Liu J, Lin H, Huang Y, Liu Y, Wang B, Su F
Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan 250012, PR China.
Central Laboratory, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, PR China.
Neuroscience. 2015 Apr 2;290:103-14. doi: 10.1016/j.neuroscience.2015.01.042. Epub 2015 Jan 28.
Menopause can cause cognitive decline. Hormone Replacement Therapy (HRT) is the most effective treatment for the climacteric symptoms. However, its cognitive effect has not been well clarified, especially for the progestin component. The study investigated the effects of dydrogesterone (DG) on spatial learning and memory of the ovariectomized (OVX) rat models and the impact of aging on its cognitive effects. Eighty female Sprague-Dawley rats were included in the experiment. They belonged to two cohorts, the adult (7 months) and the aged (18 months). Each cohort was divided into five groups: Sham, OVX, OVX+E2 (OVX+17β-estrogen), OVX+E2/DG and OVX+DG. The replacement therapy lasted for 20 weeks. Two classical behavioral tests were performed: open field test (OFT) and the Morris water maze (MWM). The breast morphology and uterine weight were obtained to assess the safety and complication of dydrogesterone. In MWM, the OVX group displayed prolonged latency and less target quadrant time than the other groups. Across 5 days' testing, all the adult groups receiving hormone therapy, except the OVX+DG group, performed better than the OVX group (P<0.001); but there was no significant difference among the aged groups. The uterus weight/body weight ratio of OVX+E2/DG group was lower than the sham and OVX+E2 group. The mammary glands of OVX+E2/DG group displayed normal structure or mild hyperplasia. The results suggested that DG-alone treatment had no significant benefit for the OVX rats of both adult and aged groups on the behavioral tests. DG combined with E2 could ameliorate cognition in adult rats with uterus protection and without breast harm. The cognitive-improve effects were more remarkable for the adult rats than the aged ones. The findings support the potential clinical application of dydrogesterone combined with estrogen in preventing cognitive decline, especially for the early iatrogenic menopausal women.
更年期可导致认知功能下降。激素替代疗法（HRT）是治疗更年期症状最有效的方法。然而，其对认知的影响尚未完全阐明，尤其是孕激素成分。本研究调查了地屈孕酮（DG）对去卵巢（OVX）大鼠模型空间学习和记忆的影响以及衰老对其认知效应的影响。实验纳入了80只雌性Sprague-Dawley大鼠。它们分为两个队列，成年组（7个月）和老年组（18个月）。每个队列又分为五组：假手术组、OVX组、OVX+E2（OVX+17β-雌激素）组、OVX+E2/DG组和OVX+DG组。替代疗法持续20周。进行了两项经典行为测试：旷场试验（OFT）和莫里斯水迷宫（MWM）。测量乳腺形态和子宫重量以评估地屈孕酮的安全性和并发症。在MWM测试中，OVX组比其他组表现出更长的潜伏期和更少的目标象限时间。在5天的测试中，除OVX+DG组外，所有接受激素治疗的成年组表现均优于OVX组（P<0.001）；但老年组之间无显著差异。OVX+E2/DG组的子宫重量/体重比低于假手术组和OVX+E2组。OVX+E2/DG组的乳腺显示正常结构或轻度增生。结果表明，单独使用DG对成年和老年OVX大鼠的行为测试无显著益处。DG与E2联合可改善成年大鼠的认知功能，同时保护子宫且不损害乳腺。成年大鼠的认知改善效果比老年大鼠更显著。这些发现支持了地屈孕酮联合雌激素在预防认知功能下降方面的潜在临床应用，尤其是对于早期医源性绝经女性。
