7α-methyl-ethinyl estradiol is not a metabolite of tibolone but a chemical stress artifact

Menopause

Volumn 14, Issue 3, 2007, Pages 474-480

  Dröge, Melloney J ^a   Oostebring, Freddy ^a   Oosting, Ep ^a   Verheul, Herman A M ^b   Kloosterboer, Helenius J ^b  

^a ABL   (Netherlands)

^b NV ORGANON   (Netherlands)

Author keywords

7 Methyl ethinyl estradiol; Aromatization; Gas chromatography; Liquid chromatography; Metabolism; Tibolone

Indexed keywords

7ALPHA METHYL ETHINYLESTRADIOL; 7ALPHA-METHYL ETHINYLESTRADIOL; DRUG DERIVATIVE; ESTRADIOL; PREGNANE DERIVATIVE; SELECTIVE ESTROGEN RECEPTOR MODULATOR; TIBOLONE; UNCLASSIFIED DRUG;

ARTICLE; CHEMISTRY; FEMALE; HUMAN; LIQUID CHROMATOGRAPHY; MASS FRAGMENTOGRAPHY; METABOLISM; MIDDLE AGED; POSTMENOPAUSE; SENSITIVITY AND SPECIFICITY;

CHROMATOGRAPHY, LIQUID; ESTRADIOL; ESTROGEN RECEPTOR MODULATORS; FEMALE; GAS CHROMATOGRAPHY-MASS SPECTROMETRY; HUMANS; MIDDLE AGED; NORPREGNENES; POSTMENOPAUSE; SENSITIVITY AND SPECIFICITY;

EID: 34447269931     PISSN: 10723714     EISSN: 15300374     Source Type: Journal    
DOI: 10.1097/01.gme.0000247015.63877.d4     Document Type: Article

References (34)

