ADHD in Reproductive-Age Women

MOST RESEARCH conducted on attention-deficit hyperactive disorder (ADHD) has primarily focused on male children. Yet, a recent study shows ADHD prescription use among reproductive-age women has increased 700 percent.¹ In addition, it is unknown why ADHD rates are increasing among this age group, but another recent study shows sex hormones might play a role in the presentation of symptoms, diagnosis and treatment.² As such, much more investigation is needed to understand how ADHD presents in these women and how ADHD medication affects them and the developing fetus.

What Is ADHD?

ADHD is a neurodevelopmental disorder characterized by a persistent pattern of inattention and/or hyperactivity and impulsivity that interferes with a person’s functioning or development.³ It begins in childhood and often continues throughout adolescence and into adulthood. The American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) lists three ADHD presentation types: predominantly inattentive presentation (PIP, includes nine symptoms), predominantly hyperactive-impulsive presentation (PHIP, includes nine symptoms) or combined (a total of 18 symptoms). Symptoms can be mild, moderate or severe. And, since ADHD symptoms can change over time, adults might fit different presentations in adulthood than in childhood.⁴

For an adult to be diagnosed with ADHD, several PIP or PHIP symptoms had to be present prior to 12 years old; manifestations have to be present in more than one setting such as home, school or work; and there must be evidence symptoms interfere with the person’s functioning in these settings.⁴

ADHD Statistics

According to DSM-5, population surveys suggest ADHD occurs in most cultures in about 5 percent of children and about 2.5 percent of adults, and a substantial proportion of children remain relatively impaired into adulthood. Differences in ADHD prevalence rates across regions appear attributable mainly to different diagnostic and methodological practices. The disorder is more frequent in males than females in the general population, with a ratio of approximately two to one in children and 1.6 to one in adults. In addition, females are more likely than males to present primarily with inattentive features.⁴

The National Resource Center on ADHD says the disorder can coexist with other psychotic or mental disorders. For adults with ADHD, more than 80 percent have at least one other disorder, more than 50 percent have two other disorders and more than 33 percent have at least three other disorders. These disorders include depression, anxiety, oppositional defiant disorder, conduct disorder and alcohol and drug use disorders. Many of these disorders’ symptoms mimic ADHD symptoms and can be mistaken for ADHD.³

ADHD Treatment for Adults

Adults diagnosed with ADHD can be treated with behavioral interventions, medication or a combination of the two. Stimulants such as methylphenidate HC1 (Ritalin, Concerta and generics) and amphetamine mixed salts (Adderall, Adderall XR and generics) are the most common types of medication used. Other medications include lisdexamfetamine dimesylate (Vyvanse), dextroamphetamine (Dexedrine and generics) and atomoxetine (Strattera). These medications are prescribed for both ADHD-diagnosed females who are and are not pregnant.⁵

The Relationship Between Pregnancy and

The Relationship Between Pregnancy and ADHD in Reproductive-Age Women

In 2014, Ronit Haimov-Kochman, MD, a physician in the IVF Unit at the Department of Obstetrics and Gynecology at the Hadassah Hebrew University Medical Center in Mount Scopus, Jerusalem, conducted a meta-analysis of previous studies that examined why ADHD in girls may be consistently underidentified and underdiagnosed. Titled Cognitive Functions of Regularly Cycling Women May Differ Throughout the Month, Depending on Sex Hormone Status; A Possible Explanation to Conflicting Results of Studies of ADHD in Females, her study demonstrated, “there is a growing body of literature showing that sex hormones have the ability to regulate intracellular signaling systems that are thought to be abnormal in ADHD. Thus, it is conceivable to believe that this functional interaction between sex hormones and molecules involved with synaptic plasticity and neurotransmitter systems may be associated with some of the clinical characteristics of women with ADHD.

“The studies of ADHD in females suggest confusing and nonconsistent conclusions. None of these studies examined the possible relationship between phase of the menstrual cycle, sex hormone levels and ADHD symptoms. The menstrual cycle should, therefore, be taken into consideration in future studies in the neurocognitive field since it offers a unique opportunity to understand whether and how subtle fluctuations of sex hormones and specific combinations of sex hormones influence neuronal circuits implicated in the cognitive relation of emotional processing. The investigation of biological models involving the role of estrogen, progesterone and other sex steroids has the potential to generate new and improved diagnostic and treatment strategies that could change the course of cognitive-behavioral disorders such as ADHD.”²

Possible Explanations for Increasing Prescription Drug Use Among Reproductive-Age Women

According to Kayla Anderson, PhD, an epidemiologist at the Center for Disease Control and Prevention’s (CDC) National Center on Birth Defects and Developmental Disabilities, “Two CDC studies have recently reported that ADHD medication use is increasing among reproductive-age and pregnant women. Based on our data, we were not able to look at why there are increasing rates of ADHD medicine prescriptions among these women. However, there are at least two possible explanations, which need additional research, for why this increase might be occurring. First, in recent decades, there have been substantial increases in the percentage of children diagnosed with and treated for ADHD. As these children age into adulthood, they may continue having ADHD symptoms and continue taking their medication as treatment for this chronic, lifespan condition. And, second, there is increasing awareness that ADHD affects people of all ages, not just children, and that ADHD symptoms may show themselves differently for adults than children. This may mean that more adults are being diagnosed with and treated for ADHD.

