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Unintended Consequences! Oral Contraceptives and Dis-ease Begins in the Gut

September 10, 2025 | 10 Comments | Clinical Tip Team

Oral intake of estrogen (with or without progestins) may promote the roots of disease in the gut.

Check out this clinical tip video for insight on oral sex hormone supplementation that might surprise you. Here are a few of the points I cover…

Oral contraceptives may increase C-reactive protein. Check out the detail here and here and here and here.

They may increase intestinal permeability and the risk of inflammatory bowel disease: check out here and here and here.
(Remember this is typically a reflection of an oral estrogen combined with a progestin. On the other hand, bio-identical, micronized progesterone does not seem to promote these effects.)

We also know oral contraceptive use may deplete micronutrients, especially Vitamin B6 (a great read for detail).

We know that higher levels of estrogenic activity promote increased histamine release (and vice versa). Unfortunately, many of your patients bring onboard a significant amount of endocrine disrupting chemicals via the oral route as well (e.g. pesticides, herbicides)? Synergistic effects are logical.

Thank you for expanding your knowledge of the functional interconnectendess of disease!
You may search by keyword for other posts of interest in this Clinical Tips area; there are hundreds of them.

Warmly,

P.S. If you are passionate about transforming healthcare through the power of functional medicine, we encourage you to learn more about SAFM’s practitioner training programs. Enrollment for our next cohort is now open!

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5

Stefanie says:

October 19, 2024 at 1:15 pm

Hi Tracey,
I know there is alot of discussion on how oral contraceptives play a role in affecting our gut. Would the same reign true with someone who has an IUD. I have had challenges finding information on this. Thanks for any insight

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  SAFM Team says:
  
  November 1, 2024 at 2:56 pm
  
  Studies suggest that IUD is not directly linked to intestinal hyperpermeability, but it is associated with increased risk of bone fractures and metabolic changes (https://journals.sagepub.com/doi/10.3233/BLC-201526). There is also evidence of acute liver injury associated with the use of levonorgestrel-releasing IUDs. In a reported case, a patient experienced liver injury that resolved upon removal of the device, with no other identifiable causes for the liver dysfunction. However, the metabolic side effects of hormone-releasing IUDs, such as those releasing levonorgestrel, are not fully understood.
  
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4

Stephanie Whitling says:

February 4, 2021 at 12:56 pm

Tracy,
I had a question today that I don’t know how to answer. Do you know what particular hormone in the OCP deplete B6? I reviewed the article posted and it does not state. I do think this is a great question because many OCP’s are combination pills and some more dominant than others. I think most are estrogen and progestin.
Thank you.

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  SAFM Team says:
  
  February 5, 2021 at 1:47 pm
  
  All hormone supplementation will make use of key nutrients to facilitate detoxification and clearance, so in a general sense, yes, they all lower available supply of B vitamins, including B6. However, the more dramatic effect of oral contraceptives on B6 sufficiency appears to be specific to estrogens and is in part influenced by estrogenic effect on tryptophan metabolism, serotonin synthesis, and metabolism. This may be of interest to you: https://www.sciencedirect.com/science/article/abs/pii/001078247490078X .
  
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3

Ashley says:

September 29, 2020 at 8:14 am

What about the absorption rate of transdermal patches and creams? They vary according to site and person depending on skin permeability. I struggle with getting patients an accurate dose, because you just never know how much they are actually getting.

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  SAFM Team says:
  
  October 9, 2020 at 1:51 pm
  
  Yes, your point is important and good justification for testing serum levels of hormones to check for optimal absorption and appropriate dosing not too far into usage onset and then episodically to confirm whether adjustments are necessary. Timing of testing will, of course, depend on usage/purpose, but if trying to mimick physiologic levels (e.g. gio-identical hormone replacement in postmenopausal women), it will perhaps make sense to test on Day 12 and Day 21.
  
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2

Michelle says:

May 26, 2018 at 8:20 am

I am a functional med practitioner. Myself and 1 other patient cannot tolerate TD progesterone or oral. It makes us both anxious and “crazy” feeling with terrible insomnia. I have tried dose 1 mg TD applying at different times. My supervising dr. has suggested that 99% of women in our practice have no problems. I am frustrated, 48, and having hot flashes. Anxiety. And insomnia no matter what I do with all of my functional knowledge. I secretly feel like I have nowhere to turn as a pt for help. Thoughts?
I am on black cohash, niacin, ashwaghanda, relora, magnesium, gaba before bed. I was on TD 1 mg progesterone x 2 months and felt awful. I have been off x 1 week and still feel pretty unlike myself. The insomnia is what’s killing me. Cbd, melatonin, nothing works and makes me feel very hung over .

