Aromatase Activity and Ovarian Growth Factors in African-American Versus Caucasian Women

NCT ID: NCT00334971

Last Updated: 2013-11-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

116 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-09-30

Study Completion Date

2018-01-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The purpose of the study is to understand how the ovarian follicle (the fluid filled structure in the ovary that contains the egg) makes estrogen and other hormones during normal aging, in women with different ethnic backgrounds, and in Fragile X premutation carriers.

During reproductive aging, estradiol levels are increased, a phenomenon that may be related to increased aromatase activity. The investigators' own preliminary data suggest that estradiol is increased in African-American women compared to Caucasian women, which may also be related to aromatase activity. In addition, the investigators have examined female fragile X premutation carriers who still have regular menstrual cycles and have demonstrated evidence of early ovarian aging compared to age-matched controls.

\*\*WE ARE RECRUITING ONLY WOMEN WITH FRAGILE-X PREMUTATION\*\*

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

The purpose of the study is to examine intrafollicular changes in aromatase and ovarian growth factors in reproductive aged women,African-American women compared to Caucasian controls, and Fragile X premutation carriers.

Hypotheses:

* Aromatase activity is up-regulated in preovulatory follicles with aging, accounting for the increased estradiol levels in the face of decreased inhibin secretion in reproductive aging.
* Increased estradiol in the face of normal inhibin A and inhibin B suggests up-regulation of aromatase in African-American women.
* Aromatase activity is down-regulated in preovulatory follicles in fragile X premutation carriers compared to age-matched controls and the activity is associated with FMR1 mRNA levels.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Healthy Fragile X Syndrome

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

African-American estradiol luteinizing hormone follicle stimulating hormone androstenedione aromatase inhibins ovarian Healthy volunteers Fragile X

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

1

Healthy Caucasian women 18-35 years old

Group Type OTHER

Follicle Aspiration

Intervention Type PROCEDURE

Follicles will be aspirated using a transvaginal ultrasound guided needle.

2

Healthy African-American women 18-35 years old

Group Type OTHER

Follicle Aspiration

Intervention Type PROCEDURE

Follicles will be aspirated using a transvaginal ultrasound guided needle.

3

Healthy Caucasian women 36-45 years old

Group Type OTHER

Follicle Aspiration

Intervention Type PROCEDURE

Follicles will be aspirated using a transvaginal ultrasound guided needle.

4

Female fragile X premutation carriers 18-45 years old

Group Type OTHER

Follicle Aspiration

Intervention Type PROCEDURE

Follicles will be aspirated using a transvaginal ultrasound guided needle.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Follicle Aspiration

Follicles will be aspirated using a transvaginal ultrasound guided needle.

Intervention Type PROCEDURE

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

Reproductively Younger Non-African-American Women:

* 18-35 years of age
* Body mass index (BMI) less than or equal to 30
* Regular menstrual cycles (25-35 days long)
* Negative beta-human chorionic gonadotrophin (HCG)
* Normal prolactin and thyroid stimulating hormone (TSH) levels
* Hemoglobin greater than or equal to 11.0 gm/dl
* Luteal phase progesterone level indicating ovulation on a previous cycle (\> 3 ng/ml)
* Not currently trying to get pregnant
* No blood donations within 2 months of initiating the blood sampling portion of the study
* On no medications thought to interfere with normal menstrual cycle dynamics
* Not current smokers or no exposure to passive smoke in the home or workplace (greater than 8 hours per day with a smoker of \> 10 cigarettes per day)
* Normal platelet count and PT/PTT
* No history of pelvic adhesions and accessible ovarian position as assessed by transvaginal ultrasound

Reproductively Younger African-American Women:

* 18-35 years of age

Reproductively Older Non-African-American Women:

* 36-45 years of age

Reproductive Aged Fragile X Premutation Carriers

* Fragile X premutation carriers, with FMR1 CGG repeat lengths between 41 and 200.
* 18-45 years of age

Exclusion Criteria

* Hemoglobin level less than 11 gm/dl at time of screening
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

Massachusetts General Hospital

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Janet E. Hall, MD

Associate Physician

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Janet E Hall, M.D.

