Adverse Event Reporting in Clinical Trials of Finasteride for Androgenic Alopecia: A Meta-analysis | Clinical Pharmacy and Pharmacology | JAMA Dermatology | JAMA Network
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1.
Han  SH, Byun  JW, Lee  WS,  et al.  Quality of life assessment in male patients with androgenetic alopecia: result of a prospective, multicenter study.  Ann Dermatol. 2012;24(3):311-318.PubMedGoogle ScholarCrossref
2.
Imperato-McGinley  J, Guerrero  L, Gautier  T, Peterson  RE.  Steroid 5alpha-reductase deficiency in man: an inherited form of male pseudohermaphroditism.  Science. 1974;186(4170):1213-1215.PubMedGoogle ScholarCrossref
3.
Fisher  LK, Kogut  MD, Moore  RJ,  et al.  Clinical, endocrinological, and enzymatic characterization of two patients with 5 alpha-reductase deficiency: evidence that a single enzyme is responsible for the 5 alpha-reduction of cortisol and testosterone.  J Clin Endocrinol Metab. 1978;47(3):653-664.PubMedGoogle ScholarCrossref
4.
Vermeulen  A, Giagulli  VA, De Schepper  P, Buntinx  A, Stoner  E.  Hormonal effects of an orally active 4-azasteroid inhibitor of 5 alpha-reductase in humans.  Prostate. 1989;14(1):45-53.PubMedGoogle ScholarCrossref
5.
Sinnecker  GH, Hiort  O, Dibbelt  L,  et al.  Phenotypic classification of male pseudohermaphroditism due to steroid 5 alpha-reductase 2 deficiency.  Am J Med Genet. 1996;63(1):223-230.PubMedGoogle ScholarCrossref
6.
Drake  L, Hordinsky  M, Fiedler  V,  et al.  The effects of finasteride on scalp skin and serum androgen levels in men with androgenetic alopecia.  J Am Acad Dermatol. 1999;41(4):550-554.PubMedGoogle Scholar
7.
Roberts  JL, Fiedler  V, Imperato-McGinley  J,  et al.  Clinical dose ranging studies with finasteride, a type 2 5alpha-reductase inhibitor, in men with male pattern hair loss.  J Am Acad Dermatol. 1999;41(4):555-563.PubMedGoogle Scholar
8.
Imperato-McGinley  J, Shackleton  C, Orlic  S, Stoner  E.  C19 and C21 5 beta/5 alpha metabolite ratios in subjects treated with the 5 alpha-reductase inhibitor finasteride: comparison of male pseudohermaphrodites with inherited 5 alpha-reductase deficiency.  J Clin Endocrinol Metab. 1990;70(3):777-782.PubMedGoogle ScholarCrossref
9.
Mahony  MC, Swanlund  DJ, Billeter  M, Roberts  KP, Pryor  JL.  Regional distribution of 5alpha-reductase type 1 and type 2 mRNA along the human epididymis.  Fertil Steril. 1998;69(6):1116-1121.PubMedGoogle ScholarCrossref
10.
Di Loreto  C, La Marra  F, Mazzon  G, Belgrano  E, Trombetta  C, Cauci  S.  Immunohistochemical evaluation of androgen receptor and nerve structure density in human prepuce from patients with persistent sexual side effects after finasteride use for androgenetic alopecia.  PLoS One. 2014;9(6):e100237.PubMedGoogle ScholarCrossref
11.
Gupta  AK, Charrette  A.  The efficacy and safety of 5α-reductase inhibitors in androgenetic alopecia: a network meta-analysis and benefit-risk assessment of finasteride and dutasteride.  J Dermatolog Treat. 2014;25(2):156-161.PubMedGoogle ScholarCrossref
12.
Mella  JM, Perret  MC, Manzotti  M, Catalano  HN, Guyatt  G.  Efficacy and safety of finasteride therapy for androgenetic alopecia: a systematic review.  Arch Dermatol. 2010;146(10):1141-1150.PubMedGoogle ScholarCrossref
13.
Irwig  MS, Kolukula  S.  Persistent sexual side effects of finasteride for male pattern hair loss.  J Sex Med. 2011;8(6):1747-1753.PubMedGoogle ScholarCrossref
14.
Irwig  MS.  Persistent sexual side effects of finasteride: could they be permanent?  J Sex Med. 2012;9(11):2927-2932.PubMedGoogle ScholarCrossref
15.
Irwig  MS.  Androgen levels and semen parameters among former users of finasteride with persistent sexual adverse effects.  JAMA Dermatol. 2014;150(12):1361-1363.PubMedGoogle ScholarCrossref
16.
Yim  E, Nole  KL, Tosti  A.  5α-Reductase inhibitors in androgenetic alopecia.  Curr Opin Endocrinol Diabetes Obes. 2014;21(6):493-498.PubMedGoogle ScholarCrossref
17.
