High and Low Estrogen Exacerbate ADHD Symptoms in Females: New Theory

January 3, 2024

The impact of rising and falling hormone levels on ADHD symptoms is compounded for females beginning in puberty, according to a review article published in Hormones and Behavior. ¹

Menstrual Cycle

ADHD symptoms correlate with hormonal fluctuations, especially declines in estrogen, argue the review authors, who present a new two-phase theory of hormonal sensitivity that asserts ADHD impairments spike during two points in the menstrual cycle:

• Periovulatory (mid-cycle)
• Perimenstrual (end-of-cycle)

Per the theory, females may be more likely to engage in risk-taking and reward-seeking behaviors in the days leading up to ovulation. These behaviors coincide with a steady rise in estrogen levels that drops off during ovulation. In contrast, withdrawal and/or depletion of estrogen at a cycle’s end may be characterized by increased negative affect, avoidant behaviors, and reduced executive functioning.

The effects of estrogen withdrawal may potentially exacerbate ADHD symptoms based on inherent individual differences in affect and impulsivity. The theory also points to luteal-bound increases in hyperactivity driven by fluctuations in progesterone metabolites.

“In the follicular phase, which is the period when estrogen levels are steadily increasing, ADHD symptoms are at their lowest,” said Jeanette Wasserstein, Ph.D., in an ADDitude webinar on hormones and ADHD. “That’s the period when estrogen and progesterone are jointly protected. They work together.”

A preliminary pilot study conducted by the authors in 2018 published similar conclusions.² Among young adult females aged 18 to 25, declines in estradiol (a type of estrogen) led to an increase in ADHD symptoms. Specifically, the study showed a two-fold increase in ADHD symptoms of inattention and hyperactivity-impulsivity, which were moderated by positive and negative urgency and by levels of progesterone.

Reproductive Periods

Adolescents are particularly vulnerable to the impact of hormones as they develop. ADHD or not, adolescent females undergoing hormonal changes experience an increase in impairments, including comorbidity, suicidality, and unplanned pregnancy, the authors said. They are also faced with unique environmental stressors including delinquent peers, strained family functioning, and psychosocial stressors. However, limited research exists on how sex hormones impact ADHD symptoms specifically across the lifespan.

Rises in estrogen and progesterone at the onset of puberty may trigger neurobiological sensitivity to hormonal changes, per the theory, and lead to structural and functional changes in the brain. “If those networks are particularly those in the executive brain, the prefrontal cortex, and its linkages throughout the brain, we could see a rise in ADHD symptoms,” said Russell Barkley, Ph.D., in a YouTube video summarizing the review article.

The authors said that the combination of transient activational effects and long-lasting organizational effects during puberty acts as a “double whammy” that is mirrored during later reproductive events, including pregnancy and menopausal periods.

“We’ve had instances where we’ve seen a rise of referrals in women to clinics that is coincidence with the onset of perimenopause or menopause,” Barkley said. “Women who weren’t necessarily ADHD previously — or were able to cope with elevated symptoms that may not have been in the clinical range — now found themselves fully, clinically ADHD as they approach mid- to late life.”

Multiple hormone sensitivity theory may help explain why rates of ADHD differ between males and females during development. As many as three males to one female are diagnosed with ADHD during childhood; by adulthood, the rates even out. While ADHD risk appears to be highest for males during the prenatal period, females experience heightened risk during multiple reproductive periods, as cited by the authors.

Treatment Implications

Timed interventions may make treatment plans more effective for females with ADHD. This might include adjusting medication dosage and type to the menstrual cycle and reproductive period. For example, the authors cited research showing heightened sensitivity to stimulants during the follicular phase of a woman’s cycle — when estrogen is high, and progesterone is low. “Changes in response to ADHD medications likely reflect the point in the menstrual cycle that a woman is and where all these different hormones are,” Wasserstein said. And “there might be different reactions depending on which presentation of ADHD the person has.”

Barkley says that some doctors are already using these practices. “Clinicians who have worked with young women have often told me that they adjust medication, and even add additional medication, at different stages of the month to help women manage their ADHD and period-related exacerbations.”

Additionally, ADHD assessments should provide a lower threshold for women and account for these behavioral changes.

Future Research

To test their theory, the authors suggest assessing for circulating hormone levels and ovulation. Future research should focus “on the hormonal impacts on females with ADHD, not just the impact of stimulant medications on fetuses.”

“This work is vitally important because knowledge of what ADHD looks like and the public health impacts of ADHD in females is limited, particularly in adolescents and young adults, which are understudied developmental periods in their own right in the ADHD field,” the authors wrote.

This review article was made available online on November 30, 2023, and will be published in Volume 158 of Hormones and Behavior in February 2024.

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