Can Menstruation Increase a Woman's HIV Risk?

Hormonal Changes Can Potentially Place Women at Higher Risk for HIV

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The risk of HIV is much higher from men to women than from women to men due to in large part to the vulnerability of the vagina, cervix and (possibly) the uterus. Not only is there greater tissue surface area in the female reproductive tract (FRT) when compared to the penis, changes in biology can often make the mucosal tissues that line the FRT even more susceptible to infection.

While the mucosal membranes of the vagina are far thicker than rectum, with around a dozen overlapping layers of epithelial tissues providing a ready barrier from infection, HIV can still gain access to the body through healthy cells.

Furthermore, the cervix, which has thinner mucosal membranes than the vagina, is lined with CD4+ T-cells, the very immune cells that HIV preferentially targets.

Many things can enhance a woman's vulnerability to HIV, including bacterial vaginosis (which can alter the vaginal flora) and cervical ectopy (also known as an "immature" cervix).

But increasing evidence has also shown that hormonal changes, either naturally occurring or induced, play a key role in increasing a women's potential for HIV acquisition.

Menstruation and HIV Risk

A 2015 study from researchers at the Dartmouth University's Geisel School of Medicine suggested that hormonal changes during the normal menstrual cycle provide HIV and other sexually transmitted infections (STIs) a "window of opportunity" to infect.  

The immune function, both innate (natural) and adaptive (acquired after a previous infection), is known to be regulated by hormones.

During menstruation, the two hormones meant to optimize the conditions for fertilization and pregnancy—estradiol and progesterone—directly affect the epithelial cells, fibroblasts (cells found in connective tissues), and immune cells that line the FRT. In doing so, the immune response is dampened, and the risk of HIV acquisition is significantly increased.

If confirmed, the study may help pave the way to therapies that can better enhance anti-viral activity and/or influence sexual practices (i.e., identifying safer times to have sex) during this so-called "window of opportunity."

Menopause and HIV Risk

Conversely, another 2015 study from the University Pittsburgh Medical Center has suggested that changes in the FRT may contribute to an increased risk of HIV in post-menopausal women.

It is well known that the immune function of the lower genital tract quickly declines during and after menopause, with the thinning of epithelial tissues and a marked decrease in the mucosal barrier. (The mucosa, known to contain a spectrum of antimicrobials, is supported by secretions from the upper FTR that provide downstream protection to the lower genital tract.)

The researchers recruited 165 asymptomatic women—including postmenopausal women; pre-menopausal women not on contraceptives; and women on contraceptives—and measured HIV vulnerability by comparing cervicovaginal fluids obtained by irrigation.

Using HIV-specific testing assays, they found that post-menopausal women had three times less "natural" anti-HIV activity (11% vs 34%) than either of the other two groups.

While conclusions are limited by the study design and size, it does suggest that hormonal changes during and after menopause may place older women at increased HIV risk. As such, greater emphasis should be placed on safer sex education for older women, as well as ensuring that HIV and other STI screenings are neither avoided nor delayed.

Hormonal Contraceptives and HIV Risk

Evidence that hormonal contraceptives can increase a woman's risk of HIV has been inconsistent, either by way of oral or injectable birth control drugs. A robust meta-analysis of 12 studies—eight done in the general population and four among high-risk women—did show a moderate, overall increase in HIV risk in women using the long-acting injectable, depot medroxyprogesterone acetate (DPMA, a.k.a. Depo-Provera). For women in the general population, the risk was seen to be smaller.

The analysis, which included over 25,000 female participants, showed no tangible association between oral contraceptives and HIV risk.

While the data is considered insufficient to suggest the termination of DPMA usage, the researchers advise that women using progestin-only injectables be informed about the uncertainty regarding DPMA and HIV risk, and that they be encouraged to use condoms and explore other preventive strategies such as HIV pre-exposure prophylaxis (PrEP).  

Sources:

Wira, C.; Rodriguez-Garcia, M.; and Patel, M. "The role of sex hormones in immune protection  of the female reproduction tract." Nature Reviews Immunology. March 6, 2015; 15:217-230.

Chappell, C.; Isaacs, C.; Xu, W.; et al. "The effect of menopause on the innate antiviral activity of cervicovaginal lavage." American Journal of Obstetrics and Gynecology. March 20, 2015; DOI: http://dx.doi.org/10.1016/j.ajog.2015.03.045.

Ralph, L.; McCoy, S.; Shiu, K.; et al. "Hormonal contraceptive use and women's risk of HIV acquisition: a meta-analysis of observational studies." Lancet Infectious Diseases. January 8, 2015; 15(2):181-189.

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