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August 22, 2024
The first-line treatment for ADHD in both adults and children is stimulant medication such as methylphenidate or amphetamines. These medications function by increasing bioavailability of the neurotransmitters dopamine and norepinephrine within the brain. Some animal studies have suggested these medications could impact gonadal function, and more specifically testosterone production.
A U.S. study team accessed electronic medical records (diagnoses, procedures, medications, and laboratory values), as well as insurance claims for about 108 million patients from 76 healthcare organizations. They used these to assess the risk of long-term ADHD stimulant medication on developing a diagnosis of testosterone deficiency in males above the age of puberty.
They compared 20-40-year-old men with a clinical diagnosis of ADHD and long-term exposure to ADHD stimulant medications – including methylphenidate, dextroamphetamine, lisdexamphetamine, amphetamine, and dexmethylphenidate – with ADHD patients who did not receive any medication.
After adjusting for confounding factors, they compared 17,224 men with a diagnosis of ADHD who had received at least 36 prescriptions of ADHD stimulant medications with an equal number with a diagnosis of ADHD who never received any ADHD medications.
ADHD patients on long-term stimulant medication had a roughly 1.75 times higher rate of subsequently being diagnosed with low testosterone levels within five years than unmedicated ADHD patients.
The team also compared 17,217 men with a diagnosis of ADHD who had received at least 36 prescriptions of ADHD stimulant medications with an equal number of men without a diagnosis of ADHD.
Again, patients on long-term stimulant medication had a 75% higher rate of subsequently being diagnosed with low testosterone levels within five years than matched individuals without an ADHD diagnosis.
The team concluded, “Long-term ADHD stimulant medication use in men was found to be associated with a significant increase in relative risk for a subsequent testicular hypofunction diagnosis. This difference was found when compared to both those with ADHD not using pharmaceutical therapy and those without ADHD. These results indicate that impaired gonadal function is a potential side effect of stimulant medications.”
Like other observational studies, this work provides an important signal that must be replicated and validated with other methods, especially those that rule out other sources of confounding not measured in this study. Moreover, diagnoses of testosterone hypofunction in this study were relatively rare to begin with. The measured 0.5% increase in testicular hypofunction diagnosis for those on long-term stimulant medication versus those not on stimulant medication would only affect roughly one in two hundred of those on stimulant medication. This small increase in risk must be weighed against the well-documented benefits of these medications.
Garett P. Ostdiek-Wille, Kyle C. Bavitz, Taylor P. Kohn, and Christopher M. Deibert, “Attention-deficit hyperactivity disorder medication use is associated with testosterone hypofunction–results from a national claims database analysis,” IJIR: Your Sexual Medicine Journal (2024), 36:403–407, https://doi.org/10.1038/s41443-023-00805-2.
Refractive errors, such as myopia (nearsightedness), hyperopia (farsightedness), and astigmatism (distorted vision due to irregular curvature of the eye or lens), are common worldwide. These conditions affect 12%, 5%, and 15% of children, and rise significantly in adults to 26.5%, 31%, and 40%. Additionally, strabismus (misalignment of the eyes) and amblyopia (reduced vision in one eye from uneven image formation, often linked to strabismus) occur globally at rates of 2% and 1.4%, respectively.
Visual impairment can affect children’s concentration in school, and studies suggest a link between eye disorders and ADHD.
To investigate this relationship, two researchers – one based in the US and the other in Israel –carried out a nationwide retrospective cohort study using electronic medical records of all insured individuals aged 5 to 30 who were part of Maccabi Health Services, Israel’s second largest health maintenance organization, between 2010 and 2022.
Of over 1.6 million insured members (2010–2020), inclusion/exclusion criteria and propensity score matching for age and sex were applied, along with a one-year wash-out period between the first eye diagnosis and ADHD diagnosis. In total, 221,707 cases were matched with controls without eye disorders at a 1:2 ratio, resulting in a cohort of 665,121 participants.
Overall, those with any previous eye diagnosis were 40% more likely to have a subsequent ADHD diagnosis. This was slightly higher for females (45%) than for males (35%). It was also slightly higher for children and adolescents (42%) than for adults (37%).
