PLUM evaluates the drug letrozole as a treatment for uterine fibroids. This study is a randomized, blinded, placebo-controlled trial of oral letrozole among premenopausal women with symptomatic uterine fibroids. Participants will be randomly assigned in a 1:1 ratio to either oral letrozole 2.5mg/day for 6 months (Group A) or intermittent dosing with letrozole 2.5mg/day and an identical placebo capsule (Group B).

Inclusion Criteria:

1. ≥21 years old
2. Premenopausal (at least one menses in last 3 months)
3. Symptomatic fibroids (fibroids visualized on ultrasound or MRI and heavy uterine bleeding, pelvic pressure or discomfort, urinary or bowel abnormalities, dyspareunia)
4. Fibroids that are ≤4 in total number or Fibroids that are ≤7 in total number if all fibroids are less than 4cm (40 mm) each
5. Fibroids that are ≤7cm in maximum diameter, on screening imaging, if ≤4 fibroids in total number(fibroid is defined as any mass with radiographic characteristics of fibroid >2cm)
6. Up to date in Pap smear screening and surveillance
7. Endometrial biopsy (required if age>45 years with irregular bleeding) does not indicate premalignant or malignant cells
8. Agree to use non-hormonal barrier method of contraception during study period if at risk for pregnancy
9. Has primary care provider or gynecologist
10. Agrees not to start new medications/treatments for fibroids during the study
11. Able to give informed consent

Exclusion Criteria:

1. Fibroids treated by surgery, radiologic procedure, or GnRH agonist or antagonist in the last 3 months
2. Any submucosal fibroid ≥2cm that is >50% in uterine cavity (FIGO Type 0 or Type 1 fibroids) amenable to hysteroscopic resection
3. Use of exogenous estrogen and/or progestin in the last month. (for 3 month long-acting depoprovera injection, no use in last 3 months)
4. Pregnant, lactating, or planning to become pregnant in the next 6 months
5. Hematocrit <27% or visit to emergency room or hospitalization for fibroid symptoms in the last 3 months (cannot be safely randomized to a placebo)
6. History of osteopenia or osteoporosis
7. History of hyperlipidemia
8. Current liver or kidney disease
9. Unable or unwilling to attend 4 study visits
10. Pelvic imaging concerning for gynecologic cancer or cancer of the genitourinary or gastrointestinal system
11. Does not have primary care provider or gynecologist

7 months. Adverse Events were collected beginning at Baseline until 1 month after study completion.