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Finasteride and sexual side effects

Authors:
  • Venkat Charmalaya Centre For Advanced Dermatology

Abstract

Finasteride, a 5-alpha reductase inhibitor, widely used in the medical management of male pattern hairloss, has been reported to cause sexual side effects. This article critically examines the evidence available and makes recommendations as to how a physician should counsel a patient while prescribing the drug.
62 Indian Dermatology Online Journal -
January-April 2012
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Volume 3
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Issue 1
Address for
correspondence:
Dr. Venkataram Mysore,
Venkat Charmalaya-
Centre for advanced
Dermatology, 3437,
1 G cross, 7th Main,
Subbanna Garden,
Vijay Nagar, Bangalore –
560040, India.
E-mail: mysorevenkat@
hotmail.com
Consultant
Dermatologist- Hair
Transplant Surgeon,
Venkat Charmalaya-
Centre for Advanced
Dermatology, Bangalore,
India
Drug Prole
Access this article online
Website: www.idoj.in
DOI: 10.4103/2229-5178.93496
Quick Response Code:
INTRODUCTION
Some of the commonly faced questions by a
physician while treating a patient of pattern
hairloss are about the possible sexual side effects
caused by finasteride. Reports in the press,
internetsites,andmisinformationbypractitioners
of alternative medicine, all have contributed
to this image of the drug, and has lead to
apprehension in the minds of patients. Often even
dermatologists seem to hesitate to prescribe the
drug on a long term basis. This article examines
this subject in the light of evidence available.
ROLE OF ANDROGENS IN
PATTERN HAIRLOSS AND
SEXUAL FUNCTION
Pattern hair loss in males is androgenic in
etiology. Antiandrogens such as finasteride
are therefore useful in the management of the
condition. Androgens, especially testosterone
increases the libido. Any drug which interferes
with the action of androgens is therefore
assumed,bythelayperson,toinduceimpotence.
However,thepreciseroleofandrogeninpenile
erection needs to be fully elucidated.[1,2] Even
an individual with low testosterone levels can
achieveerection.Inadditiontoandrogens,visual,
olfactory,tactile,auditory,andimaginativestimuli
inuencethelibido.Thepenileerectionismainly
under the control of parasympathetic nervous
system. Ejaculation and detumescence require
an intact sympathetic system.[2,3]
The androgens testosterone and
dihydrotestosterone (DHT) have somewhat
different actions. The enzyme, 5α-reductase
converts testosterone to DHT. It exists in two
isoenzyme forms. While type I is predominant in
liver,typeIIispredominantinprostate,seminal
vesicles, epididymes, hair follicles, and liver.[2]
Withinthehairfollicletoo,thetwotypeshavea
differentdistribution.TypeI5AR,ispresentinthe
sebaceousgland,whiletypeII5ARisfoundonthe
outer root sheath of the hair follicles and dermal
papillae. At all these sites, the testosterone is
converted to DHT.[4] Although the type II 5AR
enzyme has a more signicant role in pattern
hairloss (and therefore mechanism of action of
nasteride), the predominantenzyme in scalp
skinis typeI,largely becauseoflocalizationto
thesebaceousglands,whicharelargeandplenty
inscalp.Finasterideisaspecicandcompetitive
inhibitorof Type II 5—AR,andhasthereforea
selective action on hair follicles. Scalp skin DHT
levelsfallbymorethan60%afteradministrationof
nasteride,therebysuggestingthatasignicant
amount of DHT found in scalp skin is derived from
both local DHT production and circulating DHT.
Thus,theeffectof nasteride on scalp DHT is
likely because of its effect on both local follicular
DHT levels as well as serum DHT levels. This
explainswhyrelativelysmalldoseofnasteride
may be adequate therapeutically.
PHARMACOKINETICS OF
FINASTERIDE
Thebioavailability ofnasteride1mg following
oralintakerangesfrom26-170%withameanof
65%.[5] The average peak plasma concentration
hasbeenfoundto be 9.2 ng/ml measured 1-2
Finasteride and sexual side effects
Venkataram Mysore
ABSTRACT
Finasteride, a 5-alpha reductase inhibitor, widely used in the medical management of male pattern hairloss, has
been reported to cause sexual side effects. This article critically examines the evidence available and makes
recommendations as to how a physician should counsel a patient while prescribing the drug.
