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基于性别的研究强调了生物学过程、临床疾病和药物干预方面的性别差异。

Gender-based research underscores sex differences in biological processes, clinical disorders and pharmacological interventions.

机构信息

Vascular Surgery Research Laboratories, Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA.

Vascular Surgery Research Laboratories, Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA.

出版信息

Biochem Pharmacol. 2023 Sep;215:115737. doi: 10.1016/j.bcp.2023.115737. Epub 2023 Aug 6.

Abstract

Earlier research has presumed that the male and female biology is similar in most organs except the reproductive system, leading to major misconceptions in research interpretations and clinical implications, with serious disorders being overlooked or misdiagnosed. Careful research has now identified sex differences in the cardiovascular, renal, endocrine, gastrointestinal, immune, nervous, and musculoskeletal systems. Also, several cardiovascular, immunological, and neurological disorders have shown differences in prevalence and severity between males and females. Genetic variations in the sex chromosomes have been implicated in several disorders at young age and before puberty. The levels of the gonadal hormones estrogen, progesterone and testosterone and their receptors play a role in the sex differences between adult males and premenopausal women. Hormonal deficiencies and cell senescence have been implicated in differences between postmenopausal and premenopausal women. Specifically, cardiovascular disorders are more common in adult men vs premenopausal women, but the trend is reversed with age with the incidence being greater in postmenopausal women than age-matched men. Gender-specific disorders in females such as polycystic ovary syndrome, hypertension-in-pregnancy and gestational diabetes have attained further research recognition. Other gender-related research areas include menopausal hormone therapy, the "Estrogen Paradox" in pulmonary arterial hypertension being more predominant but less severe in young females, and how testosterone may cause deleterious effects in the kidney while having vasodilator effects in the coronary circulation. This has prompted the National Institutes of Health (NIH) initiative to consider sex as a biological variable in research. The NIH and other funding agencies have provided resources to establish state-of-the-art centers for women health and sex differences in biology and disease in several academic institutions. Scientific societies and journals have taken similar steps to organize specialized conferences and publish special issues on gender-based research. These combined efforts should promote research to enhance our understanding of the sex differences in biological systems beyond just the reproductive system, and provide better guidance and pharmacological tools for the management of various clinical disorders in a gender-specific manner.

摘要

早期的研究假设,除了生殖系统外,男性和女性的生物学在大多数器官中都是相似的,这导致了研究解释和临床意义上的重大误解,严重的疾病被忽视或误诊。现在仔细的研究已经确定了心血管、肾脏、内分泌、胃肠道、免疫、神经和肌肉骨骼系统中的性别差异。此外,一些心血管、免疫和神经疾病在男性和女性中的患病率和严重程度上存在差异。性染色体上的遗传变异与年轻时和青春期前的几种疾病有关。性腺激素雌激素、孕激素和睾酮及其受体的水平在成年男性和绝经前女性之间的性别差异中起作用。激素缺乏和细胞衰老与绝经后和绝经前女性之间的差异有关。具体来说,心血管疾病在成年男性中比绝经前女性更常见,但随着年龄的增长,这种趋势发生逆转,绝经后女性的发病率高于同龄男性。女性特有的疾病,如多囊卵巢综合征、妊娠高血压和妊娠期糖尿病,也引起了进一步的研究关注。其他与性别相关的研究领域包括绝经激素治疗、肺动脉高压中的“雌激素悖论”在年轻女性中更为明显但程度较轻,以及睾酮如何在肾脏中产生有害影响,而在冠状动脉循环中具有血管扩张作用。这促使美国国立卫生研究院(NIH)提出将性别视为研究中的生物学变量。NIH 和其他资助机构已经提供资源,在几个学术机构建立了妇女健康和生物学及疾病性别差异的最先进中心。科学学会和期刊也采取了类似的步骤,组织专门的会议并出版关于基于性别的研究的特刊。这些共同努力应该促进研究,以增强我们对生殖系统以外的生物学系统中的性别差异的理解,并为以性别特异性方式管理各种临床疾病提供更好的指导和药理学工具。

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