How does lithium affect the menstrual cycle?

Lithium's Effects on the Menstrual Cycle

Lithium may cause menstrual irregularities including amenorrhea, potentially through mechanisms involving hyperprolactinemia, though evidence is limited and mixed. 1

Effects on Menstrual Function

• Lithium has been associated with menstrual cycle disturbances, with a recent case report documenting amenorrhea (absence of menstruation) potentially linked to lithium-induced hyperprolactinemia 1
• Lithium can affect biological rhythms, which may influence hormonal cycling and potentially impact menstrual regularity 2
• Menstrual irregularities may occur as lithium affects various systems including hormonal balance and second messenger systems that regulate reproductive function 2

Potential Mechanisms

• Lithium may disrupt the hypothalamic-pituitary-gonadal axis, affecting hormone production and regulation that controls the menstrual cycle 1
• Elevated prolactin levels (hyperprolactinemia) have been documented with lithium use, which can directly interfere with normal menstruation 1
• Lithium affects multiple cellular pathways including inhibition of glycogen synthetase kinase-3beta (GSK3β), which may influence hormonal regulation 3
• The drug's impact on circadian rhythms could potentially disrupt the cyclic nature of menstrual function 2

Clinical Considerations

• Regular monitoring of menstrual patterns is advisable in women taking lithium, as menstrual changes may indicate hormonal disruption 1
• Serum lithium levels should be monitored regularly (twice weekly during initial treatment until stabilized) to prevent toxicity that could exacerbate side effects 4
• When lithium-related menstrual irregularities occur, clinicians should rule out other common causes of amenorrhea such as pregnancy, CNS disorders, thyroid dysfunction, and effects of other medications 1
• The therapeutic serum concentration range for lithium is 0.6-1.0 mM, with levels >1.5 mM potentially causing toxic effects on multiple organ systems 3

Special Populations

• For women with premenstrual dysphoric disorder (PDD), lithium has shown mixed results, with one case report suggesting potential benefit in selected patients, particularly those with family history of bipolar disorder 5
• However, an older study found lithium (600-900 mg/day) was generally ineffective for most women with premenstrual tension syndrome and caused significant side effects 6
• The balance of risks and benefits of lithium is different for pregnant and breastfeeding women, as lithium may cause fetal harm based on animal studies, though human data are insufficient to determine exact risk 7

Monitoring Recommendations

• Regular monitoring of lithium levels is essential, with measurements recommended twice weekly during the acute phase until stabilized 4
• When menstrual irregularities occur in patients taking lithium, prolactin levels should be checked to identify potential hyperprolactinemia 1
• Patients should be educated about potential menstrual cycle changes as a possible side effect of lithium therapy 8
• Early recognition of lithium toxicity symptoms (tremor, nausea, diarrhea, polyuria-polydipsia) is important as toxicity could worsen any existing side effects including menstrual disturbances 4