01. ADHD in Women: Estrogen Fluctuations and Stimulant Dose Adjustment

Text Version

Estrogen Fluctuations and ADHD Symptoms

Flavio Guzman, M.D.: Can you explain the biological mechanism behind how estrogen fluctuations worsen ADHD symptoms, and why this connection has been overlooked in traditional ADHD research?

Sandra Kooij, M.D., Ph.D.: Estrogen and dopamine are brother and sister in the brain, I would like to say. We all know that dopamine is important for ADHD and that dopamine helps to focus, to keep memory intact, and to stabilize mood.

Estrogen does exactly the same. Estrogen and dopamine work together in the brain, and estrogen helps to build the brain just as dopamine does.

From childhood on, estrogen enhances dopamine levels in the brain. So we can understand that when estrogen drops in the last week of the cycle, postpartum, or perimenopausally, dopamine goes down as well.

At least, that is something we consider likely based on what we know about the mutual effects of estrogen and dopamine.

As to why this has been overlooked in ADHD research: the whole cycle and female ADHD have been overlooked, and that has a reason. All medicines are based on the male body, not on the female body, which has a cycle from puberty onward.

The cycle influences the whole system, from the brain to sexuality and the genitals, but also the immune system, the heart, and bone density. Everything is involved with these hormonal fluctuations.

Therefore, we need a female-based medicine and psychiatry instead of continuing to overlook the whole difference between men and women regarding hormonal fluctuations.

Of course, men always say, “What about our hormones?” They have testosterone, which is, in a way, the male counterpart to estrogen. But male hormone levels are completely stable. From puberty, they rise, and then they remain stable until older age.

That is a completely different pattern compared to women, who have fluctuations every month in the last week of the cycle, after giving birth for months, and during perimenopause for up to 10 years. So this is really a different story.

Taking a Hormonal History

Flavio Guzman, M.D.: Moving to clinical assessment, what specific questions should clinicians ask women with ADHD to understand how their hormones affect their symptoms?

Sandra Kooij, M.D., Ph.D.: Taking a hormonal history is very important for psychiatrists and for psychologists from now on, since we know about the interaction of hormones and neurotransmitters in psychological and psychiatric disorders in women.

We should be sure that such symptoms are related to the cycle. Useful questions include:

• When do you have the most severe complaints of your mood or your ADHD?
• Is it in the week before menstruation, the last two weeks before menstruation, or shortly after ovulation (around the 14th day of the cycle)?

There may be a short episode of complaints around ovulation because estrogen drops then, rises again in the luteal phase, and drops again in the last week. It is important to understand this pattern.

Women should be asked to monitor their symptoms for two consecutive months in order to be sure that there is premenstrual depression every month as a rule, in a pattern. ADHD severity should also be monitored. There are apps for that nowadays, which help a lot to get a clear view of the pattern.

Regarding postpartum depression, we should ask:

• Did you have a baby in the last year? When was that?
• How was your mood after giving birth? How is your mood now?

It is important to understand that postpartum depression can have an onset between day 0 and one year after giving birth. So it may take some time to develop, and it is still related to hormones.

Perimenopause is the most difficult period because it lasts so long. It may last 2 to 10 years, and it differs between women.

What we should ask is whether the woman has had PMDD (premenstrual depression). She may also have had postpartum depression, and she may develop perimenopausal depression, because this pattern is seen in women who are vulnerable and sensitive to hormonal fluctuations affecting their mood and ADHD severity.

We need to know whether they had these symptoms in the past during hormonal changes. Then we can predict already that they may be vulnerable again for perimenopausal depression.

We should ask them when the symptoms start. What happens in women with a history of PMDD is that the symptoms start earlier and earlier in the cycle.

First it was one week before menstruation, then 10 days or 14 days before, and then symptoms start even three weeks before menstruation. Then it is almost the whole month that they suffer from symptoms, and the pattern gets lost.

The pattern is no longer recognized by the woman or her doctor. But we should understand that this is what perimenopause means: estrogen drops earlier in the cycle over time, first only in the last week, then the last two weeks, then the last three weeks, until it is the whole month.

