Clinical trial NCT04938622: Bioenergetics of Exercise-Induced Menstrual Disturbances
Official title: Bioenergetics of Exercise-Induced Menstrual Disturbances
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Menstruation Disturbances
Luteal Phase Defect
Amenorrhea
Oligomenorrhea
Keywords: Energy Balance
Menstrual Cycle Disturbance
Luteal Phase Defect
Amenorrhea
Oligomenorrhea
Lead sponsor: Penn State University
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2021-06-24
Enrollment: 47
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: Menstrual disturbances are frequently observed in physically active women and female athletes. Short term prospective studies have shown that diet and exercise interventions can lead to decreases in Luteinizing hormone (LH) pulsatility, however these studies are unable to capture further changes in menstrual status. One longer term prospective study over two menstrual cycles showed that weight loss elicited menstrual disturbances, but there were no quantifiable measurements of energy availability. Thus, the primary purpose of this study was to assess how varying levels of energy deficiency created through a combination of caloric restriction and exercise affect menstrual function in young, premenopausal, sedentary women.

Detailed description: Long term energy deficiency in women can lead to functional hypothalamic amenorrhea (FHA), which can cause many health detriments such as osteopenia, stress fractures, transient infertility, dyslipidemia, and impaired endothelial function. Though studies involving diet and exercise interventions have shown how energy deficiency can lead to menstrual disturbances prospectively, this study aims to extend those findings by measuring the magnitude of energy deficit that could lead to these disturbances. Hypotheses for this study are: 1) there would be a dose-response relation between the induction of menstrual disturbances (luteal phase defects, anovulation, and oligomenorrhea) and the magnitude of energy deficiency such that the intervention groups experiencing a greater energy deficit would incur a significantly greater incidence of menstrual cycle disturbances and 2) the intervention groups experiencing a greater energy deficit would incur a greater incidence of more severe menstrual cycle disturbances.

The study included one baseline menstrual cycle and 3 intervention menstrual cycles. During the baseline period, participants were randomly assigned to an experimental group for intervention menstrual cycles 1, 2, and 3 of the study. The goal of the subject groupings was to test the impact of varying levels of an energy deficit created by the combination of caloric restriction and exercise on menstrual function. They were assigned to either a control group that did not exercise and consumed a number of calories estimated to maintain body weight, a control group that exercised but received extra food calories to remain in energy balance (EXCON), or one of four groups that exercised and were prescribed reduced energy intake to create varying levels of an energy deficit. Specifically, the four groups of energy deficit were 1) an increase of 15 percent kcal of exercise (15 percent deficit, ED1), 2) an increase of 30 percent kcal of exercise (30 percent deficit, ED2), 3) a decrease of 15 percent in dietary intake combined with an increase of 15 percent of exercise, (30 percent deficit 15/15, ED2), and 4) a decrease of 30 percent in dietary intake combined with an increase of 30 percent kcal of exercise (60 percent deficit, ED3). The number of participants for analysis was 34 participants in the following groups: EXCON (n = 8), ED1 (n = 6), ED2 (n = 12), and ED3 (n = 8).

Baseline energy needs were assessed during the baseline cycle. Resting metabolic rate and nonexercise 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 percent carbohydrates, 30 percent fat, and 15 percent protein. Exercise training was also supervised, and maximal oxygen consumption (VO2 max) was calculated. Menstrual status was assessed through analysis of daily urinary metabolites of estrone-1-glucuronide (E1G), pregnanediol glucuronide (PdG), and midcycle LH. Underwater weighing and a digital scale were used to assess body composition, and fasting blood samples were collected to assess metabolic hormones.

Eligibility criteria: Inclusion Criteria:

* Weight 45-75 kg
* Body fat 15-35 percent
* BMI 18-25 kg/m2
* Nonsmoking
* \<1 hour/week of purposeful aerobic exercise for the past 6 months
* Documentation of at least two ovulatory menstrual cycles during screening.

Exclusion Criteria:

* 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 months

Primary outcomes:
measure: Change in frequency of menstrual disturbances (disturbances /cycle)
timeFrame: Baseline Menstrual Cycle (MC) (28 days (d) or the length of 1 MC, intervention MC 1 (28 days or the length of 1 MC), intervention MC 2 (28 days or the length of 1 MC), and intervention MC 3 (28 days or the length of 1 MC)
Secondary outcomes:
measure: Change in percent body fat
timeFrame: Baseline Menstrual Cycle (MC) (28 days (d) or the length of 1 MC, intervention MC 1 (28 days or the length of 1 MC), intervention MC 2 (28 days or the length of 1 MC), and intervention MC 3 (28 days or the length of 1 MC), & Post Study (days 1-7)
measure: Change in metabolic hormones
timeFrame: Baseline Menstrual Cycle (MC) (28 days (d) or the length of 1 MC, Mid- study (week 3 of MC during intervention MC 2) an (28 days (d) or the length of 1 MC), & Post Study (Days (d)1-7 of cycle
measure: Change in cycle length (days (d))
timeFrame: Baseline Menstrual Cycle (MC) (28 days (d) or the length of 1 MC, intervention MC 1 (28 days or the length of 1 MC), intervention MC 2 (28 days or the length of 1 MC), and intervention MC 3 (28 days or the length of 1 MC)
measure: Change in aerobic capacity
timeFrame: Baseline Menstrual Cycle (MC) (28 days (d) or the length of 1 MC, & Post Study (Days (d)1-7 of cycle
measure: Change in body weight
timeFrame: Baseline Menstrual Cycle (MC) (28 days (d) or the length of 1 MC, intervention MC 1 (28 days or the length of 1 MC), intervention MC 2 (28 days or the length of 1 MC), and intervention MC 3 (28 days or the length of 1 MC), & Post Study (days 1-7)
measure: Change in fat mass
timeFrame: Baseline Menstrual Cycle (MC) (28 days (d) or the length of 1 MC, intervention MC 1 (28 days or the length of 1 MC), intervention MC 2 (28 days or the length of 1 MC), and intervention MC 3 (28 days or the length of 1 MC), & Post Study (days 1-7)
measure: Change in fat free mass
timeFrame: Baseline Menstrual Cycle (MC) (28 days (d) or the length of 1 MC, intervention MC 1 (28 days or the length of 1 MC), intervention MC 2 (28 days or the length of 1 MC), and intervention MC 3 (28 days or the length of 1 MC), & Post Study (days 1-7)
measure: Change in follicular phase length
timeFrame: Baseline Menstrual Cycle (MC) (28 days (d) or the length of 1 MC, intervention MC 1 (28 days or the length of 1 MC), intervention MC 2 (28 days or the length of 1 MC), and intervention MC 3 (28 days or the length of 1 MC)
measure: Change in luteal phase length
timeFrame: Baseline Menstrual Cycle (MC) (28 days (d) or the length of 1 MC, intervention MC 1 (28 days or the length of 1 MC), intervention MC 2 (28 days or the length of 1 MC), and intervention MC 3 (28 days or the length of 1 MC)
Other outcomes:
Locations:
Study officials:
affiliation: Penn State University
name: Nancy I Williams, ScD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lieberman JL, DE Souza MJ, Wagstaff DA, Williams NI. Menstrual Disruption with Exercise Is Not Linked to an Energy Availability Threshold. Med Sci Sports Exerc. 2018 Mar;50(3):551-561. doi: 10.1249/MSS.0000000000001451.
citation: 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. 2015 Jan 1;308(1):E29-39. doi: 10.1152/ajpendo.00386.2013. Epub 2014 Oct 28.