What Women Should Know Before Taking Hormonal Birth Control | Dr. Nusa Faric #19

The XX Lab

Dr. Sarah Hill interviews Dr. Nusa Faric about her groundbreaking meta-analysis regarding the link between oral contraceptives and depression

Key takeaways

• Pill users face a 31% higher relative risk of being diagnosed with depression compared to non-users.
• Users of oral contraceptives are 25% more likely to initiate antidepressant medication.

Main topics

• Hormonal birth control
• Depression risk

Notable quotes

It's not just in your head.

Conclusion

The episode provides a vital scientific validation for women experienc

Transcript preview

Speaker 2 (0:00) Today on the XX Lab, I'm joined by Dr. Nusha Farich, a research fellow at the University of Edinburgh, whose work focuses on mental health, behavior change, and women. Dr. Farage recently conducted an important meta-analysis examining the relationship between oral contraceptive use and the risk of depression, a topic that impacts millions of women, but many people still feel confused, conflicted, or uncertain about. In this important conversation, we talk about what research actually shows regarding the links between hormonal contraceptive use and depression risk, who appears to be the most vulnerable to these effects, and why these experiences have historically been difficult to study and discuss. discuss openly. We also talk about what women can do if they suspect their hormonal birth control may be affecting their mood or mental health, how to think through the risks and trade-offs involved in contraceptive decision-making, and some of the strategies that may help mitigate these effects for women who wish to remain on hormonal contraception. This is a nuanced, compassionate, and incredibly important conversation, and not just for women using hormonal birth control, but for anyone who's interested in women's mental health. hormones, and the complex ways that biology and lived experience intersect. This is the XX Lab. I'm Dr. Sarah Hill. Let's get started. Dr. Nusha Farich, welcome to the XX Lab. Speaker 1 (1:23) Thank you for having me, Sarah. Speaker 2 (1:25) Yeah, I'm so excited to have you here today because you have a new paper out where you conducted a... broad meta-analysis looking at the relationship between hormonal birth control, in particular oral contraceptive pills, and the risk of depression. And I want to talk to you about that today. Before we like really launch into that, I just want to know what got you interested in this topic? This, you know, you spent a lot of time working on this meta-analysis and we'll spend some time talking about what that means for those of you who are listening who've never heard that word before. But it's something that takes a pretty long time to do and especially a really long time to do it well, which I think you've really done with this particular paper. And so what got you interested? Speaker 1 (2:14) Yeah, thank you for this question. So there was definitely a combination of factors that really motivated me to carry this through because it really felt like it was one of those very tough projects. One, because it's so time consuming and two, because it's kind of difficult to get these things funded. So I had to do it in my sort of like free academic time with my colleagues and also assemble the right. type of people who could help me out. So this actually started in 2011, 2012, as my master's kind of systematic review. So I only sort of scratched the surface there. And, you know, I wrote what I could in a few weeks. And then I thought, oh, my goodness, there's so much more. And I also was taking birth control. And I had some kind of quite debilitating side effects, which I noticed very early on. And I thought. I can't really continue taking it as this is a common experience for women. And I knew that probably switching to something else wouldn't work for me because I tried several times with different pills and I've always had the same side effects. And I told some of my friends and they just didn't believe me. And actually, that really fired me up. It really made me feel, well, as it would anyone when they're not believed. So just generally quite angry. And I got quite a lot of motivation from that spite, to be honest. Like not that I wanted to prove them wrong, but I wanted to know as a scientist, because I'm a very curious person, like whether there was actually any scientific base and biological base to what I was experiencing. So I then went to work in actually in regulatory medical writing. So I was actually producing documents for the Medicines and Healthcare Products Regulations Agency in the UK, so MHRA. And I learned a lot about how clinical trial data is taken and then written into patient leaflets and into, you know, materials that patients and clinicians and pharmacists receive. And I was still thinking about this project. And then I did my PhD and it was in my third year of PhD that there was an email that went round at UCL where I was based at the University College London. And they were gathering project ideas and I could be a supervisor. And I just jolted this project down thinking no one will pick it up anyway, because people kind of. don't believe there's an association. Like generally, I feel like in research, they go, yeah, but you know, but and they try and find ways to kind of talk you out of it. And actually, a young researcher came forward. She's the