REGULAR CONTENT
Introduction
With an ageing population, the prevalence of benign prostatic hyperplasia (BPH) is increasing and with it the number of men opting for conservative management over surgery. The concept behind finasteride, one of two main drugs, stemmed from the discovery of a gene mutation causing ambiguous genitalia in childhood. How did research of an intersex disorder go on to become the basis for one of the best known drugs in urology today?
History
In the 1970s Dr Julianne Imperato-McGinley, a consultant endocrinologist travelled to La Salinas in the Dominican Republic to investigate rumours of girls growing penises. Here she found guevedoces (translation: ‘men at twelve’), an inter-related population who carry an autosomal recessive mutation affecting the 5 alpha reductase (5 AR) type II gene. Homozygous carriers are deficient in 5 AR, preventing conversion of testosterone to dehydroepiandrosterone. Until puberty this manifests as the absence of a penis and testes, and as adults these men have little facial and body hair, immunity from male pattern baldness and very small prostate glands.
Application
It is this final property of 5 AR deficiency that is utilised in finasteride, a 5AR inhibitor which mimics the effect of the gene mutation, reducing the size of the prostate and thus lower urinary tract symptoms.
Conclusion
With its introduction, finasteride changed the management of BPH, introducing a viable long term alternative to prostatic surgery. What started as a rumour around gender identity continues as a drug that improves the lives of men worldwide.
Introduction
With an ageing population, the prevalence of benign prostatic hyperplasia (BPH) is increasing and with it the number of men opting for conservative management over surgery. The concept behind finasteride, one of two main drugs, stemmed from the discovery of a gene mutation causing ambiguous genitalia in childhood. How did research of an intersex disorder go on to become the basis for one of the best known drugs in urology today?
History
In the 1970s Dr Julianne Imperato-McGinley, a consultant endocrinologist travelled to La Salinas in the Dominican Republic to investigate rumours of girls growing penises. Here she found guevedoces (translation: ‘men at twelve’), an inter-related population who carry an autosomal recessive mutation affecting the 5 alpha reductase (5 AR) type II gene. Homozygous carriers are deficient in 5 AR, preventing conversion of testosterone to dehydroepiandrosterone. Until puberty this manifests as the absence of a penis and testes, and as adults these men have little facial and body hair, immunity from male pattern baldness and very small prostate glands.
Application
It is this final property of 5 AR deficiency that is utilised in finasteride, a 5AR inhibitor which mimics the effect of the gene mutation, reducing the size of the prostate and thus lower urinary tract symptoms.
Conclusion
With its introduction, finasteride changed the management of BPH, introducing a viable long term alternative to prostatic surgery. What started as a rumour around gender identity continues as a drug that improves the lives of men worldwide.