Male hormone reverses cell aging in clinical trial

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Nelson Vergel

“One of the processes associated with aging is progressive shortening of telomeres, DNA-protecting structures at the ends of chromosomes, like the plastic tips on shoelaces,” Calado said. “Each time a cell divides, its telomeres get shorter. Eventually, the cell can’t replicate anymore and dies or becomes senescent. However, telomerase can keep the length of telomeres intact, even after cell division.”
In practice, he added, telomere length is a laboratory measure of a cell’s “age.” Some cells avoid aging by using telomerase to lengthen their telomeres through the addition of DNA sequences, thereby maintaining their capacity to multiply and “stay young.”

Treatment with the steroid danazol, a synthetic male hormone, was tested for two years in 27 patients with aplastic anemia owing to telomerase gene mutations.
“In a healthy adult, telomere length varies from 7,000 to 9,000 base pairs on average. A normal person’s telomeres lose 50 to 60 base pairs per year, but a patient with telomerase deficiency can lose between 100 and 300 base pairs per year,” Calado said. “In the patients who received danazol, telomere length increased by 386 base pairs on average over two years.”

Note: Some doctors use this drug off-label to increase free testosterone

"Danazol is known to bind to two steroid hormone carrier proteins: sex hormone-binding globulin (SHBG), which binds androgens and estrogens; and transcortin (corticosteroid-binding globulin), which binds progesterone and cortisol.[SUP][18][/SUP][SUP][9][/SUP] Binding of danazol to SHBG is considered to be more important clinically.[SUP][18][/SUP] By occupying SHBG and transcortin, danazol increases the ratio of free to plasma protein-bound testosterone, estradiol, progesterone, and cortisol.[SUP][18][/SUP][SUP][9][/SUP] The following table shows the difference in testosterone levels in untreated premenopausal women and women treated with danazol:[SUP][18][/SUP]

[TH="bgcolor: #F2F2F2, align: center"]Group[/TH]
[TH="bgcolor: #F2F2F2, align: center"]Free[/TH]
[TH="bgcolor: #F2F2F2, align: center"]Albumin[/TH]
[TH="bgcolor: #F2F2F2, align: center"]SHBG[/TH]

Normal (no danazol)




Danazol treatment




As can be seen, the percentage of free testosterone is tripled in women being treated with danazol.[SUP][18][/SUP][SUP][22][/SUP] The ability of danazol to increase free testosterone levels suggests that a portion of its weak androgenic effects are mediated indirectly by facilitating the activity of testosterone and dihydrotestosterone through the displacement of them from SHBG.[SUP][18][/SUP][SUP][22][/SUP] In addition to binding to and occupying SHBG however, danazol also decreases the hepatic production of SHBG and therefore SHBG levels, and so downregulation of SHBG may be involved as well.[SUP][18][/SUP][SUP][9][/SUP] Danazol likely decreases hepatic production of SHBG by reducing estrogenic and increasing androgenic activity in the liver (as androgens and estrogens increase and decrease, respectively, hepatic SHBG synthesis).[SUP][23][/SUP] In accordance with the notion that suppression of SHBG is involved in the androgenic effects of danazol, the drug has synergistic rather than additive androgenic effects in combination with testosterone in bioassays (which is most likely secondary to the increased free testosterone levels).[SUP][20]"
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