first author on the paper, Madeline Davis Kellogg, and she did an amazing job and actually won an award at UCL for the highest project thesis grade, which was kind of unheard of. She got 89%, which on like a master's thesis in the UK is exceptionally high. Like if you get 75, it's exceptional, but 89 is sort of, wow. And we tried to publish it and we tried to publish it in the BMJ and we got back comments and reviewers comments. And some of them were reasonable, but again, some of the comments were. a little bit contentious and shocking. So for example, we got a comment back saying, one of the very well-known side effects of hormonal contraception is loss of libido. How do you know that women are not depressed because they're having less sex? And, you know, sort of these kind of comments. And again, I work off spite, honestly. I was so upset about this that I decided enough is enough. We're going to go and update this meta-analysis because of course there's time lapse. By the time you finish writing the study and you submit it and you get it reviewed, sometimes it's considered outdated. So you need to update it and it actually took us a number of years. with coordinating everybody to update it. And we went carefully through every single paper and we made sure that we included only high quality trials and studies because we noticed quite a lot of methodological issues with the one and only other meta-analysis that exists on this topic. And yeah, it was just a journey and it was actually something that just didn't leave me alone. It felt almost quite cathartic to get it finished and to say to the world and to everyone who's experiencing similar things, it's not just in your head that, you know, you're dealing with hormones. Hormones really affect you. They really change who you are in your own words. So that was really how it all started. And it was a very, very long journey. It Speaker 2 (7:21) sounds like a long journey. So the paper actually started out as, did you say a thesis? Speaker 1 (7:26) Yeah, it started off as like a little systematic review that you have to do in a few weeks. And then it started off as a master's project, which is the major master's thesis of the first author of Madeline. Then actually we said, well, we need to update it now, also based on all the comments we got back from the journal. And of course, the journal didn't accept it at the end. Speaker 2 (7:50) Yeah. And so so you were getting pushback from the reviewers. So for listeners who are not familiar with the review process in academia, it's kind of a kind of a mess. Like, I mean, because you send a paper off to other experts in the field, it's usually three, sometimes four, sometimes two. And these other experts will read the paper and then give feedback based on their sort of. understanding of the literature and then comparing their understanding of the literature to what's being submitted. And if you get reviewers who have a bias, so for example, if you have reviewers who are reading the paper who have an incentive even to believe that hormonal birth control or oral contraceptives aren't related to depression, right? They're not going to be evaluating the paper fairly, right? They're going to be unduly scrutinizing the research. And since for such a long time, the party line in academia, in psychiatry, more in psychiatry, I think, than neuroscience and psychology, but there's this, like, the party line is that you really can't demonstrate that there's a relationship between poor mental health outcomes and use of hormonal birth control. I mean, is that your understanding, too? Is that the way? way that you've sort of read the party line of the field has been sort of this endorsement of this idea that you can't really, you know, even though there's been this paper and that paper that have found a relationship that maybe it's because of something else. Speaker 1 (9:16) Yeah, I think it's often like lack of experience or having that personal experience and lack of understanding. really how I suppose endocrinology works, because if you speak to endocrinologists, they can tell you, oh yeah, you know, I suppose because the contraceptives, hormonal contraceptives can increase the risk of thrombolytic events, clotting events, and that's due to low grade inflammation, which is actually higher in users and non-users. They would say, yeah, I mean, there's an inflammatory cascade, you know, so the... It's very possible that inflammation, because there's something called inflammatory depression, which was actually studied at King's College and I believe at Oxford University, you know, there is an actual term inflammatory depression, which comes from the increased level of cytokines, which is, you know, to do with basically just high levels. Some bodies really respond quite... uh vigorously or vehemently to to just a slight change in inflammation and you also pointed out you know many times how you came across this research with the you know blunted stress response there's so much that's going on as a whole array of of changes you know your brain processes information differently so your sense of smell changes your sense of even who you're attracted to because attraction is often chemical of course you know you how you perceive facial attractiveness, body attractiveness. I mean, what changes, of course, is how much sebum is produced in your skin, because a lot of girls are given contraceptives to control