Psychiatry & Psychotherapy Podcast - Hormonal Contraceptives & Mental Health

Episode Date: May 3, 2018

New research on hormonal contraceptives, "the pill", and how it influences mental health. Dr. David Puder and Dr. Mona Mojtahedzadeh explore: Claims about the mental health consequences of hormonal contraception Unique Influences of progesterone and estrogen on the brain How ovulation changes attraction and desire Discuss the controversy around recent studies that show that hormonal contraception increases the risk of depression Critique of those studies and counters to those critiques Kelly Brogan and other contrasting views and their influence on this field By listening to this episode, you can earn 0.5 Psychiatry CME Credits. Link to blog. Link to YouTube video. Join David on Instagram: dr.davidpuder Twitter: @DavidPuder Facebook: DrDavidPuder

Welcome to the Psychiatry and Psychotherapy Podcast, the podcast to help you in your journey towards becoming a wise, empathic, genuine, and connected mental health professional. I'm your host, Dr. David Puter, a psychiatrist who splits his time practicing psychopharmacology, individual and group psychotherapy, medical director of a day treatment program, medical education research, and teaching, residents, and medical students. We are back on the podcast. I am here with a colleague of mine. as soon to be attending physician.

I know her as Mona. Do you want to pronounce your full name for me? Mona much tehered. Okay. And I'm like really happy to have Mona on here. We've been talking about this topic in our supervision. We meet together once a week and discuss patients, discuss things going on. And we've been talking about having an episode on,

kind of women's health issues. So welcome to the podcast. All right. Thanks for having me, Dr. Peter. I'm very happy to be joining you here. So, Mona, tell me a little bit about what makes you excited about studying this. Tell me a little bit about that. Oh, actually, you know, I had the opportunity to have Dr. Peter be supervising me for the past couple, since January this year. And when we started first session of supervision, Dr. Peter, you know, you were asking me, what are your career interests? So one of them is really women mental health and getting into the most recent data and news that are on top in this field. One of them is actually effects of hormonal contraceptives and mood. Yeah. So I was excited to know more about this.

Yeah. And I, a couple, like almost a year ago, one of my colleagues, one of my friends was like, hey, have you ever heard of Kelly Brogan? And I guess she was on a couple like big, you know, podcasts. Oh, so that's how you got interested. And she was like, Dr. Puter, are contraceptives going to cause me to be depressed? And she was like super worried. She's like telling me all of her girlfriends are getting off of contraceptives. I went and listened to the podcast at the time.

And at the time I was just like, oh, you know, a lot of this stuff just seems like really out there. Um, it's not like mainstream, like what, like a lot of her ideas in general. And, um, you know, I didn't know what to make of it. I really wanted to like take each individual piece of what she was saying and say, okay, I want to like, I don't want to discount that right away, but I want to actually like dig into that little piece. Good. Yeah. And so initially when I looked at Google Scholar and, you know, a lot of times people give oral contraceptives for women and like paramedopause to help them with their mood, you know, and so like often it's like a treatment for depression. And that's what confused me. It was like, where is this coming from that oral contraceptives would cause depression?

Yeah. So that's what we're going to get into today. Why don't you tell us, first of all, how commonly used our oral contraceptives? Basically, it's like one of the very most common contraceptive methods. So approximately, I think like 100 million women use it, use the pill. And approximately like 82% of sexually active women and here in America use oral contraceptive pills. About 17% of women from age 15 to 44 are on the pill. Yep. Wow. This is a big number.

And I remember when you introduced to me Kelly Brugan, I listened to her. And so I was like, oh, that's interesting. What she actually highlighted was like that, like our hormonal, you know, processes has significant, has significant role in our, like, our everyday life. And, you know, basically using something like contraceptive, hormonal contraceptives can play a significant obstacle to mental health and to appropriate hormonal balance in women. And with oral contraceptives, they may not feel like the changes. They won't feel like what it feels like to go through ovulation once a month?

Yeah, so here's the thing. Like in a normal cycle, starting day zero, you'll be in the first half of cycle, you'll be in the phase where you have, like, least amounts of your estrogen progesterones and whatever good or bad effects to those hormones are in terms of mood, you just have low levels of them.

