Farmacología Estrogénica: Desafíos y Oportunidades para el Futuro

La perspectiva a largo plazo para la farmacología crónica en el estado postmenopáusico parece prometedora. Los estudios clínicos aleatorizados que se están realizando nos proporcionarán una mayor comprensión de los beneficios y desventajas de la TRH crónica a lo largo de los próximos 5 a 10 años. Es factible que los índices globales de prescripción y cumplimiento al tratamiento mejoren, dependiendo de los resultados de estos estudios, ya que tanto la paciente como el médico entenderán mejor la relación entre riesgo y beneficio de la TRH.

No obstante, existe la posibilidad de que la relación entre riesgo y beneficio para la TRH, como se está estudiando en el Women’s Health Initiative (terapia combinada continua), no sea la adecuada para justificar su uso difundido en mujeres postmenopáusicas con útero intacto.

Esta posibilidad ha impulsado la búsqueda de estrógenos mejorados que eliminen la necesidad de la inclusión de progestinas durante la terapia estrogénica.

Una novedosa clase de compuestos descritos aquí, los MSRE, parece representar una promesa en este sentido.

Las alternativas para el uso de estrógenos no selectivos tradicionales en la terapia postmenopáusica se han convertido en una posibilidad real, y el raloxifeno es el primer ejemplo de un MSRE que manifiesta la selectividad apropiada por el hueso y el metabolismo del colesterol frente al útero en extensos estudios preclínicos y clínicos iniciales.

No obstante, falta contestar importantes interrogantes antes de que los MSRE:

Se consideren como una alternativa viable para la TRH o la TRE. Ante todo será preciso establecer su eficacia clínica con respecto a la conservación del hueso y a la enfermedad cardiovascular.

Como el estudio clínico de eventos cardiovasculares requiere trabajos prolongados, y como no está claro qué mecanismo(s) preciso(s) explica(n) el beneficio cardiovascular (“cardioprotección”) del estrógeno, también resultarán de gran importancia los datos iniciales en relación con los efectos de los fármacos sobre los factores de riesgo cardiovascular y la aterosclerosis subclínica.

También es necesario analizar la eficacia con respecto al alivio de los síntomas perimenopáusicos, tales como la inestabilidad vasomotora.

Además de la demostración de la eficacia, será importante realizar estudios de seguridad a largo plazo, particularmente con respecto al tejido uterino, para establecer una mejoría en la relación entre riesgo y beneficio en la terapia estrogénica.

Así pues, quedan por realizar extensos estudios clínicos con el objeto de determinar si algún miembro de la clase de los MSRE va a manifestar un perfil clínico global que se aproxime al estrógeno ideal para la prevención y tratamiento de las complicaciones postmenopáusicas en las mujeres.

Casi todos los estudios clínicos mencionados implican un marco de tiempo crónico (entre 3 y 10 años), extensos grupos de pacientes e importantes inversiones financieras.

En consecuencia, se requieren proporciones sustanciales de recursos y un riesgo financiero significativo para el desarrollo de un estrógeno mejorado como lo sería un MSRE.

No obstante, dada la importancia de la condición postmenopáusica como factor de riesgo que afecta a la salud de la mujer, además de los inconvenientes conocidos y potenciales de la terapia existente, la balanza se inclina de manera tal que nos indica que debemos proceder de manera expedita a satisfacer esta importante necesidad médica.

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• Raymond F. Kauffman & Col.
  Moduladores Selectivos de los Receptores de Estrógeno
  Rev. Col. de Menop. – Vol. 4 No. 2 – 1998
  1 Con permiso de los autores. Aparecido en Drug News 8 perspectives 1995; 8: 531-539.
• * Raymond F Kauffman, Ph.D., is Senior Research Scientist in the Cardiovascular Research Division and Henry U. Bryant, Ph.D., is Research Scientist in the Endocrinology Research Division, Lilly Research Laboratories, Eli Lilly and Co., Lilly Corporate Center Indianapolis, Indiana 46285, U.S.A.