Endocrine Disruptor: The birth control pill and your liver

Is the pill endocrine disrupting?

Let’s talk about one more common source of endocrine disruptors you may be taking on a daily basis without really thinking about it too much, and that’s the birth control pill. 

Whether you’re taking progestin only, a combination oral contraceptive that includes both estrogen and progestin, or have a hormonal IUD or a hormonal patch, you’re receiving a dose of endocrine disruptors daily.

The way that synthetic estrogen and progesterone work is to disrupt the normal hormonal rhythm of LH, FSH, estrogen, and progesterone in your body.  Ethinyl estradiol, a synthetic hormone, is the type of estrogen hormone used in most (and I believe all) oral contraceptives.  The dose is between 10 micrograms and 35 micrograms of ethinyl estradiol.  That low dose of 10 micrograms was approved in October 2010. 

When it comes to birth control, I’m somewhat of an oral contraceptive connoisseur.

I was first prescribed birth control sometime in my teens due to heavy periods.  This was years before I needed it for the obvious reasons.  My nearly 20-year relationship with “the pill” has been something like this… I’ll use one pill for awhile until inevitably some sort of problem comes up.  This has ranged from bleeding in the middle of a pack to not feeling like myself at all and knowing that it’s somehow pill related.

During that time span I also became adept at researching the progestins used and making recommendations to my doctor on whether I wanted one that was more or less androgenic. 

Synthetic progestins used in the pill can have estrogenic, progestational, and/or androgenic effects. 

There are also four generations of progestins with the second generation generally considered to be the safest group when looking at potential thrombotic effects.  If you’re interested in a table showing the four generations of progestins along with their estrogenic, progestational, and androgenic activities, check out the links in today's shownotes.

I also knew all about the increased risks of cardiovascular events including stroke plus increased risk of breast cancer and decreased risk of ovarian cancer. 

And, I understood that taking the pill increased my risk for autoimmune conditions. 

I even knew it wasn’t a real period during the placebo week but rather a withdrawal bleed. 

I thought I had a full understanding of the health risks associated with the pill… except I missed one critical piece of vital information hidden in plain sight in the package insert.

Oral Contraceptives and Your Gallbladder

Around 2015, I started experiencing some problems with gallbladder sludge. 

Acupuncture helped significantly at managing the symptoms over the next couple of years as my intolerance to certain foods, specifically pork and dairy, increased. 

Already gluten free, I made some additional dietary changes during that time and became an avid fan of beets as a way to improve bile production and flow, however, in 2017, the symptoms became too much and I elected to have my gallbladder removed.

Gallbladder disease runs in my family.  All of my immediate family members including my dad no longer have a gallbladder, two of my first cousins have also had theirs removed (one girl and one boy), and my maternal grandmother had hers removed when she was nearly 90.  My sis was still in her 20s when she had hers removed.  So, I chalked this up to genetics.

The Pill and Your Liver

However, over the past 6 months, I’ve had increasing problems with liver pain.  This feels like pressure and sometimes outright pain in the right side below my ribcage and it’s become so bad I can no longer sleep on my right side (and I’m not a side sleeper, I’m a right side sleeper). 

It’s important to note that liver pain and gallbladder pain can refer to other parts of your body. 

For instance, it’s common for you to feel gallbladder pain a bit higher on your right side, maybe even underneath your ribcage or in your right shoulder and you could have pain at the sphincter where the gallbladder releases bile into your small intestine.

This is known as sphincter of Oddi discomfort, and right shoulder pain on your backside is also commonly associated with gallbladder congestion.  Even if you don’t have pain, you may have extreme fullness after eating just a little bit or you may get nauseous, especially after certain foods. 

In another episode, I’ll talk about a keloid that arose on the back of my right shoulder in 2015 and how that was indicative of my gallbladder distress.