You then think this woman is completely “hysterical” or labile or whatever you call it. It looks like that, but it is just hormones taking their toll.

We should understand and treat it better in order to help those women, not with psychotherapy but with biology, I am afraid. Of course, psychotherapy is very good, but it will not solve the biological rollercoaster that perimenopause is.

This is only about mood and ADHD symptoms, but perimenopause also comes with many physical complaints: sleep problems, sweating, night sweats, joint pains, skin changes, hair loss, vaginal dryness, and sexual problems. All systems are affected, and that is what makes perimenopause such a difficult time.

It is important that psychiatrists and psychologists can recognize it, and that they use questionnaires to be sure they are facing somebody during perimenopause, in order to help them better, also with hormone therapy.

Distinguishing PMDD From Premenstrual ADHD Exacerbation

Flavio Guzman, M.D.: Now, about premenstrual worsening. What are the specific ADHD symptoms that worsen during the premenstrual phase, and how can clinicians distinguish PMDD from ADHD exacerbation?

Sandra Kooij, M.D., Ph.D.: Premenstrual worsening of symptoms basically entails both mood and ADHD symptoms.

Mood symptoms may include:

• Depressive mood
• Irritability
• Lability
• Crying easily
• Sleep difficulties that are increased compared to the rest of the month

ADHD exacerbation entails:

• More hyperactivity
• More chaotic functioning
• Less attention span
• Less memory

So all the ADHD symptoms increase, and so do the mood symptoms. It is really a danger week, according to my patients, because in that week you better not say a word wrong, or you may face an angry person, or you may even be hit, as some of them have said. It is not funny at all.

They also have suicidal thoughts in this week when they are really depressed. And in the week after, when estrogen rises again, they feel ashamed of their behavior because they feel completely different.

But at that time, in that phase of the cycle, it is all very real to the woman who has PMDD plus increased ADHD severity.

Premenstrual Stimulant Dose Adjustment

Flavio Guzman, M.D.: Let’s talk about premenstrual stimulant dosage adjustment. What practical guidance can you give clinicians about how to implement stimulant dosage adjustments during the premenstrual phase: how much to increase, for how long, and what monitoring is needed?

Sandra Kooij, M.D., Ph.D.: The premenstrual stimulant dose adjustment for premenstrual depression and premenstrual increase of ADHD severity is to increase the usual dosage of stimulant medication for ADHD by 30% to 50%.

This is not a rule. It is what we did in a small pilot study with nine women whom we followed for one and a half years. It was published by Maxime de Jong and me and colleagues in 2023, titled something like “Female-Specific Psychopharmacological Treatment of Women with ADHD.” %% FG: find reference for this %%

The question was: what is the right dosage adjustment, 30% or 50%? In that range, all women were happy with their usual stimulant medication.

What we saw was that all nine women improved, and they wanted to continue ever after with this increased dosage in the premenstrual week only.

Of course, this is something that should be tested in a randomized controlled way, but we have not had the chance to do that. Maybe somebody from the United States could do such a study. That would be great, because that is what we need to be sure this is a good and safe treatment.

What we did do: we measured pulse, blood pressure, appetite, sleep, and mood, and there were no big problems along the way during the months we followed those nine women.

In fact, we did something women had been telling us they were already doing on their own. They said that a slightly higher dosage of stimulant medication helped them to deal with this difficult week in the cycle. So this is what we have for now, and it seems a safe way to go.

Side Effects of Luteal Phase Dose Increases

Flavio Guzman, M.D.: On side effects of luteal phase dose increases, what are the most common side effects when increasing stimulant doses during the luteal phase, and how should clinicians manage them?

Sandra Kooij, M.D., Ph.D.: What we learned from our small study with nine women who increased their dosage of stimulant medication in the last week of the cycle was the following: we measured blood pressure and pulse, and we checked mood and sleep.

There were no severe side effects, and all women tolerated them easily. They were not more severe than what they were used to having in the other weeks of the cycle with a lower dose.

