Interpretation
In medical science it is generally attempted to avoid ideological
influences, e.g. a researchers own feelings about the scientific issue,
and commercial interests. I am not doubting that all three research
teams of the three studies attempted this scientific goal. Nevertheless,
as we will see, also ideological issues apply to this scientific topic.
Ideological influences are often revealed in the introduction and
discussion section but may also be apparent in methodological choices. I
think it is fair to say that most gynaecologists are appreciating
hormonal contraception, because HC beyond being an effective
contraceptive method, also provide several important non-contraceptive
benefits for diseases treated in gynaecology, e.g. endometriosis and
polycystic ovary syndrome. Therefore, doctors in this specialty are
default sceptic about claimed adverse effects. Add to this the
historical resistance towards hormonal contraception from religious
bodies such as the catholic church, a fight still ongoing from
contraceptive and gynaecological societies.
Adverse effects of HC are much more recognised by clinicians dealing
with these effects, it being thrombosis or depression. Few cardiologists
doubt the increased thrombosis risk with oral contraceptives, because
they see these women in their clinical work. Gynaecologist never see
them and are often of the opinion that we are talking about very rare
events, which also vanish by length of use.
Likewise, few psychiatrists doubt that HC might induce depression. They
see them daily in their clinical work.
It is far from random, where studies claiming adverse events with HC use
are published. Of the three studies investigated here, the first was
published in a psychiatric journal, study 2 was published in a medical
journal, whereas publication 3 with the headline: “There is no
association between combined oral hormonal contraceptives and
depression” was published in a gynaecological journal. It is
questionable whether this headline is appropriately describing a study
demonstrating significantly increased risks of depression development in
five of six product groups examined applying never-users as reference
group.
I don’t need to guess, which of the authors of the three studies will be
invited to company sponsored congresses in contraception or gynaecology
the coming years to present their results, further confirming doctors of
different specialties in their respective echo chambers.
Ideological influences are also apparent in the discussion section of
the three studies. Whereas the authors in study 1 and study 2 were
concerned about the healthy user effect , which is theattrition of susceptible women by time of use, as those
experiencing side effects stop using the product, leaving those without
mental side effect in the still user cohort. That circumstance partly
explains the decreasing relative risk of depression with length of use.
But the sensitivity is also decreasing with increasing age, demonstrated
by the low relative risk of depression among those starting use of HC at
an advanced age1.
The authors of study 3, on the other hand, were concerned about
overestimating the risk of HC due to medical conditions indicating this
treatment, e.g., endometriosis or polycystic ovary syndrome, both of
which dispose for depression development (even though they controlled
for these diseases).
About the increased risk of non-oral combined products (vaginal ring and
patches) the authors of paper 3 state; “there is no clear biological
explanation for the higher risk estimates for non-oral products”. That
is not quite true, as the plasma levels of ethinylestradiol in users of
patches have been shown to be substantially higher than the levels of
the external hormones in users of oral contraceptives with the same
hormone types4. The demonstrated difference in risk
was therefore to be expected.
And the increased risk of depression with hormone intrauterine devices
is in paper 3 explained by the attempt to provide women with mental
challenges an effective and user-independent method, which was not
controlled for3. Thus, the main concern in the
discussion of paper 3 focuses on the likely overestimation of the risk
of depression with use of hormonal contraception and suggests the
differences to other studies to be a result of residual confounding.
It is difficult not to explain the very different focus in the
discussion of the three papers by different views on HC in general among
the (senior) authors of the three publications.
Finally, the authors of study 3 find support from randomised studies.
The two referred studies found no deterioration in depressive symptoms.
But randomised studies are not free of bias.
If women are invited to participate in a randomised study on hormonal
contraceptive adverse effects, those having previous bad experience with
HC will typically decline participation, while those having good
experiences with previous use of HC, will be prone for accepting
participation. Unless a randomised study demands no previous use of HC
among the participants, these studies will a priori be biased towards
underestimating adverse effects. None of the two mentioned randomised
studies made such a demand, and that likely bias was not recognised of
the authors of paper 3.