Abnormal Cortisol Secretion and Responses to Corticotropin-Releasing Hormone in Women with Hypothalamic Amenorrhea*

Biller, Beverly M. K.; Federoff, Howard J.; Koenig, James I.; Klibanski, Anne

doi:10.1210/jcem-70-2-311

Cited by 168 publications

(57 citation statements)

References 52 publications

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“…There is evidence for both mechanisms. For example, both metabolic and psychosocial stresses can activate the hypothalamic-pituitary-adrenal (HPA) axis (7,36), and the HPA axis activation has been associated with impaired Move ϩ Exercise ϩ Diet (P ϭ 0.002). §ANOVA significant time effect; F(1,23) ϭ 7.03, P ϭ 0.014.…”

Section: Discussionmentioning

confidence: 99%

Synergism between psychosocial and metabolic stressors: impact on reproductive function in cynomolgus monkeys

Williams¹,

Berga²,

Cameron³

2007

American Journal of Physiology-Endocrinology and Metabolism

143

111

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Williams NI, Berga SL, Cameron JL. Synergism between psychosocial and metabolic stressors: impact on reproductive function in cynomolgus monkeys. Am J Physiol Endocrinol Metab 293: E270-E276, 2007. First published April 3, 2007; doi:10.1152/ajpendo.00108.2007.-The role of energy imbalance versus psychosocial stress in the pathogenesis of female reproductive dysfunction characterized by anovulation and amenorrhea remains controversial. In women, functional hypothalamic amenorrhea can develop in the absence of significant weight loss, excessive exercise, or profound psychosocial disruption. We posited, therefore, that commonplace, seemingly minor stressors that alone would have minimal impact upon reproductive function might interact synergistically such that combinations of stressors would cause a greater impairment of the reproductive axis than any single stressor alone. We then developed a monkey model to test this hypothesis. Adult female cynomolgus monkeys with normal menstrual cycles were randomized into three experimental groups and studied over four menstrual cycles. The groups were: low-level psychosocial stress (i.e., moving to a new housing environment; Move, n ϭ 8), moderate energy imbalance (Exercise ϩ Diet, n ϭ 9); and all stressors in combination (Move ϩ Exercise ϩ Diet, n ϭ 10). Food intake, body weight, menstrual cyclicity, and reproductive hormones were assessed for two control menstrual cycles followed by two experimental cycles during which the monkeys experienced the stressors. Abnormal cycles were considered to be abnormally long or anovulatory cycles. Few abnormal cycles occurred in the Move group (1 of 8 monkeys) and in the Exercise ϩ Diet group (1 of 9 monkeys). In contrast, 7 of 10 monkeys in the Move ϩ Exercise ϩ Diet group displayed at least one abnormal cycle ( 2 ϭ 9.61, P ϭ 0.008). These findings suggest that infertility due to hypothalamic hypogonadism can result from the combination of commonplace, seemingly minor stressors that often escape clinical attention. exercise; diet; psychosocial stress; reproduction CLINICALLY RECOGNIZED FORMS of stress-induced reproductive dysfunction include functional hypothalamic amenorrhea (FHA), anorexia nervosa, bulimia nervosa, and exercise-associated amenorrhea. The proximate cause of these forms of reproductive compromise is a functional and theoretically reversible reduction in central drive to the reproductive axis provided by the hypothalamic neuroendocrine hormone gonadotropin-releasing hormone (GnRH). The presence of clinical forms of stress-induced reproductive dysfunction heightens the risk for other diseases, including cardiovascular disease, osteoporosis, depression, and other psychiatric conditions as well as infertility (1,15,20,28). Stress exposure during pregnancy can also have a negative impact on fetal development. Potential fetal consequences include preterm labor, poor neurodevelopment, and compromised psychosocial development (26, 31, 35).Although it was previously believed that different forms of stress-induced reproductive dy...

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Section: Discussionmentioning

confidence: 99%

Synergism between psychosocial and metabolic stressors: impact on reproductive function in cynomolgus monkeys

Williams¹,

Berga²,

Cameron³

2007

American Journal of Physiology-Endocrinology and Metabolism

143

111

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“…AN is associated with hypercortisolemia in adults (27) and adolescents (4), and it is tempting to postulate that hypercortisolemia may contribute to hypogonadotropic hypogonadism associated with AN. However, in this study, baseline serum cortisol was higher in AN girls who recovered menses compared with the group that did not recover menses and controls, and UFC/cr·m 2 was higher in AN recovering menses versus controls.…”