In “ADHD Medication Prescription Claims Among Privately Insured Women Aged 15-44 Years — United States, 2003-2015,” CDC used the Truven Health MarketScan Commercial Database to estimate the percentage of reproductive-age women with private employer-sponsored insurance who filled prescriptions for ADHD medications each year. It found, overall, the percentage who filled at least one ADHD prescription increased 344 percent. However, prescriptions filled by women age 25 years to 29 years increased a whopping 700 percent. In 2015, the most frequently filled medications were mixed amphetamine salts (60.8 percent), lisdexamfetamine (26.7 percent) and methylphenidate (18.1 percent). Among women who filled any ADHD prescriptions, the number of prescriptions filled per year rose from an average of 5.5 in 2003 to 7.2 in 2015.¹

Potential Risks of ADHD Medicines in Reproductive-Age Women

In 2015, researchers at the Slone Epidemiology Center at Boston University wrote a letter to the editor of Pharmacoepidemiology & Drug Safety titled “Increasing Use of ADHD Medications in Pregnancy.” The letter was a summary of data from the center’s Birth Defects Study (BDS), which examined the prevalence of ADHD medications used among pregnant women from interviews conducted between 1998 and 2014. The study found 1) medication use is increasing among pregnant women, 2) the increase is entirely accounted for by increased use of Adderall and Adderall XR and 3) there is little information on possible risks to the fetus from such exposure.

According to the researchers, ADHD is one of the most common conditions of childhood and is typically treated with medication. Once initiated, medication often becomes chronic therapy, and approximately 30 percent of patients are estimated to continue pharmacologic treatment into adulthood. As a result, these drugs are likely to be used by pregnant women, raising concerns about possible fetal exposure. In addition, a recent publication noted premarket safety and efficacy studies for ADHD medications in children focused only on the short-term safety and efficacy of these medications, and no premarketing studies have focused on pregnant women and their offspring.

“Our observation … raises particular concern because pregnant women constitute a special population for whom exposure carries a potential risk not only to the woman herself, but also to the fetus she is carrying,” said the researchers. “The few human studies that have explored possible effects of these drugs on the fetus included only small numbers of subjects or were primarily focused on methylphenidate, while our experience indicates that amphetamine mixed salts are by far the most common (and most rapidly increasing) ADHD medication used by pregnant women in the United States. With exposure prevalence now approximately 1 percent, these drugs rank among the most commonly used prescription medications in pregnancy, and it is also possible that use will increase further as more women whose exposure began in childhood enter childbearing age.”⁶

Previous research has linked ADHD medication use during pregnancy with an increased risk for poor pregnancy outcomes, including spontaneous abortion, although research is limited. And, whether ADHD medications increase risk of birth defects is largely unknown, with only one published study.¹

CDC’s Treating for Two Initiative

The CDC’s National Center on Birth Defects and Developmental Disabilities is working to improve the health of women and babies through its Treating for Two: Safer Medicine Use in Pregnancy initiative. The aim of the initiative is to address medication safety by conducting research before and during pregnancy to help women and their healthcare providers make evidence-based decisions regarding the risks and benefits of pharmacologic and behavioral treatment options for common conditions, including ADHD.

Treating for Two is CDC’s prescription for this problem. Its mission is to provide evidence-based guidance on safer medication use during pregnancy and provide communication products to support shared decision-making among women and healthcare professionals.⁷ “Treating for Two works to understand trends in medicine use, including ADHD medications, among pregnant women and women of reproductive age, and to provide women and healthcare providers with information about the safety or risk of using specific medicines during pregnancy,” said Dr. Anderson. “This information will enable women and their doctors to make informed decisions about treating health conditions during pregnancy.”

In 2018, as part of its work related to Treating for Two, CDC used data from the National Birth Defects Prevention Study, a U.S. population-based case-control study conducted between 1998 and 2011 that examined risk factors for major structural birth defects, as well as the use of ADHD medications among pregnant women. The study found “early pregnancy ADHD medication use was more commonly reported by mothers of infants/fetuses with gastroschisis, omphalocele and transverse limb deficiency.”⁸

The Need for More Research

CDC says it is unknown if reproductive-age women, specifically women who are pregnant, present with increased symptoms of ADHD compared with nonpregnant women. “There is little information available about how frequently pregnant women report having ADHD diagnoses and regarding how ADHD symptoms may or may not change during pregnancy,” said Dr. Anderson.

“Until the role of sex hormones in the female human brain is understood, it is important to take into account critical variables such as menstrual cycle phase, hormonal status (for example, postpartum, perimenopause, menopause) and external hormonal use (for example, combined oral contraception, hormonal replacement therapy at menopause),” said Dr. Haimov-Kochman. “The menstrual cycle offers a unique opportunity to study whether and how subtle fluctuations of sex hormones and specific combinations of sex hormones influence neuronal circuits implicated in the cognitive regulation of emotional processing. This may lead to better understanding of the sex hormone impact on women’s brain in health, as well as in ADHD, and may resolve the inconsistency of the findings in women with ADHD.”²

“Given that nearly half of U.S. pregnancies are unintended, and early pregnancy is a critical period for fetal development, examining trends in ADHD medication prescriptions among reproductive-age women is important to quantify the population at risk for potential exposure,” explained Dr. Anderson. “Our group at CDC studies health outcomes, such as birth defects, related to medication use during pregnancy. There is currently very little information about the safety and risk of taking ADHD medications before and during pregnancy and related pregnancy, birth and infant outcomes, including birth defects. At this time, there is not enough data to determine the profile of risk or safety of taking ADHD medications during pregnancy. More research is urgently needed to understand the safety of ADHD medications before and during pregnancy.”¹