Key words: Androgenetic alopecia, nasteride, sexual side effects
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hoursafteradministration.Thebioavailabilityofnasterideisnot
related to food intake. Finasteride is extensively metabolized in
liverbyCytochromeP4503A4enzymesubfamilyandexcreted
bothinurineandfeces.Theterminalhalf-lifeisapproximately
5-6hoursinmenbetween18-60yearsofageand8hoursin
menmorethan70yearsofage.[5]
SIDE EFFECTS RELATED TO SEXUAL
FUNCTION
A number of studies have looked at the problem of side effects
causedbynasteride.[6-11] These studies which are discussed
below reveal that sexual adverse effects occur at the rates of
2.1%to3.8%,erectiledysfunction(ED)beingthecommonest
followed by ejaculatory dysfunction and loss of libido. These
effects occurred early in the therapy and returned to normal on
stopping or over a time on continuous use of the drug. The only
causalrelationbetweennasterideandsexualadverseeffects
is decreased ejaculatory volume because of predominant action
of DHT on prostate.[5]
Acomprehensivereview of a total of73papers on medical
therapiesforBPHwasconducted,withafocusontheeffects
of different pharmacological agents on sexual function.[6] The
reviewrevealedthatnasterideisinfrequentlyassociatedwith
problemsofejaculation(2.1-7.7%),erection(4.9-15.8%),and
libido(3.1-5.4%).
The role of nocebo effect in the causation of ED due to
nasteridehasbeeninvestigated.[7]Nocebo effect refers to an
adverse effect that results from the psychological awareness of
thepossibilityofthesideeffects,butisnotadirectresultofthe
specicpharmacologicalactionofthedrug.Inthisstudy,the
groupinformedaboutthesexualadverseeffectsofnasteride
reportedincreased incidence ofED, when compared to the
group without information.[7]The side effects were completely
reversible in 5 days when the medicine was discontinued,
conrmingthatnoceboeffecthasaninuenceincausationof
side effects andsuggesting the role of psychological factors.
Two studies in 1998 and 1999 showed that the incidence
of these side effects with nasteride therapy was generally
comparabletothatobservedwiththetreatmentwithplacebo,[8,9]
and there was no evidence of dose dependency or increased
incidencewithlongertherapy out to 12 months. In addition,
the side effects ceased in patients even when they continued
toreceivenasteride.
Alongtermstudyshowedthatdrug-relatedsexualsideeffects
such as decreased libido, ED, and ejaculatory disorders
occurred in <2% of men.[10] These side-effects disappeared
not only in all men who stopped the drug because of the side
effects but also in most of those who continued therapy. The
incidenceofeachsideeffectmentioneddecreasedto≤0.3%
bythefthyearoftreatmentwithnasteride.Theincidenceof
side effects were comparable to that of placebo both at one
yearandat5years.
Alargeprospectivestudyinasmanyas17,313patientswas
conducted to look into the effects of nasteride and other
covariates on sexual dysfunction as part of the analysis of The
ProstateCancerPreventionTrial(PCPT).[11] Sexual dysfunction
wasassessedinthe17,313PCPTparticipantswhoreceived
nasteride5mgduringa7-yearperiod.Finasterideincreased
sexualdysfunctiononlyslightlyevenat5mgdosage(whichis
muchhigherthanthe1mgadministeredinpatternhairloss)
and its impact diminished over time. The authors concluded
thattheeffectofnasteride onsexualfunctioning isminimal
for most men and should not impact the decision to prescribe
ortakenasteride.Arecentreviewoftheavailableliterature
too arrived at similar conclusions.[12]
However,therearemorerecentstudies,whichseemtohave
documentedcontraryndings.[13]Avery recent study by Irwig MS
et al,[13] which has beenwidely reported in lay press and internet
reportedndingsafterconductingstandardizedinterviewswith
71otherwisehealthymenaged21-46yearswhoreportednew
onset of sexual side effects associated with the temporal use of
nasterideinwhichthesymptomspersistedforatleastthree
months despite stopping the drug. The study revealed that the
subjectsreportednew-onsetpersistentsexualdysfunction(low
libido,ED,andproblemswithorgasm)associatedwiththeuse
ofnasteride. The mean number of sexual encounters per
month dropped and the total sexual dysfunction score increased
forbothbeforeandafternasterideuse(P<0.0001forboth).
Themeandurationofnasterideusewas28monthsandthe
meandurationofpersistentsexualsideeffectswas40months
from the time of nasteride cessation to the interview date.
