Episode 50: Hormonal Contraceptive Use Is Associated With a Decreased Incidence of Hypothyroidism

Summary

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Episode Overview

Podcast: AACE Podcasts
Episode: 50 - “Hormonal Contraceptive Use Is Associated With a Decreased Incidence of Hypothyroidism”
Date: June 10, 2024
Host: Dr. Vintangprecha
Guest: Dr. Ty Carroll, Endocrinologist at the Medical College of Wisconsin

This episode explores new research linking hormonal contraceptive use to a decreased incidence of hypothyroidism among women. Dr. Ty Carroll, the study’s senior author, discusses the origins of the research, its surprising findings, possible mechanisms, study design considerations, clinical implications, and practical advice for clinicians.

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Key Discussion Points and Insights

1. Genesis of the Study and Research Question

• The research was sparked by a “very eager” medical student, Shannon Glow, and was inspired by conflicting prior studies suggesting hormonal contraceptives increased hypothyroidism risk.
• Dr. Carroll explains:

  “There was a fairly recent publication... that concluded hormonal contraception increased the risk of hypothyroidism... and to really wonder what that association was. So that was sort of the genesis of this project.” ([01:52])

2. Study Design and Data Source

• Leveraged a large anonymized database (“Trinetics”) covering 5–8 million lives; the study included over 18,000 women, analyzing a 10-year period.
• They segmented groups by type of contraception: estrogen-containing, progestin (excluding IUDs), progestin IUDs, and controls.

  “We were able to query the database to find individuals who had a diagnosis of hypothyroidism... and then determine which patients had a diagnosis... or were prescribed levothyroxine.” ([02:40])

3. Primary Findings—Surprising Direction of Association

• Contrary to expectations (and previous work), hormonal contraceptive use was associated with a lower incidence of hypothyroidism—even with progestin IUDs.

  “It was a little bit to our surprise, it was contrary to the previously reported study, but the data showed... any previous hormonal contraception use decreased the risk of developing hypothyroidism.” ([03:49])

• The finding persisted after controlling for race, ethnicity, and BMI.

4. Subgroup Analysis and Complexity

• Initially, the estrogen group showed a “neutral” effect; after further adjustment (especially for race and ethnicity), estrogen users also exhibited decreased risk versus controls.

  “Once we did the analysis and looked at the different subgroups, even the oral estrogen group did have a lower risk than controls.” ([06:09])

5. Mechanistic Hypotheses (and Unknowns)

• Estrogen might dampen autoimmunity or function as an anti-inflammatory.
• The exact reason for progestin and IUD benefit is less clear.

  “Certainly, like you mentioned, whether estrogen has an anti-inflammatory component... would make sense... But then why the progesterone group, why the IUD group that had a strong decrease in the risk... isn’t quite clear.” ([06:20])

6. Study Limitations and Critiques

• Unable to account for confounders like iodine intake or detailed markers of autoimmunity (e.g., thyroid antibodies weren’t measured).

  “We did not look at thyroid antibodies... and I think that’s one... criticism of this study is that we weren’t able to look at any markers of autoimmunity.” ([07:12])

• Hypothyroidism was identified using ICD-9/10 codes and levothyroxine prescription, not TSH/lab results.

  “We did not use TSH. Again, one could argue... that might have been a good way to look at it. The data just looked a little bit more reliable... when we looked at the ICD codes.” ([08:06])

7. Comparison to Prior Studies

• Previous prominent study found increased risk with longer estrogen exposure; key differences involve follow-up length and inability to measure duration of contraceptive exposure.

  “The other study... had the ability to see how long the exposure was... in their study, longer estrogen exposure actually increased risk...” ([10:35])

8. Clinical Takeaways and Recommendations

• Dr. Carroll does not recommend prescribing hormonal contraceptives to prevent hypothyroidism yet; evidence is insufficient for clinical action.

  “I would not use this data to make that treatment decision... I think this is the first step... that may lead to some difference in treatment decisions.” ([11:46])

• For hypothyroid patients starting oral estrogen, be aware of need to adjust thyroid medication due to changes in binding globulins:

  “Certainly oral estrogen, many women need to have their dose of thyroid hormone adjusted... that’s the main caveat.” ([13:02]) “I just recommend they get another TSH in a month or two after they've started their hormonal contraception.” ([13:40])

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Notable Quotes & Memorable Moments

• Dr. Carroll on the IUD finding:

  “The one thing that I think sticks out to me that I'm still sort of scratching my head about... is even the IUD, the progestin IUD group had a lower risk. It's a little hard in my mind to kind of fathom why that is.” ([04:29])

• Host reflecting clinical curiosity:

  “I'm surprised that the estrogen group didn't pan out... I would have thought that estrogen would’ve been beneficial.” ([05:05])

