Conversion of tibolone to 7&agr;-methyl-ethinyl estradiol using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry: interpretation and clinical implications

  title={Conversion of tibolone to 7\&agr;-methyl-ethinyl estradiol using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry: interpretation and clinical implications},
  author={L. Zacharia and E. Jackson and H. Kloosterboer and B. Imthurn and R. Dubey},
Objective: Tibolone, a hormone therapy drug, is used to treat climacteric symptoms. This drug is rapidly metabolized into three major metabolites (3&agr;-hydroxytibolone, 3&bgr;-hydroxytibolone, and &Dgr;4-tibolone). One clinical study provided evidence of conversion of tibolone to another estrogenic metabolite, 7&agr;-methyl-ethinyl estradiol (MEE). However, no evidence of MEE formation was found in another study using the human aromatase enzyme. Because MEE was analyzed by gas chromatography… 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
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
Application of UPLC–MS/MS for separation and quantification of 3α-Hydroxy Tibolone and comparative bioavailability of two Tibolone formulations in healthy volunteers
It is concluded that test formulation of Tibolone is bioequivalent to reference formulation of TsI, and this method was successfully applied to a pharmacokinetic study in 50 post-menopausal/surgical menopause female human volunteers under fasting conditions. Expand
The other side of progestins: effects in the brain.
The role exerted by different progestins, currently used for contraception or in postmenopausal hormone replacement therapies, in regulating cognitive functions as well as social behavior and mood is reported. Expand
[Effect of tibolone on endometrium of castrated rats].
High doses of tibolone, given for long periods of time to castrated female rats, have an estrogenic effect which can be dose-dependent, causing proliferation in the endometrium and causing changes in the cell differentiation (squamous metaplasia), but do not lead to hyperplasia. Expand


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
Formation of 7&agr;-methyl-ethinyl estradiol during treatment with tibolone
Investigation of whether tibolone, which is orally used for hormone replacement therapy, is transformed to a derivative of ethinyl estradiol (EE), demonstrates that, during daily treatment of women with 2.5 mg tiblone, a small proportion of tIBolone is transformation to 7&agr;-methyl-EE. Expand
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
Aromatization of 7α-Methyl-19-nortestosterone by human placental microsomes in vitro
Abstract Part of the biological effects of testosterone (T) are mediated by its enzymatic reduction to 5α-dihydrotestosterone (DHT) or aromatization to estradiol (E 2 ). 7α-Methyl-19-nortestosteroneExpand
Studies of the inactivation of human placentae aromatase by 17α-ethynyl-substituted 10β-hydroperoxy and related 19-nor steroids
The inactivation of human placental aromatase by 17 alpha-ethynyl-10 beta-hydroperoxy-17 beta-hydroxy-4-estren-3-one (SCH 10015) was investigated. In either the presence or absence of added NADPH,Expand
Isolation and characterisation of a C18 neutral steroid, oestra-5(10),7-diene-3,17-diol, from pregnant mare urine and allantoic fluid. Facile oxidation to yield oestra-5(10),6,8-triene-3,17-diol (diol of Heard's ketone)
It is proposed that this, and by implication, Heard's ketone itself, are artefacts of the isolation procedures which were utilised in the original studies, implying that the two steroids are related and, furthermore, that all the sites of unsaturation are in the B ring. 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
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
Tibolone for postmenopausal women: systematic review of randomized trials.
The results from the randomized, controlled, and double blind trials of tibolone are discussed, with respect to its effects on climacteric symptoms, sexual function, endometrial and breast tissue, lipid metabolism, and bone mineral density. Expand