New findings suggest that the pill may be good for birth control, but bad for depression. Is it possible that hormonal birth control may be fueling the epidemic rise in prescriptions for antidepressant medication?

I once dated a crazy girl. This is not the politically correct way of describing her, nor is it a responsible way to talk about anyone from my present perspective as a clinical psychologist. Yet from the perspective of a naive 17 year old male new to dating, women, and sex, crazy was the only word I knew at the time to describe things. We had only been dating a few weeks, and this girl, who I will call Ingrid, was anxious to get on the pill so that that we could get on with things. I quickly became terrified as events unfolded. Not just because sex was a relatively new concept to my virgin mind, but because within days of Ingrid starting on the pill, her personality seemed to slide down a hill that ended in a black hole. She became dramatic, overly philosophical, and morbidly obsessed with the dark side of everything. Way way to heavy for my immature self to handle. Instead of getting down her pants, I spent all my free time figuring out how to get out of her life. Which I did, much to my relief and Ingrid’s near suicidal regret. My interpretation of this experience at the time was simple if not sorely misguided: don’t date crazy girls.

I would later experience a milder version of this experience with my future wife when she too started on the pill. Only this time I was part of a more mature, healthy relationship, and my wife had the benefit of some life experience and insight that told her something was wrong. It only took a week of headaches and mood swings for her to decide that natural birth control was the preferred alternative, and things quickly got better. Mind you, we also got a head start relative to all our peers in graduate school by getting pregnant, but that is another story. What mattered at the time was that I revised my opinion of Ingrid.

Maybe she was not so crazy after all, maybe the pill had something to do with the shift in her personality that I had witnessed.

Things do not appear to have changed a lot in the years that have ensued since these scenarios played out. Hormonal birth control has become the dominant contraception method not just in North America, but across the developed world, with fully 80% of women using some form of it at some time in their life. And concerns about mood swings, crying jags, irritability, and even outright depression being linked to the use of the pill still linger. Occasionally, a research study has been undertaken to explore the potential unwanted side effects of the pill in its various types and formulations, but the findings have been inconsistent and confusing. In some cases, the pill was found to contribute to mood symptoms, whereas in others, it actually seemed to buffer mood and leave women feeling better12. None of these studies were able to overcome a couple of fundamental problems. First, when everyone is taking something, it becomes challenging to compare them to people who are not. Second, because an unwanted pregnancy is viewed as a very serious and traumatic outcome for all concerned, carrying out carefully constructed studies with “placebo” controls was rightly seen as simply unethical, if not just plain reckless and dangerous.

Earlier this year an article by some researchers based in Denmark described a way to get around these problems and finally cast some light on the answer to the question of whether the pill really does contribute to depression. The facts are nothing short of astounding. But I’m getting ahead of myself. To get a full understanding of the results, it is important to understand how the researchers pulled it off.

In Denmark, all living men and women have received a personal identification number at birth, and this allows a link to be made between all the public health records that exist across the country for any individual. Recently, The Danish Sex Hormone Register Study has embarked on a project to use these records to investigate a variety of outcomes relating to the use of hormonal birth control3. Charlotte Wessel Skovlund and her colleagues decided to use these records to look at the question of hormonal birth control and mood4. To do this, they used national health records to track every woman between the age of 15 and 35 starting on January 1, 2000 or on their 15th birthday, and until the end of the study period on December 31, 2013. They looked at a wide variety of characteristics known to be associated with mood, such as age, education level, smoking,  and so on, and most notably they looked at prescriptions for antidepressants and hospitalizations where a first diagnosis was for depression. To be as thorough as possible, the researchers began looking for any such mood symptoms one year after starting on hormonal or any other birth control, and compared them to one year before birth control was started.  

It is difficult to describe just how incredible this kind of study design is. Until databases like the Danish sample became available, researchers have struggled in vain to get information about large numbers of people that is from the same cohort (i.e.,  the present sample of over 1,000,000 women living in Denmark vs samples of only thousands spread across several different countries). Furthermore, it is usually extremely difficult to draw information on a large sample like this repeatedly this over time, never mind continuously over close to 15 years as was the case for the Danish group. Finally, until now it has been virtually impossible to get more than retrospective self reports of what people have done or experienced, whereas this study managed to pull seamless pharmacy and hospital records covering the entire time span covered by the study from which they could extract the data.  Added to this is the fact that the experimenters had access to a cornucopia of demographic information about the women, not to mention specifics about exactly which types of birth control were used. Finally, the actual measures used to indicate depression were extremely conservative. The fact of the matter is when it comes to depression the majority of people don’t get any help. So setting the bar for defining an episode of depression as being prescribed antidepressant or having a first diagnosis of depression if a woman is hospitalized captures only the most severe cases of a problem whose range of symptoms also include many, many mild to moderately severe cases.

Put simply, if a very conservative test gets significant results, you can safely bet that there are a lot more examples of the problem than estimates from the study suggest, since it did not include all those milder or less certain cases in the analyses.

