Topical estrogen protects against SIV vaginal transmission without evidence of systemic effect

Stephen M. Smith, Megan Mefford, Donald Sodora, Zachary Klase, Mahender Singh, Nancy Alexander, David Hess, Preston A. Marx

Research output: Contribution to journalArticlepeer-review

93 Scopus citations


Background: Accumulating data suggest that the state of the vaginal epithelium affects a woman's risk of HIV vaginal transmission and several human and non-human primate studies have shown that the rate of HIV or SIV vaginal transmission is decreased when estrogen is dominant. Systemic estrogen can protect against SIV vaginal transmission. Objective: To determine the safety and efficacy of topical estrogen in preventing SIV vaginal transmission. Design: The non-human primate model of HIV vaginal transmission was used to assess vaginal estriol cream in ovariectomized macaques. Methods: Twelve macaques were treated intravaginally with estriol and eight with placebo cream twice a week. The vaginal and systemic effects of estriol were determined by colposcopy and serum luteinizing hormone, levels of which would decline in the presence of systemic estrogen. After 5 weeks of therapy, the animals were challenged vaginally with pathogenic SIVmac2S1. Results: Vaginal estriol resulted in minimal serum estriol levels and had no effect on serum luteinizing hormone levels. Vaginal epithelia cornified and thickened significantly in response to estriol therapy. One of the estriol-treated animals became infected after this single challenge, while six of the control animals became infected (P = 0.0044). Conclusions: These data demonstrate that topical vaginal estriol can strongly protect against SIV vaginal transmission, while having no detectable systemic effect. These results support the study of topical vaginal estriol in preventing HIV vaginal transmission in at-risk women.

Original languageEnglish (US)
Pages (from-to)1637-1643
Number of pages7
Issue number12
StatePublished - Aug 20 2004
Externally publishedYes


  • Macaques
  • SIV
  • Topical estriol
  • Vaginal viral transmission

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases


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