Energy Restriction and Hormones in Premenopausal Women
Condition: Menstruation Disturbances; Luteal Phase Defect
MeSH terms: Menstruation Disturbances
Study type: Interventional

Summary: 
      A growing body of epidemiological and biological evidence strongly suggests that physical
      activity may reduce the risk of breast cancer. Although the mechanism remains unclear,
      possible links between reduced risk and exercise include favorable alterations in body
      composition and positive changes in the hormonal milieu. One hormonal biomarker of breast
      cancer, circulating estrogen, is postulated to be reduced by chronic physical activity,
      presumably due to disruptive effects of exercise upon menstrual cyclicity, and the potential
      for loss of body fat with subsequent reductions in the peripheral biosynthesis of circulating
      estrogens. Although studies have shown that chronic exercise can reduce circulating estrogen,
      we know little about the magnitude and duration of exposure to an energy deficit required for
      these changes. Additionally, no studies have addressed the degree to which peripheral
      production of estrone, versus the ovarian production of estradiol, is altered with exercise
      that promotes weight/fat loss. A second biomarker of breast cancer, insulin-like growth
      factor-1 (IGF-1), is presumably increased with exercise but reduced with exercise if energy
      balance is negative. No prospective studies have addressed whether a moderate aerobic
      exercise program that results in weight loss will lead to significant changes in IGF-I
      levels, particularly in individuals of differing initial energy stores.

      Metabolic energy availability is an important contributing factor in the development of
      reproductive cancers. However, current methods for assessing energy availability, which
      include anthropometric measures, calculations of energy balance, evaluation of various serum
      and urinary biomarkers are prone to measurement error, not sensitive to alterations in energy
      availability, and are sometimes affected by disease states. The current project includes the
      introduction of a novel approach to estimating energy status by measuring metabolic hormones
      in plasma: insulin, IGF-I, insulin-like growth factor binding protein-3 (IGFBP-3) and leptin.

      This study tested whether a program of moderate aerobic exercise that is combined with a
      moderate level of dietary restriction would result in significant decreases in two biomarkers
      of breast cancer, circulating estrogens and IGF-I.
    

Detailed description: 
      This study used a randomized prospective design (block; 3:1 allocation) to test the effects
      of a four month (four menstrual cycles) intervention of moderate aerobic exercise (4 times
      per week, 60 minutes/session) combined with caloric restriction designed to produce a weekly
      energy deficit of -20%. The aims of the study were: 1) To test the hypothesis that a moderate
      level of low energy availability created through a combination of exercise and caloric
      restriction will lower circulating estrogens and IGF-I; 2) To test the hypothesis that
      exercise-induced decreases in body fat will contribute substantially to the lowering of
      circulating estrogens changes with training; 3) To validate a novel method of assessing
      energy status that represents an improvement of existing.

      Eumenorrheic, untrained women between 25-40 years (n=47) were randomly assigned to one of two
      treatments groups: exercise with caloric-restriction (EX+CR; n=36) or light conditioning
      reference (LC; n=11) groups. To determine treatment effects on circulating estrogens,
      reproductive function and IGF-I, both serum and urinary levels of hormones were monitored for
      a control period of 2 months (2 menstrual cycles), i.e., Screening and Baseline, followed the
      4 month (4 menstrual cycles: intervention 1-4) experimental period. The exercise/diet
      intervention began on the first day of the third month (menstrual cycle) and continue for
      four menstrual cycles thereafter (intervention 1, 2, 3, and 4). A post-study measurement was
      taken during cycles days 1-7 of the seventh menstrual cycle.

      Baseline energy needs were assessed during the baseline cycle. Resting metabolic rate and
      non-exercise physical activity were added to determine a caloric need for the day. Caloric
      intake was supervised throughout the entire study, and meals were comprised of 55%
      carbohydrates, 30% fat, and 15% protein. Exercise training was supervised, and maximal
      aerobic capacity (VO2max) was calculated. Menstrual status was assessed through analysis of
      daily urinary metabolites of estrone-1-glucuronide (E1G), pregnanediol glucuronide (PdG), and
      midcycle luteinizing hormone (LH). Underwater weighing and a digital scale were used to
      assess body composition, and fasting blood samples were collected to assess metabolic
      hormones.
    

Intervention name(s): Exercise+CR; Light Conditioning
Intervention type(s): Other; Other
Intervention description(s): Exercise with caloric-restriction; Light Conditioning Exercise
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Energy Balance; Menstrual Cycle Disturbance; Luteal Phase Defect; Menstruation Disturbances; Pathologic Processes