雌二醇或枸橼酸氯米芬长期治疗对去卵巢大鼠骨维持及垂体和子宫重量的影响。

Chakraborty P K, Brown J L, Ruff C B, Nelson M F, Mitchell A S

Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799.

J Steroid Biochem Mol Biol. 1991;40(4-6):725-9. doi: 10.1016/0960-0760(91)90297-i.

Long-term estrogen replacement therapy in postmenopausal women can bring relief to hot flushes and reduce loss of bone mass due to osteoporosis, however, such treatment often can cause uterine hyperplasia and other undesirable effects. This study compared changes in bone mineral content (BMC), uterine weight, pituitary weight and pituitary gonadotropin content in the ovariectomized rat model following treatment with estradiol (E2) or two levels of clomiphene citrate (CC), an estrogen agonist/antagonist. Groups (n = 8-12) of adult ovariectomized (OVX) rat were implanted with E2 pellets (5 micrograms/day) or injected subcutaneously with CC at 1 mg/kg body wt (CC-1) or 5 mg/kg body wt (CC-5) twice weekly for 12 months. Placebo implanted OVX and intact (INT) female rats served as negative and positive controls, respectively. Following treatment, the uterus, pituitary gland and right femur were collected from each animal. E2 treatment increased (P less than 0.05) uterine weight compared to all other treatment groups, while both CC doses increased uterine weight over the OVX group only (E2, 0.24 +/- 0.03; INT, 0.14 +/- 0.01; CC-1, 0.06 +/- 0.01; CC-5, 0.07 +/- 0.01; and OVX, 0.02 +/- 0.01 g per 100 g body wt). Pituitary weight was increased 15-fold (P less than 0.05) by E2 treatment over all other treatment groups (E2, 65.7 +/- 13.9; INT, 4.0 +/- 0.5; CC-1, 3.3 +/- 0.03; CC-5, 2.7 +/- 0.02; and OVX, 2.9 +/- 0.02 mg per 100 g body wt). Both E2 and CC treatments reduced pituitary luteinizing hormone and follicle stimulating hormone content (micrograms/pit) to INT levels and were lower (P less than 0.05) than OVX levels. Mean BMC of E2, CC-1- or CC-5-treated rats was greater (P less than 0.05) than that of either the INT or OVX groups, while INT animals had a higher BMC compared to OVX animals (E2, 0.027 +/- 0.003; CC-1, 0.026 +/- 0.001; CC-5, 0.028 +/- 0.001; INT, 0.021 +/- 0.001; and OVX, 0.017 +/- 0.001 g/cm per 100 g body wt). These data indicate that CC has the potential to reduce bone mineral loss without causing other undesirable effects, including uterine hyperstimulation, and thus needs to be further investigated.

绝经后女性长期进行雌激素替代疗法可缓解潮热症状，并减少因骨质疏松导致的骨质流失，然而，这种治疗方法往往会引起子宫增生及其他不良影响。本研究比较了在切除卵巢的大鼠模型中，经雌二醇（E2）或两种剂量的柠檬酸氯米芬（CC，一种雌激素激动剂/拮抗剂）治疗后，骨矿物质含量（BMC）、子宫重量、垂体重量及垂体促性腺激素含量的变化。将成年去卵巢（OVX）大鼠分组（每组n = 8 - 12只），分别植入E2药丸（5微克/天），或每周两次皮下注射1毫克/千克体重（CC - 1）或5毫克/千克体重（CC - 5）的CC，持续12个月。植入安慰剂的OVX大鼠和未切除卵巢的（INT）雌性大鼠分别作为阴性和阳性对照。治疗后，从每只动物身上采集子宫、垂体及右股骨。与所有其他治疗组相比，E2治疗使子宫重量增加（P < 0.05），而两种CC剂量仅使子宫重量相较于OVX组增加（E2，0.24 ± 0.03；INT，0.14 ± 0.01；CC - 1，0.06 ± 0.01；CC - 5，0.07 ± 0.01；OVX，0.02 ± 0.01克/100克体重）。与所有其他治疗组相比，E2治疗使垂体重量增加了15倍（P < 0.05）（E2，65.7 ± 13.9；INT，4.0 ± 0.5；CC - 1，3.3 ± 0.03；CC - 5，2.7 ± 0.02；OVX，2.9 ± 0.02毫克/100克体重）。E2和CC治疗均将垂体促黄体生成素和促卵泡激素含量（微克/垂体）降至INT水平，且低于OVX水平（P < 0.05）。E2、CC - 1或CC - 5治疗的大鼠的平均BMC高于INT组或OVX组（P < 0.05），而INT组动物的BMC高于OVX组动物（E2，0.027 ± 0.003；CC - 1，0.026 ± 0.001；CC - 5，0.028 ± 0.001；INT，0.021 ± 0.001；OVX，0.017 ± 0.001克/厘米/100克体重）。这些数据表明，CC有可能减少骨矿物质流失，且不会引起包括子宫过度刺激在内的其他不良影响，因此需要进一步研究。