Vaