What is the Link Between Hormones and the Effectiveness of my ADHD Medication?

After receiving my ADHD diagnosis in 2019 at age 44 I have been on a quest to find out absolutely everything I can about it. My current (hyper)focus is hormones and how they affect my ADHD. Now that I am medicated I notice a big difference in how effective my drugs are in relation to where I am in my cycle. Mid-cycle is when I feel the best – I have focus, energy, motivation and an overall sense of happiness and contentment. The week leading up to menstruation, however, things can go drastically downhill. It can get to the point where I can barely speak let alone have any motivation to do anything. My anxiety levels increase, I suffer severe fatigue and all I want to do is hide and sleep. So why is this? Why is my cycle affecting the effectiveness of my medication? Well, I am no scientist and I’m not even very scientifically minded so I have scoured the internet looking for the most straight-forward explanation. This article is an accumulation of what I have found. 

What hormones are involved? 

Dopamine

To answer our question we first need to know exactly what hormones are involved; in this case, dopamine and estrogen. As well as being a hormone, dopamine also acts as a neurotransmitter. Neurotransmitters act as chemical messengers, sending signals between the nervous system and the rest of the body. They relay information between individual neurons or between neurons and muscles and regulate a wide range of bodily functions. 

Dopamine is produced in various parts of the brain and plays a role in brain functions that affect mood, memory, motivation, concentration, sleep, learning and motor control. It also plays an important role in the brain’s “reward system”. Humans are driven by biological necessities (water, food, sleep etc.) and rewards. A reward can be anything that motivates us, leads to learning or elicits feelings of pleasure. Feeling pleasure then motivates us to repeat behaviours and actions that are essential to our existence. A reward activates cells in an area of the brain known as the VTA (Ventral Tegmental Area). When you experience pleasure, dopamine is released from the VTA to various parts of the brain: 

• the amygdala (involved with our emotions), 
• the nucleus accumbens (a key part of the reward system, which is also involved with the body’s motor functions), 
• the prefrontal cortex (involved with focus, attention, planning) and 
• the hippocampus (involved in the formation of memories).

Brain imaging on people with ADHD has shown that there are differences in the dopamine transport system. For instance, in the prefrontal cortex there are fewer dopamine receptors as well as less overall dopamine being produced. This means that aspects of the reward system are underactive and the decreased availability of dopamine can result in a decrease in motivation. This in turn can result in people with ADHD compulsively seeking dopamine ‘hits’ through stimulus that increases dopamine more quickly and intensely. This is where my medication comes in – I take Elvanse (lisdexamphetamine aka Vyyanse), this is a stimulant medication which has been shown to increase dopamine in the prefrontal cortex.

Estrogen

Hormones are also chemical messengers but instead of travelling between neurons they are released into the bloodstream. The main source of estrogen is the ovaries. Estrogen is one of the hormones that help control the menstrual cycle. On days 1 to 12 of the cycle, estrogen levels gradually rise until they peak around day 12. Levels drop during days 13 and 14 and then have a further drop around day 21 – approximately, the week leading up to menstruation.

In addition to controlling the menstrual cycle, estrogen has been shown to affect areas of brain function which relate to cognition, learning, memory and emotion and influence reward related motivation – areas, which we have already seen to be affected by dopamine levels and subsequently areas that are affected in people with ADHD.

Estrogen also increases dopamine levels by increasing dopamine synthesis and upregulating dopamine receptors: this means it increases the number of receptors on the surface of target cells, resulting in an increased availability of dopamine. Consequently, we can see that if estrogen levels are low, like during the week leading up to menstruation, dopamine levels are also going to be low.  

What is their relationship with ADHD?

So why do low levels of both these hormones affect the efficacy of ADHD medication in some women? The first thing to note when studying the relationship between hormones and ADHD is that there currently is very little information out there. The only studies I found were carried out by Professor Sandra Kooij (founder and chair of the European Network Adult ADHD) and have been summed up in this very informative webinar: Women, ADHD & Hormones. 

In short, Professor Kooij points out that women with ADHD already have low levels of dopamine, when this is then combined with low levels of estrogen (resulting in even lower levels of dopamine) we end up with “2 x low dopamine”. This explains increased mood instability and increased ADHD severity. In this situation, our current dose of ADHD medication may no longer be enough to give us the required levels of dopamine, which explains the symptoms I have been experiencing, as outlined above. 

