Long-term administration of pulsatile gonadotropin-releasing hormone for exploration of pituitary functionality in amenorrheic patients.

Differentiation between hypothalamic and pituitary amenorrhea is generally based on the luteinizing hormone-releasing hormone (LHRH) test (whether as a single dose, two consecutive doses, or pulsatile over 5-10 days), together with high-resolution imaging (computed tomography or magnetic resonance) of the sellar region. Long-term administration of gonadotropin-releasing hormone (GnRH) is generally used only for ovulation induction, and not for diagnostic purposes. Here, we report the results of long-term administration of GnRH to 19 women initially diagnosed as suffering from hypothalamic amenorrhea on the basis of LHRH testing and computed tomography imaging. During treatment, subjects received 20-micrograms pulses of GnRH every 90 min, subcutaneously from a portable infusion pump. Fourteen subjects responded (i.e. ovulated) during the first treatment cycle; one subject menstruated but did not ovulate during the first cycle, and the dropped out of the study; the remaining four subjects did not ovulate or menstruate despite at least three treatment cycles. Magnetic resonance imaging of the sellar region of these four subjects revealed pituitary lesions (partially empty sella in three cases, microadenoma in one case) which had not been detected by computed tomography. By contrast, no such abnormalities were detected in the nine responders who agreed to undergo magnetic resonance imaging. These findings suggest that long-term administration of GnRH is of value not only for ovulation induction but also for diagnostic purposes. Specifically, an initial diagnosis of hypothalamic amenorrhea is confirmed if there is a positive ovulation response after two GnRH treatment cycles; otherwise, pituitary amenorrhea should be suspected. Our results also suggest that magnetic resonance imaging is more effective than computed tomography for the detection of partially empty sella.