Tadalafil, commonly known for treating erectile dysfunction (ED), has shown interesting interactions in the context of testosterone replacement therapy (TRT) and estrogen management.

Tadalafil and Testosterone

Ratio

1. Impact on Hormone Levels:

   • Long-term administration of tadalafil has been associated with changes in sex hormone levels. A study found that taking tadalafil for 12 months resulted in a significant decrease in estradiol (E) levels. This change led to an increased testosterone
     (T
     ) ratio¹.
   • Interestingly, the reduction in estradiol was more noticeable in lean individuals compared to obese ones¹.

2. Mechanism of Action:

   • Tadalafil appears to influence hormone levels through its effects on aromatase, the enzyme responsible for converting testosterone to estrogen. Studies in vitro have shown that tadalafil can decrease aromatase mRNA and protein expression. This reduction potentially increases local testosterone levels while decreasing estrogen levels².
   • Additionally, tadalafil has been found to increase androgen receptor (AR) expression and decrease estrogen receptor (ER) expression. This shift favors an androgenic pathway over an estrogenic one².

3. Implications for TRT:

   • When used in conjunction with TRT, tadalafil could help in managing estrogen levels, which is crucial since excessive estrogen can counteract the benefits of TRT and lead to side effects like gynecomastia.
   • By modulating the T
     ratio, tadalafil may help optimize the effects of TRT, ensuring better androgenic outcomes.

Clinical Observations

• Enhanced Sexual Function: Alongside hormonal adjustments, patients have reported sustained improvements in erectile function with long-term tadalafil use¹.

In summary, tadalafil not only helps with erectile dysfunction but also has promising benefits in optimizing the testosterone

balance, especially in the context of TRT. This could be particularly beneficial for those looking to mitigate the potential estrogenic side effects of TRT.

Footnotes

1. Emanuela A Greco, "Testosterone

   ratio changes associated with long-term tadalafil administration: a pilot study," PubMed. ↩ ↩² ↩³

2. A Aversa, "Tadalafil modulates aromatase activity and androgen receptor expression in a human osteoblastic cell in vitro model," PubMed. ↩ ↩²