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  SAFM Team says:
  
  May 27, 2018 at 11:55 am
  
  Indeed, I concur that your personal experience is not typical, but I want to address it because it provides an opportunity for deeper exploration of hormones overall… I too have had two clients in my practice over the years who had a similar reaction. I do have a number of thoughts which might be helpful and perhaps one of them will resonate with you for further exploration. You don’t mention your menstrual status, so I am going to assume at 48 y/o that you are in later perimenopausal years – still menstruating but perhaps skipping cycles occasionally or experiencing irregularity in duration/intensity. I am also going to assume that the progesterone you have been using is truly bio-identical and not a progestin (because the effects of these two substances are *not* the same). Now, to begin, I have two perhaps obvious thoughts… (1) I would make sure that you need progesterone. We typically associate mid/late perimenopausal time with low progesterone in women (due to the decline in ovarian output), but absolutely *nothing* is true for *all* women. Due to individual variations in adrenal function/output and hormone metabolism, you may already have adequate progesterone; I have twice seen DUTCH test results surprising perimenopausal women in this way. (2) Make sure the cream you were using was truly only delivering 1 mg; especially transdermally, that is a tiny dose. You may have been given the wrong prescription or may be using a mislabeled product. I would also be cautious that your body’s reaction may be a sensitivity/allergy to something in the transdermal cream you are using. Obvious? Yes. Possible? Absolutely! Now thinking more about cause-and-effect…in addition to balancing estrogen, keep in mind that progesterone also primes estrogen receptors. In both cases in my own practice, the estrogen/progesterone disparity was *so* high (rock-bottom P – which means P receptors are numerous and very sensitivity – and high estrogen). The only reason these women *weren’t* suffering from estrogen dominance symptoms beforehand is *because* their P was so rock-bottom. So of course, this point demonstrates that it’s key to address other reasons for estrogen dominance *before* boosting progesterone (and yet more justification for my argument hat we *always* measure hormones before we use them supplementally). Given your particular symptoms of insomnia and anxiety, I suspect this is part of what is at play for you. As another possibility, a DUTCH panel would give you some insight on how your body metabolizes estrogen and progesterone and how downstream dynamics might be contributing to your symptoms. We also need to remember that progesterone can have androgenic effects depending on how your body metabolizes it. Higher androgens increase formation of dopamine which can be metabolized downstream to higher levels of norepinephrine and epinephrine if your body is well primed already or a strong stress response (talk about a recipe for anxiety and insomnia! And of course, DUTCH OAT data will give you some insight on this as well). On another note, If your unique immune system is alarmed by the cream you were using, then a hypercortisol state can result (which might also lead to inappropriate levels overnight). I am suspicious that both estrogen and stress hormone effects are at play in what you describe (and my final recommendations below are in line with this). I am not sure if you had already been on all your other supplements for a good ~3 months before starting the progesterone, but keep in mind there can be additive effects as well. For example, while most people find ashwaghanda has a calming effect, some few people find it quite stimulatory and contributing to insomnia. Make sure you aren’t taking a multi-vitamin, a B-complex, and/or any type of omega-3 supplement in the evening. If I were you, here’s what I would do… I would stop the black cohosh and ashwagandgha and GABA unless you are *sure* they aren’t part of the problem. If you’re taking Vitamin D right now, stop it for the next month (and note if/when you get a lot of sun exposure – for some people this exacerbates hot flashes – and their accompanying insomnia – *dramatically!). I would consider switching to magnesium taurate specifically and increasing dose (which helps to calm GABA/glutamate imbalance). No alcohol. No caffeine or chocolate at all after 11am. No red meat at dinner. I would add a B-complex in the morning which has a good complement of P5P for B6. And I would begin using calcium d-glucarate (500mg, 3x/day) to help ensure estrogen clearance. And I would take an inventory of my lifestyle choices to see where xenoestrogens (remember! these are *not* measurable on hormone tests) may be coming in and being highly potentiated by even tiny amounts of progesterone). Take 300-400mg l-theanine an hour before bedtime. Perfect your sleep hygiene (your needs may be higher than they were before!). Do this combo for the next month and then do a DUTCH panel to get some data. I wish you the best of wellness and relief – soon! And I celebrate the powerful up-close-and-personal learning experience at hand 🙂
  
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1

Mary says:

May 22, 2018 at 8:08 am

Is there any contraceptives you recommend over the pill?

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  SAFM Team says:
  
  May 31, 2018 at 3:56 pm
  
  Indeed, I don’t think it’s appropriate to give “general” recommendations on contraceptives, as there are unique, individual circumstances that must be taken into account for each person in consult with their physician (especially regarding current hormone status, cancer history/risk, fears/beliefs). These are some articles which might be helpful to share with patients/clients… http://www.saragottfriedmd.com/the-birth-control-pill-7-reasons-why-you-may-want-to-stop-and-how-to-stay-healthy-if-you-dont/ and https://www.mindbodygreen.com/articles/4-functonal-medicine-doctors-on-what-they-actually-do-for-birth-control and https://experiencelife.com/article/hormonal-birth-control-aviva-romm/ .
  
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