Neuroendocrine Aberrations in Women With Functional Hypothalamic Amenorrhea*

Abstract

To further elucidate the neuroendocrine regulation of anterior pituitary function in women with functional hypothalamic amenorrhea (FHA), we measured serum LH, FSH, cortisol, GH, PRL, TSH concentrations simultaneously at frequent intervals for 24 h in 10 women with FHA and in 10 normal women in the early follicular phase (NC). Using the same data, we separately analyzed the cortisol-PRL responses to meals in these women. In addition, the pituitary responses to the simultaneous administration of GnRH, CRH, GHRH, and TRH were assessed in 6 FHA and 6 normal women. The 24-h secretory pattern of each hormone except TSH was altered in the women with FHA. Compared to normal women, the women with FHA had a 53% reduction in LH pulse frequency (P < 0.0001) and an increase in the mean LH interpulse interval (P < 0.01); LH pulse amplitude was similar. The 24-h integrated LH and fSH concentrations were reduced 30% (P = 0.01) and 19% (P < 0.05), respectively. The mean cortisol pulse frequency, amplitude, interpulse interval, and duration were similar in the two groups, but integrated 24-h cortisol secretion was 17% higher in the women with FHA (P < 0.05). This increase was greatest from 0800-1600 h, but also was present from 2400-0800 h. Cortisol levels were similar in the two groups from 1600-2400 h, resulting in an amplified circadian excursion. In contrast, the 24-h serum PRL levels were markedly lower at all times (P < 0.0001), the sleep-associated nocturnal elevation of PRL was proportionately greater (P < 0.05), and serum GH levels were increased at night in the women with FHA (P < 0.05). Although 24-h serum TSH levels were similar at all times, T3 (P < 0.05) and T4 (P < 0.01) levels were lower in the FHA women. The responses of serum cortisol to lunch (P < 0.01) and dinner (P < 0.05) and those of serum PRL to lunch (P < 0.05) and dinner (P = 0.08) were blunted in the women with FHA. Pituitary hormone increments in response to the simultaneous iv administration of GnRH, CRH, GHRH, and TRH were similar in the two groups, except for a blunted PRL response to TRH in the women with FHA (P < 0.05). The findings of altered pituitary hormone secretion and impaired hormonal responses to meals together with the preservation of pituitary responsivity to releasing hormone collectively suggest that central neuroregulation of the secretion of multiple pituitary hormones is disturbed in women with FHA. Secretion of reproduction hormone (LH, FSH, and PRL) and TSH, as suggested by the lower serum T4 and T3 values, is suppressed, while that of cortisol and GH is increased.