January 2023
In this month's Did You Know? series, Chief Science Officer Beth DuPriest, PhD explains osmolality and why it's important to understand the effect these different fluids (hyper-, hypo-, and iso-omolar) have on the vaginal epithelium.
Q: What is osmolality and why does it matter?
Osmolality has become an important concept in manufacturing vaginal lubricants, but it’s not something that women’s healthcare practitioners think of on a daily basis otherwise. But osmolality is all about water balance, one of the most fundamentally critical functions of the body, so it’s worth taking a few minutes to understand. In the case of vaginal health, osmolality is the difference between a “do-no-harm” kind of vaginal product, and one that can desquamate the vaginal epithelium and increase risk of bacterial vaginosis (BV) and sexually transmitted infections (STIs).
Osmolality is the movement of water from one compartment to another across a semi-permeable membrane due to the different concentrations of impermeant solutes in the two compartments. For the vagina, we think of vaginal epithelial intracellular fluid as one compartment, and the vaginal fluid and/or products placed in the vaginal lumen as the other compartment (a transcellular space). Movement of water between these compartments can shift water into or out of cells, depending on the composition of the fluid in the transcellular space; extreme shifts can cause cells to rupture (hypotonic or hypo-osmolar fluid) or crenate and detach from the underlying epithelium (hypertonic or hyperosmolar fluid). When cells are surrounded by isotonic (or iso-osmolar) fluid, water flows equally in both directions between compartments, maintaining the health of the cell.
A landmark study published in 2012 by Dezzutti and colleagues was designed to reduce HIV transmission in high-risk women by using a lubricant with nonoxynol-9. In the process, the authors learned that not only did HIV transmission not fall, it actually INCREASED with use of the study lubricant. Searching for the reason, they discovered that hyperosmotic lubricants damage the vaginal epithelium. In contrast, iso-osmolar or even hypo-osmolar lubricants were shown to be safer for the vaginal epithelium1.
Prior to the Dezzutti study, other studies revealed similar effects of osmolality on cells of the rectal lining. The World Health Organization in 2011 issued an Advisory Note on lubricants to be used with condoms for public health organizations2. It contained guidance that lubricants (with no distinction made for rectal vs. vaginal use) should have an osmolality no higher than 380 mOsm/kg ideally, but made a concession allowing 1200 mOsm/kg due to lack of commercially available options meeting the ideal target osmolality. Surprisingly, there were no reported measurements of the osmolality of vaginal fluid until 2018! Ayehunie et al. showed that vaginal fluid has an osmolality of 370+/-40 mOsm/kg – much higher than the osmolality of serum (290 mOsm/kg)3. In light of this study, osmolality up to ~450 mOsm/kg can be considered safe for vaginal use.
Use of iso-osmolar lubricants should not be restricted to high-risk sex workers. A single application of a clinical lubricant for transvaginal ultrasound induced vaginal epithelial cell shedding in healthy women4, and depletion of the superficial layers is associated with asymptomatic bacterial vaginosis (BV)5. BV, whether symptomatic or not, is associated with increased risk of several bacterial and viral STIs. One potential mechanism for HIV risk is increased recruitment of CD4+ cells to the vaginal mucosa in women with polymicrobial BV-like vaginal microbiomes; these are the target cells for HIV infection6. One can easily imagine in a setting of increased mucosal CD4+ and reduced protective superficial epithelial layers, that HIV transmission would increase.
All in all, it is clear that osmolality of vaginal products – whether for personal or clinical use – needs to be considered if vaginal healthcare is to do no harm.
References
1. Dezzutti CS, Brown ER, Moncla B, et al. Is wetter better? An evaluation of over-the-counter personal lubricants for safety and anti-HIV-1 activity. PloS One. 2012;7(11):e48328. doi:10.1371/journal.pone.0048328
2. World Health Organization. Use and Procurement of Additional Lubricants for Male and Female Condoms: WHO/UNFPA/FHI360 Advisory Note.; 2012:1-8
3. Ayehunie S, Wang YY, Landry T, Bogojevic S, Cone RA. Hyperosmolal vaginal lubricants markedly reduce epithelial barrier properties in a three-dimensional vaginal epithelium model. Toxicol Rep. 2018;5:134-140. doi:10.1016/j.toxrep.2017.12.011
4. O’Hanlon DE, Brown SE, He X, et al. Observational cohort study of the effect of a single lubricant exposure during transvaginal ultrasound on cell-shedding from the vaginal epithelium. PloS One. 2021;16(5):e0250153. doi:10.1371/journal.pone.025015
5. O’Hanlon DE, Gajer P, Brotman RM, Ravel J. Asymptomatic Bacterial Vaginosis Is Associated With Depletion of Mature Superficial Cells Shed From the Vaginal Epithelium. Front Cell Infect Microbiol. 2020;10:106. doi:10.3389/fcimb.2020.0010
6. Gosmann C, Anahtar MN, Handley SA, et al. Lactobacillus-Deficient Cervicovaginal Bacterial Communities Are Associated with Increased HIV Acquisition in Young South African Women. Immunity. 2017;46(1):29-37. doi:10.1016/j.immuni.2016.12.013