Mitos e verdades a respeito da finasterida e seus efeitos sobre fertilidade e sexualidade masculina. Dr Conrado Alvarenga

1. Finasteride x Male Fertility
Testosterone and Sperm
Conrado Alvarenga
Hospital das Clinicas da FMUSP
Responsável Andrologia Clinica Vida bem Vinda - SP

2. Queda da fertilidade masculina pelo mundo
• The research = 26,600 men showed a
"significant and continuous" 32.2%
decrease in sperm concentration over 17
years.
• Sperm per millilitre of semen fell at about
2% a year between 1989 and 2005.
• In French men with an average age of 35,
sperm count reduced = 73.6 million/ml to
49.9 m/ml.

3. Queda da fertilidade masculina pelo mundo
Dr Le Moal said:
"Impairments in the quality of human gametes can be considered
as critical biomarkers of effects for environmental stresses,
including endocrine disrupters

4. Queda da fertilidade masculina pelo mundo
Dr Le Moal:
1 em cada 5 jovens europeus tem atualmente concentração
seminal abaixo ref OMS 2010 – 20%
40% deles não alcançará 40.000.000/ml – cut-off relacionado ao
tempo para gestação espontânea

5. Queda dos níveis de testosterona e
androgênios
OMS 2012
OBESIDADE
CONSUMO DE DROGAS RECREATIVAS
SEDENTARISMO
MENOR EXPOSICAO AO SOL
DISRUPTORES ENDOCRINOS
Estudos com nível sócio-econômico
Mercado de low – T - EUA 700 PARA 5 BI EM 5 ANOS

6. METAS
 Literatura de qualidade com pelo menos uma
revisão sistemática de estudos bem desenhados,
randomizados e controlados - estudos
puramente dermatológicos ou andrológicos
 Entender efeitos da finasterida na
espermatogênese e no eixo hormonal
masculino
 Espermograma e Frag DNA sêmen - pré
 Termos de consentimentos
 RECOMENDAÇOES E FUTURO

7. Finasteride is a specific and competitive
inhibitor of 5-α-reductase enzyme Type 2,
inhibiting the conversion of testosterone
to dihydrotestosterone (DHT)
A DHT é cerca de 30
vezes mais potente que a
testosterona devido à sua
afinidade aumentada
pelo receptor de
andrógenos
Aprovada pelo FDA 1997
PARAAlopecia

8. Concentração
de receptores
androgênicos
na papila é
maior

9. Millions of men have taken or are
taking finasteride
Early studies did not show significant influence of
finasteride on semen parameters
Overstreet JW, Fuh VL, Gould J, Howards SS, Lieber MM, Hellstrom W, et al. Chronic treatment with finasteride daily
does not affect spermatogenesis or semen production in young men. J Urol 1999;162:1295–300
whereas some recent observations have suggested that
in sub-fertile patients, the effects of the drug might be
amplified
Glina S, Neves PA, Saade R, Netto NR Jr, Soares JB, Galuppo AG. Finasteride- associated male
infertility. Rev Hosp Clin Fac Med Sao Paulo 2004;59:203–5. Liu KE, Binsaleh S, Lo KC, Jarvi K.
Propecia-induced spermatogenic failure: a report of two cases. Fertil Steril 2008;90:849.e17–9.Tu HY,
Zini A. Finasteride-induced secondary infertility associated with sperm DNA damage. Fertil Steril
2011;95:2125.e13–4.

10. Eur J Dermatol. 2002 Jan-Feb
Long-term (5-year) multinational experience with
finasteride 1 mg in the treatment of men with
androgenetic alopecia
1,553 men - randomized to receive finasteride 1 mg/day or placebo, and 1,215
men continued in up to four 1-year, placebo-controlled extension studies.
Treatment with finasteride led to durable improvements in scalp hair over five
years (p 3/4 0.001 versus placebo, all endpoints), while treatment with placebo
led to progressive hair loss.
Well tolerated and no new safety
concerns were identified during
long-term use

11. Dermatology. 2004;209(2):117-25.
An open, randomized, comparative study
of oral finasteride and 5% topical
minoxidil in male androgenetic alopecia
CONCLUSION: In this comparative study of systemic finasteride and topical minoxidil, it was
concluded that both drugs were effective and safe in the treatment of mild to severe AGA, although
oral finasteride treatment was more effective (p <
0.05). Adverse events were not considered important either, and
these side effects disappeared as soon as the treatment was
stopped.
NAO TINHA GRUPO CONTROLE

12. Finasteride-associated
male infertility.
Rev Hosp Clin Fac Med Sao
Paulo. 2004 Aug; 59 (4):203-5
3 cases of young patients who had very poor seminal quality during
finasteride treatment (1 mg/day), and their seminal quality greatly
improved after cessation.
2 presented with a left varicocele and the other was obese.
We hypothesize that finasteride may not dramatically change the
spermatogenesis process in healthy men, but in patients with
conditions related to infertility, an amplification of the negative
influence of finasteride could occur.