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Reproductive Endocrine Unit, Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

Welt CK, McNicholl DJ, Taylor AE, Hall JE. Female reproductive aging is marked by decreased secretion of dimeric inhibin. J Clin Endocrinol Metab. 1999 Jan;84(1):105-11. doi: 10.1210/jcem.84.1.5381.

Reference Type BACKGROUND
PMID: 9920069 (View on PubMed)

Santoro N, Brown JR, Adel T, Skurnick JH. Characterization of reproductive hormonal dynamics in the perimenopause. J Clin Endocrinol Metab. 1996 Apr;81(4):1495-501. doi: 10.1210/jcem.81.4.8636357.

Reference Type BACKGROUND
PMID: 8636357 (View on PubMed)

Reame NE, Kelche RP, Beitins IZ, Yu MY, Zawacki CM, Padmanabhan V. Age effects of follicle-stimulating hormone and pulsatile luteinizing hormone secretion across the menstrual cycle of premenopausal women. J Clin Endocrinol Metab. 1996 Apr;81(4):1512-8. doi: 10.1210/jcem.81.4.8636360.

Reference Type BACKGROUND
PMID: 8636360 (View on PubMed)

Klein NA, Battaglia DE, Fujimoto VY, Davis GS, Bremner WJ, Soules MR. Reproductive aging: accelerated ovarian follicular development associated with a monotropic follicle-stimulating hormone rise in normal older women. J Clin Endocrinol Metab. 1996 Mar;81(3):1038-45. doi: 10.1210/jcem.81.3.8772573.

Reference Type BACKGROUND
PMID: 8772573 (View on PubMed)

MacNaughton J, Banah M, McCloud P, Hee J, Burger H. Age related changes in follicle stimulating hormone, luteinizing hormone, oestradiol and immunoreactive inhibin in women of reproductive age. Clin Endocrinol (Oxf). 1992 Apr;36(4):339-45. doi: 10.1111/j.1365-2265.1992.tb01457.x.

Reference Type BACKGROUND
PMID: 1424166 (View on PubMed)

Burger HG, Dudley EC, Hopper JL, Shelley JM, Green A, Smith A, Dennerstein L, Morse C. The endocrinology of the menopausal transition: a cross-sectional study of a population-based sample. J Clin Endocrinol Metab. 1995 Dec;80(12):3537-45. doi: 10.1210/jcem.80.12.8530596.

Reference Type BACKGROUND
PMID: 8530596 (View on PubMed)

Welt CK, Smith ZA, Pauler DK, Hall JE. Differential regulation of inhibin A and inhibin B by luteinizing hormone, follicle-stimulating hormone, and stage of follicle development. J Clin Endocrinol Metab. 2001 Jun;86(6):2531-7. doi: 10.1210/jcem.86.6.7597.

Reference Type BACKGROUND
PMID: 11397851 (View on PubMed)

Schneyer AL, Fujiwara T, Fox J, Welt CK, Adams J, Messerlian GM, Taylor AE. Dynamic changes in the intrafollicular inhibin/activin/follistatin axis during human follicular development: relationship to circulating hormone concentrations. J Clin Endocrinol Metab. 2000 Sep;85(9):3319-30. doi: 10.1210/jcem.85.9.6767.

Reference Type BACKGROUND
PMID: 10999828 (View on PubMed)

Khoury MJ, Erickson JD. Maternal factors in dizygotic twinning: evidence from interracial crosses. Ann Hum Biol. 1983 Sep-Oct;10(5):409-15. doi: 10.1080/03014468300006601.

Reference Type BACKGROUND
PMID: 6638936 (View on PubMed)

KNOX G, MORLEY D. Twinning in Yoruba women. J Obstet Gynaecol Br Emp. 1960 Dec;67:981-4. doi: 10.1111/j.1471-0528.1960.tb09255.x. No abstract available.

Reference Type BACKGROUND
PMID: 13757217 (View on PubMed)

Myrianthopoulos NC. An epidemiologic survey of twins in a large, prospectively studied population. Am J Hum Genet. 1970 Nov;22(6):611-29. No abstract available.

