Minimizing the impact of elevated prolactin in children and adolescents

Absolute PRL level is not useful in guiding treatment because it is not consistently correlated with adverse effects. However, the degree of change of serum PRL levels over time or the change of PRL levels from baseline may be important in diagnosing asymptomatic hyperprolactinemia.¹⁶ Suspect pathologic hyperprolactinemia in patients (except newborns and pregnant women) with plasma PRL levels consistently >15 to 25 ng/mL.¹² This finding occurs in <1% of the population, but the rate is higher among individuals with specific symptoms attributable to hyperprolactinemia. For example, 9% of women with amenorrhea, 25% of women with galactorrhea, and 70% of women with both amenorrhea and galactorrhea have hyperprolactinemia. The prevalence is approximately 5% among men with impotence or infertility.¹⁰

If hyperprolactinemia is detected, the degree of PRL elevation can help determine etiology. In the absence of pregnancy and breastfeeding, a serum PRL level of >600 ng/mL is highly suggestive of a macroprolactinoma.¹² PRL concentrations >250 ng/mL suggest a microprolactinoma or a nonfunctioning adenoma.¹² Antipsychotics usually produce moderate PRL elevation (up to 6 times the upper limit of the reference range of 100 ng/mL).¹² In 1 study, the median time to onset of galactorrhea was 20 days after initiating antipsychotics in female patients.¹² Hyperprolactinemia-induced HPG axis dysfunction causes delayed pubertal development or loss of bone mineral deposit.¹⁶ Measuring BMD in children and adolescents with hyperprolactinemia is important during this critical time of skeletal development.¹⁶

Managing hyperprolactinemia

Before starting any antipsychotic, inform patients and families of possible side effects, including hyperprolactinemia. Educate them about recognizing the signs and symptoms of hyperprolactinemia (Table 3).¹² Although PRL blood levels typically are not routinely measured in pubertal girls who take PRL-modulating agents, consider monitoring serum PRL levels every 6 months until patients achieve sexual maturity and menstrual cycle regularity.¹⁶

If laboratory testing detects elevated PRL levels in a child or adolescent, determine if the patient had sexual intercourse, nipple stimulation, stress (including venipuncture), sleep disturbances, seizures, head injury, or surgery before the blood sample was obtained. This information will help to determine if the PRL elevation is caused by one of these factors.

To treat hyperprolactinemia, address the underlying medical cause(s). If patients using antipsychotics have signs and symptoms of hyperprolactinemia, consider discontinuing the drug or reducing the dosage.¹¹ If dose change fails to reduce hyperprolactinemia, consider a switch to a low-potency D2 agent or aripiprazole. Shim et al²⁰ studied the effects of adjunctive treatment with aripiprazole on hyperprolactinemia and psychopathology in schizophrenia patients maintained on haloperidol. In this study, aripiprazole reversed hyperprolactinemia in both sexes but plasma levels of haloperidol were not significantly altered. The authors hypothesized that decreased PRL levels may have been the result of pharmacodynamic interaction at dopamine receptors rather than pharmacokinetic interaction between aripiprazole and haloperidol. Additional studies are needed to confirm these findings.

If a medication switch is contraindicated, pharmacologic treatment for hyperprolactinemia may be required.¹¹ Bromocriptine, cabergoline, and amantadine have been used to treat hyperprolactinemia.¹¹ Bromocriptine lowers PRL levels and restores normal gonadal function for men and women with hyperprolactinemia regardless of etiology, but may worsen psychiatric symptoms and can cause nausea, headaches, dizziness, and orthostatic hypotension.¹¹ In a pilot study, amantadine, 300 mg/d, used to treat neuroleptic-induced extrapyramidal effects also decreased PRL levels and reduced galactorrhea.¹¹

Osteoporosis can be minimized by exercising, taking adequate calcium and vitamin D, and avoiding caffeinated drinks.⁹ Simmons et al²¹ found bisphosphonate treatment in children and adolescents improved bone density and fragility within 2 to 4 years. Unfortunately, information about optimal duration and long-term effects of bisphosphonate therapy is limited.²²

Surgical treatment may be necessary to remove a pituitary tumor that causes hyperprolactinemia. For some patients, referral to pediatric endocrinologist for further treatment may be needed.

Table 3

Presenting symptoms of hyperprolactinemia

Related Resources

• Ali J, Khemka M. Hyperprolactinemia: Monitoring children on long-term risperidone. Current Psychiatry. 2008;7(11):64-72.

Drug Brand Names

• Amantadine • Symmetrel
• Aripiprazole • Abilify
• Bendroflumethiazide • Naturetin
• Bromocriptine • Parlodel
• Bupropion • Wellbutrin
• Cabergoline • Dostinex
• Chlorpromazine • Thorazine
• Cimetidine • Tagamet
• Citalopram • Celexa
• Clozapine • Clozaril
• Famotidine • Pepcid
• Fluoxetine • Prozac
• Fluvoxamine • Luvox
• Haloperidol • Haldol
• Iloperidone • Fanapt
• Indinavir • Crixivan
• Methyldopa • Aldomet
• Mirtazapine • Remeron
• Nefazodone • Serzone
• Olanzapine • Zyprexa
• Omeprazole • Prilosec
• Paliperidone • Invega
• Paroxetine • Paxil
• Quetiapine • Seroquel
• Quinidine • Quinidex
• Ranitidine • Zantac
• Reserpine • Serpasil
• Risperidone • Risperdal
• Ritonavir • Norvir
• Sertraline • Zoloft
• Tamoxifen • Nolvadex
• Triptorelin • Trelstar
• Venlafaxine • Effexor
• Verapamil • Calan, Isoptin
• Zidovudine • Retrovir
• Ziprasidone • Geodon