5α-Reductase inhibitor

Source: Wikipedia, the free encyclopedia.
5α-Reductase inhibitor
Chemical class
Steroids; Azasteroids
Legal status
In Wikidata

5α-Reductase inhibitors (5-ARIs), also known as dihydrotestosterone (DHT) blockers, are a class of

transgender women.[1][2]

These agents inhibit the

androgen-associated disorders
.

Medical uses

5-ARIs are clinically used in the treatment of conditions that are exacerbated by DHT:[3]

5-ARIs can be used in the treatment of

transgender women to help reduce body hair growth and scalp hair loss.[2]

They have also been explored in the treatment and prevention of prostate cancer. While the 5-ARI finasteride reduces the cancer risk by about a third, it also increases the fraction of aggressive forms of prostate cancer. Overall, there does not seem to be a survival benefit for prostate cancer patients under finasteride.[5]

Available forms

over-the-counter dietary supplement. It is also used under the brand name Permixon[citation needed] in Europe as a pharmaceutical drug for the treatment of benign prostatic hyperplasia[citation needed
].

5α-Reductase inhibitors marketed for clinical or veterinary use
Generic name Brand name(s) Isoforms Route(s) Launch
Alfatradiol Ell-Cranell Alpha, Pantostin ? Topical ?
Dutasteride Avodart 1, 2, 3 Oral 2001
Epristeride Aipuliete, Chuanliu 2, 3 Oral 2000
Finasteride Proscar, Propecia 2, 3 Oral 1992
Saw palmetto extract[citation needed] Permixon[citation needed] ? Oral[citation needed] ?

Side effects

5-ARIs are generally

breast tenderness, gynecomastia, depression, anxiety, self-harm, and dementia.[20][21][22] In addition, although 5-ARIs decrease the overall risk of developing prostate cancer, they have been found to increase the risk of developing certain rare but high-grade forms of prostate cancer.[19] As a result, the FDA has notified healthcare professionals that the Warnings and Precautions section of the labels for the 5-ARI class of drugs has been revised to include new safety information about the increased risk of being diagnosed with these rare but more serious forms of prostate cancer.[23] Finasteride has also been associated with intraoperative floppy iris syndrome and cataract formation.[24][25] Depressive symptoms and suicidality have been reported.[26]

Sexual dysfunction

loss of libido, and reduced ejaculate, may occur in 3.4 to 15.8% of men treated with finasteride or dutasteride.[19][27] This is linked to lower quality of life and can cause stress in relationships.[28] There is also an association with lowered sexual desire.[29] It has been reported that in a subset of men, these adverse sexual side effects may persist even after discontinuation of finasteride or dutasteride.[29]

Breast changes

5-ARIs have a small risk of

breast tenderness and gynecomastia (breast development/enlargement).[20] The risk of gynecomastia is about 1.3%.[20] There is no association of 5-ARIs with male breast cancer.[20][30]

Emotional changes

A 2017 population-based, matched-cohort study of 93,197 men aged 66 years and older with BPH found that finasteride and dutasteride were associated with a significantly increased risk of depression (HRTooltip Hazard ratio, 1.94; 95% CITooltip Confidence interval, 1.73–2.16) and self-harm (HR, 1.88; 95% CI, 1.34–2.64) during the first 18 months of treatment, but were not associated with an increased risk of suicide (HR, 0.88; 95% CI, 0.53–1.45).[31][32][33][21] After the initial 18 months of therapy, the risk of self-harm was no longer heightened, whereas the elevation in risk of depression lessened but remained marginally increased (HR, 1.22; 95% CI, 1.08–1.37).[31][32][21] The absolute increase in the rate of depression was 247 per 100,000 patient-years and of self-harm was 17 per 100,000 patient-years.[21][34] As such, on the basis of these findings, it has been stated that cases of depression in patients that are attributable to 5-ARIs will be encountered on occasion, while cases of self-harm attributable to 5-ARIs will be encountered very rarely.[34] There were no differences in the rates of depression, self-harm, and suicide between finasteride and dutasteride, suggesting that the specific 5-ARI used does not influence the risks.[33][21][34] The absolute risks of self-harm and depression with 5-ARIs remain low (0.14% and 2.0%, respectively).[35]

Pharmacology

The pharmacology of 5α-reductase inhibition is complex, but involves the binding of

NADPH to the enzyme followed by the substrate.[4][37]

Substrate + NADPH + H+ → 5α-substrate + NADP+

Beyond being a catalyst in the

lens, and might help make the aqueous humor itself.[39] 5α-Dihydroaldosterone is a potent antinatriuretic agent, although different from aldosterone. Its formation in the kidney is enhanced by restriction of dietary salt, suggesting it may help retain sodium.[40] 5α-DHP is a major hormone in circulation of normal cycling and pregnant women.[41]

Other enzymes compensate to a degree for the absent conversion of 5α-reductase, specifically with local expression at the skin of reductive

3β-hydroxysteroid dehydrogenase enzymes.[42]

In BPH, DHT acts as a potent cellular androgen and promotes prostate growth; therefore, it inhibits and alleviates symptoms of BPH. In alopecia, male and female-pattern baldness is an effect of androgenic receptor activation, so reducing levels of DHT also reduces hair loss.

History

Finasteride was the first 5-ARI to be introduced for medical use.

patent protection on finasteride and dutasteride has expired and both drugs are available as generic medications.[46][47]

Research

5-ARIs have been studied in combination with the nonsteroidal antiandrogen bicalutamide for the treatment of prostate cancer.[48][49][50][51][52][53][54]

See also

References

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