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Chemical Compound Review

megestrol     (8R,9S,10R,13S,14S,17R)-17- ethanoyl-17...

Synonyms: Megestil, Megestin, Chronopil, Megestrolo, Chronopil (TN), ...
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Disease relevance of megestrol

  • Pilot trials have suggested that the progestational agent megestrol acetate can ameliorate hot flashes in both groups of patients [1].
  • We observed marked weight gain (median, 5.1 kg; range, 0.9 to 20.1 kg) and appetite enhancement in 27 of the 28 patients with breast cancer receiving treatment consisting of high doses of oral megestrol acetate (480 to 1600 mg/d) [2].
  • High-dose megestrol acetate. A possible treatment for cachexia [2].
  • Our results suggest a possible role for megestrol acetate in reversing anorexia and weight loss, thereby improving the quality of life of patients with cachexia [2].
  • A weight gain of 15 lb or more over baseline was seen in 11 of 67 (16%) patients receiving megestrol acetate compared with one of 66 (2%) given the placebo (P = .003) [3].

Psychiatry related information on megestrol

  • These data provided the impetus for a series of further studies of the role of megestrol acetate in the control of cachexia, including a randomized study in cancer cachexia, AIDS cachexia, and anorexia nervosa [4].
  • After receiving megestrol acetate continuously for 19 years for chronic hormone suppression, she began to experience progressive dementia [5].
  • Serious adverse events assessed as related to dronabinol included CNS events (e.g., confusion, anxiety, emotional lability, euphoria, hallucinations) and those assessed as related to megestrol acetate included dyspnea, liver enzyme changes, and hyperglycemia [6].
  • We report the case of a young patient with renal insufficiency due to unilateral renal agenesis who developed Cushing syndrome two months after administration of high-dose (900-mg/d) megestrol acetate for an eating disorder [7].
  • In a sample of healthy male controls, pretreatment with megestrol had a profound effect on the hypothalamic-pituitary-adrenal (HPA) axis, whereas the clinical effects on panic attacks were weak [8].

High impact information on megestrol

  • Megestrol acetate for the prevention of hot flashes [9].
  • Preliminary information has suggested that megestrol acetate leads to appetite stimulation and nonfluid weight gain in patients with breast cancer, other cancers, and AIDS [3].
  • Patients assigned to megestrol acetate more frequently reported improved appetite (P = .003) and food intake (P = .009) when compared with patients receiving the placebo [3].
  • No clinically or statistically significant toxic reactions were ascribed to megestrol acetate, with the exception of mild edema [3].
  • Patients receiving megestrol acetate reported significantly less nausea (13% vs. 38%; P = .001) and emesis (8% vs. 25%, P = .009) [3].

Chemical compound and disease context of megestrol


Biological context of megestrol


Anatomical context of megestrol

  • PATIENTS AND METHODS: Using dual-energy x-ray absorptiometry and tritiated body water methodologies, we performed body-composition measurements in 12 patients with advanced cancer before the institution of oral megestrol acetate (800 mg/d) and at subsequent 2-month intervals [19].
  • Epithelial cell PSA and DHT values significantly decreased in finasteride- and megestrol- plus estrogen-treated patients compared to controls [20].
  • As the analysis of the action of steroids in vivo is complex, we chose to examine the effects of megestrol acetate on the differentiation of a preadipocyte clone (L1) of the Swiss 3T3 mouse fibroblast cell line [21].
  • In terms of benefits over other endocrine agents, anastrozole causes significantly less weight gain than megestrol acetate; it does not have the partial agonist activity of tamoxifen, and is unlikely to lead to tumour stimulation in patients resistant to tamoxifen or to exert proliferative effects on the endometrium [22].
  • Further studies on the regulation of adipocyte differentiation and function in this model system may be important to clarify megestrol acetate's mechanism of action [21].

Associations of megestrol with other chemical compounds

  • Cortisol levels after administration of cosyntropin decreased significantly (from 27.3 +/- 3.3 pg/mL to 9.3 +/- 6.3 pg/mL; P = 0.01) during treatment with megestrol acetate [23].
  • MEASUREMENTS: Study patients had cosyntropin-stimulation testing and oral glucose tolerance testing before and after starting therapy with megestrol acetate [23].
  • PURPOSE: To compare the efficacy and tolerability of anastrozole (1 and 10 mg once daily), a selective, oral, nonsteroidal aromatase inhibitor, and megestrol acetate (40 mg four times daily), in postmenopausal women who progressed following tamoxifen treatment [11].
  • PATIENTS AND METHODS: Two randomized, double-blind for anastrozole, open-label for megestrol acetate, parallel-group, multicenter trials were conducted in 764 patients [11].
  • Thereafter the interaction of mifepristone and megestrol acetate on PRL release was investigated [24].