So the advice would be to measure during the first cycle or two cycles that the woman is increasing her dosage. Monitor:

• Pulse and blood pressure
• Mood and sleep
• Improvement of mood and ADHD severity

Flavio Guzman, M.D.: And when cyclical dosing doesn’t work, what should clinicians do when patients don’t respond to or can’t tolerate those dose adjustments? What are the alternative strategies?

Sandra Kooij, M.D., Ph.D.: I would be amazed if this happens at all, because these women are used to stimulant medication, respond to it, and tolerate it. The only thing you do is a little increase in dosage during a week when symptoms are more severe.

The alternative strategies, however, would be continuous oral contraceptives or SSRIs, as far as we know now.

Logistics of Cyclical Dosing

Flavio Guzman, M.D.: On the practical side, how do you navigate the logistical and insurance-related challenges of cyclical dosing, when patients need more medication during certain weeks of the month?

Sandra Kooij, M.D., Ph.D.: I am not sure how the system works in the US, but in my country, when you tell the doctor you need a little more in the last week, he or she can calculate with you how much more medication you need each month, and you simply indicate the right number of tablets in the prescription.

That is it for us, because we can prescribe for more than one month at a time. So in our country, this is not a real problem. I have no idea how to solve it if it is a problem in the US.

Choosing Among PMDD Treatment Options

Flavio Guzman, M.D.: About alternative treatment approaches for PMDD, when should a clinician consider each of these three options: stimulant dosage adjustment, continuous oral contraceptives, or SSRIs? How do you decide which is best for a particular patient?

Sandra Kooij, M.D., Ph.D.: There are indeed three options for PMDD now, and maybe there will be new ones in the future.

• SSRIs: These antidepressants are highly effective and have been shown to work for years on end. They are best for women with a real depressive mood during the premenstrual week, and possibly earlier in the cycle. Some women have dysthymia, so they are rather depressed but not severely so, and in the premenstrual week they develop severe depression with suicidality. Those women I would put on an SSRI.
• Stimulant dose adjustment: This is something you can do easily when a woman has a stable dose of stimulant medication and can handle the adjustment herself.
• Continuous oral contraceptive: This is used to prevent the drop in estrogen. There is no stop week in the last week of the cycle, and the pill is continued. We consider this when there are also a lot of physical symptoms, such as bloating and tender breasts. Continuing hormone therapy seems to be a good approach in those cases.

Some women need two or three of these treatments. So it depends. You have to assess the patient, decide on the first step, and then consider whether another step is still needed.

References

1. Kooij, J. J. S., de Jong, M., Agnew-Blais, J., Amoretti, S., Bang Madsen, K., Barclay, I., Bölte, S., Borg Skoglund, C., Broughton, T., Carucci, S., van Dijken, D. K. E., Ernst, J., French, B., Frick, M. A., Galera, C., Groenman, A. P., Kopp Kallner, H., Kerner Auch Koerner, J., Kittel-Schneider, S., Manor, I., … Wynchank, D. (2025). Research advances and future directions in female ADHD: the lifelong interplay of hormonal fluctuations with mood, cognition, and disease. Frontiers in global women’s health, 6, 1613628. https://doi.org/10.3389/fgwh.2025.1613628
2. Wynchank, D., de Jong, M., & Kooij, S. J. J. S. (2025). Practical tools for female-specific ADHD: The impact of hormonal fluctuations in clinical practice and from the literature. European psychiatry : the journal of the Association of European Psychiatrists, 69(1), e1. https://doi.org/10.1192/j.eurpsy.2025.10120
3. de Jong, M., Wynchank, D. S. M. R., van Andel, E., Beekman, A. T. F., & Kooij, J. J. S. (2023). Female-specific pharmacotherapy in ADHD: Premenstrual adjustment of psychostimulant dosage. Frontiers in Psychiatry, 14, 1306194. https://doi.org/10.3389/fpsyt.2023.1306194
4. Dorani, F., Bijlenga, D., Beekman, A. T. F., van Someren, E. J. W., & Kooij, J. J. S. (2021). Prevalence of hormone-related mood disorder symptoms in women with ADHD. Journal of Psychiatric Research, 133, 10–15. https://doi.org/10.1016/j.jpsychires.2020.12.005