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Menstrual IrregularityNCT00392873

Increased Calorie Intake to Reverse Energy Deficiency in Exercising Women: Impact on Bone and Menstrual Cyclicity

A study testing EAMD+Calories in people with Menstrual Irregularity, run by Penn State University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to examine the effects of increased food intake on the menstrual cycle and bone health in physically active women who have irregular or absent menstrual cycles. Read more about this study

Who is it for?
Ages 18 to 35 years, women onlyHealthy volunteers can take part
Conditions the study is for
Menstrual Irregularity
What is being tested?
EAMD+Calories
Could I receive a placebo?
No, everyone receives an active treatment
How many people
233 participants
Where
1 siteUnited States
Study dates
Sep 2006to Dec 2014
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 35 years
  • Women only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 18-35 years
  • BMI 16-25 kg/m2
  • At least 2 hr/wk of aerobic exercise
  • Gynecological age >/= 5 years
  • Weight stable (+/- 2 kg) last 6 months
  • History of regular menses for 6 months
Show all 14Show fewer
  • Inclusion Criteria for Women with Irregular or Absent Menses:
  • 18-35 years
  • BMI 16-25 kg/m2
  • At least 3 hr/wk of aerobic exercise
  • Gynecological age >/= 5 years
  • Weight stable (+/- 2 kg) last 6 months
  • No menses within past 3 months or 6 or less menses in last 12 months
  • Low to normal bone mass (L1-L4 Z score </=0)

Who cannot join

  • Hormonal contraceptives in last 6 months
  • Smoking currently
  • Current clinical diagnosis of an eating disorder
  • Use of medications incompatible with measurement of reproductive or metabolic hormones, including thyroid medications that may interfere with any of the study outcomes.
  • Dietary habits incompatible with prescribed diet for study
  • Any metabolic, reproductive or bone disease
  • Sedentary individuals with less than 120 minutes (2 hrs) of activity per week

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Women's Health and Exercise Laboratories, The Pennsylvania State University

    University Park, Pennsylvania, 16802

Other trials in United States

About this study

Official title: "REFUEL" Active Women's Study II: Increased Caloric Intake to Reverse Energy Deficiency in Exercising Women: Impact on Bone and Menstrual Cyclicity

The purpose of this study is to examine the effects of increased food intake on the menstrual cycle and bone health in physically active women who have irregular or absent menstrual cycles. This study will examine whether a 12 month period of increased food intake will cause menstrual cycles to resume and help bones get stronger.

Read the detailed description

Low levels of estrogen found in physically active, premenopausal women with irregular or absent menstrual periods is likely caused by insufficient energy (calorie) intake compared to energy expenditure. Premenopausal women with menstrual disturbances and amenorrhea suffer from reductions in bone mineral density, particularly in the lumbar spine. Bone loss observed in amenorrheic women may be serious enough to result in osteoporotic fractures, but is also associated with a high prevalence of stress fractures. Increased calorie intake should help improve energy status, menstrual status, and bone health.

Comparison: Premenopausal women with irregular or absent menstrual periods will be assigned to either receive additional calories or serve as controls. A group of premenopausal women with normal menstrual periods will also be used for comparison.

Being tested
EAMD+Calories
Keywords
Amenorrhea, Energy deficiency, Resting energy expenditure, Bone metabolism, Bone mineral density, Exercise
Medical subject headings
Menstruation Disturbances, Amenorrhea, Motor Activity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EAMD+CaloriesBehavioural

    During the 12 month intervention, volunteers in the Increased calorie intake group will follow a modified dietary plan designed to achieve and maintain a target level of 20-30% above their previously determined baseline, in an effort to achieve a chronic energy surplus of +20-30% over their baseline energy requirements.

