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

NCT03868202 | Unknown Phase 2 DMC

• 1 other identifier: 19-03-FB-0058-EVMS
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Follicle Stimulating Hormone Glycosylation; Urinary FSH21/FSH24 Ratio; Estradiol Effect

Outcome Measures

Primary Outcomes (2)

• 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

• The levels of serum estradiol and FSH in young women versus postmenopausal women.

  up to 4 weeks for each participant

Study Arms (2)

Premenopausal women

NO INTERVENTION

Participants will bring into clinic their first voided urine of the day on cycle days 9, 12 and 15 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.

Postmenopausal women

ACTIVE COMPARATOR

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.

Drug: Estradiol Transdermal Product

Interventions

Estradiol Transdermal Product DRUG

Hormone replacement therapy will be given to postmenopausal women for up to 1 month.

Also known as: Micronized progesterone

Postmenopausal women

Eligibility Criteria

• Age: 20 Years - 55 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Premenopausal (Age 20-30):
• Age between 20 - 30 years old
• Not on oral, transdermal or vaginal hormonal contraception with last use greater than 2 months (non-hormonal IUD okay)
• At least 6 weeks after removal of subdermal contraceptive implant
• At least 9 months from the last hormonal contraceptive injection
• Regular menses with a 26-32 day interval
• Willingness to abstain from heterosexual intercourse or use barrier contraception during the study
• No serious medical illness
• Not on medication(s) effecting ovarian function
• Screening ultrasound on cycle day 12-14 with at least 1 follicle measuring \>12mm.
• Normal pap smear within the last 3 years, if indicated (report needed)
• Postmenopausal (Age 45-60):
• Age between 45-60 years old
• Last spontaneous menstrual period \>1 year
• Vaginal pH \> 5.0

You may not qualify if:

• Premenopausal (Age 20-30):
• Uncorrected endocrinopathy affecting ovarian function (i.e.: Prolactinoma, thyroid disease)
• Medications affecting the hypothalamic-pituitary-ovarian axis.
• Screening ultrasound with no follicles measuring ≥11 mm
• History of pelvic surgery
• Current abnormal pap smear requiring intervention
• Postmenopausal (Age 45-60):
• Last menstrual period \<1 year
• Contraindication to hormone replacement therapy
• Use of exogenous hormone replacement therapy in the last 6 months
• Significant medical disease or current medication use that can impact estrogen metabolism
• Unwilling or unable to use transdermal estrogen and oral progestin.
• Allergy to transdermal estrogen and oral progestin.
• Unexplained vaginal bleeding within the last 6 months.

Sponsors & Collaborators

• Eastern Virginia Medical School: lead
• Wichita State University: collaborator

Study Sites (1)

Jones Institute for Reproductive Medicine

Norfolk, Virginia, 23507, United States

RECRUITING

Related Publications (13)

• Hunzicker-Dunn ME, Lopez-Biladeau B, Law NC, Fiedler SE, Carr DW, Maizels ET. PKA and GAB2 play central roles in the FSH signaling pathway to PI3K and AKT in ovarian granulosa cells. Proc Natl Acad Sci U S A. 2012 Oct 30;109(44):E2979-88. doi: 10.1073/pnas.1205661109. Epub 2012 Oct 8.

  PMID: 23045700 BACKGROUND

• Santoro N, Randolph JF Jr. Reproductive hormones and the menopause transition. Obstet Gynecol Clin North Am. 2011 Sep;38(3):455-66. doi: 10.1016/j.ogc.2011.05.004.

  PMID: 21961713 BACKGROUND

• Bousfield GR, Butnev VY, Butnev VY, Hiromasa Y, Harvey DJ, May JV. Hypo-glycosylated human follicle-stimulating hormone (hFSH(21/18)) is much more active in vitro than fully-glycosylated hFSH (hFSH(24)). Mol Cell Endocrinol. 2014 Feb 15;382(2):989-97. doi: 10.1016/j.mce.2013.11.008. Epub 2013 Dec 1.

  PMID: 24291635 BACKGROUND

• Bousfield GR, Butnev VY, Rueda-Santos MA, Brown A, Hall AS, Harvey DJ. Macro- and Micro-heterogeneity in Pituitary and Urinary Follicle-Stimulating Hormone Glycosylation. J Glycomics Lipidomics. 2014;4:1000125. doi: 10.4172/2153-0637.1000125.

