Greene R A
Specialty Care for Women, Redding, California 96001, USA.
Int J Fertil Womens Med. 2000 Jul-Aug;45(4):253-7.
Women are three times as likely to develop late-onset Alzheimer's Disease (AD) as are age-matched men. In the perimenopausal period, women typically have profound hypoestrogenism associated with vasomotor episodes. The pattern of AD development in women resembles the hormonal changes that occur in the perimenopausal period; the risk of AD is lower in menopausal women taking estrogen replacement therapy (ERT), and ERT is associated with clinical improvement in AD patients. Further, ERT has been shown to augment the therapeutic benefits of medications designed to treat AD. To understand better the relationship between ERT, hot flushes and AD, a pilot study was conducted at UCLA-Harbor Medical Center.
Twelve healthy menopausal women experiencing daily hot flushes and not on ERT were recruited to participate in a clinical study. Each patient underwent regional cerebral blood flow (CBF) measurement using single-photon emission computed tomography (SPECT) at baseline and during a hot flush episode. Patients were then randomized to receive either 0.625 mg or 1.25 mg conjugated equine estrogens (CEE) daily. During the sixth week of ERT, each patient had a repeat SPECT study. Baseline SPECT data were compared with ERT data.
Baseline examinations demonstrated CBF patterns commonly seen in patients with Alzheimer's disease. There was a global improvement in CBF associated with ERT, an average gain of 22% over baseline. Improvements were most dramatic in the temporal and parietal regions of the brain. The cortical CBF demonstrated a mean increase of 9.2 mL/100 g/min (P < .01).
CBF is diminished in hypoestrogenic women, with regional patterns resembling those of patients with mild to moderate AD. Cerebral circulation tends to be further compromised during hot flush episodes. This mechanism could be the initiating event in the metabolic process that results in dementia of the Alzheimer's type, and thus serve as the link between hypoestrogenism and neurodegenerative diseases. In this study, ERT reversed these detrimental blood flow changes back to a normal pattern after only 6 weeks of CEE therapy. With improved blood flow, the brain is protected from the metabolic injury associated with hypoxia. The study is currently being repeated with a larger population.
绝经后女性患迟发性阿尔茨海默病（AD）的可能性是同龄男性的三倍。在围绝经期，女性通常会出现与血管舒缩症状相关的严重雌激素缺乏。女性AD的发病模式与围绝经期发生的激素变化相似；接受雌激素替代疗法（ERT）的绝经后女性患AD的风险较低，并且ERT与AD患者的临床改善相关。此外，ERT已被证明可增强用于治疗AD的药物的治疗效果。为了更好地理解ERT、潮热与AD之间的关系，加州大学洛杉矶分校港湾医学中心开展了一项试点研究。
招募了12名每天经历潮热且未接受ERT的健康绝经后女性参与一项临床研究。每位患者在基线期和潮热发作期间使用单光子发射计算机断层扫描（SPECT）进行局部脑血流量（CBF）测量。然后将患者随机分为每日接受0.625 mg或1.25 mg结合马雌激素（CEE）治疗。在ERT治疗的第6周，每位患者再次进行SPECT检查。将基线SPECT数据与ERT治疗后的数据进行比较。
基线检查显示出阿尔茨海默病患者常见的CBF模式。与ERT相关的CBF有整体改善，平均比基线增加22%。改善在大脑颞叶和顶叶区域最为显著。皮质CBF平均增加9.2 mL/100 g/min（P < 0.01）。
雌激素缺乏的女性CBF减少，局部模式类似于轻度至中度AD患者。在潮热发作期间，脑循环往往会进一步受损。这种机制可能是导致阿尔茨海默型痴呆的代谢过程中的起始事件，因此可作为雌激素缺乏与神经退行性疾病之间的联系。在本研究中，仅经过6周的CEE治疗后，ERT就将这些有害的血流变化逆转回正常模式。随着血流改善，大脑免受与缺氧相关的代谢损伤。目前正在对更多人群重复该研究。