Liver, Thyroid, Gallbladder Connection

About the same time as the onset of that liver pain earlier in 2021, I’d made up my mind that I could put my Hashimoto’s into remission and read a fabulous book by Dr. Marianne Teitelbaum on healing the thyroid with Ayurveda.

I’d even implemented some of Dr. Teitelbaum’s teas into my daily routine, and those teas proceeded to make my liver pain worse. 

I scheduled an appointment with her as a patient and learned that many of those teas while supportive for the thyroid are also heating to the liver and typically with autoimmune conditions, the liver is already extremely hot, so toxins need to be removed in a way that doesn’t further increase liver heat.

Both TCM and Ayurveda believe herbs and foods can be heating or cooling, and we’ll talk about that more in future episodes.

Dr. Teitelbaum also raised concern over my long-term use of oral contraceptives as potentially contributing to my low thyroid function, and specifically the onset of autoimmune thyroiditis. 

Now, she isn’t the first doctor to mention that she’d love to see me come off the pill for one reason or another.  But, this time, a series of other things happened simultaneously that made me listen. 

Around the same time as that first appointment with Dr. Teitelbaum, I’d started listening to Stephanie Center’s podcast Daily Detox with Stephanie Center, and in one of her episodes, she interviewed Rachel Hoeppner of Real Health with Rach about ditching the pill.  In that interview, Rachel mentioned Dr. Joelene Brighten’s book Beyond the Pill, and I picked it up and read it.

While most of the book covered what I already knew about the risks associated with the pill, having learned it from the package insert, there was one very important piece of the package insert I’d failed to notice during my decades of use…

Oral Contraceptives and Liver Problems

The pill is associated with liver problems, specifically, increased risk of gallbladder disease and hepatic neoplasia.

What is neoplasia?  The term neoplasia means uncontrolled cellular growth, and this is common of cancerous tumors.  It’s also common of benign tumors.  Specifically, your risk for benign liver adenomas is statistically higher if you’re on a combined oral contraceptive.  Adenoma is the medical term for non-cancerous tumor.  Just because it’s benign doesn’t mean it’s healthy. 

Commonly in cancerous tumors, the vasculature or blood vessels within the tumor are quite leaky, and in fact, a host of anticancer drugs are formulated to take advantage of that leaky vasculature.  Even in the adenoma state, where the tumor is benign, vasculature is more leaky than in normal tissue.  Your liver is already rich in its vascular network, and it’s not uncommon for people to bleed out on the operating room table during a routine liver biopsy. 

Add an adenoma into a blood profuse organ, and it feels a bit like a ticking time bomb.  Even if the adenoma’s blood vessels remain integral, it’s possible for the adenoma to increase in size to the point where it constricts biliary flow by pressing on the bile duct.

And, adenomas can lead to carcinomas or cancerous tumors.

Going off the pill typically reverses the size of an adenoma and over time, the benign tumor can shrink and be repaired to normal tissue.

A study in rats has also shown that liver tissue is congested by ethinyl estradiol, specifically the liver vasculature is impacted as evidenced by dilated veins and distended sinusoids.  Sinusoids are a specific type of capillary found in the liver and they help your body filter & restore nutrients to your blood.

You may be wondering about progestins.  Generally, progestins are considered less hepatotoxic than estrogen.  However, there are studies that show certain progestins can elevate some liver enzymes, specifically ALT and AST.  It’s also worth noting that your liver makes SHBG.  Your circulating levels of SHBG is elevated to varying degrees by both progestins and estrogens, so progestin only pills aren't without their own set of concerns for your liver.

I’ll share with you where I’m at today.  Dr. Brighten’s book discussed the risk of liver related problems pretty late in the book, and by this point, I was a bit fed up with the anti-birth control pill rhetoric. Have you ever felt that way?  Where it feels like somebody is just beating a dead horse and you're thinking, "all right already" while dismissing their entire case?  I was so there.

Despite being fed up with the rhetoric, I ordered LH test strips, a basal body thermometer accurate to two decimal points, & dusted off my ferning microscope.

