Hormonal contraception is used by over 100 million women worldwide. 1 in 4 women in Australia between the ages of 18 and 49 are using the oral contraceptive pill (OCP). Depression affects twice as many women as men, with 1 in 4 women estimated to experience depression at some point during her lifetime. Now of course, correlation does not equal causation – but it’s a little hard not to see a link here.

It is not uncommon for patients to share with me in clinic that they have noticed changes to their mood upon starting or ceasing hormonal contraception. Those with pre-existing mood disturbance often report an exacerbation of symptoms; while those who have never experienced anxiety or depression in the past notice the onset of symptoms coincided with contraceptive use. And then others didn’t notice or put two-and-two together until they stopped using hormonal contraception and they finally felt like themselves again. Interestingly the most common reported reason for ceasing OCP use is mood disturbance (1).

Hormonal contraceptives, the pill and IUD especially, are often seen as a pretty benign medications and are very quickly prescribed to women of all ages for a whole host of symptoms. While some of the side effects, such as blood clots and stroke, are well known and well established within the literature, there are others such as depression, mood swings, anxiety and suicide that are less well known (or simply not talked about enough). That being said, in the last few years a number of studies have been released linking hormonal contraceptives with mood disturbance. Here I will share with you some of that research, while also providing you with some options to support your mental health should you so choose to use hormonal contraceptives.

When referring to hormonal contraceptives we are referring to the combined oral contraceptive pill (OCP), which contains both synthetic oestrogen and progestin; progestin only pills, the vaginal ring; IUD, implant and transdermal patch.

The largest study to examine the relationship between hormonal contraceptives and depression comes out of Denmark (2). This nationwide prospective cohort study followed over 1 million women for almost 15 years. Using Denmark’s nationalised information collection system (a record of health data including diagnostic and prescription information), the researchers looked at data from women aged 15 to 34 who had no previous history of mental illness or antidepressant use. They found that those taking hormonal contraceptives had a 70% greater risk of depression (as determined by initiation of antidepressants) compared to non-users. This risk was found across all types of hormonal contraception, with higher risk among progestin-only forms of contraception, including the IUD. They also found that the risk was higher in adolescents aged 15-19.

This same research group out of Denmark also looked into the link between hormonal contraceptive use and suicide and suicide attempts (3). They followed close to half a million women for just over 8 years. Within this group of women there were 6,999 first suicide attempts and 71 suicides. While the relative risk is considered small, for those women who had used hormonal contraception (currently or recently) the risk of attempted suicide was almost double and the risk of completed suicide was triple, when compared to women who had never used hormonal contraception.  Similar to the depression study, risk was greater in adolescents. It was also found that risk was greatest within the first 2 months of use, reducing after one year (but still remained 30% higher than non-users). The transdermal patch was linked with the greatest risk, followed by the IUD, the ring and finally the OCP.

Together these two studies demonstrate a pretty robust link between hormonal contraceptives and increased risk of depression, suicide attempt and suicide. The studies did not look at women who had a previous diagnosis of depression so it is not clear how hormonal contraceptive might influence the course of the illness – but based on these results we can make the assumption that it is unlikely to be great.

It is important to note that this risk of depression and suicide was found in those using the IUD. This is of particular importance as it is generally believed that the IUD acts locally as opposed to systemically – meaning it should not affect the rest of the body. These studies demonstrate that this is not in fact the case.

The research around anxiety and hormonal contraceptives is less robust. There are some papers highlighting anxiety as a possible side effect of contraceptive use (4), and interestingly the most common reported reason for ceasing OCP use is mood disturbance (5). Anecdotally, I have had many, many, many patients share with me that the OCP either triggered or exacerbated symptoms of anxiety for them.

What might be going on here?

The exact mechanisms of what might be going on here is not yet clear. But in sifting through the research there are a number of theories.

The researchers from Denmark are hypothesising that hormonal contraception directly influences the brain and neurotransmitter function, thereby affecting mood. They site several studies identifying the role of oestrogen and progesterone in the development of depression (6).

We know that the OCP depletes essential nutrients folic acid, vitamins B2, B6 and B12, vitamin C and E, magnesium, selenium and zinc (7); and can increase copper (8). B vitamins, vitamin C and zinc are essential for neurotransmitter synthesis – meaning they play a role in our bodies ability to make serotonin, dopamine, GABA and melatonin. And we know that neurotransmitter imbalances are involved in the development of mental illness. Deficiencies in these B vitamin specifically are linked to symptoms of depression. High levels of copper can result in feelings of depression and lack of control. And vitamin C reduces adrenaline and cortisol – high levels of which play a role in anxiety.