their, you know, it's more for aesthetic reasons rather than health reasons. And that probably speaks to a lot of teenage girls. And of course. It's completely understandable. Speaker 2 (11:06) I find it so funny that it seems like, especially in the medical establishment, it's like people are willing to accept the fact that hormones have a whole cascade of influences on the body when they do the things that they want them to do, right? So it's like the doctor will say, oh, you know, this is going to improve your skin and oh, it's going to decrease your menstrual cramps and oh, it's going to decrease your risk of ovarian cancer. But then like when it comes to, oh, well, you know, I think that this might be related to poor mental health outcomes. It's like, oh, no, no, no, it doesn't do that. Or like, I think that this might be related to changes in attraction. Oh, no, no, it doesn't do that. It's almost like magical thinking where there's like, oh, you know, hormones aren't that important except for all these other things that they do. And I think that there's a general downplaying of just how important they are in terms of shaping the activities of the brain and including, you know, through different pathways, all of which can potentially have a negative impact on mental health, as you noted. inflammatory activity. Like we know that you get changes in inflammation in response to hormonal birth control use compared to what we see in naturally cycling women. And as you noted, there's a lot of evidence that suggests that inflammatory activity can predict depression and poor mental health outcomes. And in fact, you know, I'm of the belief that, you know, 50 years from now, when we sort of get more sophisticated in terms of understanding the mechanisms behind depression, I think that we're going to find that inflammation and especially inflammation as a result of our sedentary lifestyles and processed food and lack of social connection, all these other things that we know to be related to inflammation, I think are major drivers in the depression epidemic that we see in the industrialized world. I think that that's definitely is a mechanism or a potential mechanism when it comes to hormonal birth control use. You talked about changes in the stress response that potentially can lead to changes in depression. And also, aren't there changes in neurotransmission that also happen in response to hormonal birth control use? Can you talk us through that? Speaker 1 (13:19) Yeah, that or also cortisol levels. You know, you yourself noticed in the research that there's a blunted stress response, meaning that cortisol level is higher. So you don't get an appropriate response, a physiological response to a stimuli that it's exciting, whether it's positive excitation or negative excitation, you know, whether it's... somebody's birthday or a surprise or whether you're scared of something or you need to go on stage. So you can have an overdrive of cortisol. And interestingly, you know, in some research it's noted that, for example, lower socioeconomic population, you know, they're generally more stressed because of, of course, socioeconomic. And so they are more prone to exhibiting depression. And actually, some of the studies that we needed to exclude did a very clever thing where they included a very high number of women in low socioeconomic status in the, for example, non-user groups. And then, you know, that would level up the effect. of the stress or of the pill. So that's one thing. Now, in terms of the brain, there are very different brain regions that have actually shown volumetric changes, so changes in gray matter volume. Can you tell us, Speaker 2 (14:42) can you tell listeners, what is gray matter? Speaker 1 (14:44) Gray matter is essentially, I would say, like the new brain, the part of the cortex that's like responsible for, I suppose, like... Well, I don't actually know the exact definition. I'm going to have to look that up. Speaker 2 (15:00) Okay, so with gray matter, it's like essentially the information processing in the brain. Speaker 1 (15:07) Gray matter is essentially like information processing tissue. It's the tissue, but it also works via either chemical or electrical. transference of information. And of course, hormones, like you always say, Sarah, they're not just localized, even if you're using an implant or a patch or an intrauterine device, if you're using a vaginal ring to deliver. So these are like hormone delivery systems. They... don't just enter your bloodstream locally and stay there. They actually travel and they cross the blood-brain barrier and they affect various neurotransmitters. So there have been a number of studies which we actually cite in our paper. So there is now increasing research into the underlying sort of biological mechanisms of how oral contraceptives may influence mood, such as, for example, or contraceptive induced changes to brain structure and activity in brain regions that are linked to emotional regulation and the development of certain psychiatric disorders. Also... brain regions that are responsible for altered stress responses, and the hypothalamic-territory axis, which is actually the beginning or the, you know, this is where your menstrual cycle begins. The pill actually starts working and then it tells the ovaries to stop producing or to halt production of certain hormones. So what's interesting is that some of the studies have actually