Org OD 14 and the endometrium

Genazzani, Ar; Benedek-Jaszmann, L.J.; Hart, D. M.; Andolsek, L; Kicovic, P M; Tax, L.

doi:10.1016/0378-5122(91)90199-z

Cited by 109 publications

(37 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Histological studies following treatment with tibolone for 3 months or longer revealed that the endometrium becomes atrophic, suggesting a progestagenic inhibition or lack of estrogenic stimulation of endometrial cell proliferation 3,4 . In the laboratory, the progestagenic effects of tibolone on the endometrium have been demonstrated by measuring various progesterone-regulated factors.…”

Section: Discussionmentioning

confidence: 99%

Effects of Tibolone Metabolites on Human Endometrial Cell Lines in Co-culture

Barbier

Kloosterboer²,

Kaufman

2008

Reprod. Sci.

View full text Add to dashboard Cite

In human endometrium, cell proliferation is regulated by ovarian steroids through heterotypic interactions between stromal and epithelial cells populating this tissue. We tested the proliferative effects of tibolone and its metabolites using endometrial co-cultures that mimic the normal proliferative response to hormones. We found that both the Δ 4 -tibolone metabolite and the pure progestin ORG2058 counteract estradiol-driven epithelial cell proliferation. Surprisingly, the estrogen receptor binding 3-hydroxyl-metabolites of tibolone also counteracted estradiol-driven proliferation. Inhibition of proliferation by 3β-OH-tibolone was abrogated by low doses of the progesterone receptor antagonist mifepristone, This suggests that 3β-OH-tibolone is converted to a progestagenic metabolite. We found that the stromal cells used in the co-cultures express high levels of the ketosteroid dehydrogenase, AKR1C2, which is able to oxidize 3β-OH-tibolone back to tibolone. Thus the unexpected progestagenic effect of 3β-OH-tibolone in these co-cultures may be due to metabolic activity present in the stromal cells of the co-cultures.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of Tibolone Metabolites on Human Endometrial Cell Lines in Co-culture

Barbier

Kloosterboer²,

Kaufman

2008

Reprod. Sci.

View full text Add to dashboard Cite

show abstract

“…13,14,19 Tibolone (Org OD14), a synthetic steroid [(7␣,17␣)-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one] with a combination of estrogenic, androgenic, and progestogenic properties, is clinically effective for the treatment of climacteric symptoms 39,40 and the treatment and prevention of osteoporosis in postmenopausal women, 41 with no stimulatory effect on the endometrium. 42,43 The effect on the development of atherosclerosis is not known. It has been suggested that tibolone might have less atheroprotective effect than ERT because of its progestogenic/androgenic properties.…”

mentioning

confidence: 99%

Tibolone Prevents Atherosclerotic Lesion Formation in Cholesterol-Fed, Ovariectomized Rabbits

Zandberg¹,

Peters²,

Demacker³

et al. 1998

ATVB

View full text Add to dashboard Cite

Abstract-Tibolone (Org OD14), a synthetic steroid with estrogenic and progestogenic/androgenic properties, is clinically effective for the treatment of climacteric symptoms and the prevention and treatment of osteoporosis in postmenopausal women. The effect on atherogenesis, however, is not known. In the current study, we investigated the effect of tibolone in comparison with that of estradiol and norethisterone acetate on atherogenesis in 140 ovariectomized New Zealand White rabbits that had been induced by an atherogenic diet (0.4% cholesterol, 20 weeks). Tibolone at 18, 6, or 2 mg/d orally completely prevented cholesterol accumulation and fatty streak formation in the aorta; the impairment of endothelium-dependent smooth muscle relaxation of the aorta; and complex lesion formation after endothelial denudation in the carotid artery. Tibolone also reduced the increased postovariectomy plasma lipid concentrations. Analysis of the results, however, indicated that a substantial part of the strong, beneficial effects were plasma lipid independent. Compared with subcutaneous estradiol decanoate (150 g once weekly) and oral 17␤-estradiol (4 mg/d), the effects of tibolone were more pronounced at equipotent uterotropic activity. Norethisterone acetate (1 mg/d) did not affect atherosclerotic lesion formation. There are no indications that the progestogenic/androgenic properties of tibolone counteracted its atheroprotective effect on the vessel wall. Therefore, tibolone has the intrinsic potential to be a compound that protects the arterial vessel wall against atherosclerotic processes.