Gene context of megestrol


Analytical, diagnostic and therapeutic context of megestrol


  1. Megestrol acetate for the prevention of hot flashes. Loprinzi, C.L., Michalak, J.C., Quella, S.K., O'Fallon, J.R., Hatfield, A.K., Nelimark, R.A., Dose, A.M., Fischer, T., Johnson, C., Klatt, N.E. N. Engl. J. Med. (1994) [Pubmed]
  2. High-dose megestrol acetate. A possible treatment for cachexia. Tchekmedyian, N.S., Tait, N., Moody, M., Aisner, J. JAMA (1987) [Pubmed]
  3. Controlled trial of megestrol acetate for the treatment of cancer anorexia and cachexia. Loprinzi, C.L., Ellison, N.M., Schaid, D.J., Krook, J.E., Athmann, L.M., Dose, A.M., Mailliard, J.A., Johnson, P.S., Ebbert, L.P., Geeraerts, L.H. J. Natl. Cancer Inst. (1990) [Pubmed]
  4. Studies of high-dose megestrol acetate: potential applications in cachexia. Aisner, J., Tchekmedyian, N.S., Tait, N., Parnes, H., Novak, M. Semin. Oncol. (1988) [Pubmed]
  5. Multiple meningiomas arising during long-term therapy with the progesterone agonist megestrol acetate. Case report. Gruber, T., Dare, A.O., Balos, L.L., Lele, S., Fenstermaker, R.A. J. Neurosurg. (2004) [Pubmed]
  6. The safety and pharmacokinetics of single-agent and combination therapy with megestrol acetate and dronabinol for the treatment of HIV wasting syndrome. The DATRI 004 Study Group. Division of AIDS Treatment Research Initiative. Timpone, J.G., Wright, D.J., Li, N., Egorin, M.J., Enama, M.E., Mayers, J., Galetto, G. AIDS Res. Hum. Retroviruses (1997) [Pubmed]
  7. Megestrol-induced Cushing syndrome. Caparrós, G.C., Zambrana, J.L., Delgado-Fernandez, M., Díez, F. The Annals of pharmacotherapy. (2001) [Pubmed]
  8. Megestrol attenuates the hormonal response to CCK-4-induced panic attacks. Raedler, T.J., Jahn, H., Goedeken, B., Gescher, D.M., Kellner, M., Wiedemann, K. Depression and anxiety. (2006) [Pubmed]
  9. Megestrol acetate for the prevention of hot flashes. Hughes-Davies, T.H. N. Engl. J. Med. (1995) [Pubmed]
  10. Megestrol acetate versus tamoxifen in advanced breast cancer: 5-year analysis--a phase III trial of the Piedmont Oncology Association. Muss, H.B., Wells, H.B., Paschold, E.H., Black, W.R., Cooper, M.R., Capizzi, R.L., Christian, R., Cruz, J.M., Jackson, D.V., Powell, B.L. J. Clin. Oncol. (1988) [Pubmed]
  11. Anastrozole, a potent and selective aromatase inhibitor, versus megestrol acetate in postmenopausal women with advanced breast cancer: results of overview analysis of two phase III trials. Arimidex Study Group. Buzdar, A., Jonat, W., Howell, A., Jones, S.E., Blomqvist, C., Vogel, C.L., Eiermann, W., Wolter, J.M., Azab, M., Webster, A., Plourde, P.V. J. Clin. Oncol. (1996) [Pubmed]
  12. Phase III, multicenter, double-blind, randomized study of letrozole, an aromatase inhibitor, for advanced breast cancer versus megestrol acetate. Buzdar, A., Douma, J., Davidson, N., Elledge, R., Morgan, M., Smith, R., Porter, L., Nabholtz, J., Xiang, X., Brady, C. J. Clin. Oncol. (2001) [Pubmed]
  13. Exemestane is superior to megestrol acetate after tamoxifen failure in postmenopausal women with advanced breast cancer: results of a phase III randomized double-blind trial. The Exemestane Study Group. Kaufmann, M., Bajetta, E., Dirix, L.Y., Fein, L.E., Jones, S.E., Zilembo, N., Dugardyn, J.L., Nasurdi, C., Mennel, R.G., Cervek, J., Fowst, C., Polli, A., di Salle, E., Arkhipov, A., Piscitelli, G., Miller, L.L., Massimini, G. J. Clin. Oncol. (2000) [Pubmed]
