Can hormonal birth control trigger depression?

Monique Tello, MD, MPH
Monique Tello, MD, MPH, Contributing Editor

Over the years, more than a few patients in my women’s health practice have told me that their hormonal birth control — the pill, patch, ring, implant, injection, or IUD — made them feel depressed. And it’s not just my patients: several of my friends have felt the same way. And it’s not just me who has noticed this; decades of reports of mood changes associated with these hormone medications have spurred multiple research studies.

While many of these did not show a definitive association, a recent critical review of this literature revealed that all of it has been of poor quality, relying on iffy methods like self-reporting, recall, and insufficient numbers of subjects. The authors concluded that it was impossible to draw any firm conclusions from the research on this subject.

A strong study on hormonal birth control methods and depression

However, a just-published study finally meets the criteria to qualify as high-quality, and therefore believable. The study of over a million Danish women over age 14, using hard data like diagnosis codes and prescription records, strongly suggests that there is an increased risk of depression associated with all types of hormonal contraception.

The authors took advantage of Denmark’s awesome nationalized information collection systems, including diagnosis and prescribing data. These exist because the country has had a well-run and organized national health system for decades. They have reams of data on every single person in Denmark going back to the 1970s. Additional available information used in this study included education level, body mass index, and smoking habits. All of this was de-identified to protect the individuals involved, so there was no potential violation of privacy.* Surprising connections between hormonal birth control and depression emerged.

This study looked at women aged 15 to 34 between 2000 and 2013, and excluded those with preexisting psychiatric conditions, as well as those who could not be prescribed hormones due to medical issues like blood clots, and those who would be prescribed these medications for other reasons. They also excluded women during pregnancy and for six months after pregnancy, and recent immigrants. This way they wouldn’t accidentally include women with an unrecorded history of any of these conditions.

The researchers analyzed hormonal contraceptive use and subsequent depression in two different ways. They evaluated women who had received a diagnosis of depression as well as women who had received a prescription for antidepressants; these analyses were run separately, and they obtained statistically equivalent results.

Risk of depression with hormonal birth control, small but real

All forms of hormonal contraception were associated with an increased risk of developing depression, with higher risks associated with the progesterone-only forms, including the IUD. This risk was higher in teens ages 15 to 19, and especially for non-oral forms of birth control such as the ring, patch and IUD. That the IUD was particularly associated with depression in all age groups is especially significant, because traditionally, physicians have been taught that the IUD only acts locally and has no effects on the rest of the body. Clearly, this is not accurate.

Should we stop prescribing hormonal birth control? No. It’s important to note that while the risk of depression among women using hormonal forms of birth control was clearly increased, the overall number of women affected was small. Approximately 2.2 out of 100 women who used hormonal birth control developed depression, compared to 1.7 out of 100 who did not. This indicates that only some people will be susceptible to this side effect. Which ones, we don’t know. But I plan to discuss this possibility with every patient when I’m counseling them about birth control, just as I would counsel about increased risk of blood clots and, for certain women, breast cancer. In the end, every medication has potential risks and benefits. As doctors, we need to be aware of these so we can counsel effectively.

*My medical researcher mind is boggled: all this information collected on every single citizen makes quality research studies like this easily possible. We can’t even dream of conducting such an inclusive study like this here in the United States, where yes, all these data are collected, but exist haphazardly scattered across medical offices, hospitals, and insurance companies. Most of a U.S. researcher’s funding and efforts here go into collecting subjects and data. Compared to what the Danish have, what a waste of time!

Related Information: Harvard Women’s Health Watch

Comments:

  1. L. Creyon

    This article states that the increased instances of depression were noticed “especially for non-oral, progesterone-only forms of birth control such as the ring, patch and IUD. That the IUD”. but both the ring and the patch, and certain types of IUD are of the combined hormone variety. I’ll have to double-check on the patch, but I know for a fact that the ring is combined. Unless there is something new on the market now besides Nuva Ring? My understanding was always that the method of delivery shouldn’t make a difference in side effects, that these methods, medically speaking are the same as taking the traditional pill. Is the risk really higher with slow-acting methods than with a daily pill, even if the hormone combination is the same?

    • Monique Tello, MD, MPH
      Monique Tello, MD, MPH

      Agreed, It’s supposed to read “non-oral” only so we will correct that. Appreciate your close reading.

    • Dr Sophie Fourie

      1 Comment:
      Agree that the pharmacological principle is: local acting preparations at lower doses give less systemic adverse effects.

