Effects of Simvastatin on Uterine Leiomyoma Size

Inclusion criteria

• Signed informed written consent.
• Gender: female.
• Age: 18-55 years at time of signing consent.
• BMI of subjects: \< 45 kg/m2.
• Uterine fibroids:
• Diagnosed by ultrasound (MRI will be used only if ultrasound is inconclusive).
• Number: any number of fibroids.
• Location: submucosal or intramural.
• At least one fibroid of diameter \> 3cm.
• Symptoms: one or more of the following symptoms of heavy menstrual bleeding (HMB), defined as: Experienced cyclic (22 to 35 days) abnormal uterine bleeding (heavy or prolonged) in at least 3 of the last 6 menstrual periods, including menstrual bleeding lasting 5 or more days or heavy bleeding per participant recall. Examples of heavy bleeding may include, but are not limited to the following:
• Requires the use of double protection to manage menstrual bleeding.
• Menstrual bleeding accompanied by the sensation of "gushing" or "flooding".
• Saturates more than 1 tampon or sanitary pad per hour for 3 or more consecutive hours.
• Regularly needs to change the tampon or sanitary pad at night or regularly soils bedclothes.
• Heavy bleeding that affects work, school, or social activities.
• Pelvic pain/ pressure likely caused by fibroids.
• Plan for surgery (hysterectomy or myomectomy).
• Normal Pap smear within the last year.
• Use of contraception during study such as non-hormonal oral contraceptives, intrauterine devices (IUD)/ intrauterine systems (IUS), barrier contraceptives, abstinence or sterilization.

Exclusion criteria

• Pregnancy or lactation.
• Previous or current uterine, cervical or ovarian cancer.
• Current endometrial hyperplasia or history of atypical endometrial hyperplasia. Endometrial biopsy will be done during screening (if not done within last 12 months).
• Suspicion of leiomyosarcoma.
• Recent rapid growth of fibroids (i.e. doubling in size within 1-6 months period).
• Unevaluated gynecologic abnormalities (unexplained vaginal bleeding, cervical dysplasia, or abnormal adnexal/ovarian mass).
• Menopausal status.
• Surgery is urgently indicated (\< 3 months) for medical or social reasons.
• Hemoglobin ≤ 6 g/dL.
• Currently enrolled in another investigational study.
• Mental condition or other barrier preventing informed written consent.
• Allergy or hypersensitivity to simvastatin.
• Current use of simvastatin or other drugs of the same class.
• Concomitant administration of strong CYP3A4 inhibitors including itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, and cobicistat-containing products.
• Concomitant administration of gemfibrozil, cyclosporine, or danazol, verapamil, diltiazem, amiodarone, diltiazem, dronedarone, amlodipine, ranolazine, lomitapide, and grapefruit juice.
• Active liver disease, which may include unexplained persistent elevations in hepatic transaminase levels.( elevation of aspartate transaminase and/or alanine transaminase \> 2 s.d. above the normal range at screening visit)
• Known increased risk or diagnosis of a myopathy.