Effect of HPV Adult Vaccination on Serum Anti-Müllerian Hormone Levels: Paired Measurements in a Retrospective Cohort

Background: Concerns that human papillomavirus (HPV) vaccination may adversely affect ovarian reserve contribute to vaccine hesitancy, yet longitudinal data with paired anti-Müllerian hormone (AMH) measurements are limited. We evaluated whether HPV vaccination was associated with short-term changes in AMH compared with an unvaccinated control group. Methods: In this retrospective cohort, women aged 18–45 years who completed a three-dose 9-valent HPV vaccination (Gardasil 9®, Merck Sharp p = 0.015; median percent change −10.9% vs. −20.6%; p = 0.006). In the adjusted mixed-effects model, controls showed an estimated AMH decline of −27.6% per year (95% CI −35.5% to −18.7%; p < 0.001). The time×group interaction was positive (β = 0.170, 95% CI 0.027 to 0.312; p = 0.020), corresponding to a slope ratio of 1.185 (95% CI 1.02–1.366) and an implied annual change of −14.2% per year (95% CI −21.0% to −6.7%) in vaccinated women. Results were broadly consistent in follow-up-restricted sensitivity analyses; however, in the baseline AMH 1.0–5.0 ng/mL restricted cohort (vaccinated n = 82, control n = 67), the interaction was attenuated and not statistically significant (β = 0.082, p = 0.237). Conclusions: In this retrospective cohort with paired AMH measurements, HPV vaccination was not associated with evidence of clinically meaningful short-term impairment in ovarian reserve as assessed by AMH. Observed differences in AMH alterations were modest and should be interpreted cautiously, given residual confounding, measurement variability, and reduced precision in restricted-cohort analyses.