EFFECT OF NOVEL ANDROGENS ON ECTOPIC ENDOMETRIUM IN RHESUS MACAQUES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The goal is to investigate new drug therapies for endometriosis. Macaque uterine endometrium can be auto-transplanted to ectopic intra-abdominal and subcutaneous sites. These endometrial grafts provide an excellent endometriosis-like model system for preclinical testing of novel anti-endometriotic therapies. Bayer Schering Pharma AG (BSP) is developing a testosterone analog (eF-MENT) that exerts higher androgenic activity than testosterone and is not converted to estrogens like testosterone by the liver and fat tissues. In this study we will test the effect of eF-MENT on estrogen-stimulated growth in endometrial grafts, and compare the effects of eF-MENT with the effects of dihydrotestosterone (DHT a natural androgen) as a positive control. This study had two aims: Aim 1 is to develop methods to identify nonreproductive "off-target" effects of androgens in female macaques that are analogous to the side effects of androgen therapy in women. Aim 2 is to determine if eF-MENT therapy will inhibit growth in ectopic endometrium in rhesus macaques. Dose finding studies, with eF-MENT administered by siclastic implant, are underway. We identified a implant dose that resulted in no off-target actions and compared it to doses that resulted in non-target effects. All doses of eF-MENT resulted in suppression of ectopic endometrium in the animals. In contrast only the high dose DHT implants suppress graft growth. We propose that eF-MENT can be developed as a therapy for endometriosis in women.