Secondary amenorrhea in a woman with spinocerebellar degeneration treated with thyrotropin-releasing hormone: a case report and in vitro analysis

INTRODUCTION While thyrotropin-releasing hormone is known to be a prolactin-release stimulating factor, thyrotropin-releasing hormone-tartrate and its derivative, taltirelin hydrate, are used for the treatment of spinocerebellar degeneration, a degenerative disease characterized mainly by motor ataxia. We report the case of a patient being treated with a thyrotropin-releasing hormone preparation for spinocerebellar degeneration who developed amenorrhea after a dose increase. Her hormonal background was analyzed and the effect of prolonged exposure to thyrotropin-releasing hormone on pituitary prolactin-producing cells was examined in vitro. CASE PRESENTATION Our patient was a 36-year-old Japanese woman who experienced worsening of gait disturbance at around 23 years of age, and was subsequently diagnosed as having spinocerebellar degeneration. She had been treated with thyrotropin-releasing hormone-tartrate for four years. Taltirelin hydrate was added to the treatment seven months prior to her presentation, followed by an improvement in gait disturbance. Around the same period, she started lactating and subsequently developed amenorrhea three months later. Taltirelin hydrate was discontinued and she was referred to our hospital. She was found to have normal sex hormone levels. A thyrotropin-releasing hormone provocation test showed a normal response of thyroid-stimulating hormone level and an over-response of prolactin at 30 minutes (142.7 ng/mL). Resumption of menstruation was noted three months after dose reduction of thyrotropin-releasing hormone. In our in vitro study, following long-term exposure to thyrotropin-releasing hormone, cells from the rat pituitary prolactin-producing cell line GH3 exhibited an increased basal prolactin promoter activity but showed a marked decrease in responsiveness to thyrotropin-releasing hormone. CONCLUSIONS Physicians should be aware of hyperprolactinemia-associated side effects in patients receiving thyrotropin-releasing hormone treatment. Long-term treatment with a thyrotropin-releasing hormone preparation might cause a large amount of prolactin to accumulate in prolactin-producing cells and be released in response to exogenous thyrotropin-releasing hormone stimulation.