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MGA was first synthesized, in 1959, from medroxyprogesterone acetate, which itself had been synthesized the year prior in 1958. [34] MGA in combination with ethinylestradiol (EE) was introduced in 1963 by British Drug Houses in the United Kingdom under the brand name Volidan (4 mg MGA and 50 μg EE tablets) as an oral contraceptive , [35] [36] and this was followed by Serial 28 (1 mg MGA and 100 μg EE tablets) and Volidan 21 (4 mg MGA and 50 μg EE tablets) in 1964 and Nuvacon (2 mg MGA and 100 μg EE tablets) in 1967, all by British Drug Houses also in the . [37] MGA was approved in 1967 for the treatment of breast cancer. [38] [39] In the 1970s, it was found to be associated with mammary tumors in beagle dogs, and along with several other progestogens, was withdrawn from several markets as an oral contraceptive. [38] Subsequent research revealed that there is no similar risk in humans. [40]

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Kaempferol is ingested as a glycoside , absorbed in the small intestine, usually by passive diffusion due to kaempferol’s lipophilicity, and metabolized in various areas of the body. In the small intestine, kaempferol is metabolized to glucuronides and sulfoconjugates by intestinal enzymes. It can also be metabolized by colon microflora which can hydrolyze the glycosides to aglycones or form simple phenolic compounds. These compounds can be absorbed or excreted. Kaempferol is also extensively metabolized in the liver to form glucurono-conjugated and sulfo-conjugated forms. These forms of kaempferol, and kaempferol itself, can then be excreted in urine. About % of kaempferol ingested is excreted as urine. Much of the rest of ingested kaempferol is present in the plasma and tissues in nanomolar concentrations. [2]

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