Oral Contraceptives Linked to Higher Depression Risk

Users of combined oral contraceptives may be at a higher risk of depression, especially during the first two years of use.

Although clinical data indicate that oral contraceptives (OCs) may negatively impact users' moods, evidence on OCs increasing the risk of depression has been conflicting, especially in adults. This may be because studies omit women who discontinue OCs due to adverse mood effects, leading to healthy user bias.

To estimate the risk of depression associated with the initiation of OCs, researchers at Uppsala University in Sweden used data from 264,557 women from the UK Biobank database. Of those, 80.6% were ever users.

The study that appeared in the journal Psychiatric Sciences examined the impact of combined contraceptive pills, which contain progestogen, a compound resembling the hormone progesterone, and estrogen.

On average, the participants used OCs for 10 years, and the median age at initiating and discontinuing use was 21 and 32 years, respectively. During follow-up, a total of 24,750 women received a diagnosis of depression.

According to the study, women who began to use contraceptive pills as teenagers had a 130% higher incidence of symptoms of depression. Among adult users, the incidence was 92% higher compared to never users.

The increased incidence of depression declined when the women continued to use contraceptive pills after the first two years. However, teenage users of OCs still had an increased risk of depression even after stopping using the pill.

"The powerful influence of contraceptive pills on teenagers can be ascribed to the hormonal changes caused by puberty. As women in that age group have already experienced substantial hormonal changes, they can be more receptive not only to hormonal changes but also to other life experiences," says Therese Johansson of the Department of Immunology, Genetics and Pathology at Uppsala University, one of the researchers leading the study.

The researchers emphasize that most women can tolerate OCs without experiencing negative impacts on their mood. Thus, combined OCs remain effective at avoiding unplanned pregnancies or preventing illnesses like ovarian and uterine cancers.

The study only investigated combined contraceptive pills; therefore, the findings may not apply to other contraceptive options, such as mini-pills, contraceptive patches, hormonal spirals, vaginal rings, or contraceptive rods.

Moreover, the study has several limitations, including the potential recall bias in the self-reported data, particularly regarding the age of OCs use initiation and discontinuation.

Because the UK Biobank consists of a healthier population compared to the general population of the UK, the findings may not be generalizable. Furthermore, the small number of non-white participants prevented the researchers from performing analyzes stratified by ethnic background.

"Our findings support that OC use is causally associated with an increased risk of depression in adolescents as well as in adults, especially shortly after the initiation," the study authors conclude.

The findings are comparable to a 2016 study from Denmark that included over one million women aged 15 to 34. The research associated the use of hormonal contraception with the subsequent use of antidepressants and a first diagnosis of depression, especially among teenagers. The risk, however, peaked half a year after initiation and declined with continued use.

Nearly all women use contraception in their lifetimes. From 2015 to 2017, 64.9% of American women aged 15 to 49 were using contraception, with oral contraceptive pills being the second most common (12.6%) contraceptive method after female sterilization (18.6%).

Johansson says: "Although contraception has many advantages for women, both medical practitioners and patients should be informed about the side-effects identified in this and previous research."