It can also have adverse effects on the cardiovascular system. AAS like methyltestosterone stimulate erythropoiesis (red blood cell production) and increase hematocrit levels and at high dosages can cause polycythemia (overproduction of red blood cells), which can greatly increase the risk of thrombic events such as embolism and stroke. With long-term treatment, AAS can increase the risk of benign prostatic hyperplasia and prostate cancer. Violent and even homicidal behavior, hypomania/mania, depression, suicidality, delusions, and psychosis have all been associated with very high dosages of AAS. Interactions
Aromatase inhibitors can be used to reduce or prevent the estrogenic effects of methyltestosterone and 5α-reductase inhibitors can be used to prevent its potentiation in so-called "androgenic" tissues and thereby improve its ratio of anabolic to androgenic activity and reduce its rate of androgenic side effects. Antiandrogens like bicalutamide and cyproterone acetate can block both the anabolic and androgenic effects of AAS like methyltestosterone. Pharmacology
Pharmacodynamics
As an AAS, methyltestosterone is an agonist of the androgen receptor (AR), similarly to androgens like testosterone and dihydrotestosterone (DHT). It is a substrate for 5α-reductase like testosterone, and so is potentiated analogously in so-called "androgenic" tissues like the skin, hair follicles, and prostate gland via transformation into the more potent AR agonist mestanolone (17α-methyl-DHT). As such, methyltestosterone has a relatively low ratio of anabolic to androgenic activity, with a similar ratio to that of testosterone (close to 1:1), and this makes it among the most androgenic AAS.
Due to efficient aromatization into the potent and metabolism-resistant estrogen methylestradiol (17α-methylestradiol), methyltestosterone has relatively high estrogenicity and hence potential for estrogenic side effects such as gynecomastia and fluid retention. The drug possesses negligible progestogenic activity.Due to its combined disadvantages of a relatively poor ratio of anabolic to androgenic activity, unusually high estrogenicity, and the potential for hepatotoxicity (as with other 17α-alkylated AAS), methyltestosterone has not been used as commonly as many other AAS either in medicine or for physique- or performance-enhancing purposes. Pharmacokinetics
Absorption
Methyltestosterone has dramatically improved oral bioavailability and metabolic stability relative to testosterone. This difference is due to the C17α methyl group, which results in steric hindrance and prevents metabolism. The oral bioavailability of methyltestosterone is about 70%, and it is well-absorbed from the gastrointestinal tract. Methyltestosterone can also be taken buccally or sublingually. Although effective orally, methyltestosterone is more effective by these non-oral routes, which are said to approximately double its bioavailability and require half the oral dosage.Circulating levels of methyltestosterone with administration of 1.25 to 2.5 mg/day oral methyltestosterone in women are in the range of 20 to 30 ng/dL. For comparison to testosterone, methyltestosterone is at least as potent as an AAS. However, due to the large decrease in sex hormone-binding globulin (SHBG) levels and hence increase in free unbound testosterone caused by methyltestosterone, androgenic effects may be greater than reflected merely by methyltestosterone levels. Distribution
Methyltestosterone is highly protein-bound, by approximately 98%.