Clinical use of alprostadil topical cream in patients with erectile dysfunction: a review

Figures & data

Table 1 Organic and psychogenic origins of erectile dysfunction

Organic	Psychogenic
Neurogenic	Predisposing factors
• Central: cerebrovascular accident, multiple sclerosis, spinal cord injury	• Traumatic past experiences • Strict upbringing • Inadequate sex education
• Peripheral: Postradical prostatectomy	• Physical and mental health problems • Long-term relationship problems
Endocrine	Precipitating factors
• Diabetes mellitus, hypogonadism, hyperprolactinemia	• Acute relationship problems • Major life events • Daily stressors
Vasculogenic	Other factors
• Arterial: atherosclerosis, trauma • Venous: failure of veno-occlusive mechanism	• Absence or lack of knowledge of available treatment options for erectile dysfunction
Drug- and substance-induced
• Antihypertensive agents, antidepressants, antiandrogens, central nervous system depressants (eg benzodiazepines) • Cigarettes, alcohol, recreational drugs (eg, marijuana, heroin)
Systemic disease
• Cardiovascular, pulmonary, liver, and renal disease
Local disease
• Peyronie’s disease, penile fracture

Figure 1 Physiological pathway to erectile response.

Notes: Normally (in blue), erection begins with an external stimulus, leading to an accumulation of nitric oxide (NO). NO then activates cGMP, leading to a decrease in the amount of intracellular calcium (Ca²⁺), which relaxes cavernosal smooth muscle and leads to erection. Alprostadil (in orange), a prostaglandin E1 (PGE1) analog, utilizes the cAMP pathway to decrease intracellular calcium, leading to erection. PDE5 inhibitors (in green) block PDE5, an enzyme which degrades the cGMP needed for erection, thus prolonging the duration of externally stimulated erection.
Abbreviations: PGE1, prostaglandin E1; cAMP, cyclic adenosine monophosphate; cGMP, cyclic guanosine monophosphate; PDE5, phosphodiesterase type 5.

Table 2 Limitations and adverse events of erectile dysfunction (ED) treatment with phosphodiesterase type 5 (PDE5) inhibitors

Limitation	Adverse event
Systemic side effects	• Headache • Visual disturbance • Priapism • Flushing • Muscular pain • Dyspepsia • Sinus congestion
Drug interactions • Inhibitors/inducers of P-450* • Antihypertensive agents • Alpha-blockers** • Nitrates	• Variable efficacy as a result of increased/decreased PDE5 inhibitor plasma concentration • Enhanced variable efficacy • Severe hypotension
Decreased absorption with fatty meals	• Decreased efficacy • Loss of spontaneity

Notes:

* Cytochrome P-450 inhibitors;

** alpha-blockers are used for the treatment of hypertension and benign prostatic hyperplasia.

Table 3 Efficacy and safety of topical alprostadil cream for the treatment of erectile dysfunction: summary of key clinical trials

Study	Design	Patient population	Topical alprostadil dosage	Efficacy	Treatment-related adverse eventsa
Goldstein et al^Citation37	Phase I: RCT [1:1]	n=60 31, alprostadil 29, placebo	1% alprostadil + 5% SEPA	Improvement in vaginal penetration: 12/31 (39%) in alprostadil vs 2/29 (7%) in placebo, P<0.005	30% - placebo 50% - alprostadil
Padma-Nathan et al^Citation38	Phase II: multicenter, double-blind, placebo-controlled RCT [3:1]	n=303 161 (study 1) - mild-to-moderate EDb 121, alprostadil 40, placebo 142 (study 2) - severe EDc 107, alprostadil 35, placebo	Study 1 - 50, 100, or 200 μg Study 2 - 100, 200, or 300 μg	Change in EF domain of IIEF from baseline: Study 1: 3.7±1.2 in alprostadil vs. −0.8±1.1 in placebo, P<0.01 Study 2: 9.4±1.5 in alprostadil vs. 2.7±1.3 in placebo, P<0.01	Study 1: 53% - placebo 67% - 50 μg 67% - 100 μg 78% - 200 μg Discontinuation due to AE: 14%	Study 2: 11% - placebo 30% -100 μg 60% - 200 μg 51% -300 μg Discontinuation due to AE: 11%
Padma-Nathan et al^Citation40	Phase III: multicenter, double-blind, placebo-controlled, long-termd RCT [3:1]	n=1,732 1,298, alprostadil 434, placebo	100, 200, or 300 μg	Change in EF domain of IIEF from baseline (P<0.001):  1.6 for 100 μg  2.5 for 200 μg  2.4 for 300 μg  −0.7 for placebo	12% - placebo 46% - 100 μg 62% - 200 μg 67% - 300 μg Discontinuation due to AE: 2.7%
Rooney et al^Citation44	Open label: multicenter, long-terme study	n=1,101	Before titration: 1,101, 200 μg After titration: 25, 100 μg  124, 200 μg  846, 300 μg	Change in EF domain of IIEF from baseline (P<0.001):  13.0 for 100 μg  13.2 for 200 μg  10.1 for 300 μg	Before titration: 23% - 200 μg After titration: 36% - 100 μg 42% - 200 μg 34% - 300 μg Discontinuation due to AE: 4.3%

Notes:

a Treatment-related adverse events (AEs) usually included penile burning, genital pain, and erythema, which resolved within 2 hours;

b mild-to-moderate ED defined as IIEF 14-21;

c severe EF defined as IIEF <14;

d long term defined as 3 months in this study;

e long term defined as 9 months in this study.

Abbreviations: RCT, randomized control trial; SEPA, soft enhancer of percutaneous absorption; ED, erectile dysfunction; EF, erectile function; IIEF, International Index of Erectile Function.

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