hey Alex, are you still using the egg white in your hair? thanks brother
5α-Reductase inhibitors like
finasteride and
dutasteride inhibit 5α-reductase type II and/or other isoforms and are able to decrease circulating DHT levels by 65 to 98% depending on the 5α-reductase inhibitor in question.
[26][27][28][20] As such, similarly to the case of 5α-reductase type II deficiency, they provide useful insights in the elucidation of the biological functions of DHT.
[29] 5α-Reductase inhibitors were developed and are used primarily for the treatment of BPH. The drugs are able to significantly reduce the size of the prostate gland and to alleviate symptoms of the condition.
[14][30] Long-term treatment with 5α-reductase inhibitors is also able to significantly reduce the overall risk of prostate cancer, although a simultaneous small increase in the risk of certain high-grade tumors has been observed.
[15] In addition to prostate diseases, 5α-reductase inhibitors have subsequently been developed and introduced for the treatment of pattern hair loss in men.
[31] They are able to prevent further progression of hair loss in most men with the condition and to produce some recovery of hair in about two-thirds of men.
[13] 5α-Reductase inhibitors seem to be less effective for pattern hair loss in women on the other hand, although they do still show some effectiveness.
[32] Aside from pattern hair loss, the drugs are also useful in the treatment of hirsutism and can greatly reduce facial and body hair growth in women with the condition.
[33][16]
5α-Reductase inhibitors are overall
well-tolerated and show a low incidence of
adverse effects.
[34] Sexual dysfunction, including
erectile dysfunction,
loss of libido, and
reduced ejaculate volume, may occur in 3.4 to 15.8% of men treated with finasteride or dutasteride.
[34][35] A small increase in the risk of
affective symptoms including
depression,
anxiety, and
self-harm may be seen.
[36][37][38] Both the sexual dysfunction and affective symptoms may be due partially or fully to prevention of the synthesis of
neurosteroids like
allopregnanolone rather necessarily than due to inhibition of DHT production.
[36] A very small risk of
gynecomastia has been associated with 5α-reductase inhibitors (1.2 to 3.5%).
[34][39] Based on reports of 5α-reductase type II deficiency in males and the effectiveness of 5α-reductase inhibitors for hirsutism in women, reduced body and/or facial hair growth is a likely potential side effect of these drugs in men.
[13][16] There are very few studies evaluating the side effects of 5α-reductase inhibitors in women. However, due to the known role of DHT in male sexual differentiation, 5α-reductase inhibitors may cause
birth defects such as ambiguous genitalia in the male
fetuses of
pregnant women. As such, they are not used in women during pregnancy.
[34]
MK-386 is a selective 5α-reductase type I inhibitor which was never marketed.
[40] Whereas 5α-reductase type II inhibitors achieve much higher reductions in circulating DHT production, MK-386 decreases circulating DHT levels by 20 to 30%.
[41] Conversely, it was found to decrease sebum DHT levels by 55% in men versus a modest reduction of only 15% for finasteride.
[42][43] However, MK-386 failed to show significant effectiveness in a subsequent clinical study for the treatment of acne.
[44]
Biological activity[edit]
DHT is a
potent agonist of the AR, and is in fact the most potent known
endogenous ligand of the receptor. It has an
affinity (Kd) of 0.25 to 0.5 nM for the human AR, which is about 2- to 3-fold higher than that of
testosterone (Kd = 0.4 to 1.0 nM)
[45] and 15–30 times higher than that of
adrenal androgens.
[46] In addition, the
dissociation rate of DHT from the AR is 5-fold slower than that of testosterone.
[47] The
EC50 of DHT for activation of the AR is 0.13 nM, which is about 5-fold stronger than that of testosterone (EC50 = 0.66 nM).
[48] In
bioassays, DHT has been found to be 2.5- to 10-fold more potent than testosterone.
[45]
The
elimination half-life of DHT in the body (53 minutes) is longer than that of testosterone (34 minutes), and this may account for some of the difference in their potency.
[49] A study of transdermal DHT and testosterone treatment reported terminal half-lives of 2.83 hours and 1.29 hours, respectively.
[50]
Unlike other androgens such as testosterone, DHT cannot be converted by the enzyme
aromatase into an
estrogen like
estradiol. Therefore, it is frequently used in research settings to distinguish between the effects of testosterone caused by binding to the AR and those caused by testosterone's conversion to estradiol and subsequent binding to and activation of ERs.
[51] Although DHT cannot be aromatized, it is still transformed into metabolites with significant ER affinity and activity. These are 3α-androstanediol and 3β-androstanediol, which are predominant agonists of the ERβ.
[17]