• On practical adjustment of thyroid dose:

  “Someone who's on L thyroxine, 100 micrograms, going to start an estrogen, you may have to bump up the dose, right?” ([13:23])

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Timestamps for Key Segments

• Introduction & Guest Introduction: [00:28]
• Study Inspiration & Prior Literature: [01:52]
• Database & Study Design Explanation: [02:40]
• Main Results—Surprising Findings Discussion: [03:39]
• Subgroup Analysis & Confounding Factors: [04:29] – [06:09]
• Possible Mechanisms & Limitations: [06:20] – [07:57]
• Defining Hypothyroidism & Data Methods: [08:06]
• Comparison to Previous Studies: [10:35]
• Clinical Application & Recommendations: [11:46] – [13:40]
• Take-Home Messages: [14:34]

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Take-Home Messages

• Hormonal contraceptive use, including all major types, was associated with a reduced incidence of hypothyroidism in this large retrospective study.
• The finding is unexpected and contrasts with prior research; possible mechanisms remain speculative.
• Major confounders, such as autoimmunity and iodine intake, were unaccounted for.
• Clinical implication: Do not use this data to change prescribing practice—evidence is hypothesis-generating, not conclusive.
• For hypothyroid patients starting oral estrogen, monitor and possibly increase levothyroxine dose.

“This is an interesting finding that should be a light bulb to some other investigators... to think about how can we design additional studies to confirm these results.”
— Dr. Ty Carroll ([14:34])

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For further reading:
Find Dr. Carroll and team's study in the January 2024 issue of Endocrine Practice.

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Transcript

[Dr. Ty Carroll]

Foreign.

[ACE Podcast Host]

Welcome to ACE Podcasts. Thanks for tuning in as we elevate clinical endocrinology by taking deep dives into trends and topics that can help us improve our patient care and global health. Find the latest episodes on aace.com podcasts and now let's meet the endocrine experts who will be talking with us today.

[Vintangprecha]

Hi, my name is Vintangprecha and I'm the host of today's ACE podcast. Also serve as the editor in chief of Endocrine Practice. And today we have a special guest, Dr. Ty Carroll, who has just published a paper in Integrine Practice in the January issue entitled hormonal Contraceptive Use is associated with a decreased incidence of Hypochrome Thyroidism. Hi, Dr. Carol. Thanks for joining.

[Dr. Ty Carroll]

Thanks for having me.

[Vintangprecha]

Could you introduce yourself to the audience? What you do and your clinical and research interests are sure.

[Dr. Ty Carroll]

As was stated, my name is Ty Carroll. I'm an endocrinologist at the Medical College of Wisconsin in Milwaukee. I'm a clinical endocrinologist, a fellowship program director, and have several different hats. My normal research interest is in cortisol and pituitary adrenal disease. But this was an interesting topic that actually was brought to me by a very eager medical student who was the first author, Shannon Glow. So really, she gets a lot of credit for this idea and the execution.

[Vintangprecha]

Great, thanks. I mean, this paper generated a lot of social media attention when it first got published. I think it was retweeted or re exed many times and shared among many groups and caught a lot of people's attention. So I guess my first question how did you and your medical student even come up with this idea?

[Dr. Ty Carroll]

Well, there was a fairly recent publication that looked at hormonal contraception and the risk of hypothyroidism. So they concluded that hormonal contraception increased the risk of hypothyroidism over and I guess I don't quite recall what the duration of their study was. And it was really interesting because obviously there are so many women on hormonal contraception. Hypothyroidism is probably the most common or one of the most common endocrine disorders. And to really wonder what that association was. So that was sort of the genesis of this project.

[Vintangprecha]

Right. And I mean, this was a very large study. I mean, over 18,000 patients. How did. Can you explain the database and the study setup?

[Dr. Ty Carroll]

Sure. We're fortunate to have the trinetics database from our healthcare system that I believe covers somewhere around, I want to say, 5 to 8 million lives. And so we can query the database through anonymized results and pull out all kinds of different, whether it's diagnoses, lab values, et cetera. And so we were able to query the database to find individuals who had a diagnosis of hypothyroidism. We sort of select this 10 year time period largely because when we started to go back too much farther than that, the data's a little bit scant. And that also gave us a little bit of time between the end of when we searched and the possible development of hypothyroidism. So we were able to identify the different groups, whether it was estrogen containing hormone therapy, progesterone, and we broke that off into all forms of progesterone other than IUDs and then our control groups. So we were able to sort for those and then determine which of the patients had a diagnosis of hypothyroidism or were prescribed lipothyroxine.

[Vintangprecha]

So going to the title of your paper, you concluded that women on hormonal contraceptive had less risk of hypothyroidism, is that correct?

