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

• One hundred thirty-eight patients with recurrent or metastatic breast cancer were randomized to receive megestrol acetate 40 mg orally four times daily or tamoxifen 10 mg orally twice a day [10].
• 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 [11].
• PURPOSE: To compare two doses of letrozole (0.5 mg and 2.5 mg every day) and megestrol acetate (40 mg qid) as endocrine therapy in postmenopausal women with advanced breast cancer previously treated with antiestrogens [12].
• 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 [13].
• RU 38486 (2.5 mg/kg/day) for 30 days significantly inhibited tumor size, tumor weight, and the plasma prolactin and ACTH concentrations, while the same dose of megestrol acetate only inhibited pituitary tumor weight [14].

Biological context of megestrol

• OBJECTIVE: To study the effects of a megestrol acetate liquid formulation (800 mg/d) on body weight, body composition, caloric intake, and mental outlook in patients with the acquired immunodeficiency syndrome (AIDS) who had cachexia [15].
• From baseline to week 8, the megestrol acetate group increased their daily caloric intake by 608 calories, whereas the placebo group increased intake by 134 calories (difference, 474 calories; 95% CI, -68 to 880 calories) [15].
• Apoptosis following G(1) arrest was observed in megestrol acetate-treated cells and may be a mechanism through which megestrol acetate inhibits HepG2 cells [16].
• This nonrandomized, two-period crossover study was performed to assess whether concomitant administration of megestrol acetate influences the steady-state pharmacokinetics of zidovudine and its inactive 5'-O-glucuronide metabolite [17].
• Comparative study of DNA repair induced by cyproterone acetate, chlormadinone acetate and megestrol acetate in primary cultures of human and rat hepatocytes [18].

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

• It has been shown to be superior to megestrol acetate, in terms of survival and adverse effects, as a second-line therapy in postmenopausal women with estrogen receptor (ER)- and/or progesterone receptor (PgR)-positive advanced breast cancer [25].
• Effects of megestrol acetate on circulating interleukin-15 and interleukin-18 concentrations in healthy elderly men [26].
• Therefore, the purpose of this investigation was to evaluate the effects of megestrol acetate ingestion on circulating IL-15 and IL-18 concentrations in healthy elderly men [26].
• Progesterone receptor level as a predictor of response to megestrol acetate in advanced breast cancer: a retrospective study [27].
• Studies with ACTH secretion by cultured normal rat pituitary cells showed that megestrol acetate (1 microM) did not affect corticotropin-releasing factor (CRF)-stimulated ACTH release after 4-hr exposure, but inhibited CRF-stimulated ACTH release by 50% after 24-hr preincubation [14].

Analytical, diagnostic and therapeutic context of megestrol

• Patients who received megestrol acetate had more edema (30% v 20%, P = .002), an inferior response rate to chemotherapy (68% v 80%, P = .03), and a trend for inferior survival duration (median, 8.2 v 10.0 months, P = .49) [28].
• PURPOSE: Randomized placebo-controlled clinical trials have now established that megestrol acetate causes appetite stimulation and weight gain in patients with anorexia and/or cachexia [19].
• CONCLUSION: Given a favorable tolerability profile, once-daily dosing, and evidence of clinically relevant benefit, letrozole is equivalent to megestrol acetate and should be considered for use as an alternative treatment of advanced breast cancer in postmenopausal women after treatment failure with antiestrogens [12].
• Patients treated with letrozole 0.5 mg had improvements in disease progression (P =.044) and a decreased risk of treatment failure (P =.018), compared with patients treated with megestrol acetate [12].
• PURPOSE: Several placebo-controlled randomized clinical trials have demonstrated that megestrol acetate can result in appetite stimulation and nonfluid weight gain in patients with cancer anorexia/cachexia [29].

References