  14. Comparison of the actions of RU 38486 and megestrol acetate in the model of a transplantable adrenocorticotropin- and prolactin-secreting rat pituitary tumor. Lamberts, S.W., Uitterlinden, P., Bons, E.G., Verleun, T. Cancer Res. (1985) [Pubmed]
  15. Megestrol acetate in patients with AIDS and cachexia. Oster, M.H., Enders, S.R., Samuels, S.J., Cone, L.A., Hooton, T.M., Browder, H.P., Flynn, N.M. Ann. Intern. Med. (1994) [Pubmed]
  16. The effect of megestrol acetate on growth of HepG2 cells in vitro and in vivo. Zhang, K., Chow, P.K. Clin. Cancer Res. (2004) [Pubmed]
  17. Pharmacokinetic interaction of megestrol acetate with zidovudine in human immunodeficiency virus-infected patients. Van Harken, D.R., Pei, J.C., Wagner, J., Pike, I.M. Antimicrob. Agents Chemother. (1997) [Pubmed]
  18. Comparative study of DNA repair induced by cyproterone acetate, chlormadinone acetate and megestrol acetate in primary cultures of human and rat hepatocytes. Martelli, A., Mattioli, F., Ghia, M., Mereto, E., Brambilla, G. Carcinogenesis (1996) [Pubmed]
  19. Body-composition changes in patients who gain weight while receiving megestrol acetate. Loprinzi, C.L., Schaid, D.J., Dose, A.M., Burnham, N.L., Jensen, M.D. J. Clin. Oncol. (1993) [Pubmed]
  20. Effect of finasteride, a 5 alpha-reductase inhibitor on prostate tissue androgens and prostate-specific antigen. Geller, J. J. Clin. Endocrinol. Metab. (1990) [Pubmed]
  21. Megestrol acetate-induced differentiation of 3T3-L1 adipocytes in vitro. Hamburger, A.W., Parnes, H., Gordon, G.B., Shantz, L.M., O'Donnell, K.A., Aisner, J. Semin. Oncol. (1988) [Pubmed]
  22. Aromatase inhibitors and their future role in post-menopausal women with early breast cancer. Lønning, P.E. Br. J. Cancer (1998) [Pubmed]
  23. Induction of adrenal suppression by megestrol acetate in patients with AIDS. Leinung, M.C., Liporace, R., Miller, C.H. Ann. Intern. Med. (1995) [Pubmed]
  24. Prolactin release-inhibitory effects of progesterone, megestrol acetate, and mifepristone (RU 38486) by cultured rat pituitary tumor cells. Lamberts, S.W., van Koetsveld, P., Verleun, T. Cancer Res. (1987) [Pubmed]
  25. Focus on anastrozole and breast cancer. Mokbel, K. Current medical research and opinion. (2003) [Pubmed]
  26. Effects of megestrol acetate on circulating interleukin-15 and interleukin-18 concentrations in healthy elderly men. Lambert, C.P., Flynn, M.G., Sullivan, D.H., Evans, W.J. J. Gerontol. A Biol. Sci. Med. Sci. (2004) [Pubmed]
  27. Progesterone receptor level as a predictor of response to megestrol acetate in advanced breast cancer: a retrospective study. Johnson, P.A., Bonomi, P.D., Anderson, K.M., Wolter, J.M., Bacon, L.D., Rossof, A.H., Economou, S.G. Cancer treatment reports. (1983) [Pubmed]
  28. Randomized double-blind placebo-controlled trial of cisplatin and etoposide plus megestrol acetate/placebo in extensive-stage small-cell lung cancer: a North Central Cancer Treatment Group study. Rowland, K.M., Loprinzi, C.L., Shaw, E.G., Maksymiuk, A.W., Kuross, S.A., Jung, S.H., Kugler, J.W., Tschetter, L.K., Ghosh, C., Schaefer, P.L., Owen, D., Washburn, J.H., Webb, T.A., Mailliard, J.A., Jett, J.R. J. Clin. Oncol. (1996) [Pubmed]
  29. Phase III evaluation of four doses of megestrol acetate as therapy for patients with cancer anorexia and/or cachexia. Loprinzi, C.L., Michalak, J.C., Schaid, D.J., Mailliard, J.A., Athmann, L.M., Goldberg, R.M., Tschetter, L.K., Hatfield, A.K., Morton, R.F. J. Clin. Oncol. (1993) [Pubmed]
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