Ebrahim  S, Sohani  ZN, Montoya  L,  et al.  Reanalyses of randomized clinical trial data.  JAMA. 2014;312(10):1024-1032.PubMedGoogle ScholarCrossref
18.
Arca  E, Açikgöz  G, Taştan  HB, Köse  O, Kurumlu  Z.  An open, randomized, comparative study of oral finasteride and 5% topical minoxidil in male androgenetic alopecia.  Dermatology. 2004;209(2):117-125.PubMedGoogle ScholarCrossref
19.
Brenner  S, Matz  H.  Improvement in androgenetic alopecia in 53-76-year-old men using oral finasteride.  Int J Dermatol. 1999;38(12):928-930.PubMedGoogle ScholarCrossref
20.
Camacho  FM, García-Hernández  MJ, Fernández-Crehuet  JL.  Value of hormonal levels in patients with male androgenetic alopecia treated with finasteride: better response in patients under 26 years old.  Br J Dermatol. 2008;158(5):1121-1124.PubMedGoogle ScholarCrossref
21.
D’Amico  AV, Roehrborn  CG.  Effect of 1 mg/day finasteride on concentrations of serum prostate-specific antigen in men with androgenic alopecia: a randomised controlled trial.  Lancet Oncol. 2007;8(1):21-25.PubMedGoogle ScholarCrossref
22.
Dallob  AL, Sadick  NS, Unger  W,  et al.  The effect of finasteride, a 5 alpha-reductase inhibitor, on scalp skin testosterone and dihydrotestosterone concentrations in patients with male pattern baldness.  J Clin Endocrinol Metab. 1994;79(3):703-706.PubMedGoogle Scholar
23.
Duskova  M, Hill  M, Starka  L.  Changes of metabolic profile in men treated for androgenetic alopecia with 1 mg finasteride.  Endocr Regul. 2010;44(1):3-8.PubMedGoogle ScholarCrossref
24.
Gubelin Harcha  W, Barboza Martínez  J, Tsai  TF,  et al.  A randomized, active- and placebo-controlled study of the efficacy and safety of different doses of dutasteride versus placebo and finasteride in the treatment of male subjects with androgenetic alopecia.  J Am Acad Dermatol. 2014;70(3):489-498.e3.PubMedGoogle ScholarCrossref
25.
Hajheydari  Z, Akbari  J, Saeedi  M, Shokoohi  L.  Comparing the therapeutic effects of finasteride gel and tablet in treatment of the androgenetic alopecia.  Indian J Dermatol Venereol Leprol. 2009;75(1):47-51.PubMedGoogle ScholarCrossref
26.
Kaufman  KD; Finasteride Male Pattern Hair Loss Study Group.  Long-term (5-year) multinational experience with finasteride 1 mg in the treatment of men with androgenetic alopecia.  Eur J Dermatol. 2002;12(1):38-49.PubMedGoogle Scholar
27.
Kaufman  KD, Olsen  EA, Whiting  D,  et al; Finasteride Male Pattern Hair Loss Study Group.  Finasteride in the treatment of men with androgenetic alopecia.  J Am Acad Dermatol. 1998;39(4 Pt 1):578-589.PubMedGoogle ScholarCrossref
28.
Kaufman  KD, Rotonda  J, Shah  AK, Meehan  AG.  Long-term treatment with finasteride 1 mg decreases the likelihood of developing further visible hair loss in men with androgenetic alopecia (male pattern hair loss).  Eur J Dermatol. 2008;18(4):400-406.PubMedGoogle Scholar
29.
Kawashima  M, Hayashi  N, Igarashi  A,  et al.  Finasteride in the treatment of Japanese men with male pattern hair loss.  Eur J Dermatol. 2004;14(4):247-254.PubMedGoogle Scholar
30.
Khandpur  S, Suman  M, Reddy  BS.  Comparative efficacy of various treatment regimens for androgenetic alopecia in men.  J Dermatol. 2002;29(8):489-498.PubMedGoogle ScholarCrossref
31.
Leavitt  M, Perez-Meza  D, Rao  NA, Barusco  M, Kaufman  KD, Ziering  C.  Effects of finasteride (1 mg) on hair transplant.  Dermatol Surg. 2005;31(10):1268-1276.PubMedGoogle ScholarCrossref
32.
Leyden  J, Dunlap  F, Miller  B,  et al.  Finasteride in the treatment of men with frontal male pattern hair loss.  J Am Acad Dermatol. 1999;40(6 Pt 1):930-937.PubMedGoogle ScholarCrossref
33.
Lin  JH, Chen  WC.  Finasteride in the treatment of Taiwanese men with androgenetic alopecia: a 12-month open-label study.  Kaohsiung J Med Sci. 2002;18(8):379-385.PubMedGoogle Scholar
34.
Motofei  IG, Rowland  DL, Georgescu  SR,  et al.  A pilot study on the sexual side effects of finasteride as related to hand preference for men undergoing treatment of male pattern baldness.  BJU Int. 2013;111(4 Pt B)(4, pt B):E221-E226.PubMedGoogle ScholarCrossref