  PMID: 25722940 BACKGROUND

• Wang H, May J, Butnev V, Shuai B, May JV, Bousfield GR, Kumar TR. Evaluation of in vivo bioactivities of recombinant hypo- (FSH21/18) and fully- (FSH24) glycosylated human FSH glycoforms in Fshb null mice. Mol Cell Endocrinol. 2016 Dec 5;437:224-236. doi: 10.1016/j.mce.2016.08.031. Epub 2016 Aug 22.

  PMID: 27561202 BACKGROUND

• Klein NA, Illingworth PJ, Groome NP, McNeilly AS, Battaglia DE, Soules MR. Decreased inhibin B secretion is associated with the monotropic FSH rise in older, ovulatory women: a study of serum and follicular fluid levels of dimeric inhibin A and B in spontaneous menstrual cycles. J Clin Endocrinol Metab. 1996 Jul;81(7):2742-5. doi: 10.1210/jcem.81.7.8675606.

  PMID: 8675606 BACKGROUND

• Andreasson B, Bostofte E. Influence of 2 mg estradiol-17 beta on circulating FSH, LH, total and unconjugated estradiol levels in post-menopausal women. Acta Obstet Gynecol Scand. 1981;60(6):555-8. doi: 10.3109/00016348109155485.

  PMID: 6801915 BACKGROUND

• Bunyavejchevin S, Panthong C, Limpaphayom KK. Serum estradiol and follicle-stimulating hormone levels in Thai women post total abdominal hysterectomy and bilateral oophorectomy using oral 17 beta-estradiol. J Med Assoc Thai. 2002 Jan;85(1):58-62.

  PMID: 12075721 BACKGROUND

• Fahraeus L, Larsson-Cohn U. Oestrogens, gonadotrophins and SHBG during oral and cutaneous administration of oestradiol-17 beta to menopausal women. Acta Endocrinol (Copenh). 1982 Dec;101(4):592-6. doi: 10.1530/acta.0.1010592.

  PMID: 6818806 BACKGROUND

• Robyn C, Vekemans M. Influence of low dose oestrogen on circulating prolactin. LH and FSH levels in post-menopausal women. Acta Endocrinol (Copenh). 1976 Sep;83(1):9-14. doi: 10.1530/acta.0.0830009.

  PMID: 989226 BACKGROUND

• Wide L, Naessen T. 17 beta-oestradiol counteracts the formation of the more acidic isoforms of follicle-stimulating hormone and luteinizing hormone after menopause. Clin Endocrinol (Oxf). 1994 Jun;40(6):783-9. doi: 10.1111/j.1365-2265.1994.tb02513.x.

  PMID: 8033370 BACKGROUND

• Bousfield GR, Butnev VY, Walton WJ, Nguyen VT, Huneidi J, Singh V, Kolli VS, Harvey DJ, Rance NE. All-or-none N-glycosylation in primate follicle-stimulating hormone beta-subunits. Mol Cell Endocrinol. 2007 Jan 2;260-262:40-8. doi: 10.1016/j.mce.2006.02.017. Epub 2006 Oct 31.

  PMID: 17079072 BACKGROUND

• Archer DF, Pickar JH, MacAllister DC, Warren MP. Transdermal estradiol gel for the treatment of symptomatic postmenopausal women. Menopause. 2012 Jun;19(6):622-9. doi: 10.1097/gme.0b013e31823b8867.

  PMID: 22282101 BACKGROUND

MeSH Terms

Interventions

Progesterone

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Corpus Luteum Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones

Central Study Contacts

Reem Sabouni, MD

CONTACT

757-446-7100; SabounR@evms.edu

David F Archer, MD

CONTACT

757-446-7444; ArcherDF@evms.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Fellow of Reproductive Endocrinology and Infertility

Study Record Dates

• First Submitted: March 4, 2019
• First Posted: March 11, 2019
• Study Start: July 3, 2019
• Primary Completion: November 1, 2019
• Study Completion: January 1, 2020
• Last Updated: July 12, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)