Very interested to hear your thoughts on Phexxi? I love the idea of a non hormonal method that isn’t a condom that I could use with my established partner/s, but concerned about BV, UTIs, etc. Would love to know what you think of it?
—@TheQueenComet, va Twitter
On the Fly…
Phexxi is a new on-demand prescription vaginal contraceptive gel. It has a higher failure rate than male (external) condoms. In the initial study, over 7 months 9% of women reported urinary tract infections (UTIs) and 8% bacterial vaginosis (BV), but it isn’t possible to know if that is higher than expected for these women. There is no long-term data on Phexxi and the risk of BV or UTIs.
Phexxi (rhymes with sexy) is a single-use vaginal contraceptive gel inserted up to one hour before sex and is one dose per act of vaginal intercourse. Phexxi has a rather nifty mechanism of action. Vaginal pH is normally in the 3.5-4.5 range, which is acidic (making the vagina the original Acid Queen). This acidity is toxic to sperm, so evolution’s hack is for the ejaculate to temporarily raise the pH of the vagina, allowing sperm to live long enough to swim into the uterus (ejaculate has a pH of 7.2-7.8). This effect is temporary as the vaginal microbiome quickly returns the vagina to its normal acidity. Phexxi prevents this ejaculate-induced rise in vaginal pH, so the vagina stays inhospitable to sperm. Phexxi may also have a barrier effect on sperm.
Phexxi contains lactic acid, citric acid, and potassium bitartrate (the latter you may know as cream of tartar). Lactic acid and citric acid are commonly used in a variety of vaginal products.
A total of 2,480 women used Phexxi in the two studies used for FDA approval. Over 7 menstrual cycles, 18% reported burning in the vulva and vagina, 14% itching, 9% yeast infections, 9% UTIs, and 8.4% BV. There was no placebo gel group for comparison as it would be unethical to give women a placebo contraceptive, so we don’t know if the rate of BV and UTIs with Phexxi was higher than average for a group of sexually active women of reproductive age or not. Approximately 10% of male partners reported irritation, mostly minor.
Fewer than 2% of women withdrew from the studies because of discomfort/side effects. One conclusion could be that the symptoms weren’t that severe and/or the infection rate wasn’t different for these women, hence they saw no reason to drop out, but we don’t know for sure. There are some concerns with the side-effect data. There is no mention how the diagnosis of BV and UTIs was achieved, meaning were women seen in the office and had the gold-standard tests or were they diagnosed over the phone or did they self-diagnose? This matters as diagnosis over the phone or self-diagnosis could over- or underestimate infections. Also, 18% of women were lost to follow up, and we don't know if those women had more irritation/infections, had no issues, or never used the product.
The product insert states the following about a history of recurrent UTIs:
Among 2804 subjects who received PHEXXI in Studies 1 and 2, 0.36% (n=10) reported adverse reactions of cystitis, pyelonephritis, or other upper urinary tract infection (UTI). Of these, one case of pyelonephritis was considered serious and required hospitalization. Avoid use of PHEXXI in females of reproductive potential with a history of recurrent urinary tract infection or urinary tract abnormalities.
Vaginal acidifiers have been around for some time. Phexxi isn’t actually new; it was previously known as Amphora (for contraception) and as ACIDFORM (as a contraceptive and also as potential treatment for BV), but didn’t go to market in either incarnation. None of the data show harm to the vaginal ecosystem, but the studies are small and they weren’t designed to look at long-term issues or to determine the rate of BV and UTIs. Several studies have looked at other vaginal acidifiers for BV, and there wasn’t any harm from the products, but none of these studies are long term. Contragel, a vaginal lactic acid contraceptive gel for use with a diaphragm and has the same mechanism of action as Phexxi, has been available since 1971 in Europe and seems well tolerated. But, admittedly, there are no published studies looking at side effects. Also, the formulation of Contragel isn’t the same as Phexxi, and using a product with a diaphragm may be different than using it without.
How effective is Phexxi contraception-wise? In the studies, women were having sex at least 3 times a month, and over 7 months, the pregnancy rate was 14%. That is estimated to be a 27% pregnancy rate if extrapolated to one year (meaning, if 100 women use Phexxi for one year that 27 will get pregnant). It’s possible if the study had gone on longer that the pregnancy rate might have been lower because as women get more familiar with a method, user error drops. But it’s also possible that with time, user error could increase for other reasons. Phexxi is less effective than male or external condoms (13% pregnancy rate), a diaphragm with spermicide (17% pregnancy rate), and female or internal condoms (21% pregnancy rate). These are all typical user rates, not perfect user rates. Using no method, the pregnancy rate over one year is 85%.
Whether insurance will cover Phexxi isn’t known. If you are buying it yourself, it’s approximately $267.50 for a box of twelve. “Sure, he’s nice, but is he Phexxi-worthy?” could replace the Elaine Benes sponge-worthy test from the TV show Seinfeld. After all, it’s about as effective as the sponge.
It’s always great to have another contraceptive, especially one that is on-demand. Many women want a hormone-free alternative, and condoms aren’t always an option. Some people find them irritating, but there are also situations where a woman might fear violence if she insists on a condom or she has a partner with erectile dysfunction (condoms can sometimes be a challenge). Whether the pregnancy rate is acceptable will depend on many things, including how important it is to not be pregnant, the availability of abortion for those who most definitely don’t want to be pregnant, and the availability and tolerability of other contraceptives. Another consideration is that Phexxi offers no protection from STIs.
More information will be revealed with post-marketing surveillance. It’s always important that we continue to study medications over time. For example, the spermicide nonoxynol-9 was touted as a contraceptive that also killed HIV in the 1980s. It was going to be a vital tool in the global fight against the HIV rate… that is until data eventually showed it was associated with a higher risk of acquiring HIV if exposed due to its damaging effect on the vaginal ecosystem.
Biologically, Phexxi appears safe BV and UTI-wise for women at average risk, but given the limitations of the data that comes with an asterisk. Women with recurrent UTIs probably should avoid the product until we have more data. While the ingredients and our experience with vaginal acidifiers don’t raise any red flags, the vaginal ecosystem is complex, and we likely won’t have good data about BV and UTIs for several years. That sucks, and it’s important to acknowledge that fact. If you decide to use Phexxi and develop symptoms of itch, discharge, burning or odor it’s best to be seen and get a diagnosis (irritation from the product versus infection) as opposed to being treated over the phone.
Many people are probably wondering if Phexxi could be used to treat or prevent bacterial vaginosis. After all, BV is associated with an elevated pH and Phexxi is a vaginal acidifier. Phexxi (as ACIDFORM) failed to treat BV in one study, and multiple studies have looked at treating/preventing BV with acidifying agents like lactic acid and so far the results have been poor. Attempts at vaginal acidification are not currently recommended. And yes, this includes boric acid…which does not even work in the vagina by acidification. Misinformation about boric acid on Instagram is a whole different post.
Remember, this post is not direct medical advice.