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如何在激素替代疗法中使用孕激素:一项动物实验。

How to use progestin in hormone replacement therapy: an animal experiment.

作者信息

Sun A, Wang J, Zhu P

机构信息

Division of Reproductive Endocrinology Infertility, Department of Obstetrics & Gynecology, Peking Union Medical College Hospital, Beijing 100730, China.

出版信息

Chin Med J (Engl). 2001 Feb;114(2):173-7.

PMID:11780201
Abstract

OBJECTIVE

To determine whether continuous or cyclic hormone replacement therapy (estrogen and progestogen) is better.

METHODS

One hundred and forty Sprague-Dawley rats were randomly divided into seven groups. The 1st and 2nd groups were normal estrous and ovariectomy (OVX) controls. Treatment of the other groups imitated the clinical regimen (continuous and cyclic) with estradiol valerate (E2V) and medroxy progesterone (MPA) in different ratios of combination. The rats were sacrificed and sections of uterus were stained with HE and histochemical methods to detect mitosis and proliferating cell nuclear antigen (PCNA), respectively. The mitotic index (MI) and PCNA index were calculated.

RESULTS

The MI and PCNA index were similar in luminal and glandular cells. Both markers were low in the two control groups. When E2V was given for 1 to 6 days, both the MI and PCNA index increased with duration of treatment. When MPA was added, both markers were reduced to a very low level. In the continuous regimen, both markers decreased as the MPA dosage increased. The ratio of E2V: MPA = 1:0.5 was enough to suppress markers to a low level similar to that of normal estrous rats. A further increase in the ratio to 1:1.0 showed no further decrease in PCNA index. In the cyclic regimen, MPA was added for the last 5 days. The mitotic index reached a significantly low level near 0 in all ratios, but the PCNA index in each subgroup was still as high as the positive control, even though the dosage of MPA was increased several times to 1:8.0. When MPA was added for the last 10 days, the PCNA index at a ratio of 1:4.0 could be reduced to a low level.

CONCLUSION

The results of this study suggest that the continuous regimen was better than the cyclic regimen in postmenopausal hormone replacement therapy (HRT). Progestin should be given for at least 10 days in the cyclic regimen.

摘要

目的

确定持续或周期性激素替代疗法(雌激素和孕激素)哪种更好。

方法

将140只Sprague-Dawley大鼠随机分为七组。第1组和第2组分别为正常发情和卵巢切除(OVX)对照。其他组的治疗模仿临床方案(持续和周期性),采用不同比例组合的戊酸雌二醇(E2V)和甲羟孕酮(MPA)。处死大鼠,子宫切片分别用HE染色和组织化学方法检测有丝分裂和增殖细胞核抗原(PCNA)。计算有丝分裂指数(MI)和PCNA指数。

结果

管腔和腺细胞中的MI和PCNA指数相似。两个对照组的这两个指标均较低。给予E2V 1至6天时,MI和PCNA指数均随治疗时间延长而增加。加入MPA后,两个指标均降至极低水平。在持续方案中,随着MPA剂量增加,两个指标均下降。E2V:MPA = 1:0.5的比例足以将指标抑制至与正常发情大鼠相似的低水平。比例进一步增加至1:1.0时,PCNA指数未进一步下降。在周期性方案中,在最后5天加入MPA。所有比例下有丝分裂指数均显著降至接近0的低水平,但每个亚组的PCNA指数仍与阳性对照一样高,即使MPA剂量增加数倍至1:8.0。当在最后10天加入MPA时,1:4.0比例下的PCNA指数可降至低水平。

结论

本研究结果表明,在绝经后激素替代疗法(HRT)中,持续方案优于周期性方案。在周期性方案中,孕激素应至少给予10天。

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