Neuroendocrine Aberrations in Women With Functional Hypothalamic Amenorrhea*

Department of Reproductive Medicine, School of Medicine, University of California-San Diego, La Jolla 92093.
Journal of Clinical Endocrinology & Metabolism (Impact Factor: 6.21). 03/1989; 68(2):301-8. DOI: 10.1210/jcem-68-2-301
Source: PubMed


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 less than 0.0001) and an increase in the mean LH interpulse interval (P less than 0.01); LH pulse amplitude was similar. The 24-h integrated LH and FSH concentrations were reduced 30% (P = 0.01) and 19% (P less than 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 less than 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 less than 0.0001), the sleep-associated nocturnal elevation of PRL was proportionately greater (P less than 0.05), and serum GH levels were increased at night in the women with FHA (P less than 0.05). Although 24-h serum TSH levels were similar at all times, T3 (P less than 0.05) and T4 (P less than 0.01) levels were lower in the FHA women. The responses of serum cortisol to lunch (P less than 0.01) and dinner (P less than 0.05) and those of serum PRL to lunch (P less than 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 less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

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    • "FHA is caused by an alteration in gonadotropin-releasing hormone pulsatility,48 which in turn causes a disruption of luteinizing hormone pulses from the pituitary and gonadal steroid release from the ovaries.86 It reflects a state of estrogen deficiency, which may be one of the causes of decreased BMD.85 FHA may also be associated with several physiological changes, including overactivity of the hypothalamic-pituitary-adrenal axis (causing an increase in cortisol release) and disturbances of the hypothalamic-pituitary-thyroid axis (resulting in a “sick euthyroid” pattern).21 Leptin, a cytokine expressed by adipose tissue and strongly associated with fat mass, is lower in the amenorrheic athlete, most likely due to changes in body composition, particularly a decrease in fat mass.28 "
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    • "(2) The precocious atherosclerosis that characterizes subordinate females likely results from a subclinical stress-induced, reversible ovarian impairment that resembles functional hypothalamic amenorrhea/anovulation (FHA) observed in women [165,166]. This hypothesis is supported by the observation that ovariectomy eliminates the protection of dominant females, rendering them equivalent to subordinate females and males in atherosclerosis extent [165,167]. "
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    • "In conclusion, the current findings corroborate our previous account of diminished serotonin response to citalopram, inferred from changes in prolactin, in gonadally intact s-variant females (Hoffman, et al., 2007) and extend these data by showing that this effect of 5HTTLPR is most evident when both ovarian steroid hormones, estradiol and progesterone, are restored to follicular and luteal phase concentrations, respectively. Importantly, these data suggest that clinicians should be aware of ovarian status in patients being considered for treatment with serotoninergic agents, as the hypogonadism associated with chronic psychosocial stressors in women (Berga et al., 1989) might decrease responsiveness to SSRI treatment. It is also possible that accounting for hormones in pre-, peri-, and postmenopausal women could explain some of the variability surrounding the efficacy of SSRIs in responders and non-responders to pharmacotherapy in women. "
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