What is the appropriate workup for a 37-year-old female (F) with amenorrhea while on lithium (lithium) and olanzapine (olanzapine)?

Amenorrhea Workup in a 37-Year-Old Female on Lithium and Olanzapine

The appropriate workup for amenorrhea in a 37-year-old female on lithium and olanzapine should begin with ruling out medication-induced hyperprolactinemia, as both medications can affect hormonal regulation and menstrual cycles.

Initial Evaluation

• Obtain a pregnancy test as the first step to rule out the most common cause of amenorrhea in women of reproductive age 1
• Check serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, and thyroid-stimulating hormone (TSH) 1
• Evaluate for medication-related causes, as both lithium and olanzapine can potentially affect menstrual cycles 2, 3

Medication Effects on Menstrual Cycle

Olanzapine

• Olanzapine is an atypical antipsychotic that antagonizes multiple receptors including dopamine receptors, which can lead to hyperprolactinemia 2
• Hyperprolactinemia is a known cause of amenorrhea and can be induced by antipsychotic medications 4
• Common side effects with olanzapine include fatigue, drowsiness, and sleep disturbances, but menstrual irregularities have also been reported 2

Lithium

• Lithium has been associated with amenorrhea in rare cases, with a recent case report suggesting it may cause hyperprolactinemia leading to amenorrhea 3
• The effects of lithium on prolactin levels are mixed in the literature, but monitoring is warranted 2
• Lithium requires careful monitoring for various side effects, though menstrual irregularities are not among the most commonly reported 2

Diagnostic Algorithm

1. Rule out pregnancy with urine or serum hCG test 1
2. Check hormone levels:
   • Prolactin (elevated levels suggest medication-induced hyperprolactinemia) 1
   • TSH (to rule out thyroid dysfunction) 1
   • FSH and LH (to determine if amenorrhea is due to ovarian failure, hypothalamic dysfunction, or PCOS) 1, 5
3. Evaluate medication timing:
   • Determine if amenorrhea began after starting lithium or olanzapine 3, 4
   • Consider a medication-induced cause if temporal relationship exists 6
4. Additional testing based on initial results:
   • If prolactin is elevated: consider pituitary MRI to rule out adenoma 5
   • If FSH/LH are elevated: suggests primary ovarian insufficiency 1
   • If FSH/LH are low/normal with normal prolactin: suggests hypothalamic amenorrhea 2
   • If LH is elevated with normal/low FSH: suggests PCOS 5

Management Considerations

• If hyperprolactinemia is confirmed and related to medications, consider consulting with psychiatrist about potential medication adjustments 4
• For patients with bipolar disorder, medication changes should be approached cautiously as mood stability is a priority 2
• Consider alternative antipsychotics with lower risk of prolactin elevation if clinically appropriate, such as aripiprazole 2
• For patients with hypothalamic amenorrhea, evaluate for energy deficiency and consider bone mineral density testing 2

Important Caveats

• Do not discontinue psychiatric medications without psychiatric consultation, as this could lead to relapse of mental health conditions 2
• Be aware that olanzapine should be used with caution in elderly patients (though not applicable to this 37-year-old patient) due to increased risks 7
• Amenorrhea in patients on psychotropic medications may be multifactorial, including stress, weight changes, or other medical conditions beyond medication effects 2
• Long-term amenorrhea can lead to bone density loss, so evaluation and management should not be delayed 2

Follow-up Recommendations

• If medication-induced hyperprolactinemia is confirmed, regular monitoring of prolactin levels is recommended 5
• Consider bone mineral density testing if amenorrhea has been present for more than 6-12 months 2
• Regular follow-up to assess menstrual function and medication side effects is essential 1