1. Albertazzi P, di Micco R, Zanardi E. Tibolone: a review. Maturitas 1998;30:295-305.
2. Moore RA. Livial: a review of clinical studies. Br J Obstet Gynaecol 1999;106(Suppl 19):1-21.
3. Colacurci N, Mele D, De Franciscis P, Costa V, Fortunato N, De Seta L. Effects of tibolone on the breast. Eur J Obstet Gynecol Reprod Biol 1998;80:235-238.
4. Valdivia I, Campodonico I, Tapia A, Capetillo M, Espinoza A, Lavin P. Effects of tibolone and continuous combined hormone therapy on mammographic breast density and breast histochemical markers in postmenopausal women. Fertil Steril 2004;81:617-623.
5. Volker W, Coelingh Bennink HJ, Helmond FA. Effects of tibolone on the endometrium. Climacteric 2001;4:203-208.
6. Gompel A, Chaouat M, Jacob D, Perrot JY, Kloosterboer HJ, Rostene W. In vitro studies of tibolone in breast cells. Fertil Steril 2002;78:351-359.
7. Blok LJ, De Ruiter PE, Kuhne EC. Progestogenic effects of tibolone on human endometrial cancer cells. J Clin Endocrinol Metab 2003;88:2327-2334.
8. Kloosterboer HJ, Ederveen AGH. Pros and cons of existing treatment modalities in osteoporosis: a comparison between tibolone, SERMS and estrogen/progestogen treatments. J Steroid Biochem Mol Biol 2003;83:157-165.
9. Smith CL, O'Malley BW. Coregulator function: a key to understanding tissue specificity of selective receptor modulators. Endocrine Rev 2004;25:45-71.
10. Timmer CJ, Houwing NS. Dose proportionality of three different doses of tibolone. Pharmacotherapy 2002;22:6-13.
11. Timmer CJ, Doorstman DP. Effect of renal impairment on the pharmacokinetics of a single oral dose of tibolone 2.5 mg in early postmenopausal women. Pharmacotherapy 2002;22:148-153.
12. Timmer CJ, Verheul HAM, Doorstam DP. Pharmacokinetics of tibolone in early and late postmenopausal women. J Clin Pharmacol 2002;54:101-106.
13. Vos RME, Krebbers SFM, Verhoeven CHJ, Delbressine LPC. The in vivo human metabolism of tibolone. Drug Metab Dispos 2002;30:106-112.
14. de Gooyer ME, Deckers GH, Schoonen WGEJ, Verheul HAM, Kloosterboer HJ. Receptor profiling and endocrine interactions of tibolone. Steroids 2003;68:21-30.
15. Kloosterboer HJ. Tibolone: a steroid with a tissue-specific mode of action. J Steroid Biochem Mol Biol 2001;76:231-238.
16. Chetrite GS, Kloosterboer HJ, Philippe JC, Pasqualini JR. Effects of Org OD14 (Livial) and its metabolites on 17β-hydroxysteroid dehydrogenase activity in hormone dependent MCF-7 and T-47D breast cancer cells. Anticancer Res 1999;19:261-267.
17. Pasqualini JR, Chetrite GS. Estrone sulfatase versus estrone sulfotransferase in human breast cancer: potential clinical applications. J Steroid Biochem Mol Biol 1999;59:287-292.
18. de Gooyer ME, Kleyn GT, Smits KC, Ederveen AG, Verheul HA, Kloosterboer HJ. Tibolone: a compound with tissue specific inhibitory effects on sulfatase. Mol Cell Endocrinol 2001;183:55-62.
19. Purohit A, Malini B, Hooymans C, Newman SP. Inhibition of oestrone sulphatase activity by tibolone and its metabolites. Horm Metab Res 2001;34:1-6.
20. van de Ven J, Donker GH, Sprong M, Blankenstein MA, Thijssen JH. Effect of tibolone (Org OD14) and its metabolites on aromatase and estrone sulfatase activity in human breast adipose stromal cells and in MCF-7 and T47D breast cancer cells. J Steroid Biochem Mol Biol 2002;81:237-247.
21. Wiegratz I, Sanger N, Kuhl H. Formation of 7α-methyl-ethinyl estradiol during treatment with tibolone. Menopause 2002;9:293-295.
22. Bodine PVN, Harris HA, Lyttle CR, Komm BS. Estrogenic effects of 7α-methyl-17α-ethynylestradiol: a newly discovered tibolone metabolite. Steroids 2002;67:681-686.
23. Kuhl H, Wiegratz I. Letters to the editor; reply to letter by Egarter. Menopause 2003;10:103-105.
24. Egarter C. Letters to the editor to the paper by Wiegratz et al., in Menopause 2002;9:293-295. Menopause 2003;10:102-103.
25. Pluchino N, Genazzani AD, Bernardi F, et al. Tibolone, transdermal estradiol or oral estrogen-progestin therapies: effects on circulating allopregnanolone, cortisol and dehydroepiandrosterone levels. Gynecol Endocrinol 2005;20:144-149.
26. Simpson ER, Clyne C, Rubin G, et al. Aromatase - a brief overview. Ann Rev Physiol 2002;64:93-127.
27. de Gooyer ME, Oppers-Tiemissen HM, Leysen D, Verheul HAM, Kloosterboer HJ. Tibolone is not converted by human aromatase to 7α-methyl-17α- ethynylestradiol (7α-MEE). Steroids 2003;68:235-243.
28. Jones MEE, Reutens AT, Boon WC, Ederveen AG, Kloosterboer HJ, Simpson ER. The aromatase knockout (ArKO) mouse as a model to study the oestrogenic action of tibolone. Presented at: 46th Annual Scientific Meeting of the Endocrine Society of Australia; September 14-17, 2003; Melbourne, Australia. Abstract 157.
29. Raobaikady B, Parsons MFC, Reed MJ, Purohit A. Lack of aromatization of the 4-keto-4-ene metabolite of tibolone to an estrogenic derivative. Steroids 2006;71:639-646.
30. 4, 7α-methyl norethisterone metabolite are reversible inhibitors of human aromatase. J Steroid Biochem Mol Biol. In press.
31. Thompson RM, Horning EC. Aromatization of the A-ring of norethynodrel, a steroidal contraceptive, during trimethylsilylation. Steroids Lipid Res 1973;4:135-142.
32. Zacharia LC, Jackson EK, Kloosterboer HJ, Imthurn B, Dubey RK. Conversion of tibolone to 7α-methyl-ethinyl-estradiol using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry: interpretation and clinical implications. Menopause 2006;13:926-934.
33. Klehr-Bathmann I, Kuhl H. Formation of ethinylestradiol in postmenopausal women during continuous treatment with a combination of estradiol, estriol and norethisterone acetate. Maturitas 1995;21:245-250.
34. Kuhnz W, Heuner A, Huempel M, Seifert W, Michaelis K. In vivo conversion of norethisterone and norethisterone acetate to ethinylestradiol in postmenopausal women. Contraception 1997;56:379-385.