Penile vascular abnormalities in young men with persistent side effects after finasteride use for the treatment of androgenic alopecia
Mohit Khera, Jeffrey K. Than, James E. Anaissie, Ali A. Antar, Weitao Song, Boriss Y. Losso, Alexander W. Pastuszak, Taylor P. Kohn, Jorge Rivera Mirabal
Translational Andrology and Urology2020
In plain terms
Doctors at one US clinic compared 25 men who had taken finasteride for hair loss and reported lasting side effects with 28 men who had not taken it, using standard questionnaires. The finasteride group reported more urinary symptoms and more low mood, but their overall sexual-function scores were not worse and their erection scores were similar. Of the 24 men in the finasteride group who had a blood-flow scan of the penis, 17 had an abnormal or borderline result; the comparison group was not scanned. Two men in the finasteride group died by suicide during or after the study.
What it doesn’t show: It can't show that finasteride caused these differences, because the men were patients at a clinic for sexual problems, the comparison group was older and heavier and often skipped the questionnaires, and only the finasteride group had the scan.
Summary (paraphrased)
In what the authors described as a prospective case-control study, 25 young men with persistent adverse effects after finasteride for hair loss were compared with 28 controls using validated questionnaires (IIEF, IPSS, PHQ-9, sleepiness scales, androgen-deficiency scales); only the finasteride group underwent penile duplex Doppler ultrasound. Of the 24 men scanned, 17 had some vascular abnormality: arterial insufficiency in 8, venous leak in 4 and a borderline result in 5. The finasteride group's total IIEF score was higher (better) than the controls' (median 35 vs 29), with no difference in the erectile function domain (9 vs 11, p = 0.378). The finasteride group reported more urinary symptoms (IPSS 10 vs 3) and depressive symptoms (PHQ-9 10 vs 1), and 2 of the 25 men died by suicide during or after the study.
Evidence
Extracted from the full text; page numbers refer to the paper. The library’s own notes are labelled as such.
- Design
- Case–control studySingle-centre comparison of men with persistent symptoms after finasteride for hair loss and men without 5-ARI exposure (the authors call it a prospective case-control study), with penile duplex Doppler ultrasound in the finasteride group only
- Setting
- Urology clinic, Baylor College of Medicine Medical Center, Houston, Texas (USA), March 2013 to September 2018
- Population
- Men over 18 seen for sexual dysfunction at the principal investigator's clinic. Cases, men who had taken finasteride for hair loss (one later took dutasteride for 24 months) and reported persistent effects; median age 38 (IQR 33–42), median BMI 24.5. Controls, men without 5-ARI exposure being evaluated for circumcision; median age 41 (IQR 35–62, p = 0.13), median BMI 30.6 (p < 0.001).
- Size
- 53 · 25 cases and 28 controls per the abstract and methods, though the methods also say "Twenty-five control patients" were included. Completed: IIEF 23 cases and 14 controls; IPSS 23 and 15. Doppler in 24 cases, no controls.
- Exposure
- Finasteride for hair loss, median 18 months (IQR 4–96); 11 of 25 (44%) at about 1 mg (0.2–1.25 mg), dose for the others not reported. Time since stopping is not reported.
- Compared with
- Men without 5-ARI exposure evaluated for circumcision (questionnaires only)
- Outcome
- IIEF (total and domains), IPSS (urinary symptoms), PHQ-9 (depression), Epworth Sleepiness Scale and ADAM (androgen deficiency) questionnaires. Cases only, penile duplex Doppler after intracavernosal injection (arterial insufficiency, peak systolic velocity under 25 cm/s; "gray zone" 25–35 cm/s; venous leak, end diastolic velocity over 5 cm/s) and non-validated genital and musculoskeletal symptom surveys.
- Follow-up
- None (single assessment); baseline, laboratory and questionnaire results extracted from medical records
Key results
- Doppler (cases only, 24 scanned): 17 had "some vascular abnormality", reported as 17 of 25 (68%); of the 24 scanned it is 71%. Arterial insufficiency 8 (reported as 32%; 33% of 24), gray zone 5 of 25 (20%), venous leak 4 (reported as 16%; 17% of 24). The three categories sum to 17, so the total includes the 5 gray-zone men; arterial insufficiency or venous leak alone is 12 of 24 (50%) · p. 1204
- Total IIEF was higher (better) in the finasteride group, median 35 (IQR 29–43) vs 29 (27–32), p = 0.035. Erectile function domain 9 vs 11 (p = 0.378); sexual desire 9 vs 4 and overall satisfaction 10 vs 5 were higher in the finasteride group (both p < 0.001) · pp. 1203–1205, Table 2
- Total IPSS 10 (IQR 5–16) vs 3 (2–8), p = 0.009, worse for incomplete emptying, frequency, weak stream and urinary quality of life · p. 1204, Table 3
- PHQ-9 10 (IQR 6.5–16) vs 1 (0–2), p < 0.001, higher on 8 of 9 items, including thoughts of being better off dead or of self-harm (1 [0–1] vs 0 [0–0], p = 0.007). Sleepiness (ESS) did not differ, 5.5 vs 6 (p = 0.929) · pp. 1204–1205, Table 4
- 18 of 25 cases (72%) had a chart-documented history of depression with or without anxiety; 2 of 25 (8%) died by suicide during or after the study, none of the controls · p. 1205
- Self-reported by cases: at least one genital complaint 18 of 25 (72%), genital pain or numbness 15 (60%), at least one musculoskeletal complaint 19 (76%). Fatigue is given as "12 of 25 (45%)", but 12 of 25 is 48%; muscle atrophy as "5 of 25 (25%)" on p. 1204 and 20% on p. 1206 (5 of 25 is 20%) · pp. 1204, 1206
Limitations the authors note
- Survey completion rates differed between groups
- Variable duration of 5-ARI therapy
- Selection bias
- No questionnaire data from before 5-ARI use
- No Doppler results in the control arm
- Depression and suicidality findings may be confounded by higher rates of suicidal ideation in men with hair loss
- The ADAM erection-strength item may reflect the age difference or baseline erections
Also worth weighing (library’s note)
- No control comparison exists for the vascular finding in the title, and all participants came from men seen for sexual dysfunction
- Cases scored higher than controls on IIEF sexual desire, yet on the ADAM questionnaire more often reported decreased libido (p = 0.006); the paper does not reconcile the two
- Controls were older and heavier, only half completed the IIEF, testosterone was available for 3 controls and DHT for none, and comparisons were unadjusted
- Described as prospective, but data were extracted from medical records; no definition of persistence or time since stopping is given
- Reported median DHT (366 ng/dL) lies below its own IQR (373–509), and a DHT this close to the testosterone median (450 ng/dL) would be unusual, so the figure or unit may be in error
Funding: Unrestricted grant from the Post-Finasteride Foundation; one author (Pastuszak) supported by an NIH K08 award (K08DK115835-01) and a Urology Care Foundation Rising Stars award. The paper does not state the funders' role. Interests: Khera is a consultant for Endo, AbbVie and Boston Scientific; the other authors declare none
What it can support (library’s note): That men seen at one clinic with persistent symptoms after finasteride for hair loss report more urinary and depressive symptoms than an unexposed clinic group, and that many had abnormal or borderline penile Doppler results. With no scans in controls and similar erectile-function scores, it cannot show that finasteride causes vascular changes or how common they are.
Why it’s in the corpus
Penile duplex Doppler findings in men with persistent symptoms after finasteride for hair loss, a possible peripheral vascular correlate for the corpus's clinical axis alongside neuropathy findings. Only the finasteride group was scanned, and the 68% abnormal figure includes 5 borderline results.