Androgens and erectile dysfunction: from androgen deficiency to treatment.

Androgen deficiency can be caused by multiple etiologies including hypothalamic-pituitary lesions and injuries, testicular-related diseases and injuries, endocrine and metabolic disorders, medication side effects, and age.

• The literature search covered the past 10 years using PubMed and Google Scholar databases.
• Multiple upstream and downstream causes of androgen deficiency were identified and categorized.
• Age-related decline was identified as a distinct cause of androgen deficiency separate from pathological conditions.

Androgen deficiency leads to erectile dysfunction by inhibiting the NOS/NO/cGMP pathway.

• The NOS/NO/cGMP pathway refers to the nitric oxide synthase/nitric oxide/cyclic guanosine monophosphate signaling cascade.
• This pathway is a key molecular mechanism by which androgens regulate erectile function.
• Disruption of this pathway represents one of several mechanisms by which androgen deficiency causes ED.

Androgen deficiency alters the expression of ion channel proteins in penile tissue.

• Changes in ion channel protein expression were identified as a distinct mechanism contributing to androgen deficiency-related ED.
• This mechanism was identified alongside the NOS/NO/cGMP pathway inhibition as a contributor to erectile dysfunction.
• The specific ion channels affected were discussed within the context of corpus cavernosum function.

Androgen deficiency induces oxidative stress, cell death, and fibrosis in penile corpus cavernosum cells.

• Structural changes to the penile corpus cavernosum were identified as a consequence of androgen deficiency.
• Oxidative stress, cell death, and fibrosis collectively affect both the structure and function of the penile corpus cavernosum.
• These cellular-level changes represent a pathophysiological basis for androgen deficiency-related ED.

Testosterone replacement therapy is effective at improving serum testosterone levels and erectile function in patients with androgen deficiency.

• Testosterone replacement therapy was identified as the primary treatment for androgen deficiency-related ED.
• The therapy addresses both the hormonal deficit (serum testosterone levels) and the functional outcome (erectile function).
• The review was based on literature from the past 10 years identified through PubMed and Google Scholar.

For patients who must maintain a low androgenic state, erectile function can be improved through alternative therapies.

• Alternative treatments identified include lifestyle changes, phosphodiesterase type 5 (PDE5) inhibitors, low-intensity extracorporeal shock wave therapy, and stem cell therapy.
• These options are specifically relevant for patients who cannot receive testosterone replacement therapy due to the need to maintain a low androgenic state.
• Multiple therapeutic modalities were identified, suggesting a range of options for this patient population.

The specific mechanisms by which androgen deficiency leads to erectile dysfunction are not yet fully understood, representing an area for further study.

• The authors identified ongoing gaps in understanding of how androgen replacement therapy improves erectile function.
• How to improve maintenance of erectile function in patients with hypoandrogenic status was identified as a future research priority.
• The paper calls for further study into both the mechanisms and optimal treatments for androgen deficiency-related ED.