Use of phosphodiesterase type 5 inhibitors and risk of melanoma: a meta-analysis of observational studies

Figures & data

Figure 1 Flowchart of study selection.

Abbreviation: PDE5i, phosphodiesterase type 5 inhibitor.

Table 1 Characteristics of the included studies

Study	Design	Country	Population	Study year	No of participants	Mean age	Users of PDE5i	Follow-up	Confirmation of melanoma diagnosis	No of melanoma cases	Adjusted factors	NOS
						Years	Meds (n)	Person-years
Li et al^Citation15 2014	PC	USA	US male health professionals	2000–2010	25,848	64.8	Sildenafil (1,378)	204,870	Pathologically confirmed invasive cases in the medical records	142	Age, BMI, smoking, physical activity, childhood reaction to sun, number of severe sunburns, mole count, hair color, family history of melanoma, sun exposure, UV index, and other treatments for ED	8
Loeb et al^Citation16 2015	NCC	Sweden	Swedish men with no prostate cancer	2006–2012	24,390	74.5	Sildenafil, vardenafil, or tadalafil (2,148)	NR	The Swedish Prescribed Drug Register	4,065	CCI, marital status, educational level, and disposable income	8
Pottegard et al^Citation20 2016 (DNHR)	CC	Denmark	Danish men	2000–2012	77,495	61.0	Sildenafil, or tadalafil (448)	NA	The Danish Cancer Registry	7,045	Age, calendar time, use of medications, diagnoses of NMSC, DM, COPD, alcohol-related disease, renal disease, and education status	7
Pottegard et al^Citation20 2016 (KPNC)	CC	USA	Northern California men	2000–2014	32,279	64.0	Sildenafil or vardenafil (568)	NA	KPNC Cancer Registry	2,972	Age, calendar time, use of medications, diagnoses of NMSC, DM, COPD, alcohol-related disease, renal disease, and socioeconomic status	7
Lian et al^Citation18 2016	PC	UK	ED men	1998–2015	142,983	59.0	Sildenafil, vardenafil, or tadalafil (58,732)	698,479	UK Clinical Practice Research Datalink	440	Age, year of cohort entry, alcohol-related disorders, smoking status, BMI, CCI, precancerous skin lesions, use of antiparkinsonian drugs, immunosuppression, influenza vaccination, referral to colonoscopy, and PSA	9
Boor^Citation17 2016	RC	USA	USA men	2010–2014	525,523	NR	Sildenafil, vardenafil, or tadalafil (12,357)	NR	ICD9	74	Age and race	6
Matthews et al^Citation19 2016	PC	UK	UK men	1999–2014	706,097	57.0	Sildenafil, vardenafil, or tadalafil (145,104)	3,459,875	Data by National Health Service and ICD10	1,315	Age, index year, BMI, alcohol use, current drinker	9

Abbreviations: BMI, body mass index; CC, case–control; CCI, Charlson comorbidity index; COPD, chronic obstructive pulmonary disease; DM, diabetes mellitus; DNHR, Danish Nationwide Health Registries; ED, erectile dysfunction; ICD, International Classification of Diseases; KPNC, Kaiser Permanente Northern California; NA, not applicable; NCC, nested case–control; NMSC, nonmelanoma skin cancer; NOS, Newcastle–Ottawa Scale; NR, not reported; PC, prospective cohort; PDE5i, phosphodiesterase type 5 inhibitor; PSA, prostate-specific antigen; RC, retrospective case–control; UV, ultraviolet.

Figure 2 Forest plots for the meta-analysis of the association between PDE5i use and risk of melanoma presented as adjusted RR.

Notes: (A) Forest plots for all available observational studies; (B) forest plots stratified by study design (cohort studies or case–control studies). The effect size of each study is proportional to the statistical weight. The diamond indicates the overall summary estimate for the analysis; the width of the diamond represents the 95% CI.
Abbreviations: df, degrees of freedom; DNHR, Danish Nationwide Health Registries; IV, inverse variance; KPNC, Kaiser Permanente Northern California; PDE5i, phosphodiesterase type 5 inhibitor; RR, risk ratio; SE, standard error.

Figure 3 Forest plots for the meta-analysis of the association between PDE5i use and risk of melanoma presented as adjusted RR.

Notes: (A) Forest plots stratified by the timing of PDE5i administration (recent or early use of PDE5i); (B) forest plots stratified by the categories of PDE5i prescription (lowest or highest prescription category). The effect size of each study is proportional to the statistical weight. The diamond indicates the overall summary estimate for the analysis; the width of the diamond represents the 95% CI.
Abbreviations: df, degrees of freedom; DNHR, Danish Nationwide Health Registries; IV, inverse variance; KPNC, Kaiser Permanente Northern California; PDE5i, phosphodiesterase type 5 inhibitor; RR, risk ratio; SE, standard error.

Figure 4 Forest plots for the meta-analysis of the association between PDE5i use and risk of melanoma presented as adjusted RR.

Notes: (A) Forest plots stratified by the individual PDE5i used (sildenafil, tadalafil, or vardenafil); (B) forest plots stratified by the stages of melanoma (in situ, localized, or nonlocalized melanoma). The diamond indicates the overall summary estimate for the analysis; the width of the diamond represents the 95% CI.
Abbreviations: df, degrees of freedom; DNHR, Danish Nationwide Health Registries; IV, inverse variance; KPNC, Kaiser Permanente Northern California; PDE5i, phosphodiesterase type 5 inhibitor; RR, risk ratio; SE, standard error.

Figure 5 Funnel plot for the association between PDE5i use and risk of melanoma.

Notes: Each square indicates an included study. The x-axis represents the adjusted RR of the association between PDE5i use and risk of melanoma reported in each study, and the y-axis represents the SE of log (RR).
Abbreviations: PDE5i, phosphodiesterase type 5 inhibitor; RR, risk ratio; SE, standard error.

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