When all was said and done, the results of the Danish contraception study revealed that for women not using hormonal contraceptives the incidence of first use of antidepressant use was 1.7 for every 100 women years, and the incidence of first hospitalization with diagnosis of depression was .28 for every 100 women years. For all types of hormonal contraception combined, the incidence of first use of medication jumped to 2.2 per 100 women years – a 29% increase, and first hospitalizations increased to .30. To put that into perspective, more than 130,000 first prescriptions for antidepressants were detected during the follow up phase of the study, so the increase in depression associated with hormonal birth control methods involved tens of thousands of women. When different types of hormonal birth control were compared another worrisome pattern emerged. As the relative level of progesterone used in the method increased, so did the incidence of depression. Relative Risk looks at the odds of something happening in comparison to the baseline or normal situation. In the case of women in the Danish study, the increase in risk of depression rose from 20% for users of combined oral formulations, to 300% for injectable forms. Relative Risk estimates also proved to be different for women of different ages.

Notably, adolescents showed the most alarming reaction to the use of hormonal contraception, with Relative Risk rates that were on average 1.8 fold higher for combination pills, 2.2 fold higher for progestin-only pills, and 3 times higher for non-oral forms (vaginal rings, patches or injectables).

Some critics have argued that the Danish study makes too much of small effects. But as I mentioned earlier, the way depression was measured in this study was very conservative, meaning that many cases of depression probably were not even counted. It is also well known that most doctors are generally less likely to prescribe the pill to women who are already depressed. Furthermore, women who are depressed are far less likely to take the pill in the first place. Sexual relationships generally demand a lot from a woman, and it is a well known fact that depression robs its victims of their energy, sexual libido, and social interests. If we also consider the fact that the pill can have many other unwanted effects that prompt women to discontinue its use, and you can see that if anything, the study probably underestimates the effect of the pill on women’s mood states.

Still, another very persuasive fact has kept numerous critics voicing concern – a very high risk of unwanted pregnancy may be a far worse consequence for not taking the pill in comparison to the relatively low risk of depression for those who do take it. In other words, the ends justify the means. This argument is deceptively simple, and simply deceptive. It is akin to telling a coal miner to ignore the health risks associated with high rates of lung cancer because the near certain and very dire consequences of not having a job in a place where jobs are otherwise scarce are far worse. Moreover, it is traditionally an argument put forward by men, who incidentally do not have the option of using hormonal contraception.

But what if men could and did use hormonal contraception? And what if the results of this kind of contraception were the same for men as for women? Would there be any controversy if an effective method were found that had significant risks of side effects like depression?

Believe it or not, we are beginning to learn the answer to that question. In a study whose results were also released this September, Hermann Behre and his colleagues with the WHO Department of Reproductive Health and Research describe their work looking at what happens when injections of a long-acting progestogen (which inhibits sperm production in men) are given along with replacement doses of a long-acting androgen (to compensate for the resulting shutdown of naturally produced testosterone). Behre et al.5 report that the technique was highly effective at shutting down sperm production in 274 of the 320 male participants in the study, and among those men, only four partners experienced a pregnancy over the 56-week active phase of the trial. The study authors were ecstatic in pronouncing that the effectiveness of this method was high enough to be comparable to that of the pill for women. Finally, we have evidence that a reversible method of birth control for men can work!

But there were a few slight hitches to this study, many of which are shared by other studies like it6. To start with, the injection site proved to be pretty sore for about a quarter of the men. Also, close to half of the men experienced at least a mild outbreak of acne. For close to 40% of the men there was an increase in libido. Then there were the many and varied symptoms of mood disorders, which when taken individually affected anywhere from 1.6 to 16.9% of the men. Last but not least, there was the very unfortunate fact that one of the study participants killed himself, and another attempted suicide. The study authors reassure us that their own analyses concluded that these problems were mostly trivial and “unrelated to the use of the study products”, and take pains to point out that participants at the Indonesian test site (one of ten sites around the world) accounted for a disproportionate number of the complaints. They also boast that their own oversight committee considered the study to be safe. Unfortunately, an external WHO review committee came to quite a different conclusion, and insisted that the study be prematurely terminated.

You may not be bothered by the fact that a new birth control method gives a lot of men mild acne. Perhaps you don’t consider having 40% of the men of reproductive age around the world experiencing increased libido to be a problem either.

But add in a significant portion of men experiencing mood disorders and a jump in the suicide rate from its current level at 6 per 100,0007 to the rate observed in study participants, which was about 100 times higher, and it gets hard to believe that this is a safe method, despite how effective it might be.

The fact that the study authors try to discount these facts is beyond belief if it were not for the fact that we had to wait close to 60 years to get the results of the Danish Reproductive study. That we will continue to see hormonal birth control promoted among the world’s women should hardly come as a surprise. It seems that for both men and women, introducing progesterone to our usual hormonal balance can have some pretty profound negative effects on our emotions.

Our interest in studies like these at Myndplan is not academic. Nor are we in the job of criticizing the ethics of researchers, or policing public health decisions that influence large portions of the population, even if the consequences include tremendous suffering not to mention massive social and economic costs. We just want to find the data that really counts, and present it in a way that helps consumers make the best possible decisions when they are trying to find a path to feeling better. It is already well known that rates of depression have been rising in North America for several decades8, as has the number of antidepressants that are being prescribed9. We think it is important that everyone learn the facts about issues such as whether the most common birth control method might be influencing these trends, and to what extent. After all, part of an effective approach to combating a problem like depression is accounting not just for what treatments will help, but understanding the impact of decisions that we all make every day that might increase our vulnerability to its many very serious symptoms. And if the research on male contraception is any indication, men need to be as aware of the risks and rewards as do women.