The Pill and Liver Congestion

With these tools in hand, I Googled ethinyl estradiol and liver for myself.  The first article I pulled up made me stop the pill that night.  It’s far too soon to report back on whether my liver feels less congested.  As of the date of this episode airing, I’m 2 weeks since stopping the pill.

What made me stop?

Here's what I unearthed in about 10 peer reviewed scientific articles.

  1. Birth control pill use is associated with a 50-fold increase in relative risk to develop liver adenomas, those benign liver tumors or benign liver cysts.
  2. Oral contraceptive use is associated with a 3-fold greater increase in risk of developing gallbladder disease.

    Ethinyl estradiol has been shown to decrease bile production resulting in bile saturated with cholesterol, which means thick, sludgy bile more likely to exhibit lithogenesis or presence of stones most commonly known as gallstones (even though these stones can still develop when your bile is thick and you have no gallbladder).

    By comparison, the side effects we more commonly hear about like heart attack and stroke, have a much lower relative risk.  For instance:

    • Relative risk (RR) of benign liver tumors associated with the pill: 50
    • RR of gallbladder disease:  3
    • RR melasma:  1.5
    • RR stroke:  2.5
    • RR heart attack (non-smokers): 1.0
    • RR heart attack (total):  3.3
  3. The binding affinity of ethinyl estradiol (EE) for ER alpha and ER beta has been found to be over a pretty wide range. 

    Studies pretty consistently show that EE binds ER alpha with about 20-fold greater affinity than estradiol. 

    Studies are a little more varied in their findings for binding affinities to ER beta.  One study reported 38% binding affinity to ER beta compared with estradiol while a second found ~150% greater binding affinity to ER beta compared with estradiol.

    When taken orally, ethinyl estradiol is about 100 times more potent as natural estrogens.  This is because it resists first-pass metabolism and persists in your body for far longer than estradiol.  While estradiol’s elimination half-life is about 90 minutes, EE’s elimination half-life is about 7 hours.

  4. EE also irreversibly inhibits a class of enzymes, cytochrome P450, commonly referred to as CYP450.  CYP450 enzymes primarily found in your liver are responsible for breaking down steroids like cholesterol, testosterone, estrogen, and progesterone, fatty acids, and xenobiotics.

    For CYP450, xenobiotics basically include any organic substance entering your body, or any carbon based substance not naturally produced within your body.  This includes toxins like dioxins and organo pesticides. 

    This also includes caffeine and nicotine. Furthermore, certain progestins found in COCs also inhibit CYP450 enzymes.  These progestins include desogestrel and etonogestrel.

  5. And, this was particularly disturbing... it was found that EE accumulates within your body, and a 2-fold accumulation of EE levels has been observed after one year of being on combined oral contraceptives.

    I knew none of this until after I started verifying Dr. Brighten’s claims regarding the liver toxicity of the pill.  And, this research is what made me stop taking it that same day.

    You can find links to these articles in today’s shownotes.

    Uncovering this information left me with a sense of feeling like I'd been kept in the dark for the past 20 years.  As I mentioned, this isn't the first time a doctor mentioned stopping the pill, but the important piece of this suggestion was usually missing... there was never a WHY associated with the conversation.  It was always a vague suggestion that somehow pill use might be contributing to a health condition without any follow-up conversation.

    And, this isn't the first time I've stopped using the pill.  Back in 2012, I got really sick.  I'll dive into what was going on in a future episode, but as part of that journey, my then doctor (who is also hands down the best doctor I've ever had) asked me to stop taking the pill while we worked through the process of diagnosing my condition.  I willingly stopped and used fertility awareness method as a means of contraception for several months.

    And, yes, I totally understand the pill can impact fertility especially during the first months after you discontinue use, and yet, I wanted to share use of this method with you, and full disclaimer, I'm not recommending this for you, I'm sharing how you can use it if you choose to.