show abstract

“…The ␦-4 isomer, produced primarily within the endometrium, protects the endometrium from the agonist effects of the 2 estrogenic metabolites. 13,14 Tibolone treatment of postmenopausal women has some beneficial effects on plasma lipid/lipoprotein concentrations (reductions in plasma triglyceride 15,16 and lipoprotein[a] concentrations) 17 ; however, concern has arisen about its "cardiovascular safety" because of reductions in HDLC. 15,18 We have reported the long-term effects of tibolone on coronary artery atherosclerosis of surgically postmenopausal cynomolgus monkeys relative to the effects of conjugated equine estrogen (CEE) treatment and treatment with CEE plus medroxyprogesterone (MPA) administered continuously.…”

mentioning

confidence: 99%

Comparison of Tibolone and Conjugated Equine Estrogens Effects on Carotid Artery Atherosclerosis of Postmenopausal Monkeys

Clarkson

Anthony

Mikkola

et al. 2002

Stroke

View full text Add to dashboard Cite

Background and Purpose-Tibolone is a tissue-specific compound that has favorable effects on bone and menopausal symptoms without stimulating endometrium or breast, but lowers concentrations of plasma high-density lipoprotein (HDL) cholesterol (HDLC). This study was designed to determine whether the HDL lowering with tibolone exacerbated common or internal carotid artery atherosclerosis and to evaluate tibolone treatment relative to conjugated equine estrogens (CEE) alone or in combination with medroxyprogesterone acetate (MPA). Methods-Carotid artery atherosclerosis was compared in groups of surgically postmenopausal cynomolgus monkeys treated with CEE, CEEϩMPA, or either of 2 doses of tibolone versus untreated monkeys. Results-Despite a 30% to 52% lowering of HDLC with tibolone, there was no significant effect on carotid artery atherosclerosis. CEE and CEEϩMPA, however, inhibited carotid artery atherosclerosis by Ϸ60%. Key Words: carotid atherosclerosis Ⅲ conjugated equine estrogens Ⅲ hormone replacement therapy Ⅲ tibolone Ⅲ monkeys I schemic stroke among middle-aged and older women is an important public health concern. 1 The exact pathogenesis of these events remains uncertain; however, positive associations with increasing atherosclerosis extent and inverse associations with concentrations of plasma high-density lipoprotein (HDL) cholesterol (HDLC) seem clear. [2][3][4] Although the effect of traditional hormone replacement therapy on stroke prevalence is controversial, [5][6][7][8] it is important to know whether newer menopausal therapies have either adverse or beneficial effects on atherosclerosis of common and internal carotid arteries. Conclusions-InTibolone, used widely in several countries for the treatment of menopausal symptoms 9,10 and for the prevention of postmenopausal osteoporosis, 11,12 is being considered for use in the United States. Tibolone is metabolized into 3 biologically active metabolites; the 3-␤ hydroxy metabolite and the 3-␣ hydroxy metabolite have estrogen agonist properties, whereas the ␦-4 ketoisomer has progestogenic and androgenic effects. The ␦-4 isomer, produced primarily within the endometrium, protects the endometrium from the agonist effects of the 2 estrogenic metabolites. 13,14 Tibolone treatment of postmenopausal women has some beneficial effects on plasma lipid/lipoprotein concentrations (reductions in plasma triglyceride 15,16 and lipoprotein[a] concentrations) 17 ; however, concern has arisen about its "cardiovascular safety" because of reductions in HDLC. 15,18 We have reported the long-term effects of tibolone on coronary artery atherosclerosis of surgically postmenopausal cynomolgus monkeys relative to the effects of conjugated equine estrogen (CEE) treatment and treatment with CEE plus medroxyprogesterone (MPA) administered continuously. 19 Reported herein are the common carotid and internal carotid artery atherosclerosis results from that long-term study. Specifically, we investigated whether the large decreases in HDLC associated with tibolone treatment would ...

show abstract

Org OD 14 and the endometrium

Cited by 109 publications

References 13 publications

Effects of Tibolone Metabolites on Human Endometrial Cell Lines in Co-culture

Effects of Tibolone Metabolites on Human Endometrial Cell Lines in Co-culture

Tibolone Prevents Atherosclerotic Lesion Formation in Cholesterol-Fed, Ovariectomized Rabbits

Comparison of Tibolone and Conjugated Equine Estrogens Effects on Carotid Artery Atherosclerosis of Postmenopausal Monkeys

Contact Info

Product

Resources

About