Energy Availability for Menstrual Irregularities

(FAST Trial)

Overseen By Marissa Baranauskas, PhD

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: University of Colorado, Colorado Springs

Must not be taking: Hormonal contraceptives

Disqualifiers: Pregnancy, Amenorrhea, PCOS, Diabetes, others

Compensation: Varies

Number of Visits: 5

64 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary aim of this clinical trial is to evaluate how fasted prolonged exercise may influence circulating reproductive hormones (i.e., estradiol, progesterone, luteinizing hormone) and menstrual cycle length when energy availability is maintained at or above 30 kcal/kg lean body mass/ day among women who regularly do running or cycling exercise. A secondary aim is to determine the effects of fasted prolonged exercise on serum leptin and cortisol. Participants will be asked to do the following over a \~3 month enrollment period: * attend a laboratory visit at the beginning of the study to have their resting metabolic rate, aerobic fitness, and body composition tested * monitor their menstrual cycle length, urine hormones, perceived stress levels, and diet for \~3 months * complete 3, 90-minute exercise sessions on a stationary bike or treadmill either fed (consuming a carbohydrate meal 1 h prior and 0.7 g carbohydrate/ kg body mass/ h during exercise) or fasted (consuming no meal prior and no carbohydrates during exercise) during month \~3 * saliva samples will be taken prior to and after 90-minute exercise sessions for quantification of leptin and cortisol

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are taking hormonal contraceptives or have certain medical conditions like metabolic or cardiovascular diseases.

What data supports the effectiveness of the treatment Timing of Energy Availability for menstrual irregularities?

Research shows that changes in energy availability can affect menstrual cycles, with lower energy availability linked to menstrual disturbances like luteal-phase defects and anovulation. This suggests that managing energy availability might help improve menstrual regularity. ^{1 2 3 4 5}

Is the Timing of Energy Availability treatment safe for humans?

The research does not provide specific safety data for the Timing of Energy Availability treatment, but it does indicate that energy deficiency can lead to menstrual disturbances in women. No adverse safety effects were reported in the studies related to energy availability and menstrual irregularities. ^{3 5 6 7 8}

How does the Timing of Energy Availability treatment differ from other treatments for menstrual irregularities?

The Timing of Energy Availability treatment is unique because it focuses on adjusting the timing and amount of energy intake to improve menstrual function, rather than using medications or supplements. This approach addresses the root cause of menstrual irregularities by ensuring adequate energy availability throughout the day, which is crucial for maintaining hormonal balance and reproductive health. ^{1 3 9 10 11}

Eligibility Criteria

This trial is for women who regularly run or cycle, are not pregnant or breastfeeding, haven't been in the past year, and don't plan to be. They should have regular menstrual cycles every 21-35 days, no major menstrual disorders like PCOS or endometriosis, no serious heart/lung diseases, and can't have taken hormonal contraceptives in the last 6 months.

Inclusion Criteria

I do not have any metabolic diseases like thyroid issues or diabetes.

I do not have any major heart or lung diseases.

Participates in structured running or cycling exercise for at least 30 minutes on 3 or more days per week

Exclusion Criteria

Miss more than 7 consecutive days of aerobic activity (i.e., running, cycling, cross training)

Demonstrate clinical low energy availability as defined as energy availability <30 kcal/kg fat free mass

Do not demonstrate an anticipated rise in luteinizing hormone and progesterone in the first 2 months of at-home monitoring

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Participants attend a laboratory visit to have their resting metabolic rate, aerobic fitness, and body composition tested

1 day

1 visit (in-person)

Monitoring

Participants monitor their menstrual cycle length, urine hormones, perceived stress levels, and diet

3 months

Exercise Intervention

Participants complete 3, 90-minute exercise sessions on a stationary bike or treadmill, either fed or fasted

1 month

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Timing of Energy Availability

Trial Overview The study tests how exercising while fasted affects reproductive hormones and menstrual cycle length when maintaining enough daily calories from lean body mass. Participants will exercise fed or fasted on a bike/treadmill and monitor their diet, stress levels, urine hormones for about three months.