Study groups in NCT00392873
Study groupRoleWhat they receive
EAMD+CaloriesExperimentalThis group contains women with exercise-associated menstrual disturbances (EAMD) and receives an intervention of increased caloric intake during the 12-month intervention. The targeted increase in caloric intake is 20-30% of baseline energy expenditure.
Receives: Behavioral: EAMD+Calories
EAMD ControlNo interventionThis group contains women with exercise-associated menstrual disturbances (EAMD) and undergoes the same procedures as the EAMD+Calories group. However, this group is instructed to maintain exercise and eating habits.
Heathy ControlNo interventionThis group contains exercising women with regular, ovulatory menstrual cycles. this group is instructed to maintain body weight and exercise and eating habits.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Reproductive hormones

    Measured: 1 year

  2. Metabolic hormones

    Measured: 1 year

  3. Metabolic bone markers

    Measured: 1 year

  4. Bone mineral density

    Measured: 1 year

Secondary outcomes (2)

  1. Eating Disorder Inventory-2 (EDI-2)

    Measured: 1 year

  2. Three Factor Eating Questionnaire

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Oct 2006 (estimated)
  2. Study startSep 2006
  3. Primary completionDec 2014
  4. Study completionDec 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
233 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00392873
Sponsor's protocol ID
15353
Status last verified
May 2017
First submitted
25 Oct 2006
Last updated
8 May 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • Salamunes ACC, Mallinson RJ, DE Souza MJ, Ricker EA, Allaway HCM, Williams NI. Predictors of Advanced Menstrual Recovery in Exercising Women with Oligo/Amenorrhea: A Secondary Analysis of the REFUEL Study. Med Sci Sports Exerc. 2026 Mar 1;58(3):581-596. doi: 10.1249/MSS.0000000000003877. Epub 2025 Oct 21.

    PubMed 41121582

  • Mallinson RJ, Williams NI, Ricker EA, Allaway HCM, De Souza MJ. Multiple eumenorrheic cycles are necessary to observe a significant increase in estrogen exposure and ovulation in exercising women with functional hypothalamic oligo/amenorrhea undergoing a nutritional intervention: Insights from the REFUEL study. PM R. 2026 May;18 Suppl 2(Suppl 2):S104-S116. doi: 10.1002/pmrj.70024. Epub 2025 Oct 16.

    PubMed 41099383

  • Salamunes ACC, Williams NI, Olmsted M, Koltun KJ, Kuruppumullage Don P, DE Souza MJ. Development and Validation of a Risk Assessment Tool for Energy Deficiency in Young Active Females: The Female Energy Deficiency Questionnaire (FED-Q). Med Sci Sports Exerc. 2025 Sep 1;57(9):2040-2052. doi: 10.1249/MSS.0000000000003742. Epub 2025 Apr 25.

    PubMed 40279653

  • Strock NCA, De Souza MJ, Mallinson RJ, Olmsted M, Allaway HCM, O'Donnell E, Plessow F, Williams NI. 12-months of increased dietary intake does not exacerbate disordered eating-related attitudes, stress, or depressive symptoms in women with exercise-associated menstrual disturbances: The REFUEL randomized controlled trial. Psychoneuroendocrinology. 2023 Jun;152:106079. doi: 10.1016/j.psyneuen.2023.106079. Epub 2023 Mar 8.

    PubMed 36947969

  • De Souza MJ, Ricker EA, Mallinson RJ, Allaway HCM, Koltun KJ, Strock NCA, Gibbs JC, Kuruppumullage Don P, Williams NI. Bone mineral density in response to increased energy intake in exercising women with oligomenorrhea/amenorrhea: the REFUEL randomized controlled trial. Am J Clin Nutr. 2022 Jun 7;115(6):1457-1472. doi: 10.1093/ajcn/nqac044.

    PubMed 35170727

  • De Souza MJ, Mallinson RJ, Strock NCA, Koltun KJ, Olmsted MP, Ricker EA, Scheid JL, Allaway HC, Mallinson DJ, Kuruppumullage Don P, Williams NI. Randomised controlled trial of the effects of increased energy intake on menstrual recovery in exercising women with menstrual disturbances: the 'REFUEL' study. Hum Reprod. 2021 Jul 19;36(8):2285-2297. doi: 10.1093/humrep/deab149.

    PubMed 34164675

  • Southmayd EA, Williams NI, Mallinson RJ, De Souza MJ. Energy Deficiency Suppresses Bone Turnover in Exercising Women With Menstrual Disturbances. J Clin Endocrinol Metab. 2019 Aug 1;104(8):3131-3145. doi: 10.1210/jc.2019-00089.

    PubMed 30896746

Questions about this trial

What is this clinical trial studying?

A study testing EAMD+Calories in people with Menstrual Irregularity, run by Penn State University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Reproductive hormones (time frame: 1 year). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00392873, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2017.

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