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.

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.

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.