Participant Groups

Group I: Fed with Carbohydrates Experimental Treatment 1 Intervention

Participants will complete 3, 90-minute stationary cycle or treadmill exercise sessions 1 h after consuming a meal containing 1 g carbohydrate/ kg body weight. During exercise, they will consume an artificially sweetened beverage containing 0.7 g carbohydrate/ kg body mass/ h as a 2:1 mixture of glucose and fructose.

Group II: Fasted without Carbohydrates Placebo Group 1 Intervention

Participants will complete 3, 90-minute stationary cycle or treadmill exercise sessions following an overnight fast. During exercise, they will consume an artificially sweetened beverage containing no carbohydrates.

Who Is Running the Clinical Trial?

University of Colorado, Colorado Springs

Lead Sponsor

Trials

20

Recruited

5,500+

Findings from Research

In exercising women, changes in resting energy expenditure and metabolic hormones are linked to the severity of menstrual disturbances, such as luteal-phase defects and amenorrhea.

Even small decreases in energy availability can lead to significant menstrual issues, highlighting the critical relationship between energy balance and reproductive health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severity of energy-related menstrual disturbances increases in proportion to indices of energy conservation in exercising women. De Souza, MJ., Lee, DK., VanHeest, JL., et al.[2013]

In a study of 14 previously sedentary, ovulatory women undergoing a 3-month diet and exercise program, reductions in energy availability (EA) were linked to a significant decrease in luteinizing hormone (LH) pulse frequency, which dropped from 0.82 to 0.63 pulses per hour.

Lower LH pulse frequency was associated with a higher risk of luteal phase defects (LPDs), with a 22-fold increase in odds for every 0.1-unit decrease in LH pulse frequency, indicating that maintaining adequate energy availability is crucial for normal menstrual function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Energy Availability Is Associated With Luteinizing Hormone Pulse Frequency and Induction of Luteal Phase Defects. Koltun, KJ., De Souza, MJ., Scheid, JL., et al.[2020]

A study involving 34 untrained women aged 18-30 showed that greater energy deficits during exercise led to more frequent menstrual disturbances, with moderate (ED2) and severe (ED3) deficits causing significantly more issues than a control group.

The research established a dose-response relationship, indicating that energy deficits of -22% to -42% (equating to -470 to -810 kcal/day) were linked to increased menstrual irregularities, although the severity of these disturbances did not depend on the level of energy deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnitude of daily energy deficit predicts frequency but not severity of menstrual disturbances associated with exercise and caloric restriction. Williams, NI., Leidy, HJ., Hill, BR., et al.[2022]

In a study of 57 morbidly obese women, those with menstrual dysfunction (Group 2) exhibited significantly higher insulin resistance (IR) compared to those without menstrual issues (Group 1), indicating a link between IR and menstrual irregularities.

The findings suggest that insulin resistance may contribute to menstrual dysfunctions like amenorrhea or oligomenorrhea, even when hyperandrogenism is not present, highlighting its role in ovarian function and menstrual cycle regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Menstrual irregularity: a possible clinical marker of metabolic dysfunction in women with class III obesity. Souza, FA., Dias, R., Fernandes, CE., et al.[2010]

In a 1-year study of 34 recreational female runners in France, no significant differences in energy or macronutrient intake were found among those with normal, irregular, or absent menstrual cycles, suggesting that diet may not directly influence menstrual health in this group.

However, the study revealed that amenorrhoeic and oligomenorrhoeic runners had significantly higher fluid and fiber intakes, consuming about twice the daily fluid intake compared to those with regular menstrual cycles, indicating a potential dietary pattern associated with menstrual cycle impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship between self-reported food and fluid intake and menstrual disturbance in female recreational runners. Rosetta, L., Condé da Silva Fraga, E., Mascie-Taylor, CG.[2019]

A systematic review of 28 studies found that certain foods and supplements, particularly vitamin D, calcium, zinc, and curcumin, may help reduce menstrual-related symptoms in naturally menstruating women, with no studies reporting negative effects.