Section: Discussionmentioning

confidence: 99%

Role of Cortisol in Menstrual Recovery in Adolescent Girls with Anorexia Nervosa

et al. 2006

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Neuroendocrine abnormalities in anorexia nervosa (AN) include hypercortisolemia, hypogonadism, and hypoleptinemia, and neuroendocrine predictors of menstrual recovery are unclear. Preliminary data suggest that increases in fat mass may better predict menstrual recovery than leptin. High doses of cortisol decrease luteinizing hormone (LH) pulse frequency, and cortisol predicts regional fat distribution. We hypothesized that an increase in fat mass and decrease in cortisol would predict menstrual recovery in adolescents with AN. Thirty-three AN girls 12-18 y old and 33 controls were studied prospectively for 1 y. Body composition [dual energy x-ray absorptiometry (DXA)], leptin, and urinary cortisol (UFC) were measured at 0, 6, and 12 mo. Serum cortisol was measured overnight (every 30 min) in 18 AN subjects and 17 controls. AN subjects had higher UFC/cr·m 2 and cortisol area under curve (AUC), and lower leptin levels than controls. Leptin increased significantly with recovery. When menses-recovered AN subjects were compared with AN subjects not recovering menses and controls, menses-recovered AN subjects had higher baseline cortisol levels and greater increases in leptin than controls and greater increases in fat mass than AN subjects not recovering menses and controls (adjusted for multiple comparisons). In a logistic regression model, increasing fat mass, but not leptin, predicted menstrual recovery. Baseline cortisol level strongly predicted increases in the percentage of body fat. We demonstrate that 1) high baseline cortisol level predicts increases in body fat and 2) increases in body fat predict menses recovery in AN. (Pediatr Res 59: [598][599][600][601][602][603] 2006) A N, a model of severe undernutrition, is associated with hypogonadotropic hypogonadism resulting in primary or secondary amenorrhea or delayed menarche. Weight recovery occurs in up to 50% of adolescents with AN and should result in recovery of the hypothalamo-pituitary-gonadal (H-P-G) axis (1). However, a temporal association between weight gain and menstrual recovery is not always observed (2,3). Not all adolescents with AN who resume menses are weight recovered, and not all weight-recovered adolescents with AN resume menstrual function. In addition, neuroendocrine predictors of menstrual recovery are unclear.We have demonstrated higher cortisol (4) and lower leptin levels (3,5) in AN girls compared with healthy adolescents.Leptin is an adipocytokine, and leptin-deficient or -resistant mice (6,7) and humans with leptin and leptin receptor mutations (8,9) are hypogonadal. In a recent study, leptin administration was associated with resumption of menses in five of eight women with hypothalamic amenorrhea (10). These data suggest that leptin is an important regulator of the H-P-G axis and that an increase in leptin along with an increase in fat mass may predict recovery of the H-P-G axis in AN. Conversely, Golden et al. (11) observed no differences in fat mass between AN girls who recovered menses and those who did not.In add...

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“…Other biological studies have linked functional hypothalamic amenorrhea to deficiencies in pulsatile gonadotropin releasing hormone (GnRH) secretion, 13 estrogen, 14 leptin, 15,16 insulin-like growth factor-1 (IGF-1) 17 and prolactin levels as well as increased secretion of cortisol, ACTH, CRH 18,19 and endogenous opioids 20 or nocturnal melatonin secretion. 21 It has also been hypothesized that amenorrhea is related to neurotransmitter abnormalities such as increased dopamine activity.…”

Section: Potential Biological Differences Signified By Amenorrheamentioning

confidence: 99%

Should amenorrhea be a diagnostic criterion for anorexia nervosa?

Attia

Roberto

2009

Intl J Eating Disorders

149

102

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Objective: The removal of the amenorrhea criterion for anorexia nervosa (AN) is being considered for the fifth edition of The Diagnostic and Statistical Manual (DSM-V). This article presents and discusses the arguments for maintaining as well as those for removing the criterion. Method:The psychological and biological literatures on the utility of amenorrhea as a distinguishing diagnostic criterion for AN and as an indicator of illness severity are reviewed.Results: The findings suggest that the majority of differences among patients with AN who do and do not meet the amenorrhea criterion appear largely to reflect nutritional status. Overall, the two groups have few psychological differences. There are mixed findings regarding biological differences between those with AN who do and do not menstruate and the relationship between amenorrhea and bone health among patients with AN.Discussion: Based on these findings, one option is to describe amenorrhea in DSM-V as a frequent occurrence among individuals with AN that may provide important information about clinical severity, but should not be maintained as a core diagnostic feature. The possibilities of retaining the criterion or eliminating it altogether are discussed.

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Abnormal Cortisol Secretion and Responses to Corticotropin-Releasing Hormone in Women with Hypothalamic Amenorrhea*

Cited by 168 publications

References 52 publications

Synergism between psychosocial and metabolic stressors: impact on reproductive function in cynomolgus monkeys

Synergism between psychosocial and metabolic stressors: impact on reproductive function in cynomolgus monkeys

Role of Cortisol in Menstrual Recovery in Adolescent Girls with Anorexia Nervosa

Should amenorrhea be a diagnostic criterion for anorexia nervosa?

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