About Kelly Brogan

KELLY BROGAN, MD, is a holistic psychiatrist, author of the New York Times Bestselling book, A Mind of Your Own, Own Your Self, the children’s book, A Time For Rain, and co-editor of the landmark textbook Integrative Therapies for Depression.

The evidence that our brain health depends on our immune systems and hormones continues to pile up. Given this interconnectedness, dubbed psychoneuroimmunology, it makes sense that interfering with our delicate hormonal balance can influence psychiatric diagnoses like depression.1

Yet over 100 million American women are prescribed synthetic hormones in the form of oral contraceptives (“the pill”), despite the fact that women on the pill have a higher risk of being diagnosed with depression (among other diagnoses) than those not taking oral contraceptives.2 3 4

The details of how the pill affects the brain remain controversial. Perhaps oral contraception increases depression risk by changing thyroid hormone function, depleting nutrients and minerals, altering the gut microbiota, and increasing oxidative stress - or it may interfere even more directly with the immune system, as suggested in a new scientific publication.

In a September 2017 report entitled Kynurenic acid is reduced in females and oral contraceptive users: Implications for depression,5 researchers hypothesized that the pill might affect the kynurenine pathway, a strong regulator of immune system. In the kynurenine pathway, tryptophan, the precursor of melatonin and serotonin, is broken down by enzymes into different metabolites: kynurenic acid (KynA), 3-hydroxykynurenine (3HK), and quinolinic acid (QA). The hard-to-pronounce names of these metabolites aren’t important; what’s important is that KynA is considered neuroprotective, and the other two metabolites, 3HK and QA, are considered neurotoxic.6


Therefore, it’s beneficial to have high amounts of KynA and low amounts of 3HK and QA circulating in your body.7 When the kynurenine pathway is functioning properly, it creates metabolites that enhance brain health, and when it is functioning improperly, it shifts towards neurotoxicity, creating metabolites that harm brain cells. How does this pathway shift towards neurotoxicity, producing less KynA and more 3HK and QA? High blood levels of C-reactive protein (CRP), a marker of systemic inflammation, and cortisol, associated with unresolved stress, adversely affect this pathway. Similarly, dysregulated cortisol and high CRP is associated with mood disorders like depression and generalized anxiety disorder. It is becoming generally accepted that elevated chronic, systemic inflammation can lead to brain inflammation and increase the risk of depression.8 For example, several scientific studies have shown that high blood levels of CRP is associated with a high risk of depression,9,10,11 as CRP could be considered an alarm signal of unresolved inflammation. Perhaps oral contraception could also shift this pathway towards neurotoxicity, and ultimately, depression?

In this study, researchers used these insights to test the hypothesis that oral contraception shifted the kynurenine pathway toward neurotoxic metabolites by measuring blood levels of  estradiol, progesterone, CRP, and kynurenine metabolites. Overall, healthy men had higher blood levels of the neuroprotective KA than healthy women, suggesting that women are more vulnerable to shifts in this pathway, though baseline levels of CRP were the same between men and women.

While it is not super surprising that men and women have different blood levels of hormones and metabolites (though sex differences are understudied), the next finding was striking. Women who were taking oral contraceptives had higher blood levels of CRP, a marker of chronic, systemic inflammation, than women who were not on the pill. That’s right; when controlling for all other health-related factors, the pill created inflammation. These results were highly significant, and they fit with similar studies that showed that women on the pill had blood levels of CRP three times higher than women not taking oral contraceptives.12 ,13,14,15

Similarly, women on the pill had lower levels of the neuroprotective kynurenine metabolites and increased levels of the neurotoxic kynurenine metabolites; the pill shifts this pathway towards neurotoxicity. As people with low blood levels of the beneficial KynA and high levels of the neurotoxic metabolites are more likely to be diagnosed with mood disorders,16,17 this study suggests that the pill directly increases the likelihood of depression in women.

As if that weren’t enough, a recent scientific review18 presented compelling evidence that the inflammation caused by hormonal contraceptives also increases the risk of several autoimmune disorders. Researchers analyzed data from hundreds of peer-reviewed, PubMed-indexed scientific reports, finding that progesterone-only contraceptives increased the incidence of skin conditions, including eczema, dermatitis, and acne, and the combined estrogen and progesterone contraceptives increased the risk of multiple sclerosis (MS), ulcerative colitis, Crohn's disease, interstitial cystitis (painful bladder syndrome), and lupus. Importantly, this research includes not only oral contraceptives, but also Norplant, and vaginal rings like NuvaRing and Mirena. Overall, adding synthetic hormones is a risky endeavor that can set off inflammatory cascades that can culminate in psychiatric and autoimmune diagnoses.

Perhaps this inflammatory response is the body’s way of saying - pretty please, consider an alternative! After learning this data, you may very well feel that you’d rather not take a pill or implant a vaginal ring that trashes your libido, inflames your brain, and depletes your body while hijacking the very essence of your womanhood! There are powerful and effective options: for contraception, our go-to recommendation is this one-button gadget…and it’s 99.3% effective! For hormonal balance (i.e. PCOS, endometriosis, PMS, acne, and more), learn about the possibility for simple lifestyle changes to radically heal the root cause of your symptoms, allowing you to reclaim control over your body...and your mind.

Interested in more insights and tools to help you Own Your Self?

My newest book, Own Your Self, helps you discover the meaning behind your symptoms and your struggle as a way to reclaim your health and your Self. Click below to claim your copy today.


  • 1 http://www.sciencedirect.com/science/article/pii/S0889159117304142?via%3Dihub#m0005
  • 2 https://www.ncbi.nlm.nih.gov/pubmed/27680324
  • 3 https://www.ncbi.nlm.nih.gov/pubmed/17688380
  • 4 https://www.ncbi.nlm.nih.gov/pubmed/23219471
  • 5 http://www.sciencedirect.com/science/article/pii/S0889159117304142?via%3Dihub#m0005
  • 6 https://www.ncbi.nlm.nih.gov/pubmed/25074636
  • 7 https://www.ncbi.nlm.nih.gov/pubmed/22139324
  • 8 https://www.ncbi.nlm.nih.gov/pubmed/19188531
  • 9 https://www.ncbi.nlm.nih.gov/pubmed/24909972
  • 10 https://www.ncbi.nlm.nih.gov/pubmed/23219471
  • 11 https://www.ncbi.nlm.nih.gov/pubmed/23624671
  • 12 https://www.infona.pl/resource/bwmeta1.element.elsevier-9d2f175a-e888-3008-bd94-a5b8e17c866f
  • 13 https://www.ncbi.nlm.nih.gov/pubmed/16409455
  • 14 https://www.ncbi.nlm.nih.gov/pubmed/12850240
  • 15 https://www.ncbi.nlm.nih.gov/pubmed/12616983
  • 16 https://www.ncbi.nlm.nih.gov/pubmed/26028548
  • 17 https://www.ncbi.nlm.nih.gov/pubmed/27640517
  • 18 https://www.ncbi.nlm.nih.gov/pubmed/28912620