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Clinical Use of Anabolics and Hormones
Clinical Use of Anabolics and Hormones
Current therapeutic options for cachexia
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<blockquote data-quote="madman" data-source="post: 227036" data-attributes="member: 13851"><p><strong>Adrenocortical corticosteroids. </strong></p><p></p><p><em>To treat cachexia crucial is managing inflammation. Therefore basic treatment includes steroids. Adrenocortical hormones are steroids produced and released by the adrenal cortex under corticotropin (ACTH) control. That group is divided into a few subgroups depending on their biological activity (Table 3) (44).</em></p><p><em></em></p><p><em><strong>Corticosteroids, such as <u>dexamethasone</u> (2-4 mg/day), prednisolone (15-30 mg/day), or methylprednisolone (8-24 mg/day), are used to treat cachexia (3,4). Their main mechanism of action is increased appetite and diminishing inflammation (4,36).</strong> Additionally, they inhibit prostaglandin metabolism and IL-1 activity (22). With higher steroid doses, the probability of important adverse effects increases, particularly when dexamethasone dose is above 3mg (in mice studies) or when serum levels increase in stressful situations. <strong>Corticosteroids can decrease protein synthesis and increase protein degradation, due to activation of the ubiquitin-proteasome system and muscle ring finger 1 (MuRF1) inhibition, reducing muscle strength (10,45). <u>Because of corticosteroids’ side effect profile, they are indicated only for short-term treatment – less than 4weeks</u>.</strong> <strong><u>That side effects include osteoporosis, steroid-induced myopathy, osteonecrosis, suppression of the hypothalamic-pituitary-adrenal (HPA) axis, diabetes, cushingoid features, infections, fluid retention, edema, weight gain, hypertension, and arrhythmias by increasing renal excretion of potassium, calcium, and phosphate, cataract, open-angle glaucoma, skin thinning and atrophy</u> (46).</strong></em></p><p></p><p></p><p></p><p></p><p><strong>Progesterone analogs</strong></p><p></p><p><em>Progesterone, another steroid hormone, is a natural progestin synthesized by the ovary, testis, and adrenal cortex from circulating cholesterol, also by the placenta during pregnancy (44). </em><strong><em>In wasting syndrome treatment we use synthetic progestin, which increases appetite and reduces inflammation – <u>Megestrol Acetate</u>, Medroxyprogesterone Acetate, and Fluoxymesterone.</em></strong></p><p></p><p><em>Megestrol Acetate is often used in the treatment of patients with metastatic breast cancer patients as well as in anorexia. Its mechanism may involve IL-1α and β, IL-2, IL-6, and TNF-α serum levels reduction. <strong>Megestrol acetate causes weight gain, but mainly fat tissue, not muscle (22,52,53). The dose range is 400-800 mg/day (higher doses do not bring benefits and increase the risk of adverse effects, mainly thromboembolic events and adrenal cortex suppression). Maximal weight gain is normally achieved within 8 weeks (54).</strong> In 2019 was published by Cochran Database Systemic Review, which included 35 trials comprising 3963 patients for effectiveness and 3180 for safety. Meta-analysis showed a benefit of megestrol acetate (MA) compared with placebo, especially regarding appetite improvement and weight gain in cancer, AIDS, and other underlying conditions. <strong>According to this review, MA does not improve quality of life, and in patients treated with MA side effects are more frequent. The most common adverse effect is increased risk of blood clots, therefore swelling, pain or redness of one extremity and not the other, severe headache, sudden dyspnea or vision changes, as well as fluid retention, which can lead to swelling of the feet or hands, and death (55).</strong> <strong>According to Loprinzi et al clinical trial, there is no significant distinction between dexamethasone and megestrol acetate's effectiveness on appetite stimulation as well as their influence on nonfluid weight status. However there were differences in their side effects – dexamethasone caused corticosteroid-type toxicity and a higher rate of drug discontinuation because of toxicity or patient's refusal, and megestrol acetate had a higher rate of deep venous thrombosis.</strong> A randomized, double-blind, placebo-controlled trial of megestrol acetate or dexamethasone in treating symptomatic anorexia in people with advanced cancer also showed, that there are no significant differences between treatment effects including weight, performance status (AKPS), and appetite score of megestrol acetate 480 mg or dexamethasone 4 mg compared to placebo daily. However, the study lasted only 4weeks (56). Other analogs, which is fluoxymesterone (testosterone analog), according to Loprinzi et al studies, are definitely less effective in appetite enhancement than dexamethasone or MA (57).</em></p><p><em></em></p></blockquote><p></p>
