Can 19-nortestosterone derivatives be aromatized in the liver of adult humans? Are there clinical implications?

  title={Can 19-nortestosterone derivatives be aromatized in the liver of adult humans? Are there clinical implications?},
  author={Herbert Kuhl and Inka Wiegratz},
  pages={344 - 353}
Context Previous studies in postmenopausal women have demonstrated that, after oral administration of norethisterone, a small proportion of the compound is rapidly converted into ethinylestradiol. The shape of the concentration – time curve suggested that this occurred in the liver. The results were confirmed by in vitro investigations with adult human liver tissue. In 2002, it was shown that, after oral treatment of women with tibolone, aromatization of the compound occurred, resulting in the… Expand
Tibolone is not aromatized in postmenopausal women
  • H. Kloosterboer
  • Medicine
  • Climacteric : the journal of the International Menopause Society
  • 2008
The conclusions of the study were that the THEBES results confirm previous findings that tibolone does not induce endometrial hyperplasia or carcinoma in postmenopausal women, and it is associated with a better vaginal bleeding profile than conjugated equine estrogens/medroxyprogesterone acetate. Expand
Tissue selectivity and potential clinical applications of trenbolone (17β-hydroxyestra-4,9,11-trien-3-one): A potent anabolic steroid with reduced androgenic and estrogenic activity
The metabolism of 17beta-TBOH provides a basis for future research evaluating its safety and efficacy as a means of combating muscle and bone wasting conditions, obesity, and/or androgen insensitivity syndromes in humans, similar to that of other SARMs which are currently in development. Expand
Pharmacokinetics, metabolism and serum concentrations of progestins used in contraception.
It is shown that there is a paucity of research on most of these topics for most progestins, and major impediments to clear conclusions are a lack of standardized methodologies, comparisons between non-parallel clinical studies and variability of data on serum concentrations between and within studies. Expand
Nandrolone: a multi-faceted doping agent.
A set of strict identification criteria is applied to judge correctly an analytical finding of nandrolone metabolites, and the possible influence of interfering drugs, urine storage or natural production is taken into account by applying appropriate rules and regulations. Expand
Recreational Anabolic-Androgenic Steroid Use Associated With Liver Injuries Among Brazilian Young Men
The results suggest that the risk of AAS use for the liver may be greater than the esthetic benefits, and demonstrate the importance of screening AAS users for liver injuries. Expand
Fate and behavior of progestogens in activated sludge treatment: Kinetics and transformation products.
It was observed that molecular structure played a role in the inhibition of several transformation reactions, explaining the increased recalcitrance of these compounds and the need of a more comprehensive environmental risk assessment for synthetic steroids. Expand
Clinically relevant progestins regulate neurogenic and neuroprotective responses in vitro and in vivo.
Preclinical translational findings indicate that the neurogenic response to clinical progestins varies dramatically, and progestin impact on the regenerative capacity of the brain has clinical implications for contraceptive and hormone therapy formulations prescribed for pre- and postmenopausal women. Expand
Determination and identification of estrogenic compounds generated with biosynthetic enzymes using hyphenated screening assays, high resolution mass spectrometry and off-line NMR.
The multi-target screening approach combined with full structure characterization based on high resolution MS(/MS) and NMR spectroscopy demonstrated in this paper can generally be applied to e.g. metabolism studies and compound-library screening. Expand
Synthetic Androgens as Designer Supplements
The large number of designer steroid findings in dietary supplements and the detection of new compounds combined with legal loopholes for their distribution in many countries show that stricter regulations and better information policy are needed. 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


Lack of aromatisation of the 3-keto-4-ene metabolite of tibolone to an estrogenic derivative
7alpha-methyl norethisterone does not undergo aromatisation to an estrogenic derivative, and radioactivity detected on the TLC plate or HPLC fractions revealed that similar levels were present when 7alpha- methyl norehisterone was incubated with culture medium alone or with JEG-3 cells in the absence or presence of letrozole. 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
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
Conversion of tibolone to 7&agr;-methyl-ethinyl estradiol using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry: interpretation and clinical implications
The findings prove that conversion of tibolone to MEE is an artifact that is generated in a GC- MS system and is largely due to the intense heating step involved in GC-MS. Expand
Tibolone and its metabolites: Pharmacology, tissue specificity and effects in animal models of tumors
Tibolone is a steroid with weak estrogenic, progestogenic and androgenic properties that can be used as an alternative to conventional hormone replacement therapy in postmenopausal women. Tibolone isExpand
Formation of ethinylestradiol in postmenopausal women during continuous treatment with a combination of estradiol, estriol and norethisterone acetate.
Investigation of the serum concentrations of estradiol, ethinylestradiol and norethisterone in 25 patients of a gynecological practice who were continuously treated for climacteric complaints concluded that in the presence of the highEstradiol concentrations the low conversion rate of norehisterone into ethinylstradiol is probably without clinical significance. Expand
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
In vivo conversion of norethisterone and norethisterone acetate to ethinyl etradiol in postmenopausal women.
It is concluded that at therapeutic doses of the progestogens, the exposure to metabolically derived ethinyl estradiol is probably of little clinical significance not only in fertile women using oral contraceptive combination preparations containing norethisterone and ethinyl Estradiol, but also in postmenopausal women who receive oral doses of estradio for estrogen replacement. Expand
The in vivo human metabolism of tibolone.
Tibolone and its metabolites are not likely to play a clinically significant role at the level of these cytochrome P450 enzymes with regard to the metabolism of coadministered drugs. Expand
Aromatization of norethindrone to ethynylestradiol in human adult liver [Poster 41]
The evidence of ethynylestradiol formation was obtained using a Bio-Rad AG1-X2 column, thin layer chromatographies and co-crystallization and neither acid nor base was used in any step in product identification. Expand