35.
Olsen  EA, Hordinsky  M, Whiting  D,  et al; Dutasteride Alopecia Research Team.  The importance of dual 5alpha-reductase inhibition in the treatment of male pattern hair loss: results of a randomized placebo-controlled study of dutasteride versus finasteride.  J Am Acad Dermatol. 2006;55(6):1014-1023.PubMedGoogle ScholarCrossref
36.
Olsen  EA, Whiting  DA, Savin  R,  et al; Male Pattern Hair Loss Study Group.  Global photographic assessment of men aged 18 to 60 years with male pattern hair loss receiving finasteride 1 mg or placebo.  J Am Acad Dermatol. 2012;67(3):379-386.PubMedGoogle ScholarCrossref
37.
Overstreet  JW, Fuh  VL, Gould  J,  et al.  Chronic treatment with finasteride daily does not affect spermatogenesis or semen production in young men.  J Urol. 1999;162(4):1295-1300.PubMedGoogle ScholarCrossref
38.
Price  VH, Menefee  E, Sanchez  M, Kaufman  KD.  Changes in hair weight in men with androgenetic alopecia after treatment with finasteride (1 mg daily): three- and 4-year results.  J Am Acad Dermatol. 2006;55(1):71-74.PubMedGoogle ScholarCrossref
39.
Price  VH, Menefee  E, Sanchez  M, Ruane  P, Kaufman  KD.  Changes in hair weight and hair count in men with androgenetic alopecia after treatment with finasteride, 1 mg, daily.  J Am Acad Dermatol. 2002;46(4):517-523.PubMedGoogle ScholarCrossref
40.
Rahimi-Ardabili  B, Pourandarjani  R, Habibollahi  P, Mualeki  A.  Finasteride induced depression: a prospective study.  BMC Clin Pharmacol. 2006;6:7.PubMedGoogle ScholarCrossref
41.
Rossi  A, Cantisani  C, Scarnò  M, Trucchia  A, Fortuna  MC, Calvieri  S.  Finasteride, 1 mg daily administration on male androgenetic alopecia in different age groups: 10-year follow-up.  Dermatol Ther. 2011;24(4):455-461.PubMedGoogle ScholarCrossref
42.
Rossi  A, Mari  E, Scarno  M,  et al.  Comparitive effectiveness of finasteride vs Serenoa repens in male androgenetic alopecia: a two-year study.  Int J Immunopathol Pharmacol. 2012;25(4):1167-1173.PubMedGoogle Scholar
43.
Ryu  HK, Kim  KM, Yoo  EA, Sim  WY, Chung  BC.  Evaluation of androgens in the scalp hair and plasma of patients with male-pattern baldness before and after finasteride administration.  Br J Dermatol. 2006;154(4):730-734.PubMedGoogle ScholarCrossref
44.
Sato  A, Takeda  A.  Evaluation of efficacy and safety of finasteride 1 mg in 3177 Japanese men with androgenetic alopecia.  J Dermatol. 2012;39(1):27-32.PubMedGoogle ScholarCrossref
45.
Stough  DB, Rao  NA, Kaufman  KD, Mitchell  C.  Finasteride improves male pattern hair loss in a randomized study in identical twins.  Eur J Dermatol. 2002;12(1):32-37.PubMedGoogle Scholar
46.
Van Neste  D, Fuh  V, Sanchez-Pedreno  P,  et al.  Finasteride increases anagen hair in men with androgenetic alopecia.  Br J Dermatol. 2000;143(4):804-810.PubMedGoogle ScholarCrossref
47.
Whiting  DA, Olsen  EA, Savin  R,  et al; Male Pattern Hair Loss Study Group.  Efficacy and tolerability of finasteride 1 mg in men aged 41 to 60 years with male pattern hair loss.  Eur J Dermatol. 2003;13(2):150-160.PubMedGoogle Scholar
48.
Whiting  DA, Waldstreicher  J, Sanchez  M, Kaufman  KD.  Measuring reversal of hair miniaturization in androgenetic alopecia by follicular counts in horizontal sections of serial scalp biopsies: results of finasteride 1 mg treatment of men and postmenopausal women.  J Investig Dermatol Symp Proc. 1999;4(3):282-284.PubMedGoogle ScholarCrossref
49.
Yamazaki  M, Miyakura  T, Uchiyama  M, Hobo  A, Irisawa  R, Tsuboi  R.  Oral finasteride improved the quality of life of androgenetic alopecia patients.  J Dermatol. 2011;38(8):773-777.PubMedGoogle ScholarCrossref
50.
Ioannidis  JP, Lau  J.  Completeness of safety reporting in randomized trials: an evaluation of 7 medical areas.  JAMA. 2001;285(4):437-443.PubMedGoogle ScholarCrossref
Original Investigation
June 2015