And around mid-cycle, where it's around when you start ovaries, So you will have a raise in estrogen. And basically your mood is most elevated when you have rise in estrogen without the progesterone being on board as much. And then throughout late cycle, you have increased in both hormones estrogen progesterone. So basically your mood changes, like premenstruation, you are more irritable. You can even go through premenstrual dysregistern. dysphoria. Yeah, and different, and I think it's important as we talk about this to say one size doesn't

fit all. And so, like, I think there are some patients with so much premenstrual dysphoria that they actually do a lot better when they get on the pill or they get on some sort of contraceptive and it, like, really stabilizes their mood and they feel a lot better. It's actually one of the treatments, right? It helps also with a lot of other things like appetite, weight gain. So it helps with the acne, like a lot of like herzotism. Yeah. And while we're on it, I think one of the really interesting pieces that I've heard in the news or, you know, some sort of

YouTube is they talk about how women have different attractions to men at different parts of their cycle. But basically women during the peak of their ovulation, during the three or four day period, they have an increased preference for masculine faces, for masculine voices, for more masculine voices, for taller men, for more dominant male behavior, for, you know, they have a greater interest in going to public events where they can meet men, they have more sexual fantasies. Where is this around their ovulation? Around their ovulation, where they're at the prevarieting. where they're at the peak of the estrogen.

And you can think about it to make sense, right? Because at the peak of your estrogen, that's when you have the capacity to concede. You have more tendency for social interactions just in general as well, as opposed to when you're premenstrual and you are more like isolated. You kind of want to stay away from people and from social interactions as well. Yeah, and you can think about it like this, like when you're not ovulating, when you're kind of in that pregnancy mode or, you know, low estrogen, you're really looking for a man that's more empathic

and more sort of, you know, fatherly, right? And I think we're biologically, women are biologically wired to sort of have attraction towards that type of man because that type of man is going to be the good, you know, sort of, you know, helping raise the family. Yeah, and I, I actually put up some pictures on my Instagram of different types of male faces from these studies. And most of the women actually chose the masculine face, but there were some women that chose the feminine face.

And one thing I noticed was that not all women likely, it's probably not true for all women. You know, I'm pretty sure, like personality characteristics, like some women are just going to like different types of men, you know. But it's interesting in these studies that they show that there was this change. during ovulation. What are some different ways that OCPs are used other than just to prevent pregnancy? Well, I remember, like, for my own personal history, I actually was on OCPs for, like, low-doseage OCPs for a period, a short period of time for acne and puberty. So basically, acne and herstatism is one and main reason is prevention of unintended pregnancy.

the other reasons increase risk of ovarian endometrial and colorectal cancers per preservation of bone mineral density and postmenopausal women prescribed for PMDD symptoms, also to control heavy menstrual bleeding. So there are multiple causes. So there are multiple reasons why women end up on OCPs. Okay. What happens when a woman takes hormonal contraceptive to her baseline estrogen and progesterone? So basically, taking hormonal contraception, it can go through multiple modes and, you know, basically in terms of your mood. So one of the, one of the easiest to understand or like, you know, one of the first to come to mind

is that, okay, when you are taking exogenous hormones, basically your internal system is inhibited from producing those hormones that are generally produced internally. Well, our HPA axis will be inhibited from producing your internal estrogen progester. And so you'll not go through your natural cycles of, you know, changes in your estrogen progester. And what happens is that in a natural, so your levels of estrogen hormones and progesterone hormones, are just, will be just lower. They'll be lower. They'll be lower compared to.

And also the progesterone that is produced internally, well, it's compoundly different from the progestins that are synthetically, you know, made in the pills. So that is also another difference that you'll be exposed to different types of progesterons. Yeah. One of the things that really sort of was new for me was the effect of testosterone. on women. So when you're on a hormonal contraceptive,

it immediately creates a negative feedback, so you don't produce LH, you don't produce FSAH. And these are also, and women actually produce a small amount of testosterone. And also, on the other hand, your sex hormone binding globulin is also increased. So basically you'll have smaller, free amounts of other hormones as well,

like testosterone. Really good point. So you have lower testosterone, which in women is important for, you know, maybe gaining strength. It's important for not feeling tired all the time. It's important for libido. And so that was one of the other things. I was recently talking to one of my cardiology buddies,

and he has a low T clinic where he actually prescribes very, very low doses of testosterone for older women as a way of treating some of the, the symptoms that they're having. Really interesting. Yeah. Okay, so you can think about it, oral contraceptives, decrease progesterone, estrogen, testosterone.

