Menstrual Cycle Recovery in Patients with Anorexia Nervosa: The Importance of Insulin-Like Growth Factor 1

Cominato, Louise; Silva, Mariana Moraes Xavier da; Steinmetz, Leandra; Pinzon, Vanessa; Fleitlich-Bilyk, Bacy; Damiani, Durval

doi:10.1159/000367895

Cited by 10 publications

(4 citation statements)

References 16 publications

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“…Estrogen: The association between estrogens and female weight has been previously reported (Leeners et al 2017). An increase in estradiol levels resulting from follicular maturation and conversion of androgens to estrogens in fat tissue (associated with weight gain) is confirmed in all of the studies investigating hormonal levels in resumption of menses (Arimura et al 2010;Audi et al 1998;Barakat et al 2016;Cominato et al 2014;Holtkamp et al 2003;Jacoangeli et al 2006;Karountzos et al 2017;Pitts et al 2014;Tokatly Latzer et al 2019). Estrogen increases GnRH receptor gene expression and enhances the ability of FSH to induce expression of LH receptors and promote follicular growth (Turzillo, Nolan, and Nett 1998;Richards et al 1976).…”

Section: Medicationmentioning

confidence: 86%

“…Similarly, levels of growth hormone and insulin-growth factor-1 (IGF1) are reduced in FHA (Bomba et al 2007;Miller et al 2004). An IGF-1 level of >342.8 ng/ml has been proposed to be a predictor for return of menses (Cominato et al 2014), although two other studies have found no positive correlation (Falsetti et al 2002;Arimura et al 2010).…”

Section: Body Weight and Energy Availabilitymentioning

confidence: 99%

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Recovery of menses after functional hypothalamic amenorrhoea: if, when and why

Pape

Herbison

Leeners

2020

Human Reproduction Update

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BACKGROUND Prolonged amenorrhoea occurs as a consequence of functional hypothalamic amenorrhoea (FHA) which is most often induced by weight loss, vigorous exercise or emotional stress. Unfortunately, removal of these triggers does not always result in the return of menses. The prevalence and conditions underlying the timing of return of menses vary strongly and some women report amenorrhoea several years after having achieved and maintained normal weight and/or energy balance. A better understanding of these factors would also allow improved counselling in the context of infertility. Although BMI, percentage body fat and hormonal parameters are known to be involved in the initiation of the menstrual cycle, their role in the physiology of return of menses is currently poorly understood. We summarise here the current knowledge on the epidemiology and physiology of return of menses. OBJECTIVE AND RATIONALE The aim of this review was to provide an overview of (i) factors determining the recovery of menses and its timing, (ii) how such factors may exert their physiological effects and (iii) whether there are useful therapeutic options to induce recovery. SEARCH METHODS We searched articles published in English, French or German language containing keywords related to return of menses after FHA published in PubMed between 1966 and February 2020. Manuscripts reporting data on either the epidemiology or the physiology of recovery of menses were included and bibliographies were reviewed for further relevant literature. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) criteria served to assess quality of observational studies. OUTCOMES Few studies investigate return of menses and most of them have serious qualitative and methodological limitations. These include (i) the lack of precise definitions for FHA or resumption of menses, (ii) the use of short observation periods with unsatisfactory descriptions and (iii) the inclusion of poorly characterised small study groups. The comparison of studies is further hampered by very inhomogeneous study designs. Consequently, the exact prevalence of resumption of menses after FHA is unknown. Also, the timepoint of return of menses varies strongly and reliable prediction models are lacking. While weight, body fat and energy availability are associated with the return of menses, psychological factors also have a strong impact on the menstrual cycle and on behaviour known to increase the risk of FHA. Drug therapies with metreleptin or naltrexone might represent further opportunities to increase the chances of return of menses, but these require further evaluation. WIDER IMPLICATIONS Although knowledge on the physiology of return of menses is presently rudimentary, the available data indicate the importance of BMI/weight (gain), energy balance and mental health. The physiological processes and genetics underlying the impact of these factors on the return of menses require further research. Larger prospective studies are necessary to identify clinical parameters for accurate prediction of return of menses as well as reliable therapeutic options.

