Type-IIx
Well-known Member
I was asked by PM about a drug that is used to enhance appetite, for bulking. Megestrol acetate is a very poor choice for bodybuilders to stimulate appetite because it preferentially induces fat gain. In fact, this is by design, since it is used in cachexia and disease states including HIV to put fat on people because fat loss is what KILLS you, not muscle loss (that only reduces ambulation and quality of life), believe it or not.
Megestrol acetate causes preferential fat gain via interference with the production or action of mediators such as cachectin, a hormone that inhibits adipocyte lipogenic enzymes (thereby increasing lipogenesis).
Megestrol acetate is a synthetic progestin, so it comes with the standard caveats (from Article on distinguishing progestins, prolactin, and progestagenic androgens (e.g., Tren, MENT, Deca) & SERM vs. AI logic [by Type-IIx]):
"Progestins increase estrogen sensitivity"
True:
Estrogens ↑prolactin expression (thereby suppressing LH & FSH), contributing to ↑HPG axis suppression. Progestins further directly contibute to HPG axis suppression by dysregulating hypothalamic regulation of T and gonadotropins via KNDy dendron signalling, disrupting GnRH pulsatility, and inhibiting pituitary LH secretion [11] [12]. Synthetic progestins used in contraception derive efficacy from this feature. Bebb, et al. randomized healthy men to receive either testosterone enanthate (100 mg weekly), or the same dosage of testosterone in combination with the progestin levonorgestrel, the addition of which virtually abolished LH and FSH secretion [13]. Decreased LH & FSH can cause secondary hypogonadism, thereby ↓androgen/estrogen ratio, causing gynecomastia.
Further, "progesterone and its derivatives...& progesterone mimics...were moderate binders to the AR. We earlier demonstrated that progesterone derivatives do not compete with 17β-estradiol (E₂) for ER binding (18, 30). It appears that progesterone derivatives could alter both AR- & PR- but not ER-mediated tissue responses." [3].
Estrogens up-regulate PR synthesis [2]. Further, activation of progesterone receptors has been linked to reduced expression of AR, thereby hampering the androgen-mediated inhibition on breast tissue growth observed in condition of normal hormonal homeostasis [16].
Progesterone and its derivatives may further cause gynecomastia by enhancing the effect of estradiol on breast tissues [6].
From my notes:
Megestrol acetate
17-hydroxy-6-methylpregna-3,6-diene-3,20-dione; Megace
Maygace; Megestat; Megestil; Megestin; Linmegestrol; Apo-megestrol; Endace
DrugBank (pdf)
* A progestin that is administered orally to treat anorexia and cachexia, HIV wasting, or serious unexplained weight loss and is also used as an antineoplastic agent to treat certain types of malignancy.
* ...has the same physiologic effects as natural progesterone. These effects include... increased basal body temperature, pituitary inhibition... has slight glucocorticoid activity and very slight mineralocorticoid activity...
* The precise mechanism of megestrol's antianorexic and anticachetic effects is unknown, but its progestin antitumor activity may involve suppression of LH by inhibition of pituitary function...weight gain effect is related to its appetite-stimulant or metabolic effects rather than its glucocorticoid-like effects or the production of edema.
* Megestrol may alter metabolic pathways via interference with the production or action of mediators such as cachectin, a hormone that inhibits adipocyte lipogenic enzymes (thereby increasing lipogenesis)
* Drug-Drug Interactions:
- Methyltestosterone: Megestrol acetate may decrease the excretion rate of Methyltestosterone which could result in a higher serum level
- Testosterone: The metabolism of Megestrol acetate can be increased when combined with Testosterone (applies to cypionate, enanthate, propionate, etc.)
Megestrol acetate causes preferential fat gain via interference with the production or action of mediators such as cachectin, a hormone that inhibits adipocyte lipogenic enzymes (thereby increasing lipogenesis).
Megestrol acetate is a synthetic progestin, so it comes with the standard caveats (from Article on distinguishing progestins, prolactin, and progestagenic androgens (e.g., Tren, MENT, Deca) & SERM vs. AI logic [by Type-IIx]):
"Progestins increase estrogen sensitivity"
True:
Estrogens ↑prolactin expression (thereby suppressing LH & FSH), contributing to ↑HPG axis suppression. Progestins further directly contibute to HPG axis suppression by dysregulating hypothalamic regulation of T and gonadotropins via KNDy dendron signalling, disrupting GnRH pulsatility, and inhibiting pituitary LH secretion [11] [12]. Synthetic progestins used in contraception derive efficacy from this feature. Bebb, et al. randomized healthy men to receive either testosterone enanthate (100 mg weekly), or the same dosage of testosterone in combination with the progestin levonorgestrel, the addition of which virtually abolished LH and FSH secretion [13]. Decreased LH & FSH can cause secondary hypogonadism, thereby ↓androgen/estrogen ratio, causing gynecomastia.
Further, "progesterone and its derivatives...& progesterone mimics...were moderate binders to the AR. We earlier demonstrated that progesterone derivatives do not compete with 17β-estradiol (E₂) for ER binding (18, 30). It appears that progesterone derivatives could alter both AR- & PR- but not ER-mediated tissue responses." [3].
Estrogens up-regulate PR synthesis [2]. Further, activation of progesterone receptors has been linked to reduced expression of AR, thereby hampering the androgen-mediated inhibition on breast tissue growth observed in condition of normal hormonal homeostasis [16].
Progesterone and its derivatives may further cause gynecomastia by enhancing the effect of estradiol on breast tissues [6].
From my notes:
Megestrol acetate
17-hydroxy-6-methylpregna-3,6-diene-3,20-dione; Megace
Maygace; Megestat; Megestil; Megestin; Linmegestrol; Apo-megestrol; Endace
DrugBank (pdf)
* A progestin that is administered orally to treat anorexia and cachexia, HIV wasting, or serious unexplained weight loss and is also used as an antineoplastic agent to treat certain types of malignancy.
* ...has the same physiologic effects as natural progesterone. These effects include... increased basal body temperature, pituitary inhibition... has slight glucocorticoid activity and very slight mineralocorticoid activity...
* The precise mechanism of megestrol's antianorexic and anticachetic effects is unknown, but its progestin antitumor activity may involve suppression of LH by inhibition of pituitary function...weight gain effect is related to its appetite-stimulant or metabolic effects rather than its glucocorticoid-like effects or the production of edema.
* Megestrol may alter metabolic pathways via interference with the production or action of mediators such as cachectin, a hormone that inhibits adipocyte lipogenic enzymes (thereby increasing lipogenesis)
* Drug-Drug Interactions:
- Methyltestosterone: Megestrol acetate may decrease the excretion rate of Methyltestosterone which could result in a higher serum level
- Testosterone: The metabolism of Megestrol acetate can be increased when combined with Testosterone (applies to cypionate, enanthate, propionate, etc.)