And so other than that, like modes of secretion, mode of secretion will be also different. So in natural synthetic hormone, you'll have pulsatile fashion in your hormone secretion. And that pulsatile fashion of hormone secretion

is actually very unique. And that is what leads to the positive feedback and basically increase in your upper level hormones. We're talking about going out of the tropin releasing hormone and folliclor stimulating hormone and our LH basically because that is something unique you see here that you have this positive feedback. And that's because of the pulsatile fashion of the hormone secretion. And because of that, you can go through your obvious. relation and your graphian follicle will be growing. But when you're on the exogenous hormones, you won't go through these processes. Another thing is the mode of secretion. So mode of secretion, actually it is stated that rapid declines in hormones have more negative impact on mood than the

actual hormonal levels. So when you are taking exogenous hormones, you don't have, you have a steady state of hormone exposure to your body. So you don't have this rapid declines in hormones, which is good. So this is actually a good thing because the rapid declines and hormones are the cause, are very, very much causative for depressed and depressive symptoms, which we see around premenstruration toward the end of Lusel phase. And so when you have rapid declines in hormones and then right before your period start, and the peripart of time period.

So all those are proofs for that. But when you're on the pills, you don't have those rapid declines and hormones. Right. So that was something I remembered back from Goodman and Gilman. And we actually cracked it open again. It's a big pharmacology book. And it kind of has this really nice picture. We'll include it's the picture we're including in the figures on the website.

So if you want to take a look at that. Yeah, it was a great remark. how there's a nice pulsatile sort of natural, sort of ups and downs. And that pulsatilness of cannot be mimicked by drugs, right? We cannot mimic a nice, you know, multiple times a day, pulsatile or multiple, I don't know, what was it times an hour? So I thought that was really important, too, to think about, like, how that influences, not only to produce the LH and the FSAH and the estrogen progesterone, but, you know, we don't

know all of the reasons why there's that nice pulsatile sort of thing. So we have a neural clock here termed the hypothalamic GNRH pulse generator that determines the pulse frequency but also the amount of GNRH released in each pulse. So GNRH just GNRH. And estrogen and progesterone, sorry, are estrogens and progestin have a big role here on this generator. Yeah, that's really interesting. So GNRH causes a release of FSH LH, right? Right.

And those cause the release of estrogen and progester, just to be clear. Okay, so let's get into, do you think we're ready to get into the actual studies? Yeah, the thing is that despite the fact that majority of studies point toward women's high levels of satisfaction, there have been emerging studies reporting cases of major depression developing in women with no prior psychiatric history. following consumption of pills. This is pretty significant because the last decade in USA, basically rates of teenage birth rate, along with teenage pregnancy and abortion have decreased. And well, most researchers attribute this, they see it as a victory,

and they attribute it basically to improve access to contraception. Yeah, so the rates of teenage pregnancy have decreased. And so, you know, although we're going to be talking about some sort of studies, that show that there's increased rates of depression, I think it's important to look at this sort of overall picture as well. So we're psychiatrists, so we tend to think of this in terms of mood, first and foremost. And before we get into this, I'm going to tell a little story. Had a patient that came in just the other day whose mood really tanked just a couple months ago.

And in getting the history from her, I had this on my mind, because we've been reading about this. So I asked her, you know, when she had been prescribed the pill, how long she had been taking it, and it coincided that the decrease in her mood started about two months, about two to three months after starting the oral contraceptive. And she had had some types of depression before, you know, mild maybe depressive,

symptoms, but something around that time period, it really, really worsened. And she started feeling very hopeless and helpless. And so that was kind of like, like, wow, okay, what if the OCP was in part having a role in this, okay? And so we're going to go into the study now, and maybe we can talk about the case a little bit more and like what we might recommend to this person. Good, yeah. And I'm obviously going to change a couple of the details just to protect the identity of this person.

