Recent research has resurrected the link between depression and the oral contraceptive pill. Healthed asked the experts to unpack the evidence.

A recent retrospective study of UK women has brought the topic to light again, with the authors saying it suggested a causal relationship between oral contraceptive pills and depression in the first two years of use, and a higher chance of depression later in life for those who took oral contraceptives as adolescents. The latter finding has some support from a 2016 Danish study.

However, the study has been met with stern criticism, with one US academic stating its methodology was too flawed for the results to be of any use in clinical practice. For example, the study did not distinguish between different types of oral contraceptive pills (OCPs), whose hormonal components can vary widely. The study also relied on people to recall details from 20 to 30 years ago, such as when they initiated or discontinued OCPs, and it did not factor in reasons for use, such as premenstrual dysphoric disorder, which could have impacted the results.

Proper randomised controlled trials are required

The paper is far from groundbreaking, according to Dr Terri Foran, a sexual health physician and senior lecturer at the University of NSW, since most clinicians would acknowledge that the link between the pill and depression is a fact for some women.

“Where this study really fell down for me was the suggestion that having used the pill in the past could predispose you to depression down the track. To me, that’s biologically implausible,” Dr Foran says.

“But the findings do reaffirm the fact that some women do experience depression or other emotional symptoms on the pill.”

Professor Jayashri Kulkarni, Head of Psychiatry, Central Clinical School at Monash University, is also of the view a link exists for a specific group of women. She recently co-authored an Australian Prescriber article about the link between hormonal contraception and mood disorders, but says more rigorous research is required.

“What is often done is epidemiological or retrospective studies that are easier to do. To tease out the link, we need prospective randomised controlled clinical trials with proper measures of depression that also look at the types of contraceptive pills involved,” Professor Kulkarni says.

“There is still a disconnect in thinking, where companies bringing out pills don’t have any depression data because they don’t think there’s a correlation.”

Progestogen the likely culprit

Professor Kulkarni says the link to depressed mood relates to the amount and type of progesterone in the pill. Low doses of estradiol can also be problematic, but ultimately she says it comes down to an individual’s vulnerability.

“Some women are more vulnerable to fluctuations of hormones in their brain. We suspect this is somehow related to early life traumas and other difficulties that upset brain hormone systems,” she says.

“It’s not just major depression either. It can be a subtler form of depression where women say things like: I just can’t feel the highs, I don’t feel much at all, I feel gray, or I’ve got a veil drawn over everything.”

Dr Foran says depression is more likely at times of hormonal fluctuation, such as late in the menstrual cycle, post pregnancy, and during menopause.

“They are all periods of vulnerability. So it’s not much of a stretch that putting someone on exogenous hormones may in fact expose that vulnerability. And the fact a link could be more likely to happen at adolescence is not mind blowing,” she says.

“We also know clinically that some pills may cause mood changes, which we think is probably due to progestogens, and yet when you change to another pill, the person may be absolutely fine.”

Different contraceptives may need to be trialled

Both experts say it is vital GPs listen to how a pill might be affecting a woman’s mood and be prepared to explore alternatives and work together with them to find the right contraceptive.

“The art of being a good doctor is to work with a woman to find the best contraceptive method that works with her philosophy and ongoing life plan,” says Dr Foran.

“One of the options is to change to a pill with an alternative progestogen in it, or you could go to a lower dose progestogen, or try a different delivery system like an implant or hormonal IUD. Or of course a copper IUD might be the answer if you want to avoid hormones completely.”

Dr Foran says IUDs are an excellent and effective contraception method, and despite requiring a minor procedure to insert it, the majority of insertions are considered easy.

“So again, it’s a small number of women who have difficulties and I think IUDs deserve to be brought up as an option for women who want effective and low dose contraception,” she says.

“But bear in mind some women are acutely sensitive to progestogens even in low doses, and they may still experience emotional symptoms when they’re using a hormonal IUD.”

Knowing which option is best for which patient can be tricky. Check out Healthed’s free Oral Contraceptive Pill Masterclass, which explores the latest evidence around physiology, pharmacology and prescribing.