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Neuroendocrine Aberrations in Women With Functional Hypothalamic Amenorrhea^*

S. L. BERGA, J. F. MORTOLA, L. GIRTON, B. SUH, G. LAUGHLIN, P. PHAM and S. S. C. YEN^|

Department of Reproductive Medicine, School of Medicine (T-002), and the General Clinical Research Center, University of California-San Diego La Jolla, California 92093

Address all correspondence and requests for reprints to: Dr. Samuel Yen, Department of Reproductive Medicine, University of California School of Medicine (T-002), La Jolla, California 92093.

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 hormones collectively suggest that central neuroregulation of the secretion of multiple pituitary hormones is disturbed in women with FHA. Secretion of reproductive hormones (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.

^* This work was supported by NIH Grants HD-21198 and HD-12303 and GCRC Grant RR-00827 and was conducted by the Clayton Foundation for Research. Presented in part at the 34th Annual Meeting of the Society for Gynecological Investigation, Atlanta, GA, 1987.

Recipient of the Bank of America-Giannini Foundation Fellowship and the American Fertility Society-Ortho Distinguished Fellowship in Reproduction, and a Clinical Associate Physician of the NIH (GCRC). Current address: University of Pittsburgh School of Medicine, Magee-Womens Hospital, Pittsburgh, Pennsylvania 15213.

Andrew Mellon Foundation Faculty Scholar.

Former Fellow in Reproductive Medicine. Current address: Obstetrics and Gynecology Department, Reproductive Endocrinology, University of Colorado Health Sciences Center, Denver, Colorado 80220.

^| Clayton Foundation Investigator.

Received July 18, 1988.

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