However,therewere many limitations in thestudy,such as
smallnumberofpatients,selectionbias,recallbiasforbefore
nasteridedata,andno serumhormoneanalysis.Thestudy
recommended that physicians treating male pattern hair loss
(MPHL)should discussthepotential risklevelswith patients
while prescribing the drug.
An important earlier study by Mella et al,[14] conducted a
systematic review of twelve randomized trials evaluated the
efcacyandsafetyofnasteridetherapyin3927malepatients.
Moderate-qualityevidencewasfoundforanincreaseinerectile
dysfunction (RR, 2.22 [95% CI, 1.03-4.78] and a possible
increaseintheriskofanysexualdisturbances(RR,1.39[95%
CI, 0.99-1.95]; However, the risk of discontinuing treatment
because of sexual adverse effects was similar to that of placebo
(RR,0.88[95%CI,0.51-1.49](moderate-qualityevidence).
A number of isolated case reports have also been published on
theeffectoflowdosenasterideonDNAchangesinsperms,[15]
Mysore and Charmalaya: Finasteride and sexual side effects
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onmotility,andsperm counts.[16] These patients were under
investigationforoligospermiaandinfertilitywhenthesendings
were discovered. Signicantly, these parameters improved
after stopping the drug.
Another small study[17] reported three cases of young men,
whohadusednasterideforveyears,investigatedformale
Infertility. Semen quality was investigated by light microscopy to
evaluatespermconcentrationandmotility,spermmorphology
by transmission electron microscope (TEM), presence
of Y microdeletions by PCR, and meiotic segregationby
fluorescence in situ hybridization (FISH). TEM analysis
revealed altered sperm morphology consistent with necrosis
and FISH data revealed elevated diploidy and sex chromosome
disomy frequencies. One year after the men had stopped the
use of nasteride without receiving any other treatment, a
recovery of spermatogenetic process was observed. Motility
and morphology improved whereas the meiotic pattern did
not change.
Traish[18] conducted a review of different published studies
and concluded that altered sexual functions such as erectile
dysfunction and diminished libido are reported by a subset of
men receiving nasteride, raising the possibility of a causal
relationship. The review suggested discussion with patients
on the potential sexual side effects and possible alternate
treatments before administration of the drug.
Inviewoftheconictingandcontinuingdataandimportance
of the subject, the International Society of Hair Restoration
Surgery (ISHRS) established a Task Force on Finasteride
Adverse Event Controversies to evaluate published data and
make recommendations. The taskforce posted their initial
updateonthesubjectasfollows:
“Todate,thereisnoevidence-baseddatasubstantiatingthe
linkbetweennasterideand persistentsexualsideeffectsin
thenumerousdoubleblinded,placebocontrolledstudiesusing
nasteride 1 mg for hairloss. Reports of persistent sexual
side effects have come from a variety of sources with some
internet sites attracting individuals claiming to have sexual and
psychological issues related to nasteride. While continued
difcultyhaving erections after discontinuingnasteride has
beenreportedinpost-marketingsurveillancetheincidenceof
this problem remains unknown.This rare side effect is included
inMerck’spatientproductinformationintheUnitedStates,and
in Public Assessment Reports of the Medicines and Health
Regulatory Agency of the United Kingdom and the Medical
Products Agency of Sweden.
The persistence of sexual side effects appears to be a rare
event,and ithasyetto bedeterminedwhether theserecent
reports represent a true causal relationship, or if they are
simply coincidental and related to other factors such as the high
incidenceofsexualdysfunctioninthegeneralpopulation,and/
ortheplaceboeffect. Also,littledataisavailable concerning
the medical and psychological work-up of these patients to
exclude other potential causative factors.
Atthepresenttime,themechanismofinteractionbetweenthe
brain,5alpha-reductasemetabolism,andhormonesonsexual
dysfunctionisspeculativeandpoorlyunderstood.Clearly,this
isa complicatedissue,whichoverlaps with otherdisciplines
inmedicinesuchasEndocrinology,Urology,andPsychiatry.
More research is needed to assess the actual incidence of side
effects,to determine if thereisatruecausal relationship for
persistentsideeffectsandifso,toidentifywhomaybeatrisk.
We hope to participate in a multidisciplinary forum to further
evaluate this topic.
