopausal hormone therapy (HT). This systematic review compared bleeding profiles reported in studies for continuous-combined HT approved in North America and Europe for moderate to severe vasomotor symptoms in postmenopausal women with a uterus. Non-head-to-head studies showed that uterine bleeding varies by formulation and administration route, with oral having a better bleeding profile than transdermal formulations. Cumulative amenorrhea over a year ranged from 18 to 61% with oral HT and from 9 to 27% with transdermal HT, as reported for continuous-combined HT containing 17β-estradiol (E2)/progesterone (P4) (56%), E2/norethisterone acetate (NETA) (49%), E2/drospirenone (45%), conjugated equine estrogens/medroxyprogesterone acetate (18–54%), ethinyl estradiol/NETA (31–61%), E2/levonorgestrel patch (16%), and E2/NETA patch (9–27%). Amenorrhea rates and the mean number of bleeding/spotting days improved over time. The oral E2/P4 combination was amongst those with lower bleeding rates and may be an appropriate alternative for millions of women seeking bioidentical HT and/or those who have bleeding concerns with other HT.

摘要

子宫出血是妇女中断绝经激素治疗（HT）的常见原因。本系统性综述比较了北美和欧洲批准的有子宫的绝经后女性中重度血管舒缩症状连续联合HT治疗药物在研究中报道的出血情况。非面对面的研究表明, 子宫出血因制剂和给药途径的不同而不同, 口服比经皮制剂更容易出血。闭经超过一年的人中, 大约为18%-61%采用口服HT, 9%-27%采用经皮HT治疗。据报道采用的连续联合HT治疗有17β-雌二醇（E2）/孕酮（P4）（56%）, E2/醋酸炔诺酮（NETA）（49%）、E2/屈螺酮（45%）、马结合雌激素/醋酸甲羟孕酮（18-54%）、炔雌醇/NETA（31%-61%）、E2/左炔诺孕酮贴片（16%）和E2/NETA贴片（9-27%)。闭经率和和平均出血/点滴出血天数随时间而改善。口服E2/P4组合是出血率较低的一组药物之一, 可能对于追求HT的女性和/或其他HT引起出血的女性的合适的选择。

Keywords:

• Amenorrhea
• bleeding
• continuous-combined hormone therapy
• hormone therapy
• menopause
• uterine bleeding
• vasomotor symptoms
• bioidentical

Acknowledgements

The authors would like to acknowledge the medical writing assistance of H. Zhang, PhD, D. Verlaan, PhD, and K. Ohleth, PhD, of Precise Publications, LLC.

Potential conflict of interest

J.H.P. has served as a consultant to Pfizer, Shionogi, Sojournix, and TherapeuticsMD; and has stock options with TherapeuticsMD. D.F.A. has served as a consultant to AbbVie, Actavis, Agile Therapeutics, Bayer Healthcare, Endoceutics, Exeltis, InnovaGyn, Merck, Pfizer, Radius Health, Sermonix, Shionogi, Teva Women’s Healthcare, and TherapeuticsMD; and has received research support from Actavis, Bayer Healthcare, Endoceutics, Glenmark, Merck, Radius Health, Shionogi, and TherapeuticsMD. S.R.G. has served as a consultant to Cook ObGyn, Cooper Surgical, and IBSA; is on the advisory board of AbbVie, AMAG, and TherapeuticsMD; and has also served on the speaker’s bureau of AMAG, Duchesnay, and TherapeuticsMD. R.K. has served as a consultant to Amgen, Astellas, Cooper Surgical, Jazz Pharma, Lupin, Radius Health and TherapeuticsMD; and also serves on the speaker’s bureau of AMAG, Cooper Surgical, and TherapeuticsMD. B.B. and S.M. are employees of TherapeuticsMD with stock/stock options.

Additional information

Funding

Medical writing assistance provided by H. Zhang, D. Verlaan, and K. Ohleth of Precise Publications, LLC was supported by TherapeuticsMD.