The human penis is composed of the paired dorsal corpora cavernosa and the ventrally placed corpus spongiosum. The corpus spongiosum contains the urethra and is contiguous with the glans penis distally. Each corpus is surrounded by a fibrous sheath, the tunica albuginea. Between the two corpora cavernosa is an incomplete perforated septum allowing them to function in unison.

Surrounding all three corpora is an additional fibrous layer, Buck’s fascia. Superficial to Buck’s fascia is Colles’ fascia extending from the base of the glans to the urogenital diaphragm where it is contiguous with Scarpa’s fascia.

Superficial to Colles’ fascia is the skin.
Proximally, the corpora cavernosa form the penile crura, which are anchored to the pubic rami and are covered by the ischiocavernosus muscles. The proximal corpus spongiosum forms the penile bulb, which is enveloped in the bulbospongiosus muscle. The suspensory ligament of the penis arises from the linea alba and pubic symphysis and inserts on the tunica albuginea to support the pendulous portion of the penis.

Corpora The corpora cavernosa are two spongy cylinders comprised primarily of arterial sinusoids and smooth muscle surrounded by the tunica albuginea. The cavernosal tunica albuginea is 2–3 mm thick in the flaccid state and is composed mostly of collagen fibers with a smaller portion being elastic fibers. The cavernosal tunica has an inner circular layer and an outer longitudinal layer of fibers. The histologic appearance of corpus spongiosum is similar to the corpora cavernosa and it contains larger sinusoids. Additionally, the tunica albuginea surrounding this corpus is thinner, has only one circular fiber layer, and contains more elastic fibers.

Glans The glans forms the distal portion of the penis. It is contiguous with the corpus spongiosum. It is covered with very thin, firmly adherent skin. Additionally, the tunica on the glans albuginea is absent.

The human penis is composed of the paired dorsal corpora cavernosa and the ventral corpus spongiosum each of which is encased within a fibrous sheath, the tunica albuginea, and then all of which are enclosed within Buck’s fascia, Colles’ fascia, and the skin.

The spongiosum contains the urethra and is contiguous with the glans distally. The arterial supply to the penis is from the four terminal branches of the paired penile arteries, which are themselves branches of the internal pudendal arteries. The external iliac, obturator, vesical, and femoral arteries provide accessory arterial supply to the penile artery in some cases.

Venous outflow originates from postcavernous venules that coalesce to form emissary veins. These veins empty into the cavernous vein, the deep dorsal vein, and the superficial dorsal vein depending on their origin within the penis. Efferent innervation is from parasympathetic, sympathetic, and somatic sources. Somatosensory afferents course from the penis to central sites.

The maintenance of penile flaccidity and the erectile response are controlled via intercommunicating supraspinal and spinal reflex pathways. During the flaccid state, antierectile neural input, primarily via sympathetic efferents, acts to limit blood flow to the penis to a quantity sufficient to meet physiologic needs but insufficient for erection. Following either physical or psychological sexual stimulation proerectile neural signals are sent to the penis primarily via parasympathetic tracts. This input initiates the erectile response via neurotransmitter release onto postsynaptic smooth muscle cells within the corporal bodies.

Nitric Oxide (NO) is the main proerectile neurotransmitter. The resultant molecular cascade leads to a decrease in intracellular Ca2+ and arteriolar smooth muscle relaxation.

This relaxation allows for increased blood flow and subsequent corporal engorgement with increasing penile rigidity. As the corpora become engorged, the emissary veins are compressed by within the tunica albuginea limiting venous outflow.

The increased arterial inflow and limited venous outflow increases intracorporal pressure and leads to erection. As proerectile input ceases, the secondary molecular messenger cGMP is hydrolyzed allowing for a rise intracellular Ca2+, subsequent smooth muscle contraction, decreased penile blood flow and a return to flaccid state physiology.

Overview of Trials

Two studies were identified and were judged to be eligible to address the present question. Both trials were randomized5,77 comparing the efficacy of combined treatment of testosterone (gel or patch) plus sildenafil to that of sildenafil alone in ED patients with low testosterone levels who failed to respond (score of 2–3 on IIEF–Q3/Q4) to prior treatment with sildenafil.

Gel testosterone plus sildenafil versus sildenafil. In this double-blind trial5 75 hypogonadal men (mean age: 58 years; total testosterone <400 ng/dL) with ED were randomized to 1 percent gel testosterone plus 100 mg sildenafil versus 100 mg sildenafil for 12 weeks. At the end of the study, the proportions of men with scores of 4-5 on IIEF–Q3/Q4 was statistically nonsignificantly greater in the combination therapy group than in the sildenafil only group (51.4 versus 39.4 percent; RR = 1.30, 95 percent CI 0.77–2.21). Men who received gel testosterone plus sildenafil also had greater mean change from baseline in the IIEF “EF” domain score at week 4 (4.4 versus 2.1, 95 percent CI: 0.3–4.7). One patient withdrew from the combination treatment arm due to an adverse event.

Testosterone patch plus sildenafil versus sildenafil. In this open label trial,77 20 hypogonadal men (mean age:56 years; total testosterone:10-13 nmol/L) with ED were randomized to receive either 5 mg patch testosterone plus 100 mg sildenafil or 100 mg sildenafil plus placebo patch. After one month of treatment, patients in the patch testosterone plus sildenafil group had either numerically or statistically significant improvements for the following outcomes:

• “EF domain” score (21.8 +/- 2.1 versus 14.2 +/- 0.7, WMD = 7.60, 95 percent CI: 6.23–8.97),
• number of sexual intercourses (2.8 +/- 0.9 versus 1.5 +/- 0.5, WMD = 1.30, 95 percent CI: 0.66–1.94),
• intercourse satisfaction (12.1 +/- 1.6 versus 7.7 +/- 1.2, WMD = 4.40, 95 percent CI: 3.16–5.64),
• reported improved erections (80 versus 10 percent, RR = 8.00, 95 percent CI: 1.21–52.69).