Androgenic alopecia (AGA) is a term that describes a characteristic pattern of hair loss. In men, it can appear as early as puberty and generally occurs in the third decade of life. In women, it is more frequent from the age of 60.
AGA characteristically progresses as follows: first, there is a transformation of thick, pigmented, terminal hair into small, hypopigmented, fine hairs. This transformation is caused by an increase in the affinity of hair receptors on the scalp for androgens. This increase constitutes an inherited genetic variant. Those susceptible individuals, after puberty, begin to express an increased affinity for androgens, which, by mechanisms not fully elucidated, modify the life cycle of the hair, notably decreasing the time of the anagen stage from 5 years to only a few months.
Among the androgens involved, dihydrotestosterone stands out as having a 5 times greater affinity for scalp hair.
The enzyme 5-alpha-reductase is in charge of transforming testosterone into dihydrotestosterone, and it was found that those individuals with a congenital deficit of this enzyme did not present an androgenic baldness pattern. It is for these reasons that a 5-a-reductase blocker constituted an attractive challenge to treat AGA, and so far it has shown encouraging results, however, there are some controversies about its use that are raised below.
Finasteride and Dutasteride as treatment of AGA
DHT binds to the androgen receptors present in the hair follicle with an afinity 5 times higher than testosterone, activating the genes responsible for the phenomenon of progressive follicle miniaturization. There are 3 isoenzymes of 5-a-reductase, although we will only refer to types 1 and 2: type 1 is mainly found in the sebaceous and sweat glands, and type 2 is located in the prostate and hair follicles.
Finasteride inhibits mainly type 2 isoenzyme, decreasing serum DHT by 65%, while dutasteride inhibits both isoenzymes, decreasing serum DHT by 90%. Dutasteride is 3 times more potent than finasteride in inhibiting type 2 5-alpha-reductase isoenzyme and 100 times more potent in inhibiting type 1. It also has a much longer half-life (4-5 weeks versus 6-8 h for finasteride).
In 1992, finasteride was approved by the FDA for the treatment of benign prostatic hyperplasia. 5 years later, it achieved FDA approval for the use of finasteride as a treatment for androgenic baldness. Both are approved to treat benign prostatic hyperplasia and finasteride alone for male androgenic alopecia.
Dutasteride has been shown to be effective in the treatment of male AGA (MAGA) at doses of 0.5 mg/day, significantly increasing the number of hairs after 6 months of treatment compared to placebo. And finasteride at a dose of 1mg/day.
Do Finasteride and Dutasteride cause sexual dysfunction?
Classically, these drugs have been associated with a discreet increase in the risk of adverse effects in the sexual sphere, generally minor and well tolerated; however, for some years now, the post-finasteride syndrome has been described in which the presence of sexual and non-sexual adverse effects after treatment with this drug has been described. Among the sexual ones, decreased libido, erectile dysfunction and ejaculate alteration are the most frequent, with erectile dysfunction standing out among 2-7% of patients taking finasteride. Some authors suggest that these adverse effects are more frequent in patients taking dutasteride, and that the pathogenic mechanism that could explain the erectile dysfunction is interference with the activation of the enzyme nitric oxide synthetase.
Clinical studies suggest that these adverse effects are reversible upon discontinuation of the medication, or attenuated with prolonged use of the drug; however, some authors have suggested that, in susceptible patients, these symptoms may be irreversible or persistent and could even lead to suicidal ideation. Discrepancies could be explained by possible selection biases and the absence of placebo in these studies. In addition, it has recently been shown that patients with male androgenic alopecia present psychosocial alterations due to the change in body image caused by alopecia, which could lead to alterations in sexual desire and erectile function, without being associated with the use of drugs.
It has been described that these adverse effects are more frequent in those subjects who have been previously informed, sometimes erroneously by family and friends, suggesting an underlying psychological rather than pharmacological mechanism, which is called the “nocebo effect”. It should also be considered that the most frequent causes of abandonment of finasteride treatment are not related to the presence of sexual adverse effects but to the absence of clinical results expected by the patients. In any case, well-designed studies, appropriate to pharmacovigilance programs, could provide more data in the future.