      2) Question on a patient please answer.
      A patient of 31 years has clinically confirmed major depression and has recently been prescribed fluoxetine.
      Her depression was aggravated – while taking the fluoxetine – by
      a) The injectable progestogen: norethisterone enanthate – severely
      b) Nordette (levonorgesterel 150 and oestradiool 30 microgram)

      She also develloped severe depression when she became pregnant about 4 years ago.
      About 9 years ago she developed depression for the first time while on “Triphasal”
      – (levonorgesterel and oestradiol) without taking any antidepressants.

      Q1 : Would it be of any use to try Yaz – drospirenone 3 mg ethynylestradiol 0.02 or should she abstain from any hormonal products?
      Q2: It seems as if the progestogens have more depressive side effects than the oestrogens?

  2. Kelly Wilson

    The small risk is present in the main analysis, but the risks when comparing to a group with no history of ever using hormonal birth control is substantially larger. About 70% for older women and more than double for adolescents. I have no idea why these data are relegated to the additional analyses. They seem extremely relevant to me.

    • Monique Tello, MD, MPH
      Monique Tello, MD, MPH

      OK, I’m trying to see where this is- are you looking at the sentence “When the reference group was changed to those who never used hormonal contraception, the RR estimates for users of combined oral contraceptives increased to 1.7 (95% CI, 1.66-1.71)” , as compared to the 1.23 in the main analyses? If so, it’s not easily converted to a percentage risk; rather it’s better to think of it as “1.7 times more likely” vs “1.23 times more likely”. If someone knows how to easily express these in terms of percentage risk, please, go ahead!

  3. BK

    In this country, at least, women on birth control must see their doctors regularly for prescriptions, leading to regular patient/doctor contact. Women not taking birth control do not have to see a doctor regularly, at least for this reason. Could it be that the slight difference between the groups has more to do with the patients discussing depression when they happen to be in the doctors’ offices anyway?

    • Monique Tello, MD, MPH
      Monique Tello, MD, MPH

      Yes, that certainly could be offered as a hypothesis. I think we really don’t know why there seems to be an increased risk.

  4. Liz Turnock

    I wonder about causation vs correlation. Perhaps women who are requesting the contraception at those ages are more prone to depression.

  5. TMarie

    What do we know about hormonal birth control? We know it reduces B12 levels. Take a handful of women who aleady have low B12 and give them hormonal birth control, and you get depression. Would be helpful if you knew the B12 levels of each person in the study.

    • Monique Tello, MD, MPH
      Monique Tello, MD, MPH

      A rigorous PubMed query for any research on oral contraceptives or hormonal contraceptives on serum B12 levels turned up two older studies that did suggest a negative effect. Both studies concluded that further research was needed. So, I agree with you that this idea is interesting and should be investigated, especially given this Danish study.

  6. Ashley

    Hi Monique –

    Has there been any research into patients with existing depression that are using hormonal birth control? Does it increase the effects of depression or make the depression harder to treat?

    Thank you for any comments and insight.

    • Monique Tello, MD, MPH
      Monique Tello, MD, MPH

      Yes, there has. A 2016 article in Contraception presents a systematic review of different studies examining hormonal contraception and mood in women with previously diagnosed depression found no consistent significant effect. They conclude: “Limited evidence from six studies found that OC, levonorgestrel-releasing IUD and DMPA use among women with depressive or bipolar disorders was not associated with worse clinical course of disease compared with no hormonal method use.” The authors note, however, that the studies they looked at were all very different and some were perhaps not of the highest quality.

      Citation:
      Safety of hormonal contraception and intrauterine devices among women with depressive and bipolar disorders: a systematic review.
      Pagano HP1, Zapata LB2, Berry-Bibee EN2, Nanda K3, Curtis KM2 Contraception. 2016 Jun 27.

  7. Marianne

    Dear Monique,

    It would be helpful, if it could be extracted to understand the increased risk for those one the pill – the most common form. As I read your article, it seems that IUD, ring, and patch are particularly noted for their increased risk. If you looked just at the pill, would that just take you from 1.7 to 1.8 out of 100? Or how is that assessed. Thank you for this.

    • Monique Tello, MD, MPH
      Monique Tello, MD, MPH

      Yes, the risk of depression in users of combined oral contraceptive was slightly higher than for nonusers, but lower than for all forms of hormonal contraception combined, so it fell between 1.7 and 2.2 per 100 people.