Primary Ovarian Insufficiency and Adolescent Vaccination

Pediatrics. 2018 Sep;142(3):e20180943. doi: 10.1542/peds.2018-0943. Epub 2018 Aug 21.


Background: Published case series have suggested a potential association between human papillomavirus (HPV) vaccination and primary ovarian insufficiency (POI). We describe POI incidence and estimate POI risk after HPV; tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis, adsorbed (Tdap); inactivated influenza (II); and meningococcal conjugate (MenACWY) vaccination.

Methods: We searched Kaiser Permanente Northwest electronic health records for outpatient diagnoses suggestive of POI in female patients aged 11 to 34 years between 2006 and 2014. We reviewed and adjudicated the medical record to confirm diagnoses and estimate symptom onset dates. We excluded cases with known causes and calculated the incidence of idiopathic POI. We estimated risk by calculating hazard ratios and 95% confidence intervals (CIs).

Results: From a cohort of 199 078 female patients, we identified 120 with diagnoses suggestive of POI. After adjudication and exclusion of 26 POI cases with known causes, we confirmed 46 idiopathic POI cases. POI incidence was low in 11- to 14-year-olds (0.87 per 1 000 000 person-months) and increased with age. One confirmed case patient received the HPV vaccine 23 months before the first clinical evaluation for delayed menarche. The adjusted hazard ratio was 0.30 (95% CI: 0.07-1.36) after HPV, 0.88 (95% CI: 0.37-2.10) after Tdap, 1.42 (95% CI: 0.59-3.41) after II, and 0.94 (95% CI: 0.27-3.23) after MenACWY vaccination.

Conclusions: We did not find a statistically significant elevated risk of POI after HPV, Tdap, II, or MenACWY vaccination in this population-based retrospective cohort study. These findings should lessen concern about POI risk after adolescent vaccination.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Cohort Studies
  • Diphtheria-Tetanus-acellular Pertussis Vaccines / adverse effects*
  • Female
  • Humans
  • Incidence
  • Influenza Vaccines / adverse effects*
  • Meningococcal Vaccines / adverse effects*
  • Papillomavirus Vaccines / adverse effects*
  • Primary Ovarian Insufficiency / epidemiology*
  • Primary Ovarian Insufficiency / etiology
  • Retrospective Studies
  • Risk Assessment / methods
  • Vaccination / adverse effects*
  • Young Adult


  • Diphtheria-Tetanus-acellular Pertussis Vaccines
  • Influenza Vaccines
  • Meningococcal Vaccines
  • Papillomavirus Vaccines