[Dr. Ty Carroll]

Yeah, it was a little bit to our surprise, it was contrary to the previously reported study, but the data showed it certainly when we didn't have any adjustments, that it looked like the group in the estrogen containing group was neutral, but progesterone group did have a benefit. And then when we adjusted for certainly RAS and ethnicity, which was pretty important, and also obesity or bmi, it looks like that any previous hormonal contraception use decreased the risk of developing hypothyroidism.

[Vintangprecha]

So any oral concept of use, including estrogen or progesterone, any of them, any of the formats.

[Dr. Ty Carroll]

And the one thing that I think sticks out to me that I'm still sort of scratching my head about as to why is even the iud, the progestin IUD group had a lower risk. It's a little hard in my mind to kind of fathom why that is. We really kind of went back over the data, especially in the IUD group, to see. Okay, well did, did we, did we have a problem with our data that somehow would have skewed it that way? And at least the data as it is show that even that form of hormonal contraception decreased the eventuality of developing hypothyroidism.

[Vintangprecha]

I'm surprised that the estrogen group didn't pan out. When you looked at subgroups, I mean, I could see how estrogen could be anti inflammatory, maybe, you know, Most of these women had autoimmune thyroid disease, I'm assuming, and I would have thought that estrogen would have been beneficial.

[Dr. Ty Carroll]

Yeah. So I think in the initial analysis it didn't reach statistical significance. And I think one of those reasons was that the estrogen group, it certainly was a large portion of the white population. And one thing I think that's interesting is the sort of what groups got what form of contraception. And I think that speaks a little bit to the socioeconomics of the area. And hormonal contraception, that's probably a much larger discussion for a different podcast. But I think that, that the large Caucasian population in the estrogen group probably skewed that. And then once we did the analysis and looked at the different subgroups, even the oral estrogen group did have a lower risk than the controls.

[Vintangprecha]

Oh, okay, that's good. I mean, is the potential, I think you touched upon it in your paper, the potential mechanism is through dampening autoimmunity or what do you think that.

[Dr. Ty Carroll]

I mean, I think that that's the easiest explanation, whether that's the truth. You know, often the easiest explanation isn't the truth, but certainly like you mentioned, whether estrogen has an anti inflammatory component to it, that certainly would make sense to me. But then why the progesterone group, why the IUD group that had a strong decrease in the risk, why that panned out isn't quite clear to me. And I think that's an area where we need more research and this topic, either prospectively or with other large databases to confirm these results will be important.

[Vintangprecha]

I mean, it's interesting that the IUD group had potential benefit. I mean, are there other unmeasured variables like iodine intake or better diet or something that could be associated with decreases of hypothyroidism?

[Dr. Ty Carroll]

I certainly think that there are. One thing that we saw is that the IUD group was really strongly swayed toward the white population. And again, there's probably social determinants of health in here that may play a role. And one thing we weren't able to account for in our database was markers of autoimmunity. So we did not look at thyroid antibodies. My guess is that a lot of patients that were diagnosed with hypothyroidism didn't have those measured. So I think it would have sort of skewed the groups a bit about who had antibodies measured and who didn't. But we did not look at that. And I think that's one. Certainly one criticism of this study is that we weren't able to look at any of those markers of autoimmunity.

[Vintangprecha]

I guess my other question was, how did you define hypothyroidism? Was it a ICD code diagnosis or was it based on TSH?

[Dr. Ty Carroll]

Yeah, so we looked at ICD 9 and 10 codes. Obviously we went back to 2010, so we had to use ICD 9. We used all the hypothyroidism codes and people who. Or women who were prescribed levothyroxine. We did not use tsh. Again, one could argue that that might have been a good way to look at it. The data just looked a little bit more reliable and clean when we looked at the ICD codes as opposed to lab values. Part of the problem, as I'm sure you well know, anytime you're using a large database is to get all the data that you want. I would have loved to have looked over all 18,000 charts, but that wasn't going to be a feasible, you know, study. I'm sure that many of these patients were probably only seen a few times in our healthcare system, and that's why a lot of these patients were excluded just from lack of insufficient data.

[Vintangprecha]

So I guess the reason I was asking that was maybe there be a larger population of subclinical hypothyroidism and maybe there'd be some sort of signal there. I don't know if any comments about that.

[Dr. Ty Carroll]

Yeah, I mean, I think that these are all excellent points and we kind of thought about, you know, if we want to confirm this going forward, how would we do this on a. Probably a smaller but more detailed scale. And I think that that's certainly an area where we would look at TSH, we'd look at T4, we'd look at thyroid antibodies and try to follow some of these patients perspectively, or at least go back in a smaller group and really look at some of the more detailed data.

[Vintangprecha]

Are you aware of any data in trials where women were given estrogen, maybe the Women's Health Initiative trial or something else where they looked at thyroid dysfunction status?

