By Rebecca H. Allen, MD, MPH, Editor
Synopsis: In this open label, randomized controlled trial, couples in monogamous relationships whose female partner was diagnosed with bacterial vaginosis were randomized to treatment of the female partner only or to treatment of the female partner plus the male partner. After 150 couples had completed the 12-week follow-up period, recurrence of bacterial vaginosis occurred in 24 of 69 women (35%) in the partner-treatment group and in 43 of 68 women (63%) in the control group, indicating an absolute risk difference of -2.6 recurrences per person-year (95% confidence interval, -4.0 to -1.2; P < 0.001).
Source: Vodstrcil LA, Plummer EL, Fairley CK, et al. Male-partner treatment to prevent recurrence of bacterial vaginosis. N Engl J Med. 2025;392(10):947-957.
The authors of this study sought to investigate whether treating the male partner of a female diagnosed with bacterial vaginosis (BV) would reduce recurrence rates. Males have been shown to carry bacterial vaginosis species on the penis. Previous trials of male partner treatment have not shown a benefit but were hindered by limitations and were only using systemic treatment for the male.
This was an open-label, randomized controlled trial conducted from April 2019 through November 2023 at five clinics in Australia. Adult, English-speaking, premenopausal women who had a regular male partner for the past eight weeks, who met diagnostic criteria for BV after presenting with symptoms, and who were being treated with metronidazole 400-mg tablets twice daily for seven days (or, if contraindicated, intravaginal 2% clindamycin cream for seven nights or intravaginal 0.75% metronidazole gel for five nights) were eligible to be enrolled.
Diagnostic criteria were three of four Amsel criteria (homogeneous vaginal discharge, a vaginal pH of more than 4.5, a positive amine test [fishy odor], and the presence of clue cells on microscopic examination) plus a Nugent score of 4 or more (0 to 3 represents normal vaginal microbiota, a score of 4 to 6 represents an intermediate state, and a score of 7 to 10 is indicative of BV). The male partner had to enroll within a week of their partner’s enrollment. Exclusion criteria included more than one sexual partner, human immunodeficiency virus (HIV) infection, and allergy to the study drugs. Randomization was 1:1 and was stratified by current use of an intrauterine device (IUD) and male circumcision status.
In the partner treatment group, male partners received metronidazole 400 mg twice daily for seven days and were instructed to apply a 2-cm diameter volume of 2% clindamycin cream topically to the glans penis and upper shaft (under the foreskin if the male partner was uncircumcised) twice daily for seven days synchronous to the female partner treatment. In the control group, the male partner was not treated. All couples in all groups were instructed to avoid sexual intercourse for the seven-day treatment course.
Vaginal samples for Nugent scoring were collected during clinic visits at baseline and at weeks 4 and 12, and at home on day 8 and week 8 during the study. These were scored by staff blinded to treatment assignment. Questionnaires regarding adherence and adverse events were completed by both partners at baseline, on day 8, and during weeks 4, 8, and 12. The primary outcome was recurrence of BV within 12 weeks. The investigators estimated that a sample size of 290 couples (145 per group) would provide 80% power to detect a 40% lower incidence of BV recurrence in the intervention group than in the control group, assuming an incidence of recurrence in the control group of 40% over a period of 12 weeks (two-sided alpha, 5%).
A total of 357 couples were assessed for eligibility and 164 underwent randomization; 81 couples were assigned to the partner treatment group and 83 couples were assigned to the control group. At the interim analysis, the trial was stopped after a review of the first 150 couples because of superior results in the partner treatment group. The trial ended up with 69 couples in the partner treatment group and 68 couples in the control group who were considered evaluable. The evaluable population for the modified intention-to-treat analysis included all the women who underwent randomization, passed screening, received at least one treatment dose, and were assessed for recurrence. The majority of the women (87%) had a history of BV and an uncircumcised male partner (80%), and 36% used an IUD.
