Can Medications Cause PCOS?
Medications do not cause true primary PCOS, but certain drugs—particularly valproate (an antiepileptic medication)—can trigger a secondary PCOS-like phenotype in predisposed women that is potentially reversible upon drug discontinuation. 1
Understanding Secondary vs. Primary PCOS
Primary PCOS is a genetic endocrine-metabolic disorder with unknown exact etiology that cannot be completely cured, only controlled with lifestyle modifications and medications 2
Secondary PCOS represents a PCOS-like phenotype triggered by external factors, including certain medications, and is potentially curable when the underlying cause is treated 2
Valproate: The Primary Medication Culprit
Evidence of Valproate-Induced PCOS
In women with epilepsy taking valproate monotherapy, 45% developed menstrual irregularities, 60% had polycystic ovaries, and 30% had elevated testosterone levels 1
In a cross-sectional study of 65 women with epilepsy, 64% (14 of 22 patients) taking valproate monotherapy developed polycystic ovaries or hyperandrogenism 1
Valproate-induced PCOS features were found in 40% of patients receiving valproate as part of polytherapy versus 13% in patients not treated with valproate 1
The FDA drug label for valproate explicitly states: "There have been rare spontaneous reports of polycystic ovary disease" 3
Mechanisms of Valproate-Induced PCOS
Weight gain induced by valproate reduces insulin sensitivity and promotes PCOS development in predisposed women who have no previous hormonal abnormality 1
Direct gonadal effects: Valproate alters steroidogenesis and increases testosterone to estradiol ratios in ovarian follicles (demonstrated in animal models) 1
Metabolic effects: Valproate causes hyperinsulinism and low serum levels of insulin-like growth factor binding protein 1, which can lead to hyperandrogenism and polycystic ovaries 1
Hormonal disturbances occur in both obese and lean women treated with valproate, suggesting mechanisms beyond weight gain alone 1
Reversibility of Valproate-Induced PCOS
Discontinuation of valproate led to reversal of hyperinsulinemia, hyperandrogenism, dyslipidemia, and polycystic ovaries in 12 women followed prospectively for one year 1
This reversibility confirms the causal relationship and distinguishes medication-induced secondary PCOS from primary PCOS 1
Other Medications Associated with Weight Gain and Potential PCOS Risk
Carbamazepine, vigabatrin, and gabapentin have been associated with weight gain, which theoretically could trigger PCOS manifestation in predisposed women 1
However, the evidence linking these medications directly to PCOS is less robust than for valproate 1
Two cross-sectional studies (93 and 43 patients) failed to confirm an association between menstrual disturbance and specific antiepileptic drugs other than valproate 1
Clinical Implications and Recommendations
When to Suspect Medication-Induced PCOS
New onset of menstrual irregularities, hirsutism, or weight gain after starting valproate or other weight-promoting antiepileptic drugs 1
Development of PCOS features in women with epilepsy, particularly those on valproate monotherapy 1
Presence of polycystic ovaries on ultrasound with elevated androgens in women taking valproate 1
Management Approach
Consider switching from valproate to alternative antiepileptic medications if PCOS features develop, though this carries seizure relapse risk 1
Monitor for reversal of PCOS features after valproate discontinuation over 6-12 months 1
Implement standard PCOS management strategies (lifestyle modification, metformin, oral contraceptives) while addressing the medication trigger 1
Important Caveats
Not all women on valproate develop PCOS, suggesting genetic predisposition plays a role 1
The decision to switch antiepileptic medications must balance PCOS risks against seizure control, requiring collaboration with neurology 1
Some studies showed geographic variation in valproate-related endocrine effects, with higher rates in Finland and Norway compared to the Netherlands, suggesting population-specific susceptibility 1