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ovarian function. For example, the major postlicensing study of HPV4 safety6 reviewed 189,629
vaccinated females including 44,000 who had
received three doses. Selected outcome measures
were subjects hospitalizations and emergency
department visits following vaccination. In this
study, 1112 year olds who received three doses
comprised 4.3% of the overall study population;
915 year olds comprised 12.9%.6 The consultation
context for seeking medical management of oligomenorrhea or amenorrhea is not normally the emergency
department
and
will
not
require
hospitalization. Hence, this study had no capacity to
evaluate ongoing ovarian health or to monitor ovarian safety.
Similarly, other post-licensure studies7,8 due to
their limited design and narrow range of preselected
outcomes lacked the capacity to assess the risk of
POF following HPV vaccination.
With regard to pre-licensure phase II studies (protocols 007,9 016,10 and 01811) and phase III protocols 013 (Future I)12 and 015 (Future II),13 only
phase II protocols 01610 and 01811 studied adolescents under 16 years. A vaccine report card recorded
temperatures and adverse events occurring within
2 weeks of each vaccination and prompted for
recording of local site reactions. Protocol 01610 studied 506 healthy girls aged 1015 years. Only 240
girls, 47.4%, completed the planned 12-month follow-up. The unexplained loss of the majority of participants to 12-month follow-up and small numbers
of those remaining who had reached menarche precluded this study from competence to evaluate
ongoing ovarian function.10
In preventive vaccination, where a relatively new
vaccine is administered to healthy individuals, an
increased emphasis on safety should not be viewed
as unreasonable. Thus, at present, we cannot
exclude the possibility that the reason why there
are very few POF reports in the medical literature
is simply because the medical community is not
aware of the possibility that POF may be triggered
by the HPV vaccine. We felt it was our ethical duty
to raise awareness among physicians of this possibility. Apparently, there are others who noted the
same.4,5
American Journal of Reproductive Immunology 72 (2014) 260261
2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
References
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autoimmune/inflammatory syndrome induced by adjuvants (ASIA).
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Correspondence
Yehuda Shoenfeld,
Department of Medicine, Chaim Sheba Medical Center,
Tel Hashomer 52621, Israel.
E-mail: shoenfel@post.tau.ac.il
doi: 10.1111/aji.12286
261