Millions of patients have benetted from nasteride with no
sideeffectsatall,orminimalandreversiblesideeffects.Itis
important for the medical community to verify anecdotal reports
and if necessary, conduct further studies so that accurate
information may be given to our patients to enable them to
make informed choices regarding the use of this medication.
The ISHRS Task Force on Finasteride Adverse Event
Controversies is in the process of gathering information and
forming an interdisciplinary panel to address these issues and to
keepourISHRSmembersinformedregardingpost-marketing
adverse events.”
(available fromhttp://www.ishrs.org/articles/finasteride-
announcement.htm11apr2011)
Thus, the evidence available about the safety of the drug
canbe considered asquestionable, but cannot certainly be
ignored. The matter needs further systematic investigation and
documentation.However,thereisnodoubtthattothelayman
the prospect of impotence while taking a drug for hairloss is
daunting,howevertheoreticalandsmalltheriskmaybe.The
drug brochures mention the possibility of the side effect and
the patient is often unable to distinguish between the effects
of1mgand5mg.Severalwebsitesgivearatherunfavorable
opinion about the side effects, contrary to the evidence
presentedabove.Severalblogsalsodiscussthesideeffects,
and individual and anecdotal experiences are highlighted and
often exaggerated. Any patient who reads such reviews is
understandablyapprehensive,andthereforemaystoptherapy
within afewweeksof starting or,inotherinstances, donot
start the treatment at all. Losing potency for gaining hair is not
anattractiveproposition,howeverremotethatpossibilityis!
Inviewofthis,itisveryimportanttoproperlycounselpatients
aboutthetreatment.Inparticular,thefollowingfactsneedto
bestressed:
1. Thedrugisprobablythebestavailabletotreatandrogenetic
Mysore and Charmalaya: Finasteride and sexual side effects
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Indian Dermatology Online Journal -
January-April 2012
-
Volume 3
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Issue 1
65
alopecia and the only one to address the root of the problem.
2. Itseffectsareproven.
3. Severalstudieshaveshownitssafetyoverlongduration
ofadministration.Thedosagegiven (1 mg) is small and
unlikely to cause side effects. Even in those cases where
sideeffectswerereported,thechangeswerefoundtobe
reversible.
4. Thereareveryfeweffectivealternativestothedrugandit
is therefore important for the patient not to stop the drug
unless he experiences any side effects.
5. Thepatientshouldcontactthedoctorforanyadvice,should
he experience a side effect.
6. Mostimportantly,theintakeofthedrugistotallyvoluntary,
as male pattern hair loss is only a cosmetic condition and
it is entirely up to the patient to take or not take the drug.
7. Thetreatingphysicianshouldprovidefullinformationabout
the drug to enable the patient to make an informed decision.
8. Itisbettertoavoidthedrugforanypatientwhohasprior
historyofoligospermia,infertility,particularlyifheisnewly
married and is trying to raise a family.
In addition, the author also feels that in patients who are
apprehensiveaboutthesideeffects,itisworthwhileconsidering
administration of lower daily doses or staggered pulse doses of
thedrug,toenhancepatientcompliance.Asdiscussedearlier,
there is sound rationale for such regimens. Plasma half life of
nasterideis6-8hoursandtissuebindingis4-5days.[5] Doses
of0.2mgareadequatetosuppressbothscalpskinandserum
DHTlevels.While0.2mgcaused55%DHTsuppression,5
mg per day achieved 69% DHT suppression. Efcacy has
beendemonstratedforallend pointsfornasterideatdoses
of0.2mg/dayorhigher,with1and5mgdemonstratingsimilar
efcacythatwassuperiortolowerdoses.[8,9,19] The drug may
bethereforeinitiallyadministeredat0.5mgdailyoronetablet
alternate days, to gain condence of the patient and the 1
mg/daydosagemaybe restoredoncepatientiscomfortable
about the drug. The value of such a regimen was shown in a
preliminary study.[20]However,furtherlarge,longtermstudies
are needed to establish the value of such regimens.
ACKNOWLEDGEMENT
Dr.AnithaB, Dermatologist, Venkat Charmalaya, for correcting the
draft.
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Cite this article as: Mysore V. Finasteride and sexual side effects. Indian
DermatolOnlineJ2012;3:62-5.
Source of Support:Nil,Conict of Interest: None declared.