Reference Type BACKGROUND
PMID: 5518457 (View on PubMed)

Martin NG, Robertson DM, Chenevix-Trench G, de Kretser DM, Osborne J, Burger HG. Elevation of follicular phase inhibin and luteinizing hormone levels in mothers of dizygotic twins suggests nonovarian control of human multiple ovulation. Fertil Steril. 1991 Sep;56(3):469-74. doi: 10.1016/s0015-0282(16)54542-7.

Reference Type BACKGROUND
PMID: 1894024 (View on PubMed)

Faerstein E, Szklo M, Rosenshein NB. Risk factors for uterine leiomyoma: a practice-based case-control study. II. Atherogenic risk factors and potential sources of uterine irritation. Am J Epidemiol. 2001 Jan 1;153(1):11-9. doi: 10.1093/aje/153.1.11.

Reference Type BACKGROUND
PMID: 11159140 (View on PubMed)

Sondik EJ. Breast cancer trends. Incidence, mortality, and survival. Cancer. 1994 Aug 1;74(3 Suppl):995-9. doi: 10.1002/1097-0142(19940801)74:3+3.0.co;2-m.

Reference Type BACKGROUND
PMID: 8039156 (View on PubMed)

Perry HM 3rd, Horowitz M, Morley JE, Fleming S, Jensen J, Caccione P, Miller DK, Kaiser FE, Sundarum M. Aging and bone metabolism in African American and Caucasian women. J Clin Endocrinol Metab. 1996 Mar;81(3):1108-17. doi: 10.1210/jcem.81.3.8772584.

Reference Type BACKGROUND
PMID: 8772584 (View on PubMed)

Woods MN, Barnett JB, Spiegelman D, Trail N, Hertzmark E, Longcope C, Gorbach SL. Hormone levels during dietary changes in premenopausal African-American women. J Natl Cancer Inst. 1996 Oct 2;88(19):1369-74. doi: 10.1093/jnci/88.19.1369.

Reference Type BACKGROUND
PMID: 8827014 (View on PubMed)

Woods MN, Gorbach SL, Longcope C, Goldin BR, Dwyer JT, Morrill-LaBrode A. Low-fat, high-fiber diet and serum estrone sulfate in premenopausal women. Am J Clin Nutr. 1989 Jun;49(6):1179-83. doi: 10.1093/ajcn/49.6.1179.

Reference Type BACKGROUND
PMID: 2543203 (View on PubMed)

Manson JM, Sammel MD, Freeman EW, Grisso JA. Racial differences in sex hormone levels in women approaching the transition to menopause. Fertil Steril. 2001 Feb;75(2):297-304. doi: 10.1016/s0015-0282(00)01723-4.

Reference Type BACKGROUND
PMID: 11172830 (View on PubMed)

Welt CK, Schneyer AL. Differential regulation of inhibin B and inhibin a by follicle-stimulating hormone and local growth factors in human granulosa cells from small antral follicles. J Clin Endocrinol Metab. 2001 Jan;86(1):330-6. doi: 10.1210/jcem.86.1.7107.

Reference Type BACKGROUND
PMID: 11232020 (View on PubMed)

Welt CK, Lambert-Messerlian G, Zheng W, Crowley WF Jr, Schneyer AL. Presence of activin, inhibin, and follistatin in epithelial ovarian carcinoma. J Clin Endocrinol Metab. 1997 Nov;82(11):3720-7. doi: 10.1210/jcem.82.11.4345.

Reference Type BACKGROUND
PMID: 9360531 (View on PubMed)

Shaw ND, Srouji SS, Welt CK, Cox KH, Fox JH, Adams JM, Sluss PM, Hall JE. Evidence that increased ovarian aromatase activity and expression account for higher estradiol levels in African American compared with Caucasian women. J Clin Endocrinol Metab. 2014 Apr;99(4):1384-92. doi: 10.1210/jc.2013-2398. Epub 2013 Nov 27.

Reference Type DERIVED
PMID: 24285681 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

Sundry

Identifier Type: OTHER

Identifier Source: secondary_id

2002-P-001354

Identifier Type: -

Identifier Source: org_study_id