Assessing Urinary Hormones in Female Cancer Survivors

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Follicular and Luteal Dysfunction in Cancer Survivors

Conditions
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Effects of Chemotherapy

Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 1<br>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<br>Healthy, mid-reproductive aged women between the ages of 20 to 35 who have not been exposed to cancer therapy. | |
| Group 3<br>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?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hormones, fertility, healthy, chemotherapy, oncofertility, alkylating agent, fertility after cancer, late effects, survivorship, healthy volunteers, perimenopause, middle age