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Section: Medicationmentioning

confidence: 86%

Section: Body Weight and Energy Availabilitymentioning

confidence: 99%

Recovery of menses after functional hypothalamic amenorrhoea: if, when and why

Pape

Herbison

Leeners

2020

Human Reproduction Update

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“…Although self‐reported weight and menstrual status history in adolescent ED populations are highly accurate (Swenne, Belfrage, Thurfjell, & Engström, ), this accuracy has not been established in adults. Further, menstrual function is one marker of physiological health, but we did not assess other physiological variables (e.g., hormones, body fat percentage) that are associated with menses resumption (Arimura et al, ; Cominato et al, ; El Ghoch, Calugi, Chignola, Bazzani, & Grave, ; Pitts, Blood, Divasta, & Gordon, ) and may be helpful indicators of remission. Menses resumption also does not necessarily correspond with stable menstrual recovery.…”

Section: Discussionmentioning

confidence: 99%

Menstrual cycle loss and resumption among patients with anorexia nervosa spectrum eating disorders: Is relative or absolute weight more influential?

Berner

Feig

Witt

et al. 2017

Intl J Eating Disorders

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These findings add to the literature indicating that relative and absolute weight status are dual indicators of illness severity in AN, and preliminarily suggest that a large proportion of adults who present for treatment initially may have shown symptoms of starvation at a normal BMI. Results underscore the need to focus on weight loss in early detection efforts and may inform target weight setting in the treatment of AN.

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“…Consistently, we found an inverse correlation of fT3 with the amount of weight loss and a positive correlation between fT3 and leptin levels, as previously described [ 36 ]. But in addition, here we observed a highly significant positive correlation between fT3 and estradiol, with fT3 levels tending to an earlier normalization before resumption of menses and rise of circulating estradiol in Group 0, thus indicating fT3 rise as an early marker of the resumption of hypothalamic activity.This adds to the evidence already available for IGF1 [ 37 ] as opposed to cortisol levels which are reported to be a predictor of hypothalamic inhibition [ 38 ]. Still, the usefulness of fT3 levels in this setting should always be put in context of clinical parameters.…”

Section: Discussionmentioning

confidence: 69%

Body weight variation is not an independent factor in the determination of functional hypothalamic amenorrhea in anorexia nervosa

Cacciatore,

Cangiano,

Carbone

et al. 2023

J Endocrinol Invest

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Objective Functional hypothalamic amenorrhea (FHA) is one of the foremost manifestations in anorexia nervosa (AN), but a subset of patients have menses despite marked weight loss and underweight. The aim of our study was to investigate parameters potentially influencing FHA in AN. Design and methods In this observational retrospective study, we selected 114 female patients with AN who completed a 12 months semi-residential rehabilitation program and a subsequent 12 months outpatient follow-up. We divided our sample into three groups: “Group 0” patients who experienced FHA and recovered their menses, “Group 1” persistent FHA, “Group 2” never experienced FHA, and looked for clinical and hormonal correlations. Results At the enrollment, the BMI was higher in Group 2 than in Group 1 (p = 0.0202), but the last follow-up weight was higher in Group 1 (p < 0.0001) despite persistent amenorrhea. At logistic regression, the higher BMI at which patients experienced amenorrhea was the main prediction factor for persistent FHA. Notwithstanding comparable leptin levels at admission, they improved significantly at discharge only in Groups 0 and 2 (p = 0.0054 and p = 0.0104, respectively). FT3 at admission was significantly higher in Group 2 than in Group 0 (p = 0.0249). Conclusions FHA does not correlate strictly with body weight variations in AN patients, indicating a multifactorial origin, likely including an individual predisposition. Higher FT3 levels identify patients who continue having menses at extremely low BMI. AN patients with persistent FHA constitute a subgroup in whom estroprogestins should be considered after significant weight recovery to prevent prolonged tissue hypoestrogenism.

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Menstrual Cycle Recovery in Patients with Anorexia Nervosa: The Importance of Insulin-Like Growth Factor 1

Cited by 10 publications

References 16 publications

Recovery of menses after functional hypothalamic amenorrhoea: if, when and why

Recovery of menses after functional hypothalamic amenorrhoea: if, when and why

Menstrual cycle loss and resumption among patients with anorexia nervosa spectrum eating disorders: Is relative or absolute weight more influential?

Body weight variation is not an independent factor in the determination of functional hypothalamic amenorrhea in anorexia nervosa

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