conjugated estrogens (Premarin, Enjuvia, Cenestin)

Introduction

Premarin: equine source, Enjuvia: plant-derived synthetic.

Indications

• hot flashes associated with menopause
• osteoporosis
• atrophic vaginitis, atrophy of vulva
• vaginal bleeding
• prostate cancer
• hypogonadism & primary ovarian failure
  • ovariectomy

Contraindications

• history of thromboembolism
• NOT currently indicated for prevention or treatment of Alzheimer's disease or other dementias
• estrogen receptor-positive breast cancer
• treatment with tamoxifen

Dosage

• abnormal uterine bleeding:
  • 25 mg IV/IM every 6 hours until bleeding stops
  • 2.5-5 mg PO QD for 7-10 days
  • 1.25 mg/day for 2 weeks
• hypogonadism:
  • 2.5-7.5 mg/day for 20 days
  • stop for 10 days
  • repeat until menses occur
• menopause & osteoporosis:
  • 0.625-1.25 mg for 1st 3 weeks of month
  • 0.3 mg QD effective
• postpartum breast engorgement:
  • 3.75 mg PO every 4 hours for 5 doses
  • 1.25 mg every 4 hours for 5 days

Tabs: 0.3, 0.45, 0.625, 0.9, 1.25, 2.5 mg.

Transdermal:

• NO increased risk of thrombosis? (no 1st pass metabolism)

Vaginal cream: apply QD (0.625 mg/g), also useful for epistaxis

Pharmacokinetics

• metabolized in the liver

Pregnancy category X, Safety in lactation: no

Adverse effects

• common (> 10%)
  • nausea, peripheral edema, enlargement of breasts, breast tenderness*, anorexia, bloating, pain at injection site
• less common (1-10%)
  • vomiting, diarrhea, increased libido, headache
• uncommon (< 1%)
  • intolerance to contact lenses, breast tumors, endometrial abnormalities, including breakthrough bleeding, amenorrhea, hypertension, venous thromboembolism, stroke, myocardial infarction, edema, depression, dizziness, anxiety, chloasma, melasma, rash, glucose intolerance, GI distress, increased triglycerides, increased LDL, cholestatic jaundice, increased susceptibilty to Candida infection
• other
  • endometrial abnormalities, including breakthrough bleeding
  • breast cancer
  • increased risk of urinary incontinence

* breast tenderness minimal with dose of 0.3 mg QD

• drug adverse effects of estrogens

Drug interactions

• increased therapeutic effects & toxicity of antidepressants, beta-blockers, corticosteroids, theophylline
• antibiotics, barbiturates, phenytoin, rifampin decrease effectiveness of premarin
• premarin decreases effectiveness of thyroxine (synthroid) by increasing thyroxine-binding globulin & decreasing free thyroxine levels

Mechanism of action

estrogen

More general terms

• estrogen

Component of

• bazedoxifene/conjugated estrogens (Duavee)
• conjugated estrogens/medroxyprogesterone (Prempro, Premphase)
• conjugated estrogens (Premarin)/methyltestosterone Estratest