On 2016 Nov 10, Øjvind Lidegaard commented:

Thanks to Chelsea Polis for her interest in and comments on our study.

First, the group of non-users, which was the reference group in the main analysis, includes those users of copper IUD which Chelsea Polis calls for, in addition to users of barrier methods, eventually combined with natural methods such as interrupted coitus or calendar methods. The important point here is, that those women who previously have used or in the future will use hormonal contraception are among those women. Therefore, it is not correct to consider the control group as a group of women not using contraceptive methods.

Our recommendation of further studies on this issue was not primarily due to uncertainty about the methods or the results we achieved, but more the fact that sometimes scepticism is easier to overcome when several study groups reach the same results as achieved in one sound large cohort study as the Danish study.

We also made assessments including pregnant women. For all users of oral contraceptives the relative risk of first antidepressant use actually increased with inclusion of pregnant and delivering women from 1.23 (1.22-1.25) to 1.31 (1.29-1.32) and for the 15-19 year old users the relative risk of antidepressant use was unchanged 1.8 (1.75-1.84). The increase is due to those women who begin taking oral contraceptives within the first six months after delivery, and who already have an increased risk of depression due to their delivery.

In Denmark 4% of women of reproductive age are pregnant, while 40% are current users of some kind of hormonal contraception. That is another good reason why the inclusion of pregnant women does not have much impact on the risk of depression in users of hormonal contraception. And remember that the majority of delivering women get pregnant because they want to, and not because of contraceptive failure. Women getting unwanted pregnant and choose to terminate their pregnancy, generally do not get depressed, which was demonstrated in another large Danish prospective study (1), despite the frequent claim of the opposite from especially opponents of legal abortions.

The biggest weakness of our study is in our opinion the comparison group of non-users in the main analysis. A more correct comparison group would have been never-users. The influence of hormonal contraception on depression risk increases from 1.2 to 1.7 with this change in comparison group. So if anything, our relative risk figures are underestimated.

1. Munk-Olsen T, Laursen TM, Pedersen CB, Lidegaard Ø, Mortensen PB. Induced first-trimester abortion and risk of mental disorder. NEJM 2011; 364; 332-9.

On 2016 Nov 07, Chelsea Polis commented:

This analysis by Skovlund et al. (1) suggests that Danish women who currently or recently used various types of hormonal contraception may be at greater risk of being diagnosed with depression or initiating use of antidepressants, as compared against those who formerly or never used hormonal contraception. As the authors conclude, this study suggests that “further studies are warranted to examine depression as a potential adverse effect of hormonal contraceptive use”. This is particularly important since the study was unable to provide information on these outcomes among women using non-hormonal contraceptive methods, such as a copper IUD, which may have helped to clarify whether the observed associations were related to factors common to women choosing to use contraception, or to the hormonal content of the methods assessed.

Importantly, the investigators note that they censored person-time during pregnancy and through six months post-partum. The authors characterize this as a strength of the study, noting that it was done to reduce the influence of postpartum depression on the results. However, women not using highly effective methods of contraception are presumably more likely to become unintentionally pregnant, which also has implications for women’s mental health. (2)

A sensitivity analysis not excluding pregnant and post-partum person-time could be useful in better understanding the potential competing risks faced by women in their day-to-day lives. It would be helpful for the authors to present pregnancy rates by contraceptive status, and to replicate the main analyses without excluding pregnant and post-partum person-time.

Sincerely,

Chelsea B. Polis, PhD, Senior Research Scientist, Guttmacher Institute

Ruth B. Merkatz, PhD, RN, FAAN, Director, Population Council

1. Skovlund CW, Mørch LS, Kessing LV, Lidegaard Ø. Association of hormonal contraception with depression. JAMA Psychiatry 2016 (Epub ahead of print).
2. Abajobir AA, Maravilla JC, Alati R, Najman JM. A systematic review and meta-analysis of the association between unintended pregnancy and perinatal depression. J Affect Disord 2016;192:56-63.

