Menopause Is More Than Just Loss of Fertility.
Menopause Is More Than Just Loss of Fertility.
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更年期不仅仅是生育能力的丧失。
DOI：
10.1093/ppar/prad023
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Benayoun,BéréniceA
中科院分区：
文献类型：
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作者：
Baker,Clayton;Benayoun,BéréniceA
更年期被描述为女性最后一次月经周期后12个月的时间点。更年期通常在45至55岁之间开始，平均年龄约为51岁，但对于一小部分人群（约0.1%），早在生命的第二个十年就可能发生（Davis和Baber，2022）。早期绝经和向绝经过渡伴随着无数的全身性症状（例如，月经不规律、潮热、睡眠问题等）（Santoro等人，2015）。绝经的三个主要阶段包括围绝经期、绝经期和绝经后（谢尔曼，2005）。围绝经期通常在绝经期开始前3至5年开始，并且是大多数妇女开始表现出绝经期症状但仍具有月经周期并可能怀孕的时期（Barth et al.，2015）。更年期是月经周期结束的时间点，导致卵巢停止卵子释放并显著减少雌激素的产生量（Davi s et al.，2015）。最后，绝经后被归类为绝经后妇女的余生。在此阶段，急性症状可能持续数年（Peacock和Ketvertis，2023）。值得注意的是，尽管历史上更年期的焦点主要是所导致的生育能力丧失（出于充分的理由，因为它是卵巢功能停止的最明显和直接的后果），但也存在关于由更年期引起的衰老和衰老相关疾病的显著后果（Cui et al.，2013年）。除了上述全身症状的持续之外，绝经期雌激素和其他卵巢激素的循环水平的降低与许多年龄相关的表型和疾病的风险增加有关，包括阿尔茨海默病、骨质疏松症和心血管疾病（Cheng et al.，2022; Davezac等人，2021; Paganini-Hill和亨德森，1994）。值得注意的是，雌激素主要通过结合和激活三种主要雌激素受体（ERα，ERβ和GPER 1）之一来对年龄相关疾病发挥其保护作用。因为这些受体的表达模式是非常组织和系统特异性的，所以预期绝经诱导的雌激素水平降低对每个组织或系统的影响是独特的（导致不同组织或系统之间不同程度的影响）（Chen等人，2022; Eyster，2016）。重要的是，已提出更年期加速女性的生物老化（Levine等人，2016年）。一致地，年龄-绝经仍然是女性总体寿命的最佳预测因子之一，其中较晚的绝经与降低的全因死亡率和增加的预期寿命相关（Ossewaarde等人，在这里，我们概述了更年期（主要是通过降低雌激素水平）对认知功能，骨量和强度以及心血管疾病的影响，目的是更全面地了解更年期对健康和寿命的影响（图1）。我们还强调了有关妇女健康的缺点，包括在食品和药物管理局（FDA）1/2期临床给药试验中缺乏平等代表性，缺乏对药物治疗对妇女特定不良影响的报告，对更年期作为生物变量的考虑有限，以及无法获得可靠的更年期诊断测试，所有这些都可以很容易地由政策制定者向前推进。
Menopause is described as the point in time 12 months after a woman’s last menstrual cycle. Menopause typically begins between the ages of 45 and 55, with a mean age of~ 51 years, but for a small percentage of the population (around 0.1%), it can occur as early as the second decade of life (Davis an d Baber, 2022). Early menopause and the transition to menopause are accompanied by a myriad of systemic symptoms (eg, irregular periods, hot flashes, sleep problems, and more)(Santoro et al., 2015). The three main stages of menopause include perimenopause, menopause, and postmenopause (Sherman, 2005). Perimenopause generally starts 3 to 5 years prior to the onset of menopause and is a period where most women begin to exhibit symptoms of menopause but still have menstrual cycles and can become pregnant (Barth et al., 2015). Menopause is the point where menstrual cycles have concluded, resulting in ovaries ceasing egg release and significantly reducing the amount of estrogen produced (Davi s et al., 2015). Finally, postmenopause is categorized as the rest of a woman’s life after menopause has occurred. During this stage, acute symptoms may continue for several years (Peacock and Ketvertis, 2023). Notably, although historically the focal point of menopause has primarily been the resulting loss of fertility (for good reason, as it is the most obvious and immediate consequence of the cessation of ovarian function), there are also significant consequences regarding aging and aging-related diseases caused by menopause (Cui et al., 2013). Beyond the continuation of systemic symptoms mentioned above, the reduction in circulating levels of estrogen and other ovarian hormones with menopause has been linked to increased risk for numerous age-related phenotypes and diseases, including Alzheimer’s disease, osteoporosis, and cardiovascular disease (Cheng et al., 2022; Davezac et al., 2021; Paganini-Hill and Henderson, 1994). Of note, estrogen primarily exerts its protective effects on age-related diseases through the binding and activation of one of three main estrogen receptors (ERα, ERβ, and GPER1). Because the expression pattern of these receptors is very tissue and system specific, the effects of menopause-induced reduced estrogen levels on each tissue or system are expected to be unique (resulting in varying degrees of effects between disparate tissues or systems)(Chen et al., 2022; Eyster, 2016). Importantly, menopause has been proposed to accelerate the biological aging of women (Levine et al., 2016). Consistently, ageat-menopause remains one of the best predictors of overall lifespan in women, with later menopause associating to decreased all-cause mortality and increased life expectancy (Ossewaarde et al., 2005).Here, we provide an overview of the consequences of menopause (mainly through reduced estrogen levels) on cognitive function, bone mass and strength, and cardiovascular disease, with the purpose of painting a more complete picture of the consequences of menopause on health and lifespan (Figure 1). We also highlight concerning shortcomings regarding women’s health, including lack of equal representation in Food and Drug Administration (FDA) Phase 1/2 clinical dosing trials, dearth of reporting on women-specific adverse effects to drug treatments, limited consideration of menopause as a biological variable, and inadequate access to reliable diagnostic tests for menopause, all of which could be easily addressed by policy makers moving forward.