Clinical trial NCT00392873: Increased Calorie Intake to Reverse Energy Deficiency in Exercising Women: Impact on Bone and Menstrual Cyclicity
Official title: "REFUEL" Active Women's Study II: Increased Caloric Intake to Reverse Energy Deficiency in Exercising Women: Impact on Bone and Menstrual Cyclicity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Menstrual Irregularity
Keywords: Amenorrhea
Energy deficiency
Resting energy expenditure
Bone metabolism
Bone mineral density
Exercise
Lead sponsor: Penn State University
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2006-10-26
Enrollment: 233
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. This study will examine whether a 12 month period of increased food intake will cause menstrual cycles to resume and help bones get stronger.

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.

Eligibility criteria: Inclusion Criteria for Ovulatory Control Volunteers:

* 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

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)

Exclusion Criteria for all participants:

* 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

Primary outcomes:
measure: Reproductive hormones
timeFrame: 1 year
measure: Metabolic hormones
timeFrame: 1 year
measure: Metabolic bone markers
timeFrame: 1 year
measure: Bone mineral density
timeFrame: 1 year
Secondary outcomes:
measure: Eating Disorder Inventory-2 (EDI-2)
timeFrame: 1 year
measure: Three Factor Eating Questionnaire
timeFrame: 1 year
Other outcomes:
Locations:
city: University Park
country: United States
facility: Women's Health and Exercise Laboratories, The Pennsylvania State University
state: Pennsylvania
Study officials:
affiliation: Penn State University
name: Mary Jane De Souza, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.