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The aim of this randomised-controlled trial is to examine whether the timing of oral contraceptive administration affects cognitive function, substrate metabolism and exercise performance.
Participants will attend the laboratory for a familiarisation session, followed by two main trials in which cognition and exercise metabolism and performance are measured. In one trial they will be given their oral contraceptive 60 minutes before testing begins, in the other they will be given a placebo. Following testing (~60 minutes), participants will consume the alternative pill.
Reproductive hormones, such as oestrogen and progesterone, are known to affect cognitive function (i.e. thinking, learning and processing information) and substrate metabolism (i.e. how the body uses carbohydrates and fats). Oral contraceptives contain synthetic versions of reproductive hormones and are used by approximately half of women of reproductive age. When oral contraceptives are ingested, the concentrations of these synthetic hormones spike in the blood for several hours, yet no research has explored the effect of this spike on how the body works, especially with regards to cognitive function and substrate metabolism. If this spike in synthetic hormone concentrations affects cognition or metabolism, this could influence the way in which women use oral contraceptives, such as altering the timing of ingestion to improve performance and health outcomes.
The proposed study will use participants that currently use a specific preparation of oral contraceptive (30micrograms ethinyl estradiol and 150mg Levonorgestrel) and compare cognitive function and substrate metabolism on an occasion when a placebo is consumed (lactose - no hormones), to an occasion when their oral contraceptive is consumed. It takes approximately 60-90 minutes for concentrations of hormones to peak in the blood following ingestion, therefore measurements of cognitive function and substrate metabolism will be taken at this time. Cognitive function will be measured using a battery of tests administered orally or via a laptop and substrate metabolism will be measured by collecting expired air via a mouthpiece at rest and during exercise on a treadmill, during which time perceived difficulty of the exercise (rate of perceived exertion) and feelings (felt arousal) will be measured. Venous blood samples will be drawn at baseline (immediately before consumption of first pill/placebo) and 90 minutes following this. The participants will consume either the placebo or oral contraceptive (whichever was not initially consumed) following the testing protocol to ensure that their contraceptive protection is maintained.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Oral contraceptive | Experimental | Participants existing oral contraceptive to be ingested at 8am on a day between 3 to 21 of pill consumption. Placebo consumed ~2 hours later |
|
| Placebo | Placebo Comparator | Placebo ingested at 8am on a day between 3 to 21 of pill consumption. Participants existing oral contraceptive consumed ~2 hours later |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Combined oral contraceptive pill | Drug | Ingesting their existing combined oral contraceptive pill at a specific time of day in relation to assessment of outcome measures |
|
| Measure | Description | Time Frame |
|---|---|---|
| Rey Auditory Verbal Test Performance | Acquisition, Learning rate, Proactive Interference, Retroactive interference, Forgetting | 60-90 minutes post oral contraceptive/placebo ingestion |
| Mental Rotation test | Accuracy, Response time | 60-90 minutes post oral contraceptive/placebo ingestion |
| Verbal Fluency | Words said | 60-90 minutes post oral contraceptive/placebo ingestion |
| Stroop test | Accuracy, Response time | 60-90 minutes post oral contraceptive/placebo ingestion |
| Corsi blocks | Correct sequences, longest sequence | 60-90 minutes post oral contraceptive/placebo ingestion |
| Rapid Visual Information Processing | Proportion correct, Response time | 60-90 minutes post oral contraceptive/placebo ingestion |
| Rating of perceived exertion | Borg rating of perceived exertion (RPE) scale from 6-20. Higher value indicates greater exertion | During final minute of of 6 minutes exercise at both 70 and 90% lactate threshold. Exercise takes place approximately 90 minutes post oral contraceptive/placebo ingestion |
| Felt arousal |
| Measure | Description | Time Frame |
|---|---|---|
| Seum ethinyl estradiol | Synthetic oestrogen concentrations in blood | Baseline and immediately post cognitive function tests |
| Serum Levonorgestrel | Synthetic progesterone concentrations in blood |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Dan Martin, PhD | University of Lincoln | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dan Martin | Lincoln | Lincolnshire | LN6 7TS | United Kingdom |
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| ID | Term |
|---|---|
| D003277 | Contraceptives, Oral, Combined |
| ID | Term |
|---|---|
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |
| D003276 | Contraceptives, Oral |
| D003271 | Contraceptive Agents, Female |
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Randomised-controlled crossover trial
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Random number generator, via technicians, concealed allocation
Felt arousal scale from 1-6. Higher value indicates greater level of arousal |
| During final minute of of 6 minutes exercise at both 70 and 90% lactate threshold. Exercise takes place approximately 90 minutes post oral contraceptive/placebo ingestion |
| Feeling scale | Feeling scale -5 to +5. Higher value indicates more positive feeling. | During final minute of of 6 minutes exercise at both 70 and 90% lactate threshold. Exercise takes place approximately 90 minutes post oral contraceptive/placebo ingestion |
| Heart rate | beats per minute | During final minute of of 6 minutes exercise at both 70 and 90% lactate threshold. Exercise takes place approximately 90 minutes post oral contraceptive/placebo ingestion |
| Carbohydrate oxidation | Rate of carbohydrate use | During final minute of of 6 minutes exercise at both 70 and 90% lactate threshold. Exercise takes place approximately 90 minutes post oral contraceptive/placebo ingestion |
| Fat oxidation | Rate of fat use | During final minute of of 6 minutes exercise at both 70 and 90% lactate threshold. Exercise takes place approximately 90 minutes post oral contraceptive/placebo ingestion |
| Respiratory exchange ratio | Ratio of carbohydrate and fat metabolism | During final minute of of 6 minutes exercise at both 70 and 90% lactate threshold. Exercise takes place approximately 90 minutes post oral contraceptive/placebo ingestion |
| Breathing frequency | breaths per minute | During final minute of of 6 minutes exercise at both 70 and 90% lactate threshold. Exercise takes place approximately 90 minutes post oral contraceptive/placebo ingestion |
| Maximal oxygen consumption (VO2max) | Maximal rate of oxygen used | During maximal exercise test which occurs approximately 110 minutes post oral contraceptive/placebo ingestion |
| Time to exhaustion | Time before test termination | During maximal exercise test which occurs approximately 110 minutes post oral contraceptive/placebo ingestion |
| Maximal heart rate | Maximal heart rate achieved | During maximal exercise test which occurs approximately 110 minutes post oral contraceptive/placebo ingestion |
| Baseline and immediately post cognitive function tests |
| D003270 | Contraceptive Agents |
| D012102 | Reproductive Control Agents |
| D045505 | Physiological Effects of Drugs |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D045506 | Therapeutic Uses |