13. A AZOSPERMIA COM USO DE 1MG/ DIA -
APOS CESSAR 4,4 MILHOES/ML
B OLIGOSPERMIA COM USO DE 1MG/DIA –
APOS CESSAR 18,7 MILHOES/ML
2005

14. 270 homens 14 – 58 anos com alopécia androgênica – 1mg/dia – t0, 6 meses e 1 ano
Hormônios Pré
Divididos em dois grupos de ( < = 26 anos e > 26 anos )
No grupo abaixo de 26 anos – Niveis mais altos de 5 alpha-DHT - queda de 50%
níveis apos 12 meses
ESTUDOS DERMATOLOGICOS SEM TT E ESPG PRE E POS
Estudo
puramente
dermatológico

15. 2010
We examined 12 men with premature balding
Hipótese de DHT envolvida no metabolismo da gordura
visceral
Após 12 meses de uso 1mg/dia
Melhora nos níveis de Hemoglobina Glicada e Resistência
Insulínica
12 homens ????????????

16. 2011
x
Twelve studies - (n:3927)
Moderate-quality evidence suggested an increase in
erectile dysfunction (RR, 2.22) and a possible increase in
the risk of any sexual disturbances (RR, 1.39)
After cessation of finasteride, sperm concentration
was up to more than 10 × 10(6)/mL 16 weeks after
stopping finasteride.

17. 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.

18. 1,39
2,22
ASPECTOS SEXUAIS

19. Global photographic assessment of men aged 18 to 60 years with
male pattern hair loss receiving finasteride 1 mg or placebo
Duke University Medical Center J Am Acad Dermatol. 2012
Multicenter, double-blind studies randomized patients
with vertex hair loss (men aged 18-41 and 41-60
years) to finasteride (1 mg/d) or placebo.
A slightly higher incidence of drug-related
sexual adverse experiences was reported in
the finasteride group than in the placebo
group, irrespective of age.
x

20. 2013
The mechanism of the adverse effects of
finasteride on male fertility is poorly understood
The epididymis plays a critical role in the maturation of sperm
and the development of the sperm’s ability to fertilize.
Abnormalities of epididymal function could lead directly to
infertility.

21. Danger
Routine sperm tests (count,
motility, morphology, and
leukocyte count) would
typically not identify men with
altered sperm maturation or
fertility potential

23. ESTUDO
PURAMENTE
ANDROLOGICO
CASE REPORT
IFDNA DURANTE USO > 30%
3 MESES SEM 21,2 %
APOS 6 MESES 16,5%

24. Estudo ideal - fusão
Duplo Cego - randomizado com placebo – Prospectivo
Ajustado para IMC, Hábitos, Maconha.........
Com ESPERMOGRAMA PRE COM IFDNA
Com ESPERMOGRAMA COM 90 DIAS, 6 MESES E
1 ANO
Com Perfil Hormonal Pré e Pós
Com Questionário Medicina Sexual ISSM 2014

25. Já os éxons são as partes “efetivamente”
responsáveis pela codificação de
proteínas. Durante a transcrição do DNA,
os íntrons são removidos por splicing,
editando assim o RNA mensageiro, para a
posterior produção de proteínas.

26. Justifica resposta tão diferente entre os pacientes
FUTURO
EXOMA – DECISAO BASEADA NO PAINEL GENICO
Gene do receptor androgênico (AR),
localizado no cromossomo X, possui um
segmento polimórfico da repetição CAG
localizado no éxon 1.
Indivíduos com resposta normal a ação dos
hormônios androgênicos possuem de 11 a
31 repetições (alelos).
• > 40 repetições estão relacionadas a uma
diminuição da resposta androgênica.

27. Espermograma pré - medicação
Fragmentação DNA sêmen – ISSM 2015
Atenção para sem prole
ESPG Pré Finasterida - se ok - IFDNA
- se alterado cessar
ESPG com 6 meses (Espermatogênese – 87 dias )
TT pré – Se ≤ de 300 – reconsiderar
Se IFDNA > 30% reconsiderar
Sub férteis – Mandatória Descontinuação

29. Obrigado
conradoalvarenga@gmail.com
andrologia@labmedicinamasculina.com.br