Supplementary Material for: Interpretation of Serum Gonadotropin Levels in Hyperprolactinaemia

<b><i>Background/Aims:</i></b> Hyperprolactinaemia is a common cause of amenorrhoea due to hypogonadotropic hypogonadism. Prolactin is hypothesised to impede the reproductive axis through an inhibitory action at the hypothalamus. However, limited data exist to aid the interpretation of serum gonadotropins in the context of hyperprolactinaemia. <b><i>Methods:</i></b> Serum gonadotropin values were reviewed in 243 patients with elevated serum monomeric prolactin due to discrete aetiologies at a tertiary reproductive endocrine centre between 2012 and 2015. The cause of hyperprolactinaemia was categorised by an experienced endocrinologist/pituitary multidisciplinary team, unless superseded by histology. The most frequently encountered diagnoses were microprolactinoma (<i>n</i> = 88), macroprolactinoma (<i>n</i> = 46), non-functioning pituitary adenoma (NFPA) (<i>n</i> = 72), drug-induced hyperprolactinaemia (<i>n</i> = 22) and polycystic ovarian syndrome (PCOS) (<i>n</i> = 15). <b><i>Results:</i></b> In patients with prolactinoma and modestly raised serum prolactin levels (< 4,000 mU/L), increasingly FSH-predominant gonadotropin values were observed with rising prolactin level, consistent with a progressive reduction in hypothalamic gonadotropin-releasing hormone (GnRH) pulsatility. Patients with prolactinoma and higher prolactin values (> 4,000 mU/L) were more likely to have a reduction in serum levels of both FSH and LH, consistent with direct pituitary gonadotrope dysfunction. Patients with macroadenoma and extremes of serum gonadotropin values (either serum FSH or LH > 8 IU/L) were more likely to have NFPA than prolactinoma. Patients with PCOS and hyperprolactinaemia had LH-predominant secretion in keeping with increased GnRH pulsatility despite a raised prolactin level. <b><i>Conclusion:</i></b> The pattern of gonadotropin secretion in patients with hyperprolactinaemia reflects the underlying aetiology.

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