Impact of Menstrual Phase on Oral Glucose Sensitivity

Role of Metabolic Sensing in Human Sweet Taste

In this study we are determining whether the hormones associated with the phases of the menstrual cycle (menstruation & ovulation) influence taste sensitivity to glucose. We hypothesized that women would be more sensitive to oral glucose as assessed by absolute detection threshold during ovulation than when assessed during menstruation. These phases of the cycle are associated with peak plasma estradiol levels and nadir estradiol levels. There is evidence that estrogen can increase the sensitivity of the metabolic signaling pathway of the pancreatic beta-islet cells to stimulate insulin release more readily when glucose is present by increasing sensitivity of the K-ATP channel to ATP. Since the same metabolic signaling pathway is reported to be present in taste tissue, we tested whether peak estrogen levels would enhance taste detection of glucose but not sweeteners that cannot generate ATP, such as sucralose or methyl-D-glucopyranoside (MDG).

Study Overview

• Status: Completed
• Conditions: Menstruation; Ovulation
• Intervention / Treatment: Diagnostic test: Urinary Estrogen Level

Detailed Description

Participants: The participants consisted of 15 healthy, non-obese, cycling females between the ages of 18-46 years. All participants completed informed consent and the study protocol was approved by the Rutgers University Institutional Review Board. 30 participants were screened for eligibility requirements. Inclusion criteria consisted of a regular menstrual cycle of 21-35 days. Exclusion criteria included hormonal contraceptives or other hormonal treatments, a history of polycystic ovarian syndrome (PCOS), menstrual irregularities, pregnancy, diabetes mellitus, thyroid conditions, recent COVID-19 infection, alterations in taste or smell, and medications affecting blood pressure. 23 participants were recruited and 7 participants became ineligible due to a variety of factors including: starting hormonal contraception, an irregular or missed cycle, <100 ng/mL E3G throughout periovulation, a lack of increased E3G at ovulation as compared to menstruation or lost to follow up. The participants in the control group consisted of 7 healthy, non-obese males between the ages of 18-26 years old.

Ovulation Tracking: Participants were asked to test their urine at the first urination of the day with Mira fertility MAX wands (San Francisco, CA) according to product instructions for 5 days prior to expected ovulation. Mira fertility MAX wands detect urine luteinizing hormone (LH), oestrone-3-glucuronide (E3G), and pregnanediol (PdG). E3G is a metabolite of estrone and is a marker of plasma 17-beta-estradiol. When participants' E3Gs rose above their menstruation baseline and reached > 100 ng/mL, they were asked to undergo the taste testing.

Biological males were also tested under the same conditions at comparable time differences (approximately 2 weeks apart) as a control for variation in taste testing.

Detection Threshold Testing: Participants underwent detection threshold testing with 1/8 log step serial dilutions of D-(+)-glucose (> 99.5%, Sigma-Aldrich, USA), sucralose and methyl-D-glucopyranoside (Sigma-Aldrich, USA). The participants were randomly presented with glucose or sucralose detection testing, followed by MDG detection testing. Detection threshold testing followed a 2-alternative-forced choice (2AFC) paradigm. Two medicine cups of Millipore water and dilute stimulus were presented to the participant in random order and the participant was asked which stimulus was "not water." A 4-down-1-up modified staircase method was used to obtain the oral detection threshold of the sweet stimulus. In this method, the participant is required to make the correct choice four times until the next more dilute stimulus is presented, and if the participant is wrong once, a more concentrated stimulus is presented in the next trial. Once the participant has made 5 reversals, the last 4 concentrations are averaged and defined as the detection threshold concentration for that stimulus. Participants wore nose clips throughout their testing.

Hedonic Rating Testing: Participants were trained to use the hedonic labeled magnitude scale. Participants were presented with three rows of randomized 450 mM and 900 mM glucose solutions and asked to taste and expectorate each solution and then rate their liking of the solution on a hedonic labeled magnitude scale. The solutions were presented in random order with a 30 second rinse of Millipore water in between each stimulus. Between each row there was a 2 minute break. Subjects did not wear nose clips for this part of the study.

• Study Type: Observational
• Enrollment (Actual): 22

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Department of Nutritional Sciences

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

Participants were selected from residents in the general area around New Brunswick NJ where Rutgers University is located. Women and men were recruited of all available races and ethnicities.

Description

Inclusion Criteria:

• regular menstrual cycle of 21-35 days

Exclusion Criteria:

• hormonal contraceptives or other hormonal treatments
• a history of polycystic ovarian syndrome (PCOS)
• menstrual irregularities
• pregnancy
• diabetes mellitus
• thyroid conditions
• recent COVID-19 infection
• alterations in taste or smell
• medications affecting blood pressure

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cycling Women; This is a group of women who have regular menstrual cycles.	Diagnostic test: Urinary Estrogen Level; Women had urinary estrogen metabolite levels measured daily to identify both the nadir (menstruation) and the peak (peri-ovulation) of the cycle. Men were also tested at the same time intervals, approximately two-weeks apart.
Men; These men serve as an age-matched control who do not have high estrogen levels, as males do not have menstrual cycles.	Diagnostic test: Urinary Estrogen Level; Women had urinary estrogen metabolite levels measured daily to identify both the nadir (menstruation) and the peak (peri-ovulation) of the cycle. Men were also tested at the same time intervals, approximately two-weeks apart.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oral Glucose Detection Threshold	Participants had an oral glucose detection threshold measured at menstruation (estrogen nadir) and peri-ovulation (estrogen peak). Men were tested twice two weeks apart over the same time frame as women.	Women were tested twice over the course of a cycle at menstruation and ovulation, and this was repeated for two cycles (across two months).
Oral Sucralose Detection Threshold	Participants had an oral sucralose detection threshold measured at menstruation (estrogen nadir) and peri-ovulation (estrogen peak).	Women were tested twice over the course of a cycle at menstruation and ovulation, and this was repeated for two cycles (across two months).
Oral MDG Detection Threshold	Participants had an oral s detect MDG (methyl-D-glucopyranoside) on threshold measured at menstruation (estrogen nadir) and peri-ovulation (estrogen peak).	Women were tested twice over the course of a cycle at menstruation and ovulation, and this was repeated for two cycles (across two months).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentrated Glucose Solution Preference	Participants tasted 450 and 900 mM glucose and rated liking on a labeled hedonic scale at menstruation (estrogen nadir) and peri-ovulation (estrogen peak).	Women were tested twice over the course of a cycle at menstruation and ovulation, and this was repeated for two cycles (across two months).

Collaborators and Investigators

• Sponsor: Rutgers, The State University of New Jersey
• Collaborators: National Institute on Deafness and Other Communication Disorders (NIDCD)
• Investigators: Principal Investigator: Paul A Breslin, PhD, Rutgers, The State University of New Jersey

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2021
• Primary Completion (Actual): November 12, 2024
• Study Completion (Actual): December 10, 2024

Study Registration Dates

• First Submitted: January 17, 2025
• First Submitted That Met QC Criteria: January 28, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 28, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: estrogen; progesterone; glucose; sensitivity; taste; K-ATP
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens
• Other Study ID Numbers: 2019001483; R21DC020365 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: When published the data will be available upon request of the article contact.
• IPD Sharing Time Frame: March 2025 - February 2032
• IPD Sharing Access Criteria: Those requiring data for further analysis or for publication purposes at an institute of research or higher education may request information. Requests must describe the types of analyses that will be conducted.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No