Oestrogen gel may protect cells in foreskin from HIV

Michael Carter
Published: 10 June 2008

A topical gel containing the female hormone oestrogen appears to block HIV’s infection of key cells in the foreskin, according to an article published in the online journal PLoS One. The investigators believe that the hormone, which is readily available in a cream, is a “simple, cheap, readily available natural hormone [that] could create a living barrier to HIV that preserves the natural defences of the inner foreskin.”

In 2006, there were an estimated 4 million new HIV infections around the world bringing the total number of cases of HIV to 40 million. In the absence of a vaccine, investigators are attempting to find new methods of preventing HIV infection. There has recently been some excitement about the protective effects of male circumcision, with three studies involving African heterosexual men showing that it reduced their risk of infection with HIV by 50 - 60%.

Circumcision is thought to help prevent infection with HIV because Langerhans cells, which are vulnerable to infection with HIV, are present in large numbers in the foreskin. But Langerhans cells are also part of the body’s natural defence against HIV and only become vulnerable to infection with HIV when exposed to large quantities of HIV virions.

Investigators at the University of Melbourne hypothesised that rather than removing this natural defence mechanism through circumcision, it might be better to enhance it by thickening the layer of protective keratin over the Langerhans cells, meaning that they are exposed to less HIV.

Laboratory studies have shown that the application of oestriol – a synthetic form of oestrogen - to the vaginas of rhesus monkeys reduces their risk of infection with simian immunodeficiency virus (SIV), a virus closely related to HIV. The investigators found that the increased levels of keratin in vaginal tissue protected the rhesus monkeys from infection with the virus.

The Australian investigators therefore conducted studies to see if oestriol cream helped protect the cells in the foreskin from infection with HIV.

First, their study involved the use of foreskins removed during surgical circumcision from six men aged between 30 and 65. Their analysis showed that cells in the inner foreskin responded to topical oestrogen administration.

They then examined the ability of oestriol cream to cause keratinisation of the inner foreskin in men. Therefore, topical oestrogen in a cream containing 500 micrograms of oestriol was applied daily to the inner foreskins of two men. Within 24 hours this treatment produced a significant increase in levels of protective keratin over foreskin cells. This protective effect lasted for five days after treatment was stopped.

“Our findings demonstrate that topical oestrogen can induce rapid keratinisation of the inner foreskin. Further studies are now needed to determine if this can protect Langerhans cells from contact with HIV virions”, write the investigators.

They note that topical oestriol cream has such low concentrations of oestrogen that it is safe and will not cause systemic side-effects, such as male breast enlargement.

The investigators suggest that circumcised men are still vulnerable to infection with HIV because the foreskin is not completely removed and cells in the residue remain vulnerable to infection. Application of an oestrogen cream could, they suggest, provide a protective layer of keratin over these cells.

Furthermore, there are significant obstacles to circumcision and an oestrogen gel could provide a safe and acceptable alternative where circumcision is either unacceptable or not practical.

“Oestrogen treatment could be an invaluable adjunct or alternative to surgical circumcision for reducing the incidence of HIV infection in men”, conclude the investigators.

Reference

Pask AJ et al. Topical oestrogen keratinises the human foreskin and may help prevent HIV infection. PLos One 3:6, e2308.