Finasteride x Male Fertility Testosterone and Sperm

Conrado AlvarengaHospital das Clinicas da FMUSP

Responsável Andrologia Clinica Vida bem Vinda - SP

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.

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

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

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-econômicoMercado de low – T - EUA 700 PARA 5 BI EM 5 ANOS

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

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 PARA Alopecia

Concentração de receptores androgênicos na papila é

maior

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

amplifiedGlina 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.

Eur J Dermatol. 2002 Jan-FebLong-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

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

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.

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

270 homens 14 – 58 anos com alopécia androgênica – 1mg/dia – t0, 6 meses e 1 anoHormônios 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

2010

We examined 12 men with premature balding Hipótese de DHT envolvida no metabolismo da gordura

visceralApós 12 meses de uso 1mg/dia

Melhora nos níveis de Hemoglobina Glicada e Resistência Insulínica

12 homens ????????????

2011

xTwelve 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.

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.

1,39

2,22

ASPECTOS SEXUAIS

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

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.

Danger Routine sperm tests (count, motility, morphology, and

leukocyte count) would typically not identify men with altered sperm maturation or

fertility potential

ESTUDO PURAMENTE

ANDROLOGICO

CASE REPORT

IFDNA DURANTE USO > 30% 3 MESES SEM 21,2 % APOS 6 MESES 16,5%

Estudo ideal - fusão

Duplo Cego - randomizado com placebo – ProspectivoAjustado 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

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.

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.

Espermograma pré - medicaçãoFragmentação DNA sêmen – ISSM 2015

Atenção para sem proleESPG Pré Finasterida - se ok - IFDNA

- se alterado cessarESPG com 6 meses (Espermatogênese – 87 dias )

TT pré – Se ≤ de 300 – reconsiderarSe IFDNA > 30% reconsiderar

Sub férteis – Mandatória Descontinuação

Obrigado conradoalvarenga@gmail.com

andrologia@labmedicinamasculina.com.br