Physical and Psychosocial Stress for Amenorrhea

(FHA Trial)

Overseen By Kristen Rudd, PhD

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: University of Colorado, Colorado Springs

Must not be taking: Hormonal contraceptives

Disqualifiers: Menstrual disorders, Metabolic diseases, Cardiovascular, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

54 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to determine how changes in exercise and psychosocial stress may influence the risk of menstrual cycle irregularities in female runners and cyclists. The main questions it aims to answer are: * Does the implementation of exercise or psychosocial stress effect circulating reproductive hormones (i.e., estradiol, progesterone, luteinizing hormone) and menstrual cycle length? * Is there an additive effect of combined exercise and psychosocial on circulating reproductive hormones (i.e., estradiol, progesterone, luteinizing hormone) and menstrual cycle length? Participants will be asked to do the following over the \~3 month enrollment period: * attend a laboratory visit at the beginning and end of the study to have their resting metabolic rate, aerobic fitness, and body composition tested * monitor their menstrual cycle length, daily perceived stress levels, physical activity, and diet each month * provide several urine and saliva samples each month * either maintain their usual physical activity and lifestyle habits (control group), increase the duration of their weekly running or cycling mileage by 30% (exercise stress group), complete cognitive function tasks designed to be stressful (psychosocial stress group), or increase the duration of their weekly running or cycling mileage by 30% and complete cognitive function tasks designed to be stressful (exercise + psychosocial stress group) during the final month of enrollment. Researchers will compare control, exercise stress, psychosocial stress, and exercise + psychosocial stress groups to see if there is an effect on circulating reproductive hormones (i.e., estradiol, progesterone, luteinizing hormone) and menstrual cycle length.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, you must not have used hormonal contraceptives for at least the past 6 months and should not begin taking them during the trial.

What data supports the effectiveness of the treatment for amenorrhea?

Research suggests that both physical and psychological stress can contribute to amenorrhea (absence of menstruation) in athletes. Addressing these stressors through strategies like cognitive behavior therapy has been shown to help restore reproductive and hormonal balance. ^{1 2 3 4 5}

Is the treatment involving physical and psychosocial stress generally safe for humans?

Research indicates that physical and psychosocial stress can affect hormone levels and mood, potentially leading to conditions like amenorrhea (absence of menstruation) in women. However, formal psychosocial support and cognitive behavior therapy can help restore balance, suggesting that while stress can have negative effects, these can be managed with appropriate interventions. ^{1 2 3 6 7}

How does the treatment for amenorrhea involving physical and psychosocial stress differ from other treatments?

This treatment is unique because it addresses both physical and psychological stressors that contribute to amenorrhea, rather than focusing solely on hormonal or nutritional interventions. It emphasizes the importance of managing stress through psychosocial support and lifestyle changes, which can help restore hormonal balance and menstrual function. ^{1 2 3 8 9}

Eligibility Criteria

This trial is for female runners and cyclists who can complete a 5-km race in under 25 minutes, have regular menstrual cycles every 21 to 35 days, haven't used hormonal contraceptives or been pregnant/breastfeeding for the past six months, exercise regularly, and don't have metabolic diseases or menstrual disorders.

Inclusion Criteria

Participates in structured running or cycling exercise for at least 30 minutes on 4 days per week or more

Have regular periods every 21 to 35 days

I haven't used hormonal birth control in the last 6 months.

Exclusion Criteria

I have a diagnosed menstrual cycle disorder.

I have a major heart, lung, or muscle/bone condition.

Missing > 4 consecutive days of structured running or cycling exercise

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

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

1 week

1 visit (in-person)

Intervention

Participants either maintain their usual physical activity and lifestyle habits, increase their weekly running or cycling mileage by 30%, complete cognitive function tasks designed to be stressful, or both

4 weeks

Monthly monitoring

Follow-up

Participants are monitored for changes in menstrual cycle length and reproductive hormones

3 months

Treatment Details

Interventions

• Exercise Stress
• Psychosocial Stress

Trial Overview The study examines how increased physical activity and stress affect reproductive hormones and menstrual cycle length. Women will be divided into groups: some maintain their routine while others add more exercise or stressful cognitive tasks to see if these changes impact hormone levels and menstruation.

Participant Groups

Group I: Psychosocial Stress Experimental Treatment 1 Intervention

Participants will be asked to complete cognitive function tasks designed to be stressful while maintaining their usual physical activity habits.

Group II: Exercise Stress Experimental Treatment 1 Intervention

The duration of participant's weekly running or cycling mileage will be increased by 30% while intensity is maintained.

Group III: Exercise + Psychosocial Stress Experimental Treatment 2 Interventions

Participants will be asked to complete cognitive function tasks designed to be stressful while the duration of their weekly running or cycling mileage is increased by 30% and intensity maintained.

Group IV: Control Active Control 1 Intervention

Participants will be asked to maintain their usual physical activity and lifestyle habits.

Who Is Running the Clinical Trial?

University of Colorado, Colorado Springs

Lead Sponsor

Trials

20

Recruited

5,500+

Findings from Research

Amenorrheic athletes had significantly higher cortisol levels (585 nmol/L) compared to eumenorrheic athletes (411 nmol/L) and nonathletic women (397 nmol/L), indicating that elevated cortisol may play a role in exercise-associated amenorrhea.

