Melatonin Improves Erectile Function in Rats With Chronic Lower Body Ischemia

Norifumi Sawada, Masanori Nomiya, Mona Zarifpour, Takahiko Mitsui, Masayuki Takeda, and Karl-Erik Andersson

ONLINE: February 2016 – The Journal of Sexual Medicine

DOI: 10.1016/j.jsxm.2015.12.018


Erectile dysfunction (ED) is often linked to aging, diabetes mellitus, hypercholesterolemia, and hypertension. Ischemia and oxidative stress are thought to impair the NO system and interfere with relaxation of the corpus cavernosum.

Similarly, arterial occlusive disease (atherosclerosis), along with penile ischemia, can lead to ED. However, the mechanisms are not completely known.

Melatonin has free radical scavenging and antioxidative properties. While some studies have shown increased sexual activities in rats taking melatonin, others have found that melatonin inhibits sexual activity.

This study investigates whether treatment with melatonin can reduce damage and improve function in rats with chronic lower body ischemia-induced ED.


The study involved 44 adult male Sprague-Dawley rats, divided into three groups: control, sham (treated with pelvic ischemia alone), and treatment (pelvic ischemia and melatonin).  Pelvic ischemia was induced via mechanical injury of the iliac arteries combined with a 2% cholesterol diet for eight weeks.

Eight weeks after endothelial injury, erectile responses were assessed in all rats. Further studies were done on extracted tissues to identify potential underlying mechanisms observed. 


The researchers found the following:

• Assessment of erectile function showed improved responses in melatonin treated rats (improved engorgement and pelvic thrusts) compared to sham rats and similar responses compared to controls.
• Endothelial damage to the internal iliac arteries was similar between sham and treated rats, suggesting that melatonin did not reduce the extent of ischemia produced, but rather helped to preserve erectile function via other mechanisms.
• Increased collagen was noted in both sham and treatment animals, but not in controls.
• Melatonin improved protein expression of eNOS, nNOS, and iNOS compared to sham animals, although these values were still inferior to control animals.
• Smooth muscle relaxation was also partially preserved in melatonin-treated animals compared to sham treated animals.


The authors noted that melatonin treatment in this study did the following:

• preserved the erectile responses to apomorphine
• decreased collagen deposition in the corpus cavernosum
• preserved contractile and relaxant responses in isolated corpus cavernosum strips to electrical field stimulation and sodium nitroprusside
• increased eNOS and nNOS and decreased iNOS expression in the corpus cavernosum

“These results indicate that melatonin protects endothelial as well as muscle- and nerve-related functions,” the authors wrote.

They added, “Chronic administration of melatonin may exert its protective effects on the chronically ischemic [corpus cavernosum] through its free radical scavenging and antioxidative properties.”