Abstract
To The Editor:
A
Case Report
A 17-year-old-girl had been diagnosed 5 years earlier with ADHD-inattentive type, and mild MR, according to the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (American Psychiatric Association 1994), at the Child and Adolescent Psychiatry Department of Bakirkoy Prof Dr Mazhar Osman Research and Training Hospital for Psychiatry, Neurology, and Neurosurgery. She presented with lack of attention to detail, distractibility, forgetfulness, and difficulty in learning as the symptoms of ADHD and MR. Physical examination did not reveal any abnormality. ADHD treatment was initiated with OROS-MPH, 27 mg/day, for a body weight of 53 kg. She experienced significant but eventually reduced improvement in ADHD symptoms in the first 4 years of the treatment. Because of the increasing severity of her ADHD symptoms in the previous year, the dose of OROS-MPH was increased to 36 mg/day (for a body weight of 52 kg), at which her menstrual cycle length increased. Before increasing the dose, she had had formerly had regular menstrual cycles of 27–29 days. Her age at menarche was 12 years. At the 2 month follow-up, she had experienced minimal improvement in ADHD symptoms, while her menstrual cycle length had increased immediately by ∼15 days after the increase in OROS-MPH dose. After this longer menstrual cycle, her mother had decided to decrease the dose of OROS-MPH to 27 mg/day, and regular menstrual cycles were established immediately. Subsequently, in order to improve the ADHD symptoms, her mother had increased the dose to 36 mg/day and her menstrual cycle length had increased by ∼15 days again. After this, she had continued using OROS-MPH, 27 mg/day, and the increase in her menstrual cycle length disappeared immediately. No any other abnormalities of the menstrual cycle, including dysmenorrhea, duration, and amount of menstrual bleeding were reported. The patient still receives 27 mg/day of OROS-MPH, with no reported side effects.
Discussion
In this case with no confounding medications, the sudden onset of the increased menstrual cycle with the increasing dose of MPH, and its subsequent disappearance after decreasing the dose of the drug, strongly suggested a causal link. No previous reports identify an increase in menstrual cycle length in a female with ADHD who was treated with MPH. Menstrual cycles are regulated by interactions of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), estrogen, and progesterone (Golden and Carlson 2008). Also, pulsatile secretion of GnRH is regulated by a number of neurotransmitters, including dopamine and norepinephrine (Golden and Carlson 2008), and is affected by stress, nutrition, exercise, neurosteroids, and neuropeptides such as leptin and ghrelin (Meczekalski et al. 2008). It was reported that dopamine agonists (i.e., bromocriptine, cabergoline) could reduce or impair pulsatile secretion of LH (Papaleo et al. 2001), and inhibit the response of ovaries to human chorionic gonadotropin (hCG) (Youssef et al. 2010). It was found that dopamine infusion significantly reduced LH and FSH responses to GnRH in normal women (Nicoletti et al. 1986) and inhibited the LH pulsatile release (Ropert et al. 1984). Moreover, Sahin et al. (2014) reported an increase in ghrelin levels and a decrease in leptin levels after MPH treatment. Higher ghrelin and lower leptin secretion may alter LH pulsatility (Ackerman et al. 2012). Our case supports the positive scientific findings about the association of MPH, a dopamine and norepinephrine reuptake inhibitor, and abnormality of the menstrual cycle. According to the above literature findings, MPH treatment may cause an increase in menstrual cycle length. Inhibition of pulsatile GnRH and LH secretion via dopamine and inhibition of pulsatile LH release via possible increase of ghrelin levels and decrease of leptin levels may be suggested as possible mechanisms of the increase in menstrual cycle length. Nevertheless, the relationship between the increase in menstrual cycle length and MPH has not precisely been established. It seems that MPH may affect the menstrual cycle at various levels. This case suggests that the increase in menstrual cycle length may occur in adolescents as the dosage of MPH is increasing, and this side effect quickly responds to decreasing the dose of the drug. As a result, we should carefully monitor for side effects, including menstruation abnormalities at times when MPH doses are increased.
Footnotes
Disclosures
No competing financial interests exist.