The impacts of menopausal hormone therapy on longer-term health consequences of ovarian hormone deficiency

Abstract

This study on the longer-term health consequences of ovarian hormone deficiency (OHD) received the Henry Burger Prize in 2022. Osteoporosis, cardiovascular disease and dementia are major degenerative diseases that are also causally associated with OHD. Two randomized controlled trials (RCTs) revealed no significant difference in bone mineral density by adding alendronate to ongoing menopausal hormone therapy (MHT) or combining alendronate at MHT initiation. Another RCT pursuing the effects on fracture recurrence and total mortality in women with hip fracture disclosed that MHT with percutaneous estradiol gel (PEG) and micronized progesterone (MP4) was comparable to risedronate. Basic studies reported that 17β-estradiol exerted direct beneficial actions on vascular smooth muscle in cell proliferation, fibrinolysis and apoptosis. A fourth RCT showed that MP4 had a neutral impact on the PEG response of blood pressure and arterial stiffness. A fifth RCT suggested that the combination therapy of conjugated equine estrogen and MP4 was superior to tacrine in preserving activities in daily living in women with Alzheimer’s disease. In addition, PEG plus MP4 attenuated cognitive decline in women with mild cognitive impairment in a sixth RCT. Finally, the all-cause mortality in recently menopausal women receiving MHT was updated using an adaptive meta-analysis of four RCTs.

摘要

这项关于卵巢激素缺乏的长期健康后果的研究(OHD)获得了2022年的亨利·伯格奖。骨质疏松症、心血管疾病和痴呆是主要的退行性疾病, 也通常与OHD有关。两项随机对照试验(RCT)显示, 在正在进行的绝经期激素治疗(MHT)中添加阿仑膦酸盐或在MHT开始时联合应用阿仑膦酸盐, 在骨密度方面没有显著差异。另一项RCT研究了对髋部骨折女性的骨折复发和总死亡率的影响, 发现应用经皮雌二醇凝胶（PEG）和微粉化黄体酮（MP4）的MHT与利塞膦酸钠相当。基础研究显示, 17β-雌二醇在细胞增殖、纤维蛋白溶解和细胞凋亡中对血管平滑肌发挥直接有益作用。第四篇RCT显示MP4对血压和动脉僵硬度的PEG反应有中性影响。第五项RCT显示, 结合雌激素和MP4联合方案在保护阿尔茨海默症女性的日常生活活动方面优于他克林。此外, 第六项RCT中PEG联合MP4减缓了轻度认知障碍妇女的认知下降。最后, 四项随机对照试验的适应性荟萃分析更新了接受MHT治疗的绝经妇女的全因死亡率。

Keywords:

• Menopausal hormone therapy
• osteoporosis
• hip fracture
• cardiovascular disease
• arterial stiffness
• Alzheimer’s disease
• mild cognitive impairment
• estrogen
• vascular smooth muscle

Acknowledgements

The author would like to thank the following major collaborators: Yong-Ki Min and Duk-Kyung Kim at the Department of Medicine, Youn-Soo Park at Orthopedic Surgery and Duk L. Na at Neurology at the Samsung Medical Center for Clinical Research and Jong-Myon Bae at the Department of Preventive Medicine at Jeju National University School of Medicine for the adaptive meta-analysis, and Chi-Duck Kang at the Department of Biochemistry at Pusan National University School of Medicine for basic research.

Potential conflict of interest

The author reports no conflict of interest.

Source of funding

None.