Comparative effects of tibolone and conjugated equine estrogens with and without medroxyprogesterone acetate on the reproductive tract of female cynomolgus monkeys

被引:34
作者
Cline, JM [1 ]
Register, TC [1 ]
Clarkson, TB [1 ]
机构
[1] Wake Forest Univ, Sch Med, Comparat Med Clin Res Ctr, Winston Salem, NC 27157 USA
来源
MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY | 2002年 / 9卷 / 04期
关键词
tibolone; hormone replacement therapy; Macaca fascicularis; conjugated estrogens; medroxyprogesterone acetate; endometrium;
D O I
10.1097/00042192-200207000-00005
中图分类号
R71 [妇产科学];
学科分类号
100211 ;
摘要
Objective: To measure the effects of 2 years' treatment with tibolone on the reproductive tract of female monkeys (Macaca facicularis) in comparison with conventional hormone replacement therapy. Design: Ovariectomized adult female monkeys were randomized for 2 years of treatment into five groups: controls (n = 31); tibolone at 0.05 mg/kg (LoTIB group; n = 30); tibolone at 0.2 mg/kg (HiTIB group; n = 31); conjugated equine estrogens (CEE) at 0.042 mg/kg (CEE group; n = 28); or CEE + medroxyprogesterone acetate (MPA) at 0.167 mg/kg (CEE + MPA group; n = 29). Endpoints included vaginal cytology; uterine weight; histopathologic evaluation of the uterus, vagina, and cervix; histomorphometry of the endometrium; and immunohistochemical detection of the proliferation marker Ki67 and progesterone receptor in endometrial tissue. Results: Endometrial atrophy was found in 29 of 30 and 23 of 31 animals in the LoTIB and HiTIB groups, respectively, compared with 0 of 28 and 11 of 29 in the CEE and CEE + MPA groups, respectively. All ovariectomized control animals had atrophic endometria. No complex or atypical hyperplasia was seen. Simple endometrial hyperplasia of a significant degree was seen in 3 of 31 HiTIB-treated animals, I of 30 LoTIB-treated animals, 26 of 28 CEE-treated animals, and 16 of 29 CEE + MPA-treated animals, and in none of the control animals. Marked simple endometrial hyperplasia and Ki-67 expression was induced by CEE and partially antagonized by MPA. LoTIB and HiTIB slightly increased endometrial thickness, whereas CEE and CEE + MPA induced a marked increase of 350% and 200%, respectively. Neither LoTIB nor HiTIB increased endometrial proliferation (Ki67 labeling) or induced vaginal keratinization. Endometrial bleeding was not seen in tibolone-treated animals but was present in 10 of 29 animals given CEE + MPA. Conclusions: The effect of tibolone on the uterus and lower reproductive tract was minimal. The lack of a proliferative response of the endometrium to tibolone, coupled with the lower incidence of endometrial bleeding, suggests that tibolone may have advantages over CEE and CEE + MPA regarding endometrial safety and efficacy.
引用
收藏
页码:242 / 252
页数:11
相关论文
共 46 条
[1]   DIFFERENTIAL GENE-REGULATION BY ESTROGEN AND PROGESTERONE IN THE PRIMATE ENDOMETRIUM [J].
ACE, CI ;
OKULICZ, WC .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 1995, 115 (01) :95-103
[2]  
Attia MA, 1998, DEUT TIERARZTL WOCH, V105, P399
[3]  
Beral V, 1997, LANCET, V350, P1047, DOI 10.1016/S0140-6736(97)08233-0
[4]  
BRENNER RM, 1991, ANN NY ACAD SCI, V622, P149
[5]  
Brenner Robert M., 1994, P541
[6]   MONOCLONAL-ANTIBODIES AGAINST RECOMBINANT PARTS OF THE KI-67 ANTIGEN (MIB-1 AND MIB-3) DETECT PROLIFERATING CELLS IN MICROWAVE-PROCESSED FORMALIN-FIXED PARAFFIN SECTIONS [J].
CATTORETTI, G ;
BECKER, MHG ;
KEY, G ;
DUCHROW, M ;
SCHLUTER, C ;
GALLE, J ;
GERDES, J .
JOURNAL OF PATHOLOGY, 1992, 168 (04) :357-363
[7]   ANTIGEN UNMASKING ON FORMALIN-FIXED, PARAFFIN-EMBEDDED TISSUE-SECTIONS [J].
CATTORETTI, G ;
PILERI, S ;
PARRAVICINI, C ;
BECKER, MHG ;
POGGI, S ;
BIFULCO, C ;
KEY, G ;
DAMATO, L ;
SABATTINI, E ;
FEUDALE, E ;
REYNOLDS, F ;
GERDES, J ;
RILKE, F .
JOURNAL OF PATHOLOGY, 1993, 171 (02) :83-98
[8]  
Chetrite GS, 1999, ANTICANCER RES, V19, P269
[9]  
Chetrite GS, 1999, ANTICANCER RES, V19, P261
[10]   A comparison of tibolone and conjugated equine estrogens effects on coronary artery atherosclerosis and bone density of postmenopausal monkeys [J].
Clarkson, TB ;
Anthony, MS ;
Wagner, JD .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2001, 86 (11) :5396-5404