Oral Contraceptive Consumption Timing and Cognition and Metabolism

Effects of Oral Contraceptive Consumption Timing on Cognition and Metabolism

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.

Study Overview

• Status: Completed
• Conditions: Cognitive Change
• Intervention / Treatment: Drug: Combined oral contraceptive pill

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Lincolnshire
    • Lincoln, Lincolnshire, United Kingdom, LN6 7TS
      • Dan Martin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Female
• Aged 18-35 years
• The use of the same oral contraceptive (30 micrograms ethinyl estradiol and 150mg levonorgestrel) for at least 6 months
• Physically active and able to take part in treadmill-based exercise
• Speak fluent English

Exclusion Criteria:

• Use of any other type of hormonal contraception
• Aged < 18 or > 35 years
• Poly-cystic ovarian syndrome
• Endometriosis
• Pregnant
• Child birth or lactation in the previous 6 months
• Body mass index < 18.5 or > 30 kg.m2
• Any disorder known to affect metabolic health
• History of head injury/neurological disorders
• Use of any steroid-based medication or medications known to influence the central nervous system
• History of psychiatric disorders such as major depression or an anxiety disorder
• Smokers
• Suffer from (or have suffered from) a heart complaint
• Advised by medical professional to refrain from high intensity exercise
• Current muscle or joint injury

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral contraceptive; Participants existing oral contraceptive to be ingested at 8am on a day between 3 to 21 of pill consumption. Placebo consumed ~2 hours later	Drug: Combined oral contraceptive pill; Ingesting their existing combined oral contraceptive pill at a specific time of day in relation to assessment of outcome measures
Placebo Comparator: Placebo; Placebo ingested at 8am on a day between 3 to 21 of pill consumption. Participants existing oral contraceptive consumed ~2 hours later	Drug: Combined oral contraceptive pill; Ingesting their existing combined oral contraceptive pill at a specific time of day in relation to assessment of outcome measures

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Secondary Outcome Measures

Outcome Measure	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	Baseline and immediately post cognitive function tests

Collaborators and Investigators

• Sponsor: University of Lincoln
• Investigators: Principal Investigator: Dan Martin, PhD, University of Lincoln

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2020
• Primary Completion (Actual): January 20, 2024
• Study Completion (Actual): January 20, 2024

Study Registration Dates

• First Submitted: June 27, 2023
• First Submitted That Met QC Criteria: August 15, 2024
• First Posted (Actual): August 19, 2024

Study Record Updates

• Last Update Posted (Actual): August 21, 2024
• Last Update Submitted That Met QC Criteria: August 19, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Reproductive Control Agents; Contraceptive Agents, Female; Contraceptive Agents; Contraceptives, Oral; Contraceptives, Oral, Combined
• Other Study ID Numbers: 718

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No