I also wanted to highlight something here. But we can go through this study. And if there is a flag, then I'll bring that up. Okay. So this study was in 2016. So this is pretty recent. And it was one million women out of Denmark in a national registry that were followed per for 6.4 years. And I think this is the first...

For an average of 6.4. But basically between 2000 to 2013. Okay. So the real interesting aspect of this is one, it's a national registry. So you're able to get a ton of people in this study. And in this national registry, you know, they're not like deciding to do this study before they're recording this data. they're deciding afterwards. And so after they're deciding, okay, we're going to follow this people.

We're going to exclude people who had a prior history of depression or whatnot. So we're going to follow a group of women for a number of years. And we're going to see if their mood changes after they start any type of hormonal contraceptive. Yeah. And anybody with any history of depression, or any kind of major psychiatric illness was excluded from the study, right? Yeah. So they followed these people, and what they found was that the hormonal contraceptive group

had an increased relative risk of first onset of a depression diagnosis in a psychiatric hospital, and they had an increased risk of the first time they used in antidepressant. and specifically the highest risk group was ages 15 to 19 and they had an increased relative risk of the first diagnosed depression episode of 1.7 meaning they were like 1.7 times more likely than the other group, the group that were not on the hormonal contraceptives, to have been diagnosed with depression in a psychiatric hospital. And the hormonal contraceptive group age 15 and 19,

had an increased relative risk of 1.8, so 1.8 times more likely to have their first prescription of an antidepressant. And so in hard numbers, we're looking at the difference in this like 1.1 million group of people of basically there were 10,000 prescriptions in 1.1 million person years in the non-contraceptive users, and there was 18.5,000 antidepressant prescriptions over 0.9-1 million person years. So basically, you know, an increase in about 8,000, 9,000 to 9,000 prescriptions based on the, you know, the people who were on the hormonal contraceptives. Now, I think it's really important to say this is a correlational study. So this is not a randomized control trial that can show causation.

This is not showing causation. This is showing that these things are correlated. And so that's important. So correlation does not equal causation. The all progestin group had an even higher relative risk. So it seems like just purely being on a progestin, a progesterone and not an estrogen, cause an even higher risk. And that makes sense here because we are, we, we talked about estrogen is more responsible

making us feeling better and elevating mood, but progesterone is more of like, you know, bringing mood down, causing more irritability. So this, this really correlates here. The other big kind of aha, and maybe this is that like the nuance that I think made reading this in detail really worth it, was the risk did not increase till two months after initiation of the hormonal contraceptive use. So, you know, month one and month two, it's not like they really saw...

Much of a change. Much of a change. But after two months, and it peaked at six months, and after a year, it decreased significantly. So really like, okay, if you're listening to this and you're like starting to wonder, oh, no, is my, you know, hormonal contraceptives is making me more depressed or could it make me more depressed in the future.

But you've been on it for like three years and doing fine. I would say, well, this evidence shows that really, number one, the higher risk group is the young people, age 15 to 19. And number two, it took about two months to about a year. And that was when this really occurred. Yeah. And so when I looked at my patient who had had the increased incidence of depression at like two to three months, I was like, that kind of in the time course is where I would think that

that makes sense. Okay? Yeah. Now, this person in particular had a lot of things other than that going on. So this is just a very small portion of my overall plan for this person, you know? But it was important to think through like, okay, what might be the best complete picture of how to treat this person? That's a good one, right?

Yeah. Yeah. It's one small hammer in the tool shed, right? So it's like as a mental health provider, you know, we want to think of all of the different things that can influence mental health. And we don't want to be monolithic, like we don't want to only have one hammer. Like everything is, you know, a serotonin issue, right? We don't want to think like that because there's really like a ton of different reasons why

people get depressed, why their mood gets off. And it's not something that we can really deter. determine in a five-minute visit. Sometimes a lot of my patients, it's after like bringing them into my treatment program and the therapist have seen them every day for about two or three weeks that we're like, oh, this is the big issue, right? And it takes like sometimes weeks to get to know someone to the point that you like really understand them well enough to kind of make that like, oh, okay, here are the big

issues in their life, you know? Right. So, you know, contraception, what is the right? contraceptive for yourself, that's definitely a discussion you should have with your doctor. Non-hormonal IUDs, I will say, are a lot more commonly used in Europe. They're like, I think it's like 2% of women use it in the U.S., whereas like in Europe, it's like 15, 20%. So I think there is a big difference, and I'll put that citation up on the website as well. But that might not be the right fit for you.

