Energy Restriction and Hormones in Premenopausal Women

NCT05107804 | Completed

• 4 other identifiers: 01M0088M01RR010732DAMD 17-01-1-0361DAMD 17-01-109360
• Study Type: interventional
• Target: 47
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Menstruation Disturbances; Luteal Phase Defect

Keywords

Energy Balance; Menstrual Cycle Disturbance; Luteal Phase Defect; Menstruation Disturbances; Pathologic Processes

Outcome Measures

Primary Outcomes (1)

• Change in estrogen and IGF-1

  Change in urine estrone-1-glucuronide (E1G ng/mL) and serum IGF-1 (ng/mL)

  Baseline Menstrual Cycle (MC) (28 days (d) or the length of 1 MC, intervention 1 (28 d or 1 MC), intervention 2 (28 d or 1 MC), intervention 3 (28 d or 1 MC), intervention 4 (28 d or 1 MC), and Post Study (days 1-7 last MC)

Secondary Outcomes (9)

• Change in body composition

  Baseline Menstrual Cycle (MC) (28 days (d) or the length of 1 MC, intervention 1 (28 d or 1 MC), intervention 2 (28 d or 1 MC), intervention 3 (28 d or 1 MC), intervention 4 (28 d or 1 MC), and Post Study (days 1-7 last MC)

• Change in body composition

  Baseline Menstrual Cycle (MC) (28 days (d) or the length of 1 MC, intervention 1 (28 d or 1 MC), intervention 2 (28 d or 1 MC), intervention 3 (28 d or 1 MC), intervention 4 (28 d or 1 MC), and Post Study (days 1-7 last MC)

• Change in reproductive hormones

  Baseline Menstrual Cycle (MC) (28 days (d) or the length of 1 MC, intervention 1 (28 d or 1 MC), intervention 2 (28 d or 1 MC), intervention 3 (28 d or 1 MC), intervention 4 (28 d or 1 MC), and Post Study (days 1-7 last MC)

• Change in reproductive hormones

  Baseline Menstrual Cycle (MC) (28 days (d) or the length of 1 MC, intervention 1 (28 d or 1 MC), intervention 2 (28 d or 1 MC), intervention 3 (28 d or 1 MC), intervention 4 (28 d or 1 MC), and Post Study (days 1-7 last MC)

• Change in metabolic hormones

  Baseline Menstrual Cycle (MC) (28 days (d) or the length of 1 MC, intervention 1 (28 d or 1 MC), intervention 2 (28 d or 1 MC), intervention 3 (28 d or 1 MC), intervention 4 (28 d or 1 MC), and Post Study (days 1-7 last MC)

Study Arms (2)

Exercise with caloric-restriction

EXPERIMENTAL

Exercise: Participants engaged in supervised exercise training sessions (to expend \~20% of baseline energy needs) in Noll Laboratory; 4 times per week. Diet: Participants consumed meals in the General Clinical Research Center metabolic kitchen that reduced dietary intake 20-35% of baseline energy needs. Diet composition was 55% carbohydrates, 30% fat, and 15% protein.

Other: Exercise+CR

Light Conditioning (reference group)

ACTIVE COMPARATOR

Exercise: Participants engaged in supervised exercise training sessions (to expend \~10% of baseline energy needs) in Noll Laboratory; 1-2 times per week. Diet: Participants consumed meals in the General Clinical Research Center metabolic kitchen that had calories sufficient to maintain body weight and additional calories to remain in energy balance. Diet composition was 55% carbohydrates, 30% fat, and 15% protein.

Other: Light Conditioning

Interventions

Exercise+CR OTHER

Exercise with caloric-restriction

Exercise with caloric-restriction

Light Conditioning OTHER

Light Conditioning Exercise

Light Conditioning (reference group)

Eligibility Criteria

• Age: 25 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Weight 50-90 kg
• BMI 18-35 kg/m2
• Nonsmoking
• \<1 hour/week of purposeful aerobic exercise for the past 6 months
• Gynecological age ≥10 years
• Documentation of at least two ovulatory menstrual cycles during screening.

You may not qualify if:

• History of serious medical conditions
• Medication use that would alter metabolic hormone levels
• Significant weight loss/gain (±2.3 kg) in the last year
• Current evidence of disordered eating or history of an eating disorder
• Taking exogenous hormonal contraceptives for the past 6 month
• Smoking

Sponsors & Collaborators

• Penn State University: lead
• National Institutes of Health (NIH): collaborator
• United States Department of Defense: collaborator
• National Center for Research Resources (NCRR): collaborator

Related Publications (1)

• Williams NI, Reed JL, Leidy HJ, Legro RS, De Souza MJ. Estrogen and progesterone exposure is reduced in response to energy deficiency in women aged 25-40 years. Hum Reprod. 2010 Sep;25(9):2328-39. doi: 10.1093/humrep/deq172. Epub 2010 Jul 6.

  PMID: 20605898 RESULT

MeSH Terms

Conditions

Menstruation Disturbances; Pathologic Processes

Condition Hierarchy (Ancestors)

Pathological Conditions, Signs and Symptoms

Study Officials

• Nancy Williams, ScD

  Penn State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Head, Department of Kinesiology

Study Record Dates

• First Submitted: October 6, 2021
• First Posted: November 4, 2021
• Study Start: March 1, 2001
• Primary Completion: November 1, 2006
• Study Completion: November 1, 2006
• Last Updated: November 4, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share