Adverse Event Reporting in Clinical Trials of Finasteride for Androgenic Alopecia: A Meta-analysis

Author Affiliations
  • 1Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
  • 2Division of General Internal Medicine and Geriatrics, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
  • 3Optimal Data Analysis LLC, Evanston, Illinois
  • 4Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
  • 5Department of Dermatology, University of Catania, Catania, Italy
JAMA Dermatol. 2015;151(6):600-606. doi:10.1001/jamadermatol.2015.36
Abstract

Importance  Two meta-analyses conclude that finasteride treatment of androgenic alopecia (AGA) is safe but do not assess quality of safety reporting.

Objective  To assess safety reporting for clinical trial reports of finasteride for AGA.

Data Sources  MEDLINE, ClinicalTrials.gov, and a clinical data repository for an academic medical center.

Study Selection  Published clinical trial reports for finasteride treatment of AGA.

Data Extraction and Synthesis  For each trial, we assessed quality of adverse event reporting, extracted the number and type of adverse events in treatment and placebo groups, and assessed duration of safety evaluation and adequacy of blinding. Two observers independently extracted the data; differences were resolved by consensus. We assessed generalizability in a large cohort of men prescribed finasteride, 1.25 mg/d or less, by assessing for eligibility in the finasteride-AGA pivotal trials.

Main Outcomes and Measures  Quality was assessed as adequate, partially adequate, inadequate, or no events reported. We used funnel plots of the hazard ratio to assess bias.

Results  Of 34 clinical trials, none had adequate safety reporting, 19 were partially adequate, 12 were inadequate, and 3 reported no adverse events. Funnel plots were asymmetric with a bias toward lower odds ratio for sexual adverse effects, suggesting systematic underdetection. No reports assessed adequacy of blinding, 18 (53%) disclosed conflicts of interest, and 19 (56%) received funding from the manufacturer. Duration of drug safety evaluation was 1 year or less for 26 of 34 trials (76%). Of 5704 men in the clinical data repository who were treated for AGA with finasteride, 1.25 mg/d or less, for AGA, only 31% met inclusion criteria for the pivotal trials referenced in the manufacturer’s full prescribing information and 33% took finasteride for more than 1 year.

Conclusions and Relevance  Available toxicity information from clinical trials of finasteride in men with AGA is very limited, is of poor quality, and seems to be systematically biased. In a cohort of men prescribed finasteride for routine treatment of AGA, most would have been excluded from the pivotal studies that supported US Food and Drug Administration approval for AGA. Published reports of clinical trials provide insufficient information to establish the safety profile for finasteride in the treatment of AGA.

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