More specifically:
The authors concluded that eye disorders are associated with ADHD. They noted these associations were more marked in females and children and adolescents, although, as noted above, those differences were small. They recommended that primary care providers and neurologists consider risk stratification for early screening, and that ophthalmologists refer high-risk patients for ADHD evaluation.
Acid-suppressive medications, including proton pump inhibitors (PPIs) and histamine-2 (H2) receptor antagonists, are often prescribed during pregnancy to treat heartburn and gastroesophageal reflux disease.
Research shows changes in the gut microbiome can negatively affect neurodevelopment. Since acid-suppressive medications alter gut microbiota, maternal use during pregnancy may impact offspring’s neurodevelopment. Because PPIs and H2 receptor antagonists readily cross the placental barrier, they could potentially influence fetal neurodevelopment.
The link between prenatal exposure to acid-suppressive medications and major neuropsychiatric disorders is not well understood. With the use of these medications during pregnancy rising, it is important to assess their impact on children's long-term neurodevelopment. This study examined whether maternal use of acid-suppressive drugs is associated with increased risk of neuropsychiatric disorders in children, using a large, nationwide birth cohort from South Korea.
South Korea operates a single-payer health insurance system, providing coverage for over 97% of its citizens. The National Health Insurance Service (NHIS) maintains a comprehensive database with sociodemographic details, medical diagnoses, procedures, prescriptions, health examinations, and vital statistics for all insured individuals.
A Korean research team analyzed data from over three million mother-child pairs (2010–2017) to assess the risks of prenatal exposure to acid-suppressing medications. They applied propensity scoring to adjust for maternal age, number of children, medical history, and outpatient visits before pregnancy, to minimize confounding factors. That narrowed the cohort to just over 800,000 pairs, with half in the exposed group.
With these adjustments, prenatal exposure to acid-suppressing medications was associated with 14% greater likelihood of being subsequently diagnosed with ADHD.
Yet, when 151,737 exposed births were compared to the same number of sibling controls, no association was found between prenatal exposure and subsequent ADHD, which suggests unaccounted familial and genetic factors influenced the preceding results.
The Take-Away:
Evidence of these medications negatively affecting pregnancies is mixed, mostly observational, and generally reassuring when these medications are used appropriately. Untreated GERD and gastritis, however, have known risks and associations with the development of various cancers. With no evidence of an association with ADHD (or for that matter any other neuropsychiatric disorder), there is no current evidence-based reason for expectant mothers to discontinue use of acid-suppressing medications.
For years, a persistent concern has shadowed the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD): Does the medication eventually stop working? Patients often report that their symptoms seem to return despite consistent use, leading to "dose escalation" or "medication holidays." A new systematic review from Sam Cortese’s team published in CNS Drugs finally puts these concerns to the test by synthesizing decades of empirical research.
Before diving into the findings, you must understand two often-confused phenomena:
The review analyzed 17 studies covering over 10,000 individuals, and the results provide a much-needed reality check for the clinical community.
The researchers found preliminary evidence that acute tolerance (tachyphylaxis) can occur within a 24-hour window.
The most important finding is that tolerance does not commonly develop to the therapeutic effects of ADHD medication in the long term. In one landmark study following children for up to 10 years, only 2.7% of participants lost their response to methylphenidate without a clear external explanation. Doses, when adjusted for natural body growth, remained remarkably stable over years of treatment.
Consistent with the lack of therapeutic tolerance, the body does not become tolerant to the physical side effects of stimulants. Increases in heart rate and blood pressure typically persist for as long as the medication is taken. This underscores why clinicians must continue monitoring cardiovascular health throughout the entire duration of treatment.
If it’s Not Tolerance, What Is It?
If "tolerance" isn't real, why do some patients feel their medication is failing? The review suggests clinicians look at these alternative explanations:
Why This Matters
These results provide clinicians the confidence to tell patients that their medication is unlikely to "wear out" permanently. Rather than immediately increasing a dose when symptoms flare, the first step should be a "clinical deep dive" into the patient's lifestyle, stress levels, and adherence.
For researchers, the review highlights a major gap: most existing studies are small, dated, or of low quality. There is a dire need for robust, longitudinal studies that track both the brain's response and the patient's environment over several years.
For people with ADHD, while your body might get "used to" the initial "buzz" of a stimulant within hours, its ability to help you focus and manage your life remains remarkably durable over the years.
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