Finasteride's Mechanism of Action and Effects

Hormonal Effects

Finasteride works by inhibiting the 5α-reductase type II enzyme, which normally converts testosterone to the more potent androgen DHT, thereby increasing serum testosterone by approximately 10-20% while dramatically reducing DHT by about 70% 1, 2, 3
The American Urological Association notes that finasteride increases serum testosterone levels, which remain within the normal physiologic range, despite this increase 1, 2, 3

The European Association of Urology guidelines state that despite the increase in serum testosterone, sexual side effects still occur, with sexual dysfunction occurring in approximately 2-4% more patients taking finasteride compared to placebo 4
The Prostate Cancer Prevention Trial found that 67.4% of men on finasteride reported erectile dysfunction compared to 61.5% on placebo, with a relative risk of 1.10 4
Finasteride contributes 3.21 points on the sexual function scale, while each year of aging contributes 1.26 points, according to the guidelines from the American Urological Association 4

The European Association of Urology recommends that when monitoring patients on finasteride, remember that PSA levels are suppressed by approximately 50% after 12 months of therapy, due to the reduction in prostatic DHT and subsequent prostate volume reduction 4, 5, 6, 7
Both 1mg and 5mg doses of finasteride produce similar hormonal effects in men aged 50 years and older, according to the guidelines from the American Urological Association 4

Clomiphene citrate acts as a selective estrogen‑receptor modulator that blocks hypothalamic estrogen receptors, thereby increasing GnRH release and stimulating pituitary LH and FSH secretion, which directly enhances testicular testosterone production (European Association of Urology) 8.
Finasteride inhibits peripheral 5α‑reductase type II, reducing conversion of testosterone to DHT; because it works downstream of the hypothalamic‑pituitary axis, its pathway does not overlap with that of clomiphene (European Association of Urology) 8.

Finasteride lowers serum prostate‑specific antigen (PSA) by ~50 % after 12 months; when assessing prostate health in patients taking both drugs, the measured PSA should be doubled to obtain the true value (American Urological Association) 9.

Finasteride is associated with gynecomastia in 4.5 % of users versus 2.8 % on placebo (relative risk ≈ 1.64); clinicians should be aware of this risk when combining it with clomiphene, which can raise estradiol (American Society of Clinical Oncology) 10.
If clomiphene‑induced estradiol elevation produces symptoms (e.g., gynecomastia or nipple tenderness), adding an aromatase inhibitor such as anastrozole or letrozole can normalize estradiol levels and improve hormonal and semen parameters without serious adverse effects (European Association of Urology) 8.

In men treated with finasteride, sexual side effects such as decreased libido, erectile dysfunction, and ejaculatory dysfunction are generally reversible and become uncommon after the first year of therapy, as reported in three 2003 studies published in The Journal of Urology【11】【12】【13】.