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.