Lower bone mineral density was observed in amenorrheic athletes, suggesting that high cortisol levels not only affect menstrual cycles but may also contribute to bone health issues, putting these athletes at risk for prolonged menstrual irregularities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High serum cortisol levels in exercise-associated amenorrhea. Ding, JH., Sheckter, CB., Drinkwater, BL., et al.[2019]

Athletic women are at risk for ovulatory dysfunction, which can lead to menstrual irregularities due to a combination of metabolic and psychogenic stressors affecting hormone release.

Cognitive behavior therapy has been shown to effectively restore reproductive and endocrine balance in these athletes, highlighting the importance of addressing both physical and psychological stressors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Athletic amenorrhea: energy deficit or psychogenic challenge? Pauli, SA., Berga, SL.[2022]

In a study of 61 exercising women aged 18-35, those with functional hypothalamic amenorrhea (FHA) exhibited lower metabolic rates and hormonal levels, indicating that both psychological and metabolic factors contribute to this condition.

Women with FHA showed significant psychological stress indicators, such as a greater drive for thinness and need for social approval, which were correlated with stress and mood issues, highlighting the importance of addressing psychological factors in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eating behaviours related to psychological stress are associated with functional hypothalamic amenorrhoea in exercising women. Strock, NCA., De Souza, MJ., Williams, NI.[2020]

Amenorrhea is a common issue among athletes, particularly adolescents, and can lead to serious health problems like stress fractures and osteoporosis if not properly managed.

The article emphasizes the importance of recognizing and addressing the underlying causes of amenorrhea, including body composition and disordered eating, and calls for improved prevention and education strategies in sports medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amenorrhea in the athlete. Gidwani, GP.[2015]

Secondary amenorrhea in athletes can vary widely in incidence, ranging from 1% to 44%, largely due to inconsistent definitions and differences in surveyed populations.

Current treatments for athletic amenorrhea focus on addressing factors like body composition, training intensity, and psychological stress, but no definitive mechanism for the condition has been established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Athletic amenorrhea: a review. Loucks, AB., Horvath, SM.[2015]

In a study of 12 physically-active women, salivary estradiol levels increased significantly from the early follicular phase to the mid luteal phase, but this was associated with a decrease in VO2max performance during aerobic exercise.

The findings suggest that while there is a natural rise in estradiol during the menstrual cycle, most exercise performance and emotional states did not show significant differences between the two phases, indicating that menstrual cycle phase may not greatly impact exercise outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of menstrual-cycle phase on basal and exercise-induced hormones, mood, anxiety and exercise performance in physically active women. Paludo, AC., Cook, CJ., Owen, JA., et al.[2021]

In a study involving 22 females (14 aerobically fit and 8 unfit), aerobic fitness was found to have no significant effect on stress reactivity during mental stress tests, as both groups showed similar responses.

Despite differences in baseline heart rate, the study concluded that being aerobically fit does not reduce stress responses or anxiety levels in women before menopause.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of aerobic fitness on the physiological stress response in women. Summers, H., Lustyk, MK., Heitkemper, M., et al.[2017]

Hypothalamic amenorrhea (HA) is a condition where stress, undernutrition, or excessive training disrupts the hypothalamus-pituitary-ovarian (HPO) axis, leading to reduced ovarian function and amenorrhea, particularly affecting young women and adolescents.

Clinicians should be vigilant about delayed menarche or amenorrhea, especially when associated with weight loss, as these symptoms may indicate underlying stress and potential risks for conditions like osteopenia and osteoporosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroendocrine aspects of amenorrhea related to stress. Genazzani, AD.[2008]

In a study of 32 runners (13 amenorrheic and 19 regularly menstruating), the amenorrheic group showed a significant prevalence of major affective disorders and eating disorders, with 11 reporting such issues.

In contrast, the regularly menstruating runners had no reported eating disorders and only one had a family history of major affective disorders, suggesting a potential link between athletic amenorrhea and these psychiatric conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Athletic amenorrhea, major affective disorders, and eating disorders. Gadpaille, WJ., Sanborn, CF., Wagner, WW.[2015]

References

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

High serum cortisol levels in exercise-associated amenorrhea. [2019]

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

Athletic amenorrhea: energy deficit or psychogenic challenge? [2022]

3. England pubmed.ncbi.nlm.nih.gov

Eating behaviours related to psychological stress are associated with functional hypothalamic amenorrhoea in exercising women. [2020]

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

Amenorrhea in the athlete. [2015]

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

Athletic amenorrhea: a review. [2015]

6. Italy pubmed.ncbi.nlm.nih.gov

The impact of menstrual-cycle phase on basal and exercise-induced hormones, mood, anxiety and exercise performance in physically active women. [2021]

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

Effect of aerobic fitness on the physiological stress response in women. [2017]

8. Israel pubmed.ncbi.nlm.nih.gov

Neuroendocrine aspects of amenorrhea related to stress. [2008]

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

Athletic amenorrhea, major affective disorders, and eating disorders. [2015]