For many years, it’s been clear that males and females represent two distinct subgroups of the same species when it comes to physical conditions and disorders. However, this understanding has yet to fully permeate the field of psychiatry. This week’s blog post is a summary of key findings and takeaways from a Harvard review article by Handy et al. underscoring the profound connection between female sex hormone status and several psychiatric symptoms and disorders, including psychosis, addiction, eating disorders, anxiety, and PTSD.
Incorporating a biological and gender perspective into standard care remain a mission for future precision health.
The Female Menstrual Cycle
To grasp the impact of sex hormones on mental health, it’s essential to understand the female menstrual cycle. Simplified, this cycle consists of two main phases: the follicular phase, which spans from menstrual bleeding to ovulation, and the luteal phase, which occurs from ovulation to the next period. Typically, a regular menstrual cycle is around 28 days, with each phase lasting about 14 days when ovulation takes place on day 14. The days leading up to menstruation are sometimes referred to as the premenstrual phase, but it’s actually part of the luteal phase. Women’s menstrual cycles can vary in length, with variations of several days still considered regular.
Hormone levels during the menstrual cycle play a crucial role. During menstruation, estrogen and progesterone levels are low. As the follicular phase progresses (days 1-14), estrogen rises, stimulating the release of follicle-stimulating hormone (FSH) and luteinizing hormone-stimulating substance (LH), preparing the ovaries for egg release. Once the most mature egg is released on day 14, the remaining follicle transforms into a corpus luteum, producing progesterone, which rises during the luteal phase (days 14-28). Although estrogen levels stabilize, they do not rise further during the luteal phase. If the mature egg remains unfertilized, estrogen and progesterone levels decrease, leading to the shedding of the endometrium in menstrual bleeding that typically lasts 1 to 7 days. And then the cycle starts anew!
How the Brain, Body and Hormones are Connected
Given that estrogen and progesterone receptors exist in the brain, it’s plausible that fluctuating hormone levels can affect women’s emotions and behavior. Many women experience physical symptoms during their menstrual cycle, including period pain, breast tenderness, muscle and joint pain. Psychological symptoms, too, are often reported, ranging from difficulty sleeping, low mood, heightened anxiety, and low self-esteem to impulsivity and increased conflict propensity. Severe psychiatric conditions, such as addiction relapse, depressive symptoms, and self-harm, can also be linked to menstrual cycle variations and most studies suggested that the risk for exacerbation was highest during the luteal phase (i.e., day 15 to 28 of the menstrual cycle).
What about ADHD and hormones?
Even though the relationship between ADHD and the menstrual cycle was not specifically investigated in this study, estrogen and progesterone play a pivotal role here as well, impacting dopamine, a central neurotransmitter associated with ADHD symptoms as well as ADHD medication. Lower estrogen levels, such as during the luteal phase, may therefore affect and worsen ADHD symptoms, impact the effect and risk for side effects of ADHD medication and increase the risk of triggering other forms of psychiatric comorbidity such as anxiety, depression, or eating disorders. On the other hand, progesterone has an anti-anxiety effect by influencing the neurotransmitter GABA. However, progesterone’s breakdown products can be less favorable, especially during periods of stress when they convert into the stress hormone cortisol. This suggests a connection between progesterone and symptoms of PMS/PMDD during the luteal phase, especially pronounced in women with ADHD (Dorani et al. 2020).
So, what about hormone treatment during menopause or oral hormonal contraceptives? Do they worsen or improve ADHD symptoms? Well, the jury is still out on at least part of that question. But, members from our GODDESS ADHD we found a much higher risk of developing depression when on the pill among ADHD women compared to non-ADHD women. In fact, those with ADHD that used combined oral contraceptives (pills that contain both estrogen and progesterone) had a five times higher risk to develop depression compared with non-ADHD women who were not using these pills. However, we didn’t find any difference in risk between combined pills (estrogen and progesterone) and progestogen-only pills, so we don’t think that the hormones in the pill per se is the reason why women with ADHD are at risk for depression. Rather this may indicates that rapid hormone level changes might be more relevant for the exacerbation of psychiatric conditions and symptoms than the specific hormone itself.
Interestingly also the study by Handy et al. found that alcohol consumption was linked to the menstrual cycle. Women reported drinking alcohol to alleviate negative emotions in the premenstrual phase and for social and enjoyment reasons more during ovulation. Also, nicotine cravings increased and nicotine effectiveness decreased during the luteal phase.
A Call to Action!
In conclusion, we can’t keep ignoring the association between sex hormones and mental health even though its probably much more complex than our simplistic theoretical models suggest. Until the jury is back in, we may need to trust our own understanding of how our hormones affect our own mental well-being while awaiting further scientific revelations. And there is a lot you can do right now! Here are some simple lifehacks from our Letterlife users:
Together, we can address the current gaps in understanding. Now, the next step is to keep developing LETTERLIFE together. By empowering healthcare professionals with better information and giving women with ADHD new tools for improved self-care, we can collectively advance our understanding and management of women’s mental health. Stay tuned through our social media channels and reach out if you want to join this important journey.
Together, we can make a difference!
/Team Letterlife
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