Magnitude of daily energy deficit predicts frequency but not severity of menstrual disturbances associated with exercise and caloric restriction

Abstract

Williams NI, Leidy HJ, Hill BR, Lieberman JL, Legro RS, De Souza MJ. Magnitude of daily energy deficit predicts frequency but not severity of menstrual disturbances associated with exercise and caloric restriction. Am J Physiol Endocrinol Metab 308: E29 -E39, 2015. First published October 28, 2014; doi:10.1152/ajpendo.00386.2013.-We assessed the impact of energy deficiency on menstrual function using controlled feeding and supervised exercise over four menstrual cycles (1 baseline and 3 intervention cycles) in untrained, eumenorrheic women aged 18 -30 yr. Subjects were randomized to either an exercising control (EXCON) or one of three exercising energy deficit (ED) groups, i.e., mild (ED1; Ϫ8 Ϯ 2%), moderate (ED2; Ϫ22 Ϯ 3%), or severe (ED3; Ϫ42 Ϯ 3%). Menstrual cycle length and changes in urinary concentrations of estrone-1-glucuronide, pregnanediol glucuronide, and midcycle luteinizing hormone were assessed. Thirty-four subjects completed the study. Weight loss occurred in ED1 (Ϫ3.8 Ϯ 0.2 kg), ED2 (Ϫ2.8 Ϯ 0.6 kg), and ED3 (Ϫ2.6 Ϯ 1.1 kg) but was minimal in EXCON (Ϫ0.9 Ϯ 0.7 kg). The overall sum of disturbances (luteal phase defects, anovulation, and oligomenorrhea) was greater in ED2 compared with EXCON and greater in ED3 compared with EXCON AND ED1. The average percent energy deficit was the main predictor of the frequency of menstrual disturbances (f ϭ 10.1, ␤ ϭ Ϫ0.48, r 2 ϭ 0.23, P ϭ 0.003) even when weight loss was included in the model. The estimates of the magnitude of energy deficiency associated with menstrual disturbances ranged from Ϫ22 (ED2) to Ϫ42% (ED3), reflecting an energy deficit of Ϫ470 to Ϫ810 kcal/day, respectively. This is the first study to demonstrate a dose-response relationship between the magnitude of energy deficiency and the frequency of exercise-related menstrual disturbances; however, the severity of menstrual disturbances was not dependent on the magnitude of energy deficiency. energy balance; menstrual cycle disturbances; luteal phase; amenorrhea; oligomenorrhea MENSTRUAL IRREGULARITIES in physically active women and female athletes are observed frequently. Commonly reported irregularities and corresponding prevalence rates include luteal phase defects (29%), anovulation (20%), oligomenorrhea (7%), and amenorrhea (37%) (12). A large body of evidence in a variety of mammalian species has demonstrated a causal link between chronic energy deficiency and the suppression of reproductive function involving the central inhibition of gonadotropin-releasing hormone (GnRH) pulsatility (34). In humans, long-term energy deficiency can result in functional hypothalamic amenorrhea (FHA) and therefore decrease estrogen exposure, diminishing estrogen's impact on bone, reproductive, and cardiovascular regulation, often resulting in osteopenia (29, 34), stress fractures (1, 3, 5), transient infertility, dyslipidemia, and impaired endothelial function (14,15,26). Prospective studies support a causal role of low energy availability on the suppression of reproductive function that commonly occurs in p...

Less-than-expected weight loss in normal-weight women undergoing caloric restriction and exercise is accompanied by preservation of fat-free mass and metabolic adaptations

“…The study was originally designed to assess the impact of energy deficiency on reproductive function and was conducted over the course of three academic years. 20 Because primary outcome measures were related to reproductive function, the study duration was adjusted to each participants' menstrual cycle. Following a baseline cycle (~28 days), participants were randomly assigned to experimental groups for three menstrual cycles (~3 months).…”

“…Screening included medical and menstrual histories, assessment of eating attitudes and behavior, a complete blood count, basic chemistry and endocrine panels, an interview to assess the risk of eating and other psychiatric disorders, and verification of menstrual status via calendars and confirmation of ovulation. 20 …”

“…Baseline caloric intake matched baseline energy expenditure, calculated as baseline RMR adjusted for physical activity measured during the first week of baseline using accelerometry (RT3, Stayhealthy, Monrovia, CA, USA). 20,27 Minor adjustments in caloric intake (±100 kcal) were made if fasting body weight changed by 40.5 kg during the first week. 28,29 Intervention Following completion of baseline, food intake was adjusted per group assignment and participants conducted supervised exercise on 5 days per week.…”

“…Significance was considered for P<0.05 and was Bonferroniadjusted for multiple comparisons. On the basis of previously published data, 20 group sizes of n = 7 were required to detect a 0.5 kg difference in weight loss among study groups (P<0.05) with 80% power. Data from all study groups were combined to identify predictors of weight loss.…”

“…For this purpose, we retrospectively analyzed data from a randomized controlled trial that assessed the impact of caloric restriction and exercise on reproductive function. 20 Primary outcomes included body weight, body composition, RMR and metabolic hormones linked to energy conservation and future weight regain, including leptin, 16,21,22 ghrelin, 21,23 triiodothyronine (T3) 24,25 and insulin-like growth factor-1 (IGF-1). 26 We hypothesized that 3 months of caloric restriction combined with exercise would result in significant weight loss, but that exercise would preserve lean mass and promote loss of fat mass such that actual weight loss would be less than predicted.…”