The human papillomavirus vaccine does not appear to be associated with an increased risk of ovarian insufficiency, according to researchers.

A child receives a vaccine injection. Choreograph/Thinkstock

Allison L. Naleway, PhD, of the Center for Health Research at Kaiser Permanente Northwest, Portland, Ore., and her coauthors wrote that a previous case series had raised concerns about a possible link between the human papillomavirus (HPV) vaccine and primary ovarian insufficiency (POI) in six young women who developed the condition within 12 months of vaccination.

Using EHR data, researchers identified 46 women aged 11-34 years with idiopathic POI – 33 probable cases and 13 possible cases – after excluding cases with known causes. Eighteen of these cases also were excluded because they were diagnosed before the HPV vaccine was available.

They found that only 1 of the remaining 28 patients had been vaccinated against HPV before the symptom onset: a 16-year-old girl who was vaccinated about 23 months before the first clinical evaluation for delayed menarche. Their report was published in Pediatrics.

The adjusted hazard ratio for POI was therefore 0.30 after HPV vaccine, compared with 0.88 after Tdap, 1.42 after inactivated influenza vaccine, and 0.94 after meningococcal conjugate vaccine.

More than one-half of the 46 confirmed POI cases were diagnosed at age 27 years or older, and only one patient was diagnosed under 15 years of age.

“If POI is triggered by HPV or other adolescent vaccine exposure, we would have expected to see elevated incidence in the younger women who were most likely to be vaccinated, but instead we observed higher incidence in older women (greater than 26 years of age), which is consistent with 1 other population-based study of POI prevalence,” the authors wrote.

They acknowledged that studying POI as a vaccine-related adverse event was challenging because the time from symptom onset to diagnosis was variable. However, they said that 81% of their cohort was followed up for more than 2 years, and a mean of 5.14 years, so the potential for misclassification was “minimal.”

Dr. Naleway and her associates also noted that diagnoses of POI can be difficult to accurately identify, and symptoms may be masked by oral contraceptive use.

“Despite the challenges and limitations discussed above, we believe this study should lessen concern surrounding potential impact on fertility from HPV or other adolescent vaccination,” they wrote.

The Centers for Disease Control and Prevention supported the study. Three authors declared funding from pharmaceutical companies for unrelated studies. No other conflicts of interest were declared.

SOURCE: Naleway A et al. Pediatrics 2018;42(3):e20180943.