    Contraception without the pill

    First, let's talk about what your options are for birth control aside from oral contraceptives.

    1. You can switch from combined oral contraceptive containing both estrogen and progestin to progestin only. Because I’m experiencing liver problems to the point of having pain and pressure and am not convinced the synthetic progestins alone are safe for your liver, I opted not to do this.

    2. You can use a condom, a diaphragm, a sponge. Most condoms and all sponges are coated with spermicide.  A diaphragm has to be coated with spermicide and it also typically has to be fitted by your doctor.  The problem with spermicide?  If it's toxic to one type of body cell, it's typically toxic to other types of body cells.

      Spermicide free condoms are a good non-toxic option.

    3. You can have a tubal ligation, and if you opt for this, please don’t let yourself be talked into the Essure.

      The Essure is a device that effectively scars your Fallopian tubes, basically a non-surgical tubal ligation, and its side effects were so well described in Dr. Brighten’s book that I decided there’s no way in hell I’m doing that and cannot believe it hasn’t been pulled off the market. 

      The thing about a regular tubal ligation is that it’s a surgery, and you have to undergo general anesthesia, and any kind of surgery is not without risks.

      Plus, if you’re planning to have children one day, it’s just not a great choice.

    4. Likewise, the copper IUD is off the table because at high levels copper is a cellular toxin, in fact, this is how it works to provide birth control, it induces oxidative species like the hydroxyl radical creating an environment of oxidative stress that is potent enough to kill both egg and sperm. And, that copper IUD does this within your uterus.  The copper IUD is also linked with heavier periods.

    5. Your partner can have a vasectomy. Vasectomies are not without their risks. 

      Post-vasectomy pain syndrome or PVPS is a chronic condition that may develop immediately or years following a vasectomy.  In a study conducted by the American Urology Association’s Vasectomy Guidelines in 2012 and amended in 2015, the study found a 14.7% incidence of new-onset scrotal pain 7 months after vasectomy.

      There’s also a slight increase in risk of mortality from cancer, specifically lung cancer, in men who’ve had a vasectomy at least 20 years prior.  There’s also a slight increased risk in developing prostate cancer for at least 30 years after vasectomy, and there’s an increased risk of forming kidney stones.

    6. You can practice fertility awareness method. For me, I have no intentions of having children, so I want the most comprehensive FAM possible in order to avoid pregnancy.

      So, how do you use a method that's for increasing your fertility to avoid pregnancy?

      Here's what's available. 

      You can monitor your luteinizing hormone or LH.

      What does the LH strip tell you?  Your luteinizing hormone rises about 24 to 36 hours before you ovulate.  While an egg can live up to 24 hours, sperm can live about 6 days, so it’s important to use a back-up contraceptive method for the 6 days before you ovulate plus a couple days just to be on the safe side after ovulation.

      Since LH test only provide insight into ovulation about a day to a day and a half before ovulation, they aren’t sufficient alone although they can be once you've established that you have a regular cycle.

      Basal Body Temperature:  BBT is the same way, your basal body temperature typically spikes after you ovulate and remains elevated for a few days.  Just before ovulation, you’ll typically see a dip, but again, this alone won’t help you predict very well when you should avoid unprotected sex for pregnancy prevention.

      The saliva ferning test isn’t talked about very much, and I’m not sure why.  It’s been around for a while, and I feel like it was even easier to find information on this back in 2012.  FDA has a whole webpage linked in today’s shownotes on ferning as a way to predict ovulation.

      Saliva Ferning:  The premise behind ferning is this… you take a bit of saliva, let it dry on a microscope slide, look at it under microscope to check for the appearance of crystals.  This will show up in a fern pattern and coincides with the spike in estrogen ahead of ovulation.  Generally, the fern pattern is seen up to 72 hours before ovulation, the only problem is that in some women, it may show up only about 24 hours in advance.