[Dr. Ty Carroll]

Yeah, I'm not aware of any specific trials where this has been sort of tested, if you will.

[Vintangprecha]

I wonder if there would be some blood or cohort data you can look at from these trials. It might be easy to measure some TSHs and antibodies.

[Dr. Ty Carroll]

Yeah, I mean, that's certainly that. These large databases that are very well documented and have health outcomes, have a lot of blood work. That's a fantastic idea, is to have access to those and be able to look at it. In a more detailed fashion.

[Vintangprecha]

You mentioned there was another study that was different from your study. What I mean, which showed like the opposite finding. I mean, why do you think the studies were so different?

[Dr. Ty Carroll]

Yeah, they were performed in a little different manner. So their study, and I'm trying to recall the specifics of, I believe it was key and all that, they looked at patients over, I believe, a shorter duration, but they also took into account the exposure of the estrogen. And that's one thing we weren't able to do with our database, is to look at the overall exposure of these medications. So if a woman was prescribed or received estrogen at any time during, during our study period, they fell into the estrogen group or, you know, progesterone, etc. Whereas the other study, they had the ability to see how long the exposure was and were able to say, well, with longer exposure of estrogens, in particular, they didn't look at progestins, but they just looked at estrogen. And the longer the estrogen exposure actually increased risk in their study with hypothyroidism.

[Vintangprecha]

Now, some people might read this paper and say, oh, well, Aunt Betty has thyroid disease, maybe she should go on estrogen. Is this, is that something we're ready to say yet?

[Dr. Ty Carroll]

Yeah. I would not use this data to make that treatment decision. I certainly think that this is food for thought about how do we design a trial looking at women who are receiving hormonal contraception and does it decrease the risk of hypothyroidism, especially in perhaps women who have autoimmunity, who have a high risk of developing hypothyroidism, strong family history and look to see if there's another indication to use hormonal contraception. Does that decrease their risk in the long run? And that's where I think I would use this data. I think this data to me is a prompt as to, okay, what do we study now? How can we look at this in a real more detailed, treatment driven fashion? But I certainly wouldn't use this to say, well, somebody's already got hypothyroidism, we should give them some form of hormonal contraception. And I think we need to prove this going forward that it really does decrease the risk. But I think this is the first step of a couple that may lead to some difference in treatment decisions.

[Vintangprecha]

Someone who already has hypothyroidism and goes on hormone contraceptive. Is there any money pitfalls, anything we need to worry about?

[Dr. Ty Carroll]

Well, certainly oral estrogen. Many women need to have their Dose of thyroid hormone adjusted obviously because of binding globulins, et cetera. But I think that's really the main caveat here is oral estrogens and need for adjustment of thyroid hormone. The other forms, progestins and non oral forms of hormonal contraception probably don't play much role.

[Vintangprecha]

Okay, so that's probably a very important thing to remember. Someone who's on L thyroxine, 100 micrograms going to start an estrogen, you may have to bump up the dose, right?

[Dr. Ty Carroll]

Absolutely.

[Vintangprecha]

I mean, how much would you bump up the dose if they're in a hundred?

[Dr. Ty Carroll]

You know, I think there's several different ways to approach it. My general take is it's pretty easy for most of our patients to get another tsh. And so I just recommend they get another TSH and a month or two after they've started their hormonal contraception. And some would just increase the dose right away a little bit akin to a woman in pregnancy, though I think we've got a little bit more leeway if we're just starting an oral contraceptive as opposed to a woman who is pregnant and has hypothyroidism on therapy where many people would just increase their dose by two tablets a week.

[Vintangprecha]

Okay, that's good, that's good approach. How about the other way around? Someone on oral contraceptives and starts on hormone therapy, that's not going to be less effective or contraceptive, is it?

[Dr. Ty Carroll]

No, we don't think so.

[Vintangprecha]

Just want to make sure. So yeah. This has been a great conversation. Do you have a few take home messages for audience listening today?

[Dr. Ty Carroll]

I really think that this is an interesting finding that should kind of be a light bulb to some other investigators that might be interested in this topic and to think about how can we design additional studies to confirm these results. I think any time when you have studies that have differing results, we need to figure out which direction the truth lies. I'm sure there are nuances that, as in every situation are the case, but to kind of help us know how to use this data later on.

[Vintangprecha]

Thank you so much, Dr. Carroll for joining us. This has been a very enlightening talk and for people who want to read his article by him and his medical student, you can read it at Endocrine Practice in the January issue. Thanks so much, Ty again for joining us and hope you continue forward with this research.

[Dr. Ty Carroll]

It's been my pleasure. Thanks for having me.

[ACE Podcast Host]

Thanks for listening to another great ACE podcast. Join us for another [e-mail] podcasts and help us in our mission to elevate clinical endocrinology. Together, we are ACE.