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

Massachusetts General Hospital116 enrolled

Overview

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\*\*

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Masking

NONE

Enrollment

116

Conditions

Healthy

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

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 * Meets all other inclusion criteria for the reproductively younger non-African-American population outlined above Reproductively Older Non-African-American Women: * 36-45 years of age * Meets all other inclusion criteria for the reproductively younger non-African-American population outlined above. Reproductive Aged Fragile X Premutation Carriers * Fragile X premutation carriers, with FMR1 CGG repeat lengths between 41 and 200. * 18-45 years of age * Meets all other inclusion criteria for the reproductively younger non-African-American population outlined above. Exclusion Criteria: * Hemoglobin level less than 11 gm/dl at time of screening

Outcomes

Primary Outcomes

Serum androstenedione, E2, A/E2, inhibin A, and inhibin B

Time frame: at first day of menses until day after aspiration procedure

Follicular fluid androstenedione, E2, A/E2, inhibin A, and inhibin B

Time frame: after aspiration procedure

RT-PCR results for aromatase in aspirated follicular fluid, when follicle is > 14 mm