Professor Kooij has also found (in two studies using self-report questionnaires, the 1st with 200 women, the 2nd with 209 women) that women with ADHD have a 9/10-fold increase in having Premenstrual Dysphoric Disorder (PMDD) when compared with the general population. The symptoms of PMDD are similar to, but more severe than, those experienced in PMS and include:

• severe fatigue
• mood changes, including irritability, nervousness, depression, and anxiety
• crying and emotional sensitivity
• difficulty concentrating
• coordination difficulties
• forgetfulness
• abdominal bloating, increased appetite and gastrointestinal upset
• headaches
• sleeplessness
• decreased libido
• heightened sensitivity

In conclusion, we can see that the relationship between estrogen and dopamine and the increased likelihood of PMDD in women with ADHD can result in the feelings that I, and many other women have reported, in the lead up to menstruation. So, what can we do about it?

“Women with ADHD have a 9/10-fold increase in having Premenstrual Dysphoric Disorder (PMDD) when compared with the general population.”

What can we do to improve this situation?

There are three recommendations in the webinar: the contraceptive pill, without a stopweek; SSRIs for mood symptoms and speaking to your psychiatrist about a temporary higher dose of ADHD meds for this week. As Prof. Kooij points out – this approach has not been studied, so there is no official evidence that it works. 

It is also worth considering natural options for increasing dopamine levels. These include: exercise, eating more protein and less saturated fat, listening to music, meditating, getting enough sunlight, having a massage and taking supplements. None of this is easy when all you want to do is sleep and hide; avoiding feelings of overwhelm and shame that are so common for us ADHDers is key. Maybe just trying one thing first – listening to music for example, consistently when we are feeling our lowest; noticing and journaling about any effects it may have. Having a gentle walk or even just sitting outside having a cup of tea on a regular basis may be good places to start. 

I recently watched a very informative video by The Nomad Apothecary titled Hormones and ADHD. Shannon Stone is a Master Holistic Herbalist who also has ADHD. In the video she gives lots of information on herbs that can be used during the menstrual cycle and that can help alleviate the symptoms that many women with ADHD are affected by. Shannon is based in America but offers online consultations to clients worldwide.

On discovering the connection between the hormones, estrogen and dopamine, and the effectiveness of my ADHD meds, I have been documenting my moods etc. throughout my cycle and noting what helps me. In the last month, I have noticed a dramatic difference in how I feel if I surround myself with the people who nourish my soul; the people who energise and inspire me and help me kindle my fire. Drs Ratey and Hallowell talk about the power of social connection in their new book ADHD 2.0. – they refer to Vitamin Connect and Dr Hallowell says “social isolation is as dangerous a risk factor for early death as cigarette-smoking, high blood pressure, and obesity”, he also says “the lack of connection particularly hurts people who have ADHD”. Clearly, connection is of great importance to us, so why not harness that power when you are feeling your lowest. Let others help bolster you during this time. I notice big differences in how I feel during this week if I spend time laughing with others, hugging and chatting. Again, this can be difficult to do when all you feel like doing is hiding – but the effects are immediate, that effort in reaching out to others, really is worthwhile. 

Carrying out this research has not only given me the information I need but also the knowledge that I am not alone in this. I feel empowered to start doing something about it. At age 45, I also feel motivated to make these changes now in preparation for the menopause – when our estrogen levels drop to an all-time low and stay there.

“women with ADHD have too often been undiagnosed/misdiagnosed, forgotten and deliberately left out of scientific studies”

As Professor Kooij highlights in her webinar, women with ADHD have too often been undiagnosed/misdiagnosed, forgotten and deliberately left out of scientific studies. This is due to a number of factors including the bias towards hyperactive symptoms and the higher prevalence (2x) of inattentive symptoms amongst women; girls and women being more likely to cover up and compensate for their symptoms (‘masking’), and because the criteria doctors use to diagnose ADHD are outdated. However, the tide is turning, change is happening. Thanks to social media platforms and scientists such as Professor Kooij and Herbalists like Shannon Stone, knowledge and information is being shared and studies are being carried out. The future is looking much brighter for women with ADHD.