Tuesday, August 12, 2014

Historical Contribution: 1939, Vest and Howard, Testosterone Implants


1939

Clinical experiments with androgens IV A method of implantation of crystalline testosterone S. A. Vest and J. E. Howard Journal of the American Medical Association 1939  113: 1869-1872

In 1939, it was well-understood that testosterone was rapidly metabolized in the human circulation and therefore, to treat hypogonadism, injections had to be given as testosterone propionate, an oily formulation of the compound that would be absorbed (and metabolized) slowly. This allowed patients to be treated every 3-4 days. Several attempts were made to create depot injections, through crystals or pellets that would slowly release testosterone into the blood stream and change the interval needed for injections. 

Drs. Vest and Howard created one of the first successful testosterone implants by creating large, 800mg pellets which could be injected subcutaneously. They successfully placed pellets in thirteen patients, effectively treating their hypogonadism.

These pellets were injected into the soft tissues of the leg, arm, back and scrotum. The pellets were later retrieved and measured to calculate the amount of testosterone absorbed over time (reported in a different manuscript).

The interesting points to take-home from this manuscript include:

  • The method of drug preparation and implantation served as a prototype for other medications. Interestingly, the method for implanting these testosterone depots (Figure 3, right) is similar to methods we use today for testosterone supplementation (i.e. Testopels) or androgen-ablation for advanced prostate cancer (i.e. Zoladex).
  • The clinical outcomes are impressive. The figures provided demonstrate men aged 21 and 34, who are "prepubertal" by appearance, who are rapidly masculinized with testosterone implants.
  • The tissues surrounding the pellets were excised for fear that the foreign-body reaction could lead to "unusual cellular reaction, metaplasia or carcinogenic activity."
To read the manuscript, click on the link above or click here.


HISTORICAL CONTRIBUTIONS highlight the greatest academic manuscripts from the Brady Urological Institute over the past 100 years.  As the Brady Urological Institute approaches its centennial, we will present a HISTORICAL CONTRIBUTION from each of the past 100 years.  In the most recent experience, the most highly cited article from each year is selected; older manuscripts were selected based on their perceived impact on the field.  We hope you enjoy! 

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