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Science Advances—FY 2014

NIAID conducts and supports research to prevent, diagnose, and treat infectious and immunological diseases that affect the health of women and girls.

HIV/AIDS
Immunology
Infectious Diseases (Other Than HIV/AIDS)

HIV/AIDS

A Protein in Breast Milk Inhibits HIV Transmission From Mothers to Their Infants

To achieve an AIDS-free generation, strategies that prevent the transmission of HIV from mother to child after birth are critical, particularly in developing countries. Surprisingly, more than 90 percent of children breastfed from HIV-infected mothers do not contract HIV. NIAID-funded researchers identified a specific protein in breast milk, called Tenascin-C, which neutralizes HIV. Researchers believe that the anti-HIV properties of Tenascin-C contribute to protecting infants against infection. This knowledge about protective proteins in breast milk could be used to develop new safe and effective treatments to prevent postnatal and other types of HIV transmission.

Reference: Fouda GG, Jaeger FH, Amos JD et al. Tenascin-C is an innate broad-spectrum, HIV-1-neutralizing protein in breast milk. Proc Natl Acad Sci U S A. 2013 Nov 5;110(45):18220-5.

Social and Cultural Factors Influence Effectiveness of HIV Prevention Strategies in Women

Pre-exposure prophylaxis (PrEP) is a Food and Drug Administration-approved HIV prevention approach for people at high risk of contracting HIV. To prevent infection, healthy individuals take daily doses of antiviral therapy. NIAID-funded researchers evaluated the results from a 2010–2012 clinical study in South Africa, which showed that two PrEP strategies in women were ineffective because of lack of patient adherence to daily treatment regimens. The researchers found that social and cultural factors influenced women’s daily use of antiviral therapy. Misunderstandings about the trial were common, including about the rationale for having healthy individuals take antiviral drugs when not infected with HIV. In addition, women were challenged with physical side effects and negative attributes of the treatments and faced social stigmas associated with being on HIV therapy. These results suggest that social and cultural factors must be considered when designing and implementing future HIV PrEP clinical trials.

Reference: van der Straten A, Stadler J, Montgomery E et al. Women's experiences with oral and vaginal pre-exposure prophylaxis: the VOICE-C qualitative study in Johannesburg, South Africa. PLoS One. 2014 Feb 21;9(2):e89118.

Immunology

Loss of Estrogen-Mediated Immune Response Makes Females More Susceptible to Crohn’s Disease

Crohn’s disease is a form of inflammatory bowel disease that affects women with increased severity and at a higher rate than men. To investigate possible mechanisms for this disparity, NIAID-funded researchers studied a strain of mice known as SAMP mice that spontaneously develop chronic intestinal inflammation resembling human Crohn’s disease, with a similar disparity between females and males. They found that T regulatory (Treg) cells, which are known to modulate immune responses, were reduced in frequency and activity in female mice compared to male mice. Male SAMP mice treated with estrogen responded by increasing Tregs that reduced Crohn’s-like symptoms, whereas females were resistant to the effect of estrogen. Further studies showed that estrogen signaling at the receptor level in female mice is disrupted and leads to fewer protective Treg cells. These findings suggest that therapies designed to enhance protective estrogen-mediated signaling in Tregs may be beneficial for treating chronic inflammatory disorders such as Crohn’s disease.

Reference: Goodman WA, Garg RR, Reuter BK et al. Loss of estrogen-mediated immunoprotection underlies female gender bias in experimental Crohn's-like ileitis. Mucosal Immunol. 2014 Sep;7(5):1255-65.

Infectious Diseases (Other Than HIV/AIDS)

Testosterone Suppresses Response to Influenza Vaccination

Females often have more robust immune responses than males to infections and vaccination for reasons that scientists do not fully understand. NIAID-funded researchers showed that, after seasonal influenza vaccination, women produced more antibodies that could effectively neutralize the virus compared to men. Gene expression studies showed that men with weak vaccine responses had high expression levels in a cluster of lipid metabolism genes that may be controlled by the male hormone testosterone. Men with high testosterone levels and elevated gene expression of this cluster exhibited a lower immune response to influenza vaccination compared to women or to men with low testosterone. The results suggest that male hormones may suppress immune responses to vaccines by altering expression of specific genes.

Reference: Furman D, Hejblum BP, Simon N et al. Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination. Proc Natl Acad Sci U S A. 2014 Jan 14;111(2):869-74.

Male Circumcision Does Not Protect Female Partners From Mycoplasma genitalium

Mycoplasma genitalium is a sexually transmitted disease associated with inflammation of the reproductive system. Among women, the worldwide prevalence of M. genitalium infection is approximately 1 to 5 percent. For men, previous studies have shown that circumcision reduced the risk of acquiring M. genitalium. To determine whether circumcision would also protect female partners of circumcised men, NIAID-funded researchers conducted a clinical trial in Uganda and found that male circumcision did not protect female partners from M. genitalium infection. The researchers suggested that multiple factors may have contributed to the study results. For example, female partners may have engaged in outside relationships, or circumcision may not have affected the infected genital areas of men, such as the urethra.

Reference: Tobian AAR, Gaydos C, Gray RH et al. Male circumcision and Mycoplasma genitalium infection in female partners: a randomised trial in Rakai, Uganda. Sex Transm Infect. 2014 Mar;90(2):150-4.

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Last Updated January 13, 2015