Assessing Urinary Hormones in Female Cancer Survivors (AUHS)

Follicular and Luteal Dysfunction in Cancer Survivors

Women of late to mid reproductive age may participate in a study using novel methodology to identify subtle changes in the reproductive endocrine axis via daily urine hormone analysis, which may have important implications for reproduction and may signal reproductive senescence.

Study Overview

• Status: Completed
• Conditions: Effects of Chemotherapy

Detailed Description

Women with a reduced follicular pool either from natural aging or previous chemotherapy, may not have any clinical signs or symptoms and traditional measures of ovarian reserve, such as basal Follicle Stimulating Hormone may be within the normal range. However, there may be alterations in the luteal or follicular phases(shortened follicular phase and luteal insufficiency) due to compromised follicle competency and alterations in the H-P-O axis. Therefore this aim uses novel methodology to identify subtle changes in the reproductive endocrine axis which may have important implications for reproduction and may signal reproductive senescence. Compared to yearly follicular measures of reproductive hormones, daily urine hormone analysis provides a more integrative assessment.

Three groups of subjects will be recruited:

Group 1: Otherwise healthy, mid-reproductive aged women between the ages of 20 and 35 years previously exposed to high dose alkylating agent therapy (or have an alkylator score of 1 or more), and at least 1 year from cancer treatment.

Group 2: healthy, mid-reproductive aged women between the ages of 20 to 35 who have not been exposed to cancer therapy.

Group 3: healthy, late reproductive aged women between the ages of 43-50 who have not been exposed to cancer therapy, nor have a history of infertility.

Subjects in all groups must have regular menstrual cycles every 21-35 days, and have a uterus and both ovaries. Each participant will complete daily urinary collections for 2 menstrual cycles to assess reproductive hormones. The ultimate goal of this work is to better estimate the reproductive window, or time to menopause.

• Study Type: Observational
• Enrollment (Actual): 38

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania, Reproductive Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

• Regularly menstruating postmenarchal, mid-reproductive aged female cancer patients treated with high dose alkylating agent chemotherapy or with an alkylator score of 1 or more.
• Unexposed, regularly menstruating mid-reproductive aged women, and unexposed, regularly menstruating late reproductive aged women.

Description

Inclusion Criteria for Group 1:

• Otherwise healthy, mid-reproductive aged women between the ages of 20 and 35 years previously exposed to high dose alkylating agent therapy (or have an alkylator score of 1 or more), and at least 1 year from cancer treatment.

Inclusion Criteria for Group 2:

• Healthy, mid-reproductive aged women between the ages of 20 to 35 who have not been exposed to cancer therapy.

Inclusion Criteria for Group 3:

• Healthy, late reproductive aged women between the ages of 43-50 who have not been exposed to cancer therapy, nor have a history of infertility.

Exclusion Criteria for all subjects:

• Pregnancy or lactation within the previous 3 months
• Use of hormonal contraception or replacement within the previous 3 months
• Body Mass Index greater than 30 kg/m2
• Excessive exercise greater than 1 hour per day
• Any medical condition other than cancer known to be associated with premature ovarian failure (such as Turners Syndrome or Fragile X) or ovulatory dysfunction (such as thyroid disease, congenital adrenal hyperplasia, Cushings syndrome, hyperprolactinemia, and polycystic ovary syndrome)

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Group 1; Otherwise healthy, mid-reproductive aged women between the ages of 20 and 35 years previously exposed to high dose alkylating agent therapy (or have an alkylator score of 1 or more), and at least 1 year from cancer treatment.
Group 2; Healthy, mid-reproductive aged women between the ages of 20 to 35 who have not been exposed to cancer therapy.
Group 3; Reproductive aged women between the ages of 43-50 who have not been exposed to cancer therapy, nor have a history of infertility

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urinary Follicle Stimulating Hormone (FSH)	Integrated urinary follicular-phase Follicle Stimulating Hormone (FSH) in urine samples collected daily for 2 menstrual cycles will be measured in mIU/mL by means of two-site chemiluminescent immunoassay with the use of two monoclonal antibodies.	up to 49 days each menstrual cycle
Urinary Luteinizing Hormone (LH)	Integrated urinary follicular-phase Luteinizing Hormone (LH) in urine samples collected daily for 2 menstrual cycles will be measured in mIU/mL by means of two-site chemiluminescent immunoassay with the use of two monoclonal antibodies.	up to 49 days each menstrual cycle
Urinary Estrone Conjugate (E1C)	Estrone Conjugate (E1C) in urine samples collected daily for 2 menstrual cycles will be measured in ug/dL by means of E1C immunoassay.	up to 49 days each menstrual cycle
Urinary Pregnanediol-glucuronide	Pregnanediol-glucuronide (PDG) in urine samples collected daily for 2 menstrual cycles will be measured in ug/mL by means of PDG immunoassay.	up to 49 days each menstrual cycle
Urinary Creatinine	Urinary Creatinine in urine samples collected daily for 2 menstrual cycles will be measured in mg/mL by means of spectrophotometric assay.	up to 49 days each menstrual cycle

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Luteal and follicular phase lengths	Participants will be provided with calendars on which to record detailed menstrual cycle information during the study. The total menstrual cycle length will be defined as the number of days from day 1 of menses to the day before the next menses. The Kassam method will be used to determine evidence of luteal activity, presumably ovulation. Follicular phase will be defined as the number of days from day 1 of menses up to the day of luteal transition and the luteal phase length will be defined as the number of days beginning from the day after the day of luteal transition to the day before the next menses.	up to 49 days each menstrual cycle

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Clarisa R Gracia, MD, MSCE, University of Pennsylvania, Reproductive Research Unit

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (ACTUAL): May 1, 2016
• Study Completion (ACTUAL): May 1, 2016

Study Registration Dates

• First Submitted: July 22, 2013
• First Submitted That Met QC Criteria: June 22, 2017
• First Posted (ACTUAL): June 23, 2017

Study Record Updates

• Last Update Posted (ACTUAL): November 20, 2020
• Last Update Submitted That Met QC Criteria: November 19, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: chemotherapy; healthy volunteers; survivorship; healthy; fertility; hormones; perimenopause; oncofertility; middle age; late effects; alkylating agent; fertility after cancer
• Other Study ID Numbers: 811323

Plan for Individual participant data (IPD)

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