[QUOTE="madman, post: 227036, member: 13851"] [B]Adrenocortical corticosteroids. [/B] [I]To treat cachexia crucial is managing inflammation. Therefore basic treatment includes steroids. Adrenocortical hormones are steroids produced and released by the adrenal cortex under corticotropin (ACTH) control. That group is divided into a few subgroups depending on their biological activity (Table 3) (44). [B]Corticosteroids, such as [U]dexamethasone[/U] (2-4 mg/day), prednisolone (15-30 mg/day), or methylprednisolone (8-24 mg/day), are used to treat cachexia (3,4). Their main mechanism of action is increased appetite and diminishing inflammation (4,36).[/B] Additionally, they inhibit prostaglandin metabolism and IL-1 activity (22). With higher steroid doses, the probability of important adverse effects increases, particularly when dexamethasone dose is above 3mg (in mice studies) or when serum levels increase in stressful situations. [B]Corticosteroids can decrease protein synthesis and increase protein degradation, due to activation of the ubiquitin-proteasome system and muscle ring finger 1 (MuRF1) inhibition, reducing muscle strength (10,45). [U]Because of corticosteroids’ side effect profile, they are indicated only for short-term treatment – less than 4weeks[/U].[/B] [B][U]That side effects include osteoporosis, steroid-induced myopathy, osteonecrosis, suppression of the hypothalamic-pituitary-adrenal (HPA) axis, diabetes, cushingoid features, infections, fluid retention, edema, weight gain, hypertension, and arrhythmias by increasing renal excretion of potassium, calcium, and phosphate, cataract, open-angle glaucoma, skin thinning and atrophy[/U] (46).[/B][/I] [B]Progesterone analogs[/B] [I]Progesterone, another steroid hormone, is a natural progestin synthesized by the ovary, testis, and adrenal cortex from circulating cholesterol, also by the placenta during pregnancy (44). [/I][B][I]In wasting syndrome treatment we use synthetic progestin, which increases appetite and reduces inflammation – [U]Megestrol Acetate[/U], Medroxyprogesterone Acetate, and Fluoxymesterone.[/I][/B] [I]Megestrol Acetate is often used in the treatment of patients with metastatic breast cancer patients as well as in anorexia. Its mechanism may involve IL-1α and β, IL-2, IL-6, and TNF-α serum levels reduction. [B]Megestrol acetate causes weight gain, but mainly fat tissue, not muscle (22,52,53). The dose range is 400-800 mg/day (higher doses do not bring benefits and increase the risk of adverse effects, mainly thromboembolic events and adrenal cortex suppression). Maximal weight gain is normally achieved within 8 weeks (54).[/B] In 2019 was published by Cochran Database Systemic Review, which included 35 trials comprising 3963 patients for effectiveness and 3180 for safety. Meta-analysis showed a benefit of megestrol acetate (MA) compared with placebo, especially regarding appetite improvement and weight gain in cancer, AIDS, and other underlying conditions. [B]According to this review, MA does not improve quality of life, and in patients treated with MA side effects are more frequent. The most common adverse effect is increased risk of blood clots, therefore swelling, pain or redness of one extremity and not the other, severe headache, sudden dyspnea or vision changes, as well as fluid retention, which can lead to swelling of the feet or hands, and death (55).[/B] [B]According to Loprinzi et al clinical trial, there is no significant distinction between dexamethasone and megestrol acetate's effectiveness on appetite stimulation as well as their influence on nonfluid weight status. However there were differences in their side effects – dexamethasone caused corticosteroid-type toxicity and a higher rate of drug discontinuation because of toxicity or patient's refusal, and megestrol acetate had a higher rate of deep venous thrombosis.[/B] A randomized, double-blind, placebo-controlled trial of megestrol acetate or dexamethasone in treating symptomatic anorexia in people with advanced cancer also showed, that there are no significant differences between treatment effects including weight, performance status (AKPS), and appetite score of megestrol acetate 480 mg or dexamethasone 4 mg compared to placebo daily. However, the study lasted only 4weeks (56). Other analogs, which is fluoxymesterone (testosterone analog), according to Loprinzi et al studies, are definitely less effective in appetite enhancement than dexamethasone or MA (57). [/I] [/QUOTE]
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Clinical Use of Anabolics and Hormones
Clinical Use of Anabolics and Hormones
Current therapeutic options for cachexia
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