The REgistry of Very Early Estrogen and AnovuLation (REVEAL)

The purpose of this study is to to build a registry of women with early estrogen loss due to Functional Hypothalamic Amenorrhea (FHA) to understand the prevalence, racial and ethnic diversity of this condition.

Study Overview

• Status: Recruiting
• Conditions: Hypothalamic Amenorrhea; Hypothalamic Amenorrhea, Functional; Functional Hypogonadotropic Hypogonadism
• Intervention / Treatment: Other: Automated Self-Administered 24-hour Dietary Assessment Tool (ASA24); Other: REVEAL Questionnaire

• Study Type: Observational
• Enrollment (Estimated): 100000

Contacts and Locations

• Study Contact: Name: Chandler E. Palmer, MHA; Phone Number: 904-953-5438; Email: palmer.chandler@mayo.edu
• Study Contact Backup: Name: Chrisandra L Shufelt, MD; Phone Number: 904 953-7224; Email: DLREVEAL@exchange.mayo.edu

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic
      • Principal Investigator: Chrisandra Shufelt, MD
      • Contact: Chrisandra Shufelt, MD; Email: DLREVEAL@exchange.mayo.edu
      • Sub-Investigator: Stephanie Faubion, MD
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
      • Contact: Chandler E. Palmer, MHA; Phone Number: 904-953-5438; Email: palmer.chandler@mayo.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study subjects are women aged 18-40 years old with a diagnosis of Functional Hypothalamic Amenorrhea (FHA) or lab results that are within the inclusion criteria. To ensure accurate case ascertainment before enrollment into the study, volunteers must have a diagnosis of FHA from a provider with previously performed lab tests, which will be reviewed and adjudicated by a women's health expert to confirm a diagnosis of FHA. If the potential participant doesn't have access or cannot obtain the required lab results, they can contact the study team to receive an at-home finger-stick hormone test (U.S. Specialty Labs) paid for by the study.

Description

Inclusion Criteria:

• 3 or more months of consecutive amenorrhea with a diagnosis of functional hypothalamic amenorrhea or screening hormones consistent with functional hypothalamic amenorrhea including but not limited to:

  • Estradiol: < 50pg/mL
  • LH: < 10 IU/mL
  • FSH: < 10 IU
  • Testosterone: 2 - 45 ng/dL
  • Free Testosterone: 0.1 - 6.4 pg/mL
  • FT4: 0.93 - 1.70 ng/dL
  • Prolactin: < 20 ng/mL
  • AMH: > 1 ng/mL
  • Urine or serum human chorionic gonadotropin: Negative
• LH:FSH Ratio <1
• No signs of male-like hair growth on the upper lip, chin, chest, abdomen, buttocks, or back
• Does not have a diagnosis for secondary amenorrhea, including prolactinoma, PCOS, premature ovarian insufficiency, pituitary surgery, infection, or infarction
• Premenopausal status determined by WISE criteria
• Able to give informed consent
• Able to read English

Exclusion Criteria:

• Parturition/lactating in the last 6-12 months
• Lack of consent

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Women with > 3 months amenorrhea; Women aged 18-40 years old with a diagnosis of functional hypothalamic amenorrhea, or lab results that are within the inclusion criteria.	Other: Automated Self-Administered 24-hour Dietary Assessment Tool (ASA24); Subjects will complete the ASA food diary for 2 weekdays and 1 weekend day; Other: REVEAL Questionnaire; Subjects will complete the REVEAL questionnaire form. This form includes questions about current and past medical history, including reproductive history, lifestyle specifics, and assessment of current health status.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Study Participants	Establish and maintain a comprehensive registry of patients diagnosed with Functional Hypothalamic Amenorrhea (FHA). This registry will include detailed demographic information, clinical data, and longitudinal follow-up to track the prevalence, underlying causes, risk factors, and prognosis of FHA. It will also facilitate the collection of data on racial and ethnic disparities, lifestyle factors, psychological stressors, hormonal imbalances, and the impact of various treatment interventions on long-term health outcomes collected through questionnaires done at baseline and yearly.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessing the Impact of Amenorrhea on Women's Health: Symptoms, Care Experiences, and Work Productivity	Improve understanding of women's overall experience of Functional Hypothalamic Amenorrhea (FHA) by documenting the types of care received, frequency and quality of healthcare interactions, and patient satisfaction with the care provided. This includes detailed assessments of specific treatments or therapies received, the involvement of multidisciplinary care approaches, and the extent of follow-up care. Additionally, to quantify the impact of FHA on lost work productivity, including the number of workdays missed, impact on work performance, and economic burden associated with amenorrhea-related issues, measured at baseline and then yearly using questionnaires.	5 years
Impact of Social, Early Life, and Pregnancy Factors on Functional Hypothalamic Amenorrhea	Enhance the understanding of how social determinants of health-such as socioeconomic status, education, access to healthcare, and community environment-contribute to the development of Functional Hypothalamic Amenorrhea (FHA). Additionally, the study will explore the impact of childhood adversity, including exposure to trauma, abuse, neglect, or chronic stress, on the likelihood of developing FHA. The relationship between pregnancy complications, such as preterm birth, miscarriage, or gestational conditions, and the onset of FHA will also be analyzed. Data will be collected through baseline and annual questionnaires throughout the study, providing a comprehensive understanding of these factors' roles in the development of FHA.	5 years

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Chrisandra Shufelt, MD, Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2024
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2029

Study Registration Dates

• First Submitted: August 22, 2024
• First Submitted That Met QC Criteria: August 30, 2024
• First Posted (Actual): September 4, 2024

Study Record Updates

• Last Update Posted (Actual): November 21, 2025
• Last Update Submitted That Met QC Criteria: November 18, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Anovulation; Hypoestrogenemia; Estrogen Loss
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Diseases, Female; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Anovulation
• Other Study ID Numbers: 24-000952

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
• product manufactured in and exported from the U.S.: No