Mysore and Charmalaya: Finasteride and sexual side effects
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To describe a male patient with finasteride-associated infertility. Case report. Tertiary-care clinic for male infertility. A patient with azoospermia who had been taking finasteride (1-mg dose) for 1 year for androgenic alopecia. He had been diagnosed with oligospermia 5 years before. Discontinuation of finasteride. Improvement of semen parameters. After cessation of finasteride, the patient's semen volume increased immediately, and sperm concentration was up to more than 10 × 10(6)/mL 16 weeks after stopping finasteride. He is now trying to achieve pregnancy by intrauterine insemination. Cessation of finasteride improved spermatogenesis and allowed the couple to attempt less-invasive fertility therapy. In this case, the patient had impaired spermatogenesis before he started the drug. In such patients, the drug may further decrease spermatogenesis. We suggest that drug cessation could be taken into consideration for infertile male patients with impaired semen parameters who are taking finasteride at a 1-mg dose.
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5α-reductase inhibitors (5α-RIs), finasteride and dutasteride, have been approved for treatment of lower urinary tract symptoms, due to benign prostatic hyperplasia, with marked clinical efficacy. Finasteride is also approved for treatment of hair loss (androgenetic alopecia). Although the adverse side effects of these agents are thought to be minimal, the magnitude of adverse effects on sexual function, gynecomastia, depression, and quality of life remains ill-defined. The goal of this review is to discuss 5α-RIs therapy, the potential persistent side effects, and the possible mechanisms responsible for these undesirable effects. We examined data reported in various clinical studies from the available literature concerning the side effects of finasteride and dutasteride. Data reported in the literature were reviewed and discussed. Results.  Prolonged adverse effects on sexual function such as erectile dysfunction and diminished libido are reported by a subset of men, raising the possibility of a causal relationship. We suggest discussion with patients on the potential sexual side effects of 5α-RIs before commencing therapy. Alternative therapies may be considered in the discussion, especially when treating androgenetic alopecia.
Article
Androgenetic alopecia is the most common form of alopecia in men. To determine the efficacy and safety of finasteride therapy for patients with androgenetic alopecia. MEDLINE, EMBASE, CINAHL, Cochrane Registers, and LILACS were searched for randomized controlled trials reported in any language that evaluated the efficacy and safety of finasteride therapy in comparison to treatment with placebo in adults with androgenetic alopecia. Two reviewers independently evaluated eligibility and collected the data, including assessment of methodological quality (Jadad score). Outcome measures included patient self-assessment, hair count, investigator clinical assessment, global photographic assessment, and adverse effects at short term (≤12 months) and long term (≥24 months). Heterogeneity was explored by testing a priori hypotheses. Twelve studies fulfilled the eligibility criteria (3927 male patients), 10 of which demonstrated a Jadad score of 3 or more. The proportion of patients reporting an improvement in scalp hair was greater with finasteride therapy than with placebo treatment in the short term (relative risk [RR], 1.81 [95% confidence interval (CI), 1.42-2.32]; I², 64%) and in the long term (RR, 1.71 [95% CI, 1.15-2.53]; I², 16%); both results were considered to have moderate-quality evidence. The number needed to treat for 1 patient to perceive himself as improved was 5.6 (95% CI, 4.6-7.0) in the short term and 3.4 (95% CI, 2.6-5.1) in the long term. Moderate-quality evidence suggested that finasteride therapy increased the mean hair count from baseline in comparison to placebo treatment, expressed as a percentage of the initial count in each individual, at short term (mean difference [MD], 9.42% [95% CI, 7.95%-10.90%]; I², 50%) and at long term (MD, 24.3% [95% CI, 17.92%-30.60%]; I², 0%). Also, the proportion of patients reported as improved by investigator assessment was greater in the short term (RR, 1.80 [95% CI, 1.43-2.26]; number needed to treat, 3.7 [95% CI, 3.2-4.3]; I², 82%) (moderate-quality evidence). Moderate-quality evidence suggested an increase in erectile dysfunction (RR, 2.22 [95% CI, 1.03-4.78]; I², 1%; number needed to harm, 82.1 [95% CI, 56-231]) and a possible increase in the risk of any sexual disturbances (RR, 1.39 [95% CI, 0.99-1.95]; I², 0%). The risk of discontinuing treatment because of sexual adverse effects was similar to that of placebo (RR, 0.88 [95% CI, 0.51-1.49]; I², 5%) (moderate-quality evidence). Moderate-quality evidence suggests that daily use of oral finasteride increases hair count and improves patient and investigator assessment of hair appearance, while increasing the risk of sexual dysfunction.