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The goal of this experimental study is to determine how stressors that do not directly impact energy state or energy demands (hereafter called "non-energetic stressors") affect reproductive health in pre-menopausal women. It aims to do this by answering the following main questions: Do non-energetic stressors create a stress response? How does the stress response impact sex hormone concentration and thus menstrual dysfunction? If stress caused by non-energetic stressors does impact sex hormone concentration, does it do so primarily at the level of the brain or the level of the ovary? Participants will be enrolled in this study for 6 months. For two of these months, they will undergo a short stress intervention and provide samples to measure hormone concentration and total energy expenditure.
The Reproductive Suppression Model posits that due to the high cost and failure rate of human reproduction, the female body maximizes lifetime reproductive fitness by suppressing reproduction during poor conditions (where likelihood of offspring survival is low) until conditions are more favorable. The hormonal mechanism for this suppression when calories are scarce and the female body is in low energy availability (LEA) has been studied. However, the mechanism for this suppression in the presence of stressors unrelated to low energy availability, but which could still negatively impact offspring survival, is much less clear. The investigators define such stressors, which do not impact energy state or energetic demands, as "non-energetic stressors." Thus, the aim of this study is to determine if non-energetic stressors drive reproductive suppression in humans. The investigators will assess this by testing the impact of a stress intervention on the stress hormones cortisol and norepinephrine, and in turn if the levels of these stress hormones predict the levels of sex hormones associated with the menstrual cycle. Finally, the investigators will assess if changes in stress hormones change total and basal energy expenditure.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Heat Stress | Experimental | Heat stress via 70-80°C sauna exposure for 45-min sessions on 5 consecutive days (days 4-8 or 5-9 of follicular phase). |
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| Sleep Stress | Experimental | Sleep restriction to 4-6 hours/night for 5 consecutive nights (on days 3-8 or 4-9 of follicular phase). |
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| Exercise Stress | Experimental | One-hour cycling at 60-75% predicted max HR for 5 consecutive days (days 4-8 or 5-9 of follicular phase). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Heat stress | Other | Stress-Heat participants will undergo supervised 40-min sessions in a 70-80ËšC sauna |
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| Measure | Description | Time Frame |
|---|---|---|
| Total daily energy expenditure (TDEE) | TDEE (kcal) will be measured over a 7-day period during the Baseline and first Intervention month using the doubly-labeled water (DLW) method. DLW is a safe and reliable method for capturing free-living TDEE and has been validated for human studies. The DLW method adds a known amount of stable isotopes, oxygen-18 (18O) and deuterium (2H), to a participant's total body water (TBW) via ingestion and then measures the depletion rate of these isotopes as they are removed from the body via urine and exhalation. | Baseline (Month 2), Intervention (Month 4) |
| Basal metabolic rate (BMR) | BMR (kcal/d) will be estimated via indirect calorimetry. Participants will be asked to come in for a lab visit on a day of their choice within 2-7 days post-ovulation prior to consuming breakfast or any non-water beverage and after having refrained from exercise for 24 hours pre-measurement. Participants will lie on an exam bed in the Pontzer Lab and have a clear plastic hood connected to a COSMED Quark RMR machine placed over their head for approximately 25-30 minutes. This hood will collect exhaled air, which will be measured for CO2 production to estimate BMR. | Baseline (Month 2), Control (Month 3), Intervention (Months 4-5), and Follow-up (Month 6) |
| Sex hormone concentration (estradiol) | Samples will be assayed via enzyme-linked immunosorbent assay (ELISA) in the Pontzer Lab. | Baseline (Month 2), Control (Month 3), Intervention (Months 4-5), and Follow-up (Month 6) |
| Sex hormone concentration (progesterone) | Samples will be assayed via enzyme-linked immunosorbent assay (ELISA) in the Pontzer Lab. | Baseline (Month 2), Control (Month 3), Intervention (Months 4-5), and Follow-up (Month 6) |
| Measure | Description | Time Frame |
|---|---|---|
| Stress hormone concentration (norepinephrine) | Samples will be assayed via enzyme-linked immunosorbent assay (ELISA) in the Pontzer Lab. | Baseline (Month 2), Control (Month 3), Intervention (Months 4-5), and Follow-up (Month 6) |
| Stress hormone concentration (cortisol) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Herman Pontzer, PhD | Duke University Evolutionary Anthropology Department | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Duke University | Recruiting | Durham | North Carolina | 27708 | United States |
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| ID | Term |
|---|---|
| D018869 | Heat-Shock Response |
| D005080 | Exercise Test |
| ID | Term |
|---|---|
| D013312 | Stress, Physiological |
| D010829 | Physiological Phenomena |
| D006334 | Heart Function Tests |
| D003935 | Diagnostic Techniques, Cardiovascular |
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| Sleep stress | Other | Stress-Sleep participants will be asked to sleep for between 4 and 6 hours per night, with compliance monitored via their activity monitors and self-reported sleep diaries. Participants will be requested to maintain normal wake cycles without midday sleep. |
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| Exercise stress | Other | Stress-Exercise participants will come to the Pontzer Lab to complete a one-hour cycling workout on a Lode Corival CPET ergometer/exercise bike at 60-75% predicted maximum heart rate. |
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Samples will be assayed via enzyme-linked immunosorbent assay (ELISA) in the Pontzer Lab. |
| Baseline (Month 2), Control (Month 3), Intervention (Months 4-5), and Follow-up (Month 6) |
| Stress hormone concentration (salivary alpha-amylase) | Samples will be assayed via enzyme-linked immunosorbent assay (ELISA) in the Pontzer Lab. | Baseline (Month 2), Control (Month 3), Intervention (Months 4-5), and Follow-up (Month 6) |
| Sex hormone concentration (luteinizing hormone (LH)) | Samples will be assayed via enzyme-linked immunosorbent assay (ELISA) in the Pontzer Lab. | Baseline (Month 2), Control (Month 3), Intervention (Months 4-5), and Follow-up (Month 6) |
| Sex hormone concentration (follicle-stimulating hormone (FSH)) | Samples will be assayed via enzyme-linked immunosorbent assay (ELISA) in the Pontzer Lab. | Baseline (Month 2), Control (Month 3), Intervention (Months 4-5), and Follow-up (Month 6) |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D012129 | Respiratory Function Tests |
| D003948 | Diagnostic Techniques, Respiratory System |
| D016552 | Ergometry |
| D008919 | Investigative Techniques |