These same nutrient depletions may also interfere with thyroid function. We need B vitamins to synthesise thyroid hormone, and zinc and selenium to convert thyroid hormone from its inactive to its active form. Without these nutrients thyroid hormone production and utilisation may be disrupted. And symptoms of disrupted thyroid function include anxiety, depression, low mood, fatigue and lethargy. Furthermore, the pill increases thyroid binding globulin (TBG) (9), which binds to thyroid hormone making it unavailable for use. So even if we were able to maintain healthy nutritional status, this increase in THB caused by the pill would make our thyroid hormones unavailable to our cells.

We also know that just like antibiotics, the OCP wreaks havoc on our gut microbiome. Studies show that the OCP is linked to inflammatory bowel disease, specifically Crohn’s and ulcerative colitis (10); as well as poor immune function (11). Given the fact that a good proportion of our neurotransmitters are synthesised through the gut and that an imbalance in specific bacteria is linked to poor mental health (12) – it would not be unreasonable to infer that the impact of the OCP on the gut may be contributing to the poor mental health outcomes of users.

There is also emerging research demonstrating that the OCP might alter the size of women’s brains (13). It has been found that those taking the OCP have a smaller hypothalamus when compared to women not taking the pill, and a smaller hypothalamus is associated with symptoms of depression. These are only preliminary findings – but very interesting to note!

Of course, we cannot ignore the psycho-social aspect, especially among the adolescent and young adult population – whereby these women may be entering relationships for the first time which opens one up to increased emotional vulnerability (3).

Are you using hormonal contraception and experiencing symptoms of low mood, depression or anxiety? It’s not all bad news. Pop on over here to discover how we can best support your body and mental health – whether you choose to use and transition off hormonal contraception – there is so much we can do!

If you are feeling suicidal, in an emergency or at immediate risk of harm please contract emergency services on 000. You can also contact lifeline on 13 11 14 or the suicide call back service on 1300 659 467.

References

(1) Kulkarni, J. (2007). Depression as a side effective of the contraceptive pill. Expert Opinion on Drug Safety, 6(4), 371-374.

(2) Skovlund, C. W., Mørch, L. S., Kessing, L. V. & Lidegaard, Ø. (2016). Association of hormonal contraception with depression. JAMA Psychiatry, 73(11), 1154-11672.

(3) Skovlund, C. W., Mørch, L. S., Kessing, L. V., Lange, T. & Lidegaard, Ø. (2018). Association of hormonal contraception with suicide attempts and suicides. The American Journal of Psychiatry, 175(4), 336-342.

(4) Robinson, S. A., Dowell, M., Pedulla, D. & McCauley, L. (2004). Do the emotional side effects of hormonal contraceptives come from pharmacologic or psychological mechanisms? Medical Hypotheses, 63(2), 268-273.

(5) Kulkarni, J. (2007). Depression as a side effective of the contraceptive pill. Expert Opinion on Drug Safety, 6(4), 371-374.

(6) Joffe, H. & Cohen, L. S. (1998). Oestrogen, serotonin, and mood disturbance: where is the therapeutic bridge? Biological Psychiatry, 44(9), 798-811.

(7) Palmery, M., Saraceno, A., Vaiarelli, A. & Carlomango, G (2013). Oral contraceptives and changes in nutritional requirements. European Review for Medical and Pharmacological Sciences, 17(13), 1804-1813.

(8) Babić, Ž., Tariba, B., Kovačić, J., Pizent, A., Varnai, V. M. & Macan, J. (2013). Relevance of serum copper elevation induced by oral contraceptives: a meta-analysis. Contraception, 87(6), 790-800.

(9) Sorger, D., Schenk, S. & Schneider, G. (1992). Effects of various contraceptives on laboratory parameters in diagnosis of thyroid gland function with special reference to the free hormones FT4 and FT3. Zeitschrift Für die Gesamte Innere Medizin und Ihre Grenzgebiete, 47(2), 58-64.

(10) Cornish, J. A., Tan, E., Simillis, C., Clark, S. K., Teare, J. & Tekkis, P.P. (2008). The risk of oral contraceptives in the aetiology of inflammatory bowel disease: a meta-analysis. The American Journal of Gastroenterology, 103(9), 2394-2400.

(11) Khalili, H. (2016). Risk of inflammatory bowel disease with oral contraceptives and menopausal hormone therapy: current evidence and future directions. Drug Safety, 39(3), 193-197.

(12) Caspani, G., Kennedy, S., Foster, J. A. & Swann, J. (2019). Gut microbial metabolistes in depression: understanding the biochemical mechanisms. Microbial Cell, 6(10), 454-481.

(13) Gallagher, P. (2019). Birth control pills ‘alter the structure of women’s brains’ which could make them angry or depressed. Sourced from https://inews.co.uk/news/science/birth-control-pills-womens-brains-shrink-study-1332815

Join the discussion One Comment

Leave a Reply