And, you know, I think there's a lot of concern in the U.S. more than in Europe about that. Other types of contraceptives, you know. But even among oral contraceptives, there are different types based on the type of progestants that are in there and the amount of progestants. And the amount of estrogens. Some of the newer ones have higher estrogen. Lower or higher. But usually the amount of estrogen is really low. But, I mean, having spoken also to some of my OBGYN friends and mentors and just reading more.

about these stuff, it's got me into like there is really not a one-size-fits-all here. And even with the oral contraceptive group, we have a lot of varieties here. Okay, so is that it's that the Denmark study was a large cohort population based study and if like data was from an administrative database. And so there is more chances to just find a statistically significant result, even if was clinically significant. Right. So I would say to speak to that point, I think that more and more we're going to see big clinical databases showing us what's important.

I work, the statistician, Dr. Michael Cashner that I work with, he is like the king of big databases and how helpful they can be in really getting good results. So I think we're heading there. I hope eventually like the whole world can almost have like a, a world database of all medications, all like medical issues, or just at least the U.S. Because I think we'll be able to have better health care long term if we can have those huge databases. It is actually greatly helpful to have those systems.

One of the criticizers here, Dr. Grimmis, who is an OBGYN and also a public health specialist and researcher, he is one of the big, he talks about this a lot. And his main point is that this is not about, like, these databases are not main, um, you know, initially made for research and for clinical studies. See, but talking to Dr. Cashner, my research guy who builds these databases, like he is totally thinking of research when he builds these. So, I mean, I'm sure, like, if you, like, there's a group of people who build these databases. Some are people who are the researchers, and some are the people who are, like, mental health

professionals or just, like, there's, like, teams of people that think through how do we build the databases, how do we make them most accurate? What can we record, right? We can actually record prescriptions because we have access to all the pharmacies. We can actually record who was hospitalized because we have all, in Denmark, they have all the hospitalizations, you know, type of thing. So, I don't know. The other thing about like correlations, like, you know, in these large studies, you may have a rogue correlation that's statistically significant, but it doesn't really mean anything. And that's usually when the relative risk is like 1.1, not like 2.0, right? When the 1.1, it's like almost like it could happen. Like it's a very,

very small change, right? And when it's 1.1 and it's like suicide, that's like a big deal. Like that might actually matter or even less than that. The other thing is like all, if all the correlations are pointing in the same direction, that gives you a link that there is actually something going on here. So it's not like 50% of the contraceptives caused an increase in depression. Now, all of the hormonal contraceptives caused an increase in depression, which I think is important. That is actually one of the critiques as well, because the hormonal IUDs did also cause a significant increase in depression in this study, which is not absorbed systemically as much. So that's one of those critics that why does hormonal IUDs actually can cause

Yeah, and I think that's a fair. I would like to learn more about that, like how much actually does get through. Are there any studies that show that, you know, ovulation is 100% ongoing when people are on hormonal? IUDs. And that's something that's beyond my scope of knowledge. There's also this other critique talking about the reason that you had increased, like, in rates of depression, in women who were on hormonal contraceptives was maybe because those women are also, like the women who were accessing hormonal contraceptive methods were actually those who were more accessing health care

systems just in general, more, had more chances to be appropriately diagnosed and treated for depression with antidepressants. Yeah, and my critique against that, if I was to just try to create critiques here to show the opposite side, is are they, why are they, why are they, there was an increase in the hospitalization, which a lot of hospitalizations are like, you know, kind of forced. Like, hey, this teen is suicidal. They're going to an ER now. The ER puts them on a 5150 or some sort of hold.

