Follicle Stimulating Hormone (FSH) Glycosylation in Women: Effect of Estradiol

Phase 2

• Conditions: Follicle Stimulating Hormone Glycosylation; Urinary FSH21/FSH24 Ratio; Estradiol Effect
• Interventions: Drug: Estradiol Transdermal Product

• Registration Number: NCT03868202
• Lead Sponsor: Eastern Virginia Medical School

Brief Summary

This clinical trial is an investigational research study to determine the ratio of glycosylated FSH21/FSH24 in premenopausal women and postmenopausal women as well as determining if estradiol can increase this ratio in postmenopausal women.

Detailed Description

Follicle Stimulating Hormone (FSH), is secreted by the pituitary gland at the base of the brain, and is the primary stimulus for growth of the ovarian follicle that contains the egg. Glycosylation, or adding glucose, to FSH is critical for its bioactivity on stimulating the ovarian follicle. The FSH with less glycosylation (FSH21) has a higher affinity for the FSH receptor and activates more pathways than does fully-glycosylated FSH (FSH24). Previous studies showed pituitaries from young women contain a high ratio of FSH21/FSH24 while pituitaries from older and postmenopausal women have a lower ratio of FSH21/FSH24. The investigators hypothesize that the higher FSH21/FSH24 ratio found in young women is responsible for normal follicle growth.

This study is intended to provide the first determination of systemic changes in the ratio of FSH21/FSH24 and determine if estradiol increases the FSH21/FSH24 ratio in the first morning urine of women. To take part in this study, the participant must be willing to collect the first morning urine on particular mornings of the menstrual cycle and be available for blood draws on those mornings. Additionally for postmenopausal participants, the participant must be willing to use topical estrogen, EstroGel©, for 14 days and be willing to collect the first morning urine on particular mornings and again be available for blood draws on those mornings. For the postmenopausal participants with an intact uterus, the participants must be willing to take an oral progestin, micronized progesterone, for 12 days following the completion of the study.

Study Timeline

• Study First Submitted: 2019-03-04
• Study First Submitted QC: 2019-03-07
• Study First Posted: 2019-03-11
• Status Verified: 2019-07
• Study Start: 2019-07-03
• Last Update Submitted: 2019-07-10
• Last Update Posted: 2019-07-12
• Primary Completion: 2019-11
• Study Completion: 2020-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 10

Inclusion Criteria

Premenopausal (Age 20-30):

1. Age between 20 - 30 years old
2. Not on oral, transdermal or vaginal hormonal contraception with last use greater than 2 months (non-hormonal IUD okay)
3. At least 6 weeks after removal of subdermal contraceptive implant
4. At least 9 months from the last hormonal contraceptive injection
5. Regular menses with a 26-32 day interval
6. Willingness to abstain from heterosexual intercourse or use barrier contraception during the study
7. No serious medical illness
8. Not on medication(s) effecting ovarian function
9. Screening ultrasound on cycle day 12-14 with at least 1 follicle measuring >12mm.
10. Normal pap smear within the last 3 years, if indicated (report needed)

Postmenopausal (Age 45-60):

1. Age between 45-60 years old
2. Last spontaneous menstrual period >1 year
3. Vaginal pH > 5.0
4. No contraindications to hormonal replacement therapy
5. No major medical condition/current medication(s) that would impact use of hormone replacement therapy
6. Never have been on hormone replacement therapy or last use greater than 6 months
7. Mammogram within the last 1 year that is normal (report needed)
8. Pap smear within the last 3-5 years that is normal (report needed)
9. Willing to use hormone replacement therapy

Exclusion Criteria

Premenopausal (Age 20-30):

1. Uncorrected endocrinopathy affecting ovarian function (i.e.: Prolactinoma, thyroid disease)
2. Medications affecting the hypothalamic-pituitary-ovarian axis.
3. Screening ultrasound with no follicles measuring ≥11 mm
4. History of pelvic surgery
5. Current abnormal pap smear requiring intervention

Postmenopausal (Age 45-60):

1. Last menstrual period <1 year
2. Contraindication to hormone replacement therapy
3. Use of exogenous hormone replacement therapy in the last 6 months
4. Significant medical disease or current medication use that can impact estrogen metabolism
5. Unwilling or unable to use transdermal estrogen and oral progestin.
6. Allergy to transdermal estrogen and oral progestin.
7. Unexplained vaginal bleeding within the last 6 months.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Postmenopausal women	Estradiol Transdermal Product	Participants will bring into clinic their first voided urine of the day on assigned days 1, 4 and 7 in a urinary collection kit that will be given. A urine dip stick will be performed on the samples. Each time they bring in a sample, they will have a serum blood draw for estradiol and FSH. The participants will then be started on EstroGel© for 14 days from day 7-21. During that time that they are on EstroGel©, the participants will bring into clinic their first voided urine of the day on assigned days 15, 18, and 21 in a urinary collection kit that will be given. A urine dip stick will be performed on the samples. Each time they bring in a sample, they will have a serum blood draw for estradiol and FSH. After the last urinary collection and blood draw, they will discontinue the EstroGel and be started on micronized progesterone if they have a uterus for 12 days.

Primary Outcome Measures

Name	Time	Method
The levels of serum estradiol and FSH in young women versus postmenopausal women.	up to 4 weeks for each participant
The ratio of urinary FSH21/FSH24 and total FSH levels in urine of young women versus postmenopausal women.	up to 4 weeks for each participant

Trial Locations

Locations (1)

Jones Institute for Reproductive Medicine; 🇺🇸 Norfolk, Virginia, United States