On 2016 Nov 07, Chelsea Polis commented:

This analysis by Skovlund et al. (1) suggests that Danish women who currently or recently used various types of hormonal contraception may be at greater risk of being diagnosed with depression or initiating use of antidepressants, as compared against those who formerly or never used hormonal contraception. As the authors conclude, this study suggests that “further studies are warranted to examine depression as a potential adverse effect of hormonal contraceptive use”. This is particularly important since the study was unable to provide information on these outcomes among women using non-hormonal contraceptive methods, such as a copper IUD, which may have helped to clarify whether the observed associations were related to factors common to women choosing to use contraception, or to the hormonal content of the methods assessed.

Importantly, the investigators note that they censored person-time during pregnancy and through six months post-partum. The authors characterize this as a strength of the study, noting that it was done to reduce the influence of postpartum depression on the results. However, women not using highly effective methods of contraception are presumably more likely to become unintentionally pregnant, which also has implications for women’s mental health. (2)

A sensitivity analysis not excluding pregnant and post-partum person-time could be useful in better understanding the potential competing risks faced by women in their day-to-day lives. It would be helpful for the authors to present pregnancy rates by contraceptive status, and to replicate the main analyses without excluding pregnant and post-partum person-time.

Sincerely,

Chelsea B. Polis, PhD, Senior Research Scientist, Guttmacher Institute

Ruth B. Merkatz, PhD, RN, FAAN, Director, Population Council

1. Skovlund CW, Mørch LS, Kessing LV, Lidegaard Ø. Association of hormonal contraception with depression. JAMA Psychiatry 2016 (Epub ahead of print).
2. Abajobir AA, Maravilla JC, Alati R, Najman JM. A systematic review and meta-analysis of the association between unintended pregnancy and perinatal depression. J Affect Disord 2016;192:56-63.

On 2016 Nov 10, Øjvind Lidegaard commented:

Thanks to Chelsea Polis for her interest in and comments on our study.

First, the group of non-users, which was the reference group in the main analysis, includes those users of copper IUD which Chelsea Polis calls for, in addition to users of barrier methods, eventually combined with natural methods such as interrupted coitus or calendar methods. The important point here is, that those women who previously have used or in the future will use hormonal contraception are among those women. Therefore, it is not correct to consider the control group as a group of women not using contraceptive methods.

Our recommendation of further studies on this issue was not primarily due to uncertainty about the methods or the results we achieved, but more the fact that sometimes scepticism is easier to overcome when several study groups reach the same results as achieved in one sound large cohort study as the Danish study.

We also made assessments including pregnant women. For all users of oral contraceptives the relative risk of first antidepressant use actually increased with inclusion of pregnant and delivering women from 1.23 (1.22-1.25) to 1.31 (1.29-1.32) and for the 15-19 year old users the relative risk of antidepressant use was unchanged 1.8 (1.75-1.84). The increase is due to those women who begin taking oral contraceptives within the first six months after delivery, and who already have an increased risk of depression due to their delivery.

In Denmark 4% of women of reproductive age are pregnant, while 40% are current users of some kind of hormonal contraception. That is another good reason why the inclusion of pregnant women does not have much impact on the risk of depression in users of hormonal contraception. And remember that the majority of delivering women get pregnant because they want to, and not because of contraceptive failure. Women getting unwanted pregnant and choose to terminate their pregnancy, generally do not get depressed, which was demonstrated in another large Danish prospective study (1), despite the frequent claim of the opposite from especially opponents of legal abortions.

The biggest weakness of our study is in our opinion the comparison group of non-users in the main analysis. A more correct comparison group would have been never-users. The influence of hormonal contraception on depression risk increases from 1.2 to 1.7 with this change in comparison group. So if anything, our relative risk figures are underestimated.

1. Munk-Olsen T, Laursen TM, Pedersen CB, Lidegaard Ø, Mortensen PB. Induced first-trimester abortion and risk of mental disorder. NEJM 2011; 364; 332-9.