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Testosterone and Sexual Function

Erections are clearly androgen-dependent. Testosterone has always been assumed to play a major role in erectile dysfunction (ED) because of the following reasons:

  • A decline in testosterone levels happens with ageing and a time period when the incidence of ED increases. [404]
  • Castration usually leads to impairment in sexual function. [405]
  • Sexual function returns to normal in castrated men with severe testosterone deficiency who undergo testosterone replacement therapy. [406]

A number of high quality studies clearly support the benefits of testosterone replacement therapy in men with ED. In one study assessing the benefits of testosterone for ED, Kalinchenko et al. reported that combining oral testosterone undecanoate with anti-diabetic drugs in diabetic patients who do not respond to Viagra therapy, has been observed to restore sexual function. [407] This strongly suggests that testosterone is more potent than drugs for ED.
In a double-blind placebo controlled, cross-over study, Schiavi et al. treated healthy men with erectile dysfunction with biweekly injections of 200 mg of testosterone enanthate for over a period of 6 weeks separated by a washout period of 4 weeks. [408] Results suggest that testosterone administration among the subjects was able to increase ejaculatory frequency, reported sexual desire, masturbation, sexual experiences with partner, and sleep erections.
A recently published, multicenter study by Shabsigh et al. evaluated the safety and efficacy of testosterone gel in conjunction with sildenafil, a drug for ED. [409] The study involved hypogonadal men who did not respond to treatment with sildenafil alone for erectile dysfunction. After 12 weeks of testosterone gel therapy, the participants reported improved erectile response to sildenafil, suggesting that testosterone therapy may be considered for the treatment of ED in men with low testosterone levels, who have failed prior treatment with sildenafil alone.
In one meta-analysis covering several studies, Isidori et al. reported that the effect of testosterone replacement therapy in men with ED was directly related to blood levels of testosterone. [410] When compared to placebo, study participants who benefited most from the therapy were those with lower blood levels of testosterone, and those with near the normal testosterone levels had no benefit at all.
Larger meta-analyses of studies assessing the clinical benefits of testosterone concluded that testosterone therapy was able to increase libido in seven of eight studies and improved erections in five of six studies. [411] Interestingly, most of these studies report that testosterone replacement therapy has no adverse side effects.
In a well-designed intervention study, Aversa et al. reported that testosterone does have a specific mechanism of action on the erectile tissues of the penis. [412] The researchers assessed the effects of testosterone administration in 20 patients with ED who failed to respond to treatment with sildenafil. After the study period, treatment with transdermal testosterone raised the blood testosterone levels of the patients and led to an increase of arterial blood flow into the erectile tissues of the penis. This effect led to improvement in the symptoms of ED and enhanced the response to treatment with ED drugs.
In line with the above findings, Foresta et al. have documented that normal blood testosterone level is required for proper erectile function. [413] In severely hypogonadal men, the nocturnal penile tumescence (spontaneous erection of the penis during sleep or when waking up), ultrasound measurement of arterial blood flow within the erectile tissues of the penis, and visually stimulated erection in response to ED drugs were minimal. Surprisingly, the researchers reported that these parameters were normalized after six months of administration of testosterone patches, evidencing the crucial role of normal blood levels of testosterone for proper erectile function.
There are also numerous clinical trials that support the safety and efficacy of testosterone replacement therapy in treating low libido in both men and women. Results from these clinical trials have shown that men and women who received testosterone replacement therapy had better scores in various tests assessing sexual function, had increased sexual desire and improved self-confidence. [414-447]
Taken together, these available data suggest that higher circulating levels of testosterone are essential for normal erection and that testosterone replacement therapy may help improve low libido. Therefore, screening for hypogonadism in men and women with reduced libido and sexual dysfunction is crucial to identify the severity of testosterone deficiency and determine which patients may benefit from testosterone replacement therapy.

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