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Hormone or agents related to hormones are being used in combination with other methods to treat some types of hormone-dependent cancer (e.g. breast cancer, ovarian cancer, prostrate cancer). By which progestational agents are useful as second-line hormonal therapy for metastatic, hormone-dependent breast cancer and in the management of endometrial carcinoma previously treated by surgery and radiotherapy. Progesterone itself is inactive when given orally due to first-pass hepatic metabolism. However, substitutions of such 17-esters at the 6-position of the B ring yield orally active compounds such as medroxyprogesterone acetate (MPA). MPA is one group of progestins contains the 21-carbon skeleton of progesterone. It is highly selective and have a spectrum of activity very similar to that of the endogenous hormone. In many biological systems, progestins enhance differentiation and oppose the actions of estrogens to stimulate cell proliferation. This action of progestins may involve decreases in estrogen receptor levels, increases in local metabolism of estrogens to less active metabolites, or the induction of gene products that blunt cellular responses to estrogenic agents. MPA also has androgenic and anabolic effect without estrogenic effect. The drug is metabolized in liver and excreted in urine so that it is contraindicated in severe hepatic diseases, as metabolism of MPA will be decreased and accumualation of active drug will occur. Uncommon adverse effects are similar to those found in other progestins, included psychic depression (due to increase level of monoamine oxidase). MPA has been reported to cause either no effects or modest reductions in serum HDL levels. In a number of placebo-controlled clinical trials, high-dose medroxyprogesterone acetate (HD-MPA) was shown to be effective in treatment of hormone-dependent cancer when used in combination with chemotherapeutic drugs or irradiation. HD-MPA help reducing hematological toxicity from radiation. It also has myeloprotective effect thus prevent leukopenia in patients on chemotherapy as well as pain relief in bone metastases. Moreover, HD-MPA will improve quality of life, as it will stimulate appitite and gain weight in patients taking the drug. This is due to its anabolic effect.
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