Isolation and partial synthesis of a new metabolite of medroxyprogesterone acetate

Article abstract of DOI:10.1016/0039-128X(79)90126-0

3α-Hydroxy-17-acetoxy-6α-methyl-5β-pregnan-20-one (IIIa) has been isolated from urine of patients receiving medroxyprogesterone acetate (MPA). It was characterized by partial synthesis from MPA by catalytic reduction with palladium-charcoal to 17-acetoxy-6α-methyl-5β-pregnan-3,20-dione (IV) and reduction of the latter with sodum borohydride. The isolation of 6β,17,21-trihydroxy-6α-methyl-pregn-4-ene-3,20-dione (IIc) is reported for the first time. The 17- and 21-monoacetates of this compound have been isolated and characterized earlier by other investigators. 7α-³H-Medroxyprogesterone acetate was administered to 4 subjects by intravenous and intramuscular injections and by mouth. The ring A saturated metabolite IIIa was excreted in 0.1% to 4.0% of the administered dose; the highest excretion was after the intravenous dose and lowest after oral ingestion. 6β,17,21-Trihydroxy-6α-methylpregn-4-ene-3,20-dione (IIc) and its 17- and 21-monoacetates were excreted in about 5% of the doses in all subjects. No increase in 6β-hydroxylation was observed in the patient treated with o,p'-DDD, 2,2-bis (2-chlorophenyl, 4'-chlorophenyl)-1,1-dichloroethane.