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.

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])

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])

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]

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])

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