For the primary outcome, recurrence of BV within 12 weeks was diagnosed in 24 of 69 women (35%) in the partner treatment group (recurrence rate, 1.6 per person-year; 95% confidence interval [CI], 1.1 to 2.4) and in 43 of 68 women (63%) in the control group (recurrence rate, 4.2 per person-year; 95% CI, 3.2 to 5.7). Females in the partner treatment group had a lower risk of recurrence than those in the control group over 12 weeks (hazard ratio, 0.37; 95% CI, 0.22 to 0.61). There was no difference in the primary outcome between those who had IUDs and those who were circumcised.
A total of 67 women reported taking 70% or more of the medication prescribed compared to 47 of the men. In the per protocol analysis, which included those who were adherent 70% or more to the antibiotics, the recurrence rate was 1.5 per person-year (95% CI, 0.9 to 2.5) in the partner-treatment group and 4.2 per person-year (95% CI, 3.1 to 5.7) in the control group, which was not different from the modified intention-to-treat analysis. There was no difference between the two groups in adverse events.
Commentary
Whether BV constitutes a sexually transmitted infection has always been controversial. BV is not an infection, per se, but rather a vaginal dysbiosis where the normal lactobacilli of the vagina that keep the vaginal pH low are replaced with anaerobic bacteria such as Gardnerella vaginalis, Prevotella species, and Mobiluncus species that increase the pH.1 There is evidence that men can carry the bacteria associated with BV on their penis.2
BV is the most common cause of abnormal vaginal discharge. Risk factors for BV include multiple sexual partners, lack of condom use, douching, genital herpes simplex virus, and current menstruation. Male circumcision reduces the risk for BV among women.1 Per the authors of this study, past trials studying whether treatment of the male partner can reduce the risk of BV recurrence have been limited by only giving the men systemic treatment rather than topical as well, the use of a single-dose treatment for the male, lack of assessment of adherence, and small sample sizes.2 In contrast, this study, with an appropriate sample size, found robust evidence that treating the male partner simultaneously to the female partner with both oral and topical treatment can prevent BV recurrence.
The authors noted some limitations, including the fact that nine couples had sexual intercourse with an additional person and some couples may not have disclosed sexual activity outside the trial. In addition, the clinics where subjects were enrolled were two sexual health clinics and three family planning clinics, where patients may have a higher risk for BV than the general population. Nevertheless, a large difference was shown between the two groups. Therefore, this treatment likely will be recommended in national guidelines in the future.
Currently, in the United States, recommended treatments for BV include:1
- metronidazole 500 mg, orally two times/day for seven days;
- metronidazole gel 0.75%, one full applicator (5 g) intravaginally, once a day for five days;
- clindamycin cream 2%, one full applicator (5 g) intravaginally at bedtime for seven days.
This is only slightly different than the treatments used in Australia during the trial. Patients are no longer advised to abstain from alcohol during metronidazole use. Patients should not have sexual intercourse during BV treatment; if they do, they should use condoms.1 In conclusion, recurrent BV is a bothersome problem for some patients. This trial may give hope to those patients who are in a monogamous relationship that, if their partner also is treated, the risk of recurrence will be lower.
Rebecca H. Allen, MD, MPH, is Professor, Department of Obstetrics and Gynecology, Warren Alpert Medical School of Brown University, Women & Infants Hospital, Providence, RI.
References
1. Workowski KA, Bachmann LH, Chan PA, et al. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep. 2021;70(4):1-187.
2. Vodstrcil LA, Muzny CA, Plummer EL, et al. Bacterial vaginosis: Drivers of recurrence and challenges and opportunities in partner treatment. BMC Med. 2021;19(1):194.
In this open label, randomized controlled trial, couples in monogamous relationships whose female partner was diagnosed with bacterial vaginosis were randomized to treatment of the female partner only or to treatment of the female partner plus the male partner. After 150 couples had completed the 12-week follow-up period, recurrence of bacterial vaginosis occurred in 24 of 69 women (35%) in the partner-treatment group and in 43 of 68 women (63%) in the control group, indicating an absolute risk difference of -2.6 recurrences per person-year (95% confidence interval, -4.0 to -1.2; P < 0.001).
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