I don't know how they do it in Europe, but there's some sort of hold where they kind of say, no, this person really needs to be in an inpatient setting. So a lot of that's not like they're looking for care necessarily. I don't know. Like you're saying it's inpatient mostly? But there's, you know, but I think that there is something about there are probably

groups of people that are not going to seek medications. I just don't know if it's like that large of a group. Yeah. I think also there's another study, and we'll put this in our show notes, another study of 1,236 women, age 20 to 39, that showed that women who used oral contraceptives during adolescents had a 1.7 times higher one-year prevalence of depression in adulthood. That was a very nice study. And so I think there's other studies that are pointing to this as well that are...

Yeah, I think it is actually well understood that you want to try to avoid hormonal contraceptives if you can, if you can actually in that age group, in the adolescent age group. just because it's the age where brain is still developing and the HPA axis, you know, is still developing and you don't want to really impose something external on that unless, you know, you really run out of all the other methods that could be helpful to prevent pregnancy. Yeah. So they've done this one study where they looked at how in puberty, it seems like the surges of the sex hormones, both for men and women, call or cause a lot of the,

a little bit of pruning, which is really, really important for frontal lobe sort of growth. So the frontal part of the brain, you know, as you move into adolescence and all the way to the 30s, is pruning. So neurons are actually being taken away, and it's a really good thing. It allows the brain to function better. And they're finding that the gray matter decreases in the prefrontal, parietal, temporal cortices. And this is. is related to the increased estradiol, the estrogen in girls, and increased testosterone in men. Yeah, it was interesting. There's also a decreased effect of oxytocin in the brain when you take an OCP.

And so oxytocin is important for bonding, connecting, and it seems to not be as influential if you're on an OCP. So those are the immediate effects, but there's also the epigenetic processes, you know, the process that take one to two months to start working. I will leave up more detailed notes on the website, but I really want to briefly say, you know, that hormonal contraceptives decrease the ability to have fear extinction. And so the ability to have fear extinction is the ability to overcome fears. So, you know, whether it's, you know, maybe a girl who's playing sports and the fear, of competing, the fear of shooting, difficult hoops, we need the ability to slowly extinguish to decrease the amount of fear that that takes place. But on OCPs, there's a decreased ability

to have that. For empathy, there's several studies that look at empathy and OCPs, and specifically how does estrogen influence empathy? And in one study on men, a single dose of estrogen increase the amount of empathy in them. Wow. I really think there needs to be done more studies on this. But it seems like there's a role of estrogen on empathy and on feeling the pain of others.

Estrogen also increases reward pathways by increasing dopamine, whereas if you're on an oral contraceptive, you have a dampened reward processing. And so there's maybe a decrease in the amount of pleasure that someone might experience. And you can think about like the estrogen peaking right before ovulation. It's, you know, it's a biologically sort of programmed function for you to have increased pleasure with things like sex or just social connectedness.

And so those things are decreased when you don't have that peak of estrogen. I believe that overall it's really difficult to, to, to come with a set conclusion as far as like one size fits all. And I think like, but this is really valuable to, you know, study about these, to know more about the effects of hormones, just because this is very much widely used. And so we can hopefully incorporate some by knowing more into our practice. Specifically adolescent patients, I'm going to be looking at what they taking hormonal contraceptives? How are they doing contraceptives? You know, are they,

if they're at higher risk for mood type symptoms, you know, is that playing a role? And if it is, what are some options that we have? Work with their OBGYN, work with their primary care, to sort of address and treat them holistically. Holistically. Yeah. And to be more aware of, we're at the preliminary stage still. And I am hoping that hopefully in the, in the, in, the next, you know, hopefully more cohort studies come out on hormonal contraceptives because there's a lot that we don't know here. Yeah. I would like to see a like almost a randomized control trial with crossover design.

So you put someone on the hormonal contraceptive for maybe six months and then you put them on nothing for six months and then you put them on. So that way you can control for a lot of the different factors. Cool. And differences in personality and behavior and stuff. Thank you, Dr. Peter. Mona, thank you so much for coming on. And if this was of help to you, I'll put some links to the resources.

And we'll have a very, we have a nice full, detailed PDF that you can download from the website on this. And going through all of the studies and the citations. And if you disagree with something, hey, love to hear from you, throw it up on my social media. And we'll leave it there.