Lack of aromatisation of the 3-keto-4-ene metabolite of tibolone to an estrogenic derivative

  title={Lack of aromatisation of the 3-keto-4-ene metabolite of tibolone to an estrogenic derivative},
  author={B. Raobaikady and M. F. Parsons and M. Reed and A. Purohit},
Tibolone is used for the treatment of climacteric symptoms in postmenopausal women. It is metabolised in a tissue-specific manner so that while some metabolites exert estrogenic effects on bone and the CNS, others are thought to protect the breast and endometrium from estrogenic stimulation. Tibolone is a 7alpha-methyl derivative of 19-norethynodrel. Since the introduction of synthetic progestagens for therapeutic use there has been considerable controversy as to whether they can undergo… Expand
Can 19-nortestosterone derivatives be aromatized in the liver of adult humans? Are there clinical implications?
  • H. Kuhl, I. Wiegratz
  • Medicine
  • Climacteric : the journal of the International Menopause Society
  • 2007
19-nortestosterone derivatives (norethisterone, norethynodrel, tibolone) can readily be aromatized in the adult human liver, which leads to the formation of the potent estrogens ethinylestradiol from norehisterone or nore fourthodrel and 7α-methyl-ethinylest radiol from tibiaolone. Expand
Dimethandrolone (7α,11β-dimethyl-19-nortestosterone) and 11β-methyl-19-nortestosterone are not converted to aromatic A-ring products in the presence of recombinant human aromatase
Data support the notion that in the absence of the C19-methyl group, aromatization of androgenic substrates proceeds slowly or not at all and that this reaction is impeded by the presence of a methyl group at the 11beta position. Expand
7&agr;-Methyl-ethinyl estradiol is not a metabolite of tibolone but a chemical stress artifact
7&agr;-MEE is not a metabolite of tibolone but is a chemical artifact generated during analytical procedures with derivatization, and cannot be demonstrated in plasma from postmenopausal women after single or multiple doses of tIBolone. Expand
Detection of the misuse of steroids in doping control
  • M. Parr, W. Schänzer
  • Chemistry, Medicine
  • The Journal of Steroid Biochemistry and Molecular Biology
  • 2010
The list of prohibited substances of the World Anti-Doping Agency (WADA) classifies the administration of several steroids in sports as doping. Their analysis is generally performed using urineExpand
TLC of Steroids and Analogs


Tibolone is not converted by human aromatase to 7α-methyl-17α-ethynylestradiol (7α-MEE): Analyses with sensitive bioassays for estrogens and androgens and with LC-MSMS
To exclude that aromatization plays a role in the estrogenic activity of tibolone, we studied the effect tibolone and metabolites on the aromatization of androstenedione and the aromatization ofExpand
Estrogenic effects of 7α-methyl-17α-ethynylestradiol: a newly discovered tibolone metabolite
Abstract Tibolone is a synthetic steroid that is prescribed to postmenopausal women for relief of climacteric symptoms and prevention of osteoporosis. It has been reported to be metabolized in aExpand
Human endometrial 3β-hydroxysteroid dehydrogenase/isomerase can locally reduce intrinsic estrogenic/progestagenic activity ratios of a steroidal drug (Org OD 14)
Local conversion of Org OD 14 to the 4-ene isomer, a metabolite with higher progestagenic and lower estrogenic potencies than those of its precursor, selectively prevents undesirable proliferative stimulation of the endometrium in postmenopausal users while preserving its beneficial effects on other tissues, including bone. Expand
Tibolone: a steroid with a tissue-specific mode of action
  • H. Kloosterboer
  • Medicine, Biology
  • The Journal of Steroid Biochemistry and Molecular Biology
  • 2001
It is concluded that tibolone acts as a tissue-specific compound by mediating its effects via steroid receptors and enzymatic pathways, and avoids stimulation of the endometrium and breast tissue. Expand
Effect of tibolone (Org OD14) and its metabolites on estrone sulphatase activity in MCF-7 and T-47D mammary cancer cells.
A very significant inhibitory effect of Tibolone and of its metabolites Org 4094 and Org 30,126 on the enzymes involved in the biosynthesis of E2 in human breast cancer cells, points to a potential beneficial effect ofibolone which may be of relevance in its application for the treatment of climacteric complaints. Expand
Aromatization of norethindrone to ethinyl estradiol by human placental microsomes.
The results suggest that NET is enzymatically aromatized to EE by human placental microsomes, and that spontaneous aromatization of metabolites of NET did not contribute to results. Expand
In vitro evaluation of estrogenic, estrogen antagonistic and progestagenic effects of a steroidal drug (Org OD-14) and its metabolites on human endometrium.
The estrogenic and progestagenic actions of these compounds are in general agreement with their relative affinity for binding to the estradiol and progesterone receptors, although their actions may be influenced by intracellular metabolism in the endometrial tissue. Expand
Receptor profiling and endocrine interactions of tibolone
It is concluded that the progestagenic and androgenic activities of tibolone are mediated by the Delta(4)-isomer, and the estrogenic activity, by the 3-hydroxytibolones. Expand
Aromatization of the A-ring of norethynodrel, a steroidal oral contraceptive, during trimethylsilylation.
Treatment of the steroidal oral contraceptive norethynodrel under persilylation conditions with trimethylsilylimidazole yielded two products that were characterized by gas chromatography-mass spectrometry comparisons with the diTMS-derivatives of the corresponding estradiols. Expand
Studies on the mechanism of estrogen biosynthesis. IV. Ovarian metabolism of estr-4-ene-3,17-dione.
The demonstration of 1β-hydroxylase activity in human ovary provides an explanation of the formation of urinary estrogen artifacts from labile 1 β-hydroxy-19-nor steroids during studies of ig-nor steroid metabolism in non-pregnant women. Expand