Differentiating hormone-induced mania from bipolar disorder: a 13-year longitudinal case after in vitro fertilization treatment

Background

Hormonal treatments used in assisted reproductive technologies can influence central neurotransmitter systems and affect mood regulation [2,3]. While mild mood changes during these treatments are relatively common, the occurrence of a first manic episode with psychotic features is rare and presents a diagnostic challenge. In such cases, it may be difficult to determine whether the episode reflects a medication-related effect or the initial manifestation of bipolar disorder, as defined in current diagnostic classifications [1]. This distinction is clinically important, as it directly influences long-term management decisions, particularly regarding the continuation of mood stabilizer treatment.

Previous reports have described mood symptoms associated with hormonal interventions, but long-term follow-up data remain limited [4]. Longitudinal observations extending over many years are still scarce. This issue remains clinically relevant in everyday psychiatric practice, particularly in patients exposed to hormonal treatments.

Methods

We describe the clinical course of a woman who developed a first manic episode with psychotic features during in vitro fertilization treatment. Clinical data were obtained from psychiatric assessments, medical records, and continuous outpatient follow-up over a 13-year period.

Symptom onset, clinical features, treatment interventions, medication adherence, and functional outcome were reviewed. Particular attention was given to the temporal relationship between hormonal treatment and symptom emergence, as well as to the presence or absence of subsequent mood episodes during long-term follow-up.

Results

A 48-year-old woman with no prior psychiatric or family history presented with acute onset of manic symptoms shortly after initiation of hormonal treatment. The episode was preceded by a depressive period during the treatment process.

Clinical features included reduced need for sleep, increased psychomotor activity, elevated mood, grandiosity, paranoid delusions, and auditory hallucinations. The patient improved with olanzapine and valproic acid. Antipsychotic treatment was discontinued, and valproic acid was maintained as monotherapy, with serum levels consistently around 70 µg/mL.

During 13 years of follow-up, the patient remained clinically stable, with no recurrence of manic, hypomanic, or depressive episodes. She maintained good occupational functioning, preserved insight, and adherence to treatment, despite exposure to psychosocial stressors.

The close temporal association with hormonal treatment and absence of recurrence support a medication-related mechanism. However, the presence of depressive symptoms prior to onset, severity of the episode, and sustained stability under mood stabilizer treatment suggest a possible underlying bipolar vulnerability.

Conclusions

Even after long-term follow-up, distinguishing hormone-related mania from the first presentation of bipolar disorder may remain challenging. Both triggering factors and individual vulnerability likely contribute to the clinical picture.

This distinction is relevant when considering the duration of maintenance treatment and potential risks of discontinuation. The absence of treatment discontinuation limits our ability to determine whether the episode represents a medication-induced phenomenon or an underlying bipolar disorder, which is particularly relevant in patients undergoing fertility treatment. Long-term follow-up and individualized assessment remain essential in such cases.

References

1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC: APA; 2013.
2. Seeman MV. Hormones and schizophrenia. Clin Schizophr Relat Psychoses. 2012;6(1):33–39.
3. Sherwin BB. Estrogen and cognitive functioning in women. Endocr Rev. 2003;24(2):133–151.
4. Brockington I. Reproductive psychiatry: the role of the obstetrician. BJOG. 2017;124(11):1741–1745.