found that the effects of hormonal contraception can actually be so severe that it can be similar to some psychological stressors, like long-term stressors, such as, for example, certain patients with PTSD. So in some women, it can actually really cascade into an extreme form of stress response. Speaker 2 (17:03) So before we get into the weeds with your meta-analysis and start to talk about what you found, I'm just wondering if you can orient listeners to a natural menstrual cycle and then how that changes with hormonal birth control. Speaker 1 (17:18) Well, really, the hormones are quite leveled out. So during the menstrual cycle, you have in the first... half the cycle you have the rise in oestrogen and then that fall around you know a drastic fall just just before ovulation and then progesterone rises in the second half of the cycle but with the pill this has actually leveled out so that it's almost just continuously the same and some authors have argued that you know this is The pill or the appearance of hormonal contraception is one of the early biomedical interventions that stops a natural process because really we have biomedical interventions to help us fix something that has gone wrong. Yet in a natural menstrual cycle, nothing has really gone wrong. It's a natural process. But what we're doing with biomedical intervention here is that we're stopping it. altering that natural process. You still have a bleed when you are on hormonal contraception, depends on what kind, but that bleed is similar to a period and it's not really a period. They call it a sham period. And that's because the lining of the uterus doesn't really thicken in the same way. It shows that it has a slightly different appearance also under a microscope. So because it's like, it's grown by, by almost like propelled by different information, because really hormones are agents of information. They travel from one part of the body and go to the other part of the body and tell it what to do and tell that tissue, oh, can you behave this way? Or can you do this? Can you release that? So it's really all communication. And that communication is changed. It's altered. And of course, that shows in our behavior. It shows in... in many different ways, how we think, how women relate to one another, how women relate to the world, because the brain really processes information very differently. Speaker 2 (19:14) Yeah, it's like our brain is hormonal. you know, it's wired to be sensitive to our cycling sex hormones. And so when you take a naturally cycling woman who, as you noted, has this big rise and then the fall of estrogen in the first half of the menstrual cycle, and then the big rise and fall of progesterone, and also some estrogen in the second half of the cycle, that creates a very different experience, both from the neck down, like including the building and the differentiating of endometrial tissue. So you get that differs. And also what's happening psychologically, right? You get these changes in the way that women experience themselves and the way that they experience the world around them. And for, you know, a long time, there's been this debate about mental health. and whether hormonal birth control use may be related to changes in mental health. And as you noted from your own experiences, it's like a hot button topic. Like people get really fired up about it, about with women who are like you, who've had experiences, like bad experiences with mental health using hormonal birth control. I actually had, and I didn't write about this in my book, but for the most part, because I was on hormonal birth control for like... about 12 years in total. And I didn't have any bad mental health experiences except for on one particular type of hormonal birth control. It was the Speaker 1 (20:34) hormonal birth control shot. Speaker 2 (20:36) And I was on it for one, you know, shot cycle, which is about three months long. And it was, I cried every day. I bled and cried every day. I cried and it was, it was just terrible. And the worst thing about that shot is that you can't undo it once you get it. And, and then I'm crying every day and I knew exactly what was going on. And but there's nothing I could do, you know, so I just had for the next three months had to like cry my eyes out. And it was my spring semester in my freshman year of college. And I was actually traveling in Paris with my boyfriend at the time, crying my eyes out all the way up and down the Champs Elysees. Speaker 1 (21:14) It was so difficult. It Speaker 2 (21:18) was so difficult. So you have people like you and I, where we've had this experience where we say, you know, we know that this. is a result of this. And then you have people who are very strongly, you know, no, you can't demonstrate that hormonal birth control is related to a greater risk of developing depression. There's so much confusion around this issue, which is why I was so excited that you wrote this really beautiful paper that recently was published looking at a meta-analysis. And for those of you who don't know what that is, a meta-analysis is essentially a study of studies. It's like a super study. where you're looking at and pooling together the results of different research papers that have already been published on a topic. So it's almost like a scoping review, but using data. So in addition to just reviewing things verbally, you're also going back and looking at the magnitude of