Metabolism of 4-14C–Ethynyl Oestradiol in Women

Kamyab, S.; Fotherby, K.; Steele, S. J.

doi:10.1038/221360a0

Cited by 28 publications

(6 citation statements)

References 5 publications

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“…Metabolism of synthetic oestrogens in humans After the administration of labelled ethynyloestradiol to humans up to 60 % of the dose may be excreted in the urine within 5 days (Kamyab et al 1969; Abdel-Aziz 8c Williams 1970; Reed et al 1972 ; Kulkarni 8c Goldzieher 1970a). There appears to be no difference between orally or intravenously administered steroid.…”

Section: -Epioestriolmentioning

confidence: 98%

Metabolism of Synthetic Steroids by Animals and Man

Fotherby

1974

Acta Endocrinologica

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The metabolism of naturally occurring oestrogens in humans is outlined and compared with that in other species and with the metabolism of synthetic oestrogens. There is a close similarity in humans between the metabolism of the naturally occurring oestrogens and that of ethynyl \x=req-\ oestradiol with the exception that the latter is less extensively metabolised than the former. With the exception of the baboon, the metabolism of oestrone and oestradiol appears to differ significantly in other species from that of the human. Our knowledge of the metabolism of oestrone and oestradiol and the synthetic oestrogens in the baboon is still meagre and much more information is required before one can ascertain to what extent metabolism in this species can serve as a model for that in humans.Little information is available concerning the metabolism of synthetic progestogens in species other than man and rabbits. There are many similarities between these two species both in the metabolism of progesterone and of synthetic progestogens related both to 19-nortestosterone and to 17\g=a\-hydroxyprogesterone. Insufficient information is available to know how far these similarities extend.Little is known about the in vitro metabolism of either the synthetic oestrogens or synthetic progestogens. Such information as is available does not suggest that in vitro metabolic studies, with their well-known limitations, are likely to be helpful. In vivo metabolism of oestrogensThe metabolism in humans of the naturally occurring oestrogens is briefly outlined to aid comparison with that in other species and also with the meta¬ bolism of synthetic oestrogens.A. Metabolism of oestrone and oestradiol in humans The major pathways for the metabolism of oestrogens are outlined in Fig. 1.Oestrone and oestradiol are interconvertible by 17/3-hydroxysteroid oxidoreductase, the dehydrogenation of oestradiol to oestrone being more rapid than the reduction of oestrone to oestradiol so that the equilibrium between oestrone and oestradiol favours oestrone. Although a 17a-hydroxysteroid oxidoreductase is present in man (Breuer 8c Schott 1966), 17a-oestradiol is not an important metabolite but it is important in some species. One of the main metabolic pathways for oestrone is 16a-hydroxylation leading to 16a-hydroxyoestrone and oestriol. Some of the oestriol produced is oxidized to 16-oxo-oestradiol which can undergo reduction to 16/?-hydroxyoestradiol (16-e/«oestriol). The second major pathway appears to be hydroxylation at C-2 with the formation of 2-hydroxyoestrone which is readily converted to 2-methoxyoestrone by an 0-methyl transferase. Demethylation of 2-methoxyoestrogens occurs to only a slight extent. It seems likely that oestrone sulphate rather than oestrone is the precursor for the hydroxylated metabolites found in urine (Fishman 8c Hellman 1973). Hydroxylation may also occur at C-6. Oestradiol -17 a Ha^/V^" HC 2-Hydroxyoestrone 16a-Hydroxyoestrone lóB-Hydroxyoestrone * OH O Me O HO OH -OH 2-Methoxyoestrone Oestriol Fig. 1.Metabolism of oestrog...

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Section: -Epioestriolmentioning

confidence: 98%

Metabolism of Synthetic Steroids by Animals and Man

Fotherby

1974

Acta Endocrinologica

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“…Following administration of radioactive EE 2 to humans, the drug is primarily recovered in bile or urine as glucuronide or sulphate conjugates (Figure 1). Urinary recovery of EE 2 derived radioactivity reported ranges from 16 to 54% of an EE 2 dose [ 9–15] and from 28 to 59% is excreted in the faeces [ 12–15]. Ring ‘A’ hydroxylation, of which 2‐hydroxy‐EE 2 is probably the most important primary oxidative metabolite, can be followed by methylation by catechol‐ O ‐methyltransferase to form a secondary metabolite, 2‐methoxy‐EE 2 .…”

Section: Introductionmentioning

confidence: 99%

Effects of cytochrome P450 inducers on 17α‐ethinyloestradiol (EE₂) conjugation by primary human hepatocytes

Hartman

et al. 1999

Brit J Clinical Pharma

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“…Other investigators arrived at similar figures for the extent of renal excretion of radiolabeled EE and mestranol (REED et al 1972;KAMYAB and FOTHERBY 1969;ABDEL-AzIZ and WILLIAMS 1970;KULKARNI and GOLDZIEHER 1970;MAGGS et a1.1983a). Only about 6% (range 3.2-8.4%) of the dose appeared as unchanged EE in the urine and about 7% (range 2.4-16.5%) was excreted as EE-conjugates (REED et al 1972).…”

Section: Excretionmentioning

confidence: 70%

“…The major part of the radiolabeled compounds that was excreted in the urine was represented by conjugated and non-conjugated metabolites of EE. Approximately 80% of the conjugates were glucuronides (3-glucuronides, 17 -glucuronides and 3,17-diglucuronides) and only 8-10% were sulfates (WILLIAMS and GOLDZIEHER 1980;KAMYAB and FOTHERBY 1969;CARGILL et al 1969). …”

Section: Excretionmentioning

confidence: 99%