Despite some positive findings, the review highlighted a lack of consistency in how menstrual symptoms were measured and the dosages used, indicating that more rigorous research is needed to establish clear guidelines for dietary interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nutritional practices to manage menstrual cycle related symptoms: a systematic review. Brown, N., Martin, D., Waldron, M., et al.[2023]

In a study of 4863 pregnant women, daughters of non-obese women with irregular menstrual cycles had significantly lower birth weights compared to those with regular cycles, with this effect being even more pronounced in obese women.

While the initial impact of maternal menstrual irregularity on birth weight was significant, it did not affect the daughters' growth in weight from birth to age five, indicating that the early weight differences may not have long-term implications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Birth weight and childhood growth in daughters of women with irregular menstrual cycles. Wang, ET., Cirillo, PM., Kao, CN., et al.[2021]

In a study of 352 young women from the Pittsburgh Girls Study, early menarche (before age 11) was linked to increased waist circumference, indicating potential risks for future health issues.

Adolescents with irregular menstrual cycles showed significantly higher levels of insulin, glucose, and triglycerides, as well as elevated blood pressure, suggesting that menstrual irregularity may be an important indicator of future cardiometabolic health risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Menstrual Cycle Irregularity in Adolescence Is Associated With Cardiometabolic Health in Early Adulthood. Keenan, K., Hipwell, AE., Polonsky, TS.[2023]

Athletes with menstrual dysfunction (MD) spent significantly more hours in a catabolic state compared to eumenorrheic athletes, despite having similar 24-hour energy availability and balance, indicating a potential risk for metabolic disturbances.

Within-day energy deficiency in MD athletes was linked to lower resting metabolic rate and estradiol levels, as well as higher cortisol levels, suggesting that energy balance may impact hormonal health and metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Within-day energy deficiency and reproductive function in female endurance athletes. Fahrenholtz, IL., Sjödin, A., Benardot, D., et al.[2018]

Amenorrhoea in female athletes is often a sign of low energy availability and should not be considered normal, as it can lead to serious health issues like poor bone density and growth problems, especially during adolescence.

Addressing amenorrhoea requires a comprehensive approach involving screening for energy availability and collaboration among healthcare professionals to effectively treat the underlying causes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amenorrhoea in adolescent female athletes. Ackerman, KE., Misra, M.[2020]

Chronic energy deficiency leads to significant metabolic changes, including reduced levels of important hormones like IGF-1 and leptin, which can affect overall health and energy balance.

These hormonal alterations can suppress the hypothalamic-pituitary-ovarian axis, resulting in menstrual dysfunction due to decreased secretion of gonadotropin-releasing hormone and subsequent hormones like luteinizing hormone and follicle-stimulating hormone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The physiology of functional hypothalamic amenorrhea associated with energy deficiency in exercising women and in women with anorexia nervosa. Allaway, HC., Southmayd, EA., De Souza, MJ.[2016]

References

1. United States pubmed.ncbi.nlm.nih.gov

Severity of energy-related menstrual disturbances increases in proportion to indices of energy conservation in exercising women. [2013]

2. United States pubmed.ncbi.nlm.nih.gov

Energy Availability Is Associated With Luteinizing Hormone Pulse Frequency and Induction of Luteal Phase Defects. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Magnitude of daily energy deficit predicts frequency but not severity of menstrual disturbances associated with exercise and caloric restriction. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Menstrual irregularity: a possible clinical marker of metabolic dysfunction in women with class III obesity. [2010]

5. England pubmed.ncbi.nlm.nih.gov

Relationship between self-reported food and fluid intake and menstrual disturbance in female recreational runners. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Nutritional practices to manage menstrual cycle related symptoms: a systematic review. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Birth weight and childhood growth in daughters of women with irregular menstrual cycles. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Menstrual Cycle Irregularity in Adolescence Is Associated With Cardiometabolic Health in Early Adulthood. [2023]

9. Denmark pubmed.ncbi.nlm.nih.gov

Within-day energy deficiency and reproductive function in female endurance athletes. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Amenorrhoea in adolescent female athletes. [2020]

11. Germany pubmed.ncbi.nlm.nih.gov

The physiology of functional hypothalamic amenorrhea associated with energy deficiency in exercising women and in women with anorexia nervosa. [2016]