      While 1 day and even 3 days isn’t enough to avoid pregnancy, the beauty of ferning is that there’s a transitional period ahead of the estrogen rise that you can use to help predict ovulation and you can go ahead and use a back-up contraceptive method once that pattern appears.

      The problem with ferning is that not all women produce enough estrogen to see a ferning pattern.

      Cervical Mucus Monitoring:  This is an easy way to keep an eye on your fertility without any sort of equipment.  You can find the link in today's shownotes for how to monitor your fertility using your cervical mucus.

      Estrogen Monitoring:  Mira offers a device that can measure both your estrogen levels and your luteinizing hormone (this is an affiliate link).  Estrogen typically surges before ovulation and provides information about your entire fertile window.

      This device is the only one I've found that monitors estrogen levels at home, and it's a game changer for using FAM as a means of contraception.

      I'm all for using as many methods as possible to really get to know your body, and I think it's especially important when you're first coming off the pill or if you have irregular periods to quantitate your estrogen production so you can be more confident in knowing when you're fertile and reduce your risk of pregnancy. 

      Another disclaimer:  I make no claims you won't get pregnant by using estrogen monitoring combined with any of these methods, I'm just sharing what I've learned while researching this for my own needs.

    Okay, today’s episode took a major side road which is why it’s being delivered as a bonus episode.  I realize it’s a stretch to start out a conversation on endocrine disruptors and wind up talking about FAM, but if anybody can find a crazy connection, it’s me, and this conversation has been weighing heavily on my heart and felt even more pertinent than a conversation about sunscreens and EDCs which we are finally getting around to next week.

    I sincerely hope you walk away from today’s conversation with something useful for your life, and I apologize if this was too much information.  I’ll be back next week on point, and until then would you be open to leaving a review for this podcast? 

    You can leave a review on iTunes.  Also, please follow the podcast from your favorite listening platform and if you know somebody who you feel might benefit from today’s conversation, take a quick second to share this episode with them.

    Until next time,

    References

    Angiogenic switch from adenoma to adenocarcinoma

    https://drive.google.com/file/d/1TSI79D0W_C8TRl_SwQSuaShFqJS6HAtF/view?usp=sharing effect of oral contraceptives on the liver

     

    effects of oral and transvaginal ethinyl estradiol on hemostatic factors and hepatic proteins in a randomized crossover study

     

    effects of subdermal levonorgestrel implant (Norplant) on serum cholesterol triglycerides and liver enzymes

     

    Experimental Hepatotoxicity Produced by Ethinyl estradiol

     

    https://drive.google.com/file/d/1W7qMmSexuCx7NbVMUkf5dYjZG5oetBiZ/view?usp=sharing oral contraceptives

    A guide to progesterones: by generation and androgenicity

    https://www.uofmhealth.org/health-library/hw214032#hw214056 fertility awareness for contraception

    https://www.nejm.org/doi/full/10.1056/NEJM199205213262104 A longterm study of mortality in men who’ve undergone vasectomy

    https://www.ajkd.org/article/S0272-6386(97)90031-7/pdf Vasectomy is associated with an increased risk for urolithiasis

     Saliva Ferning for Predicting Ovulation

    Cervical Mucus Method for Predicting Ovulation

    Brandy Searcy founder Rain Organica

    About the Author

    Brandy's a formulation scientist and self-proclaimed health geek who loves hiking, gardening, bird-watching, and body boarding. 

    Her struggle with acne during her teens and 20s led to a holistic and healthy approach to skincare, embracing skin as an organ to be loved and cared for rather than a canvas to wage war on. 

    Since 2008, she's been developing all-in-one products for a simple routine at home, & Rain Organica started when her backpacking friends asked for a portable skincare routine to keep their skin healthy & happy on and off the trails.

    You can try Rain Organica for yourself with The Essentials Kit, a complete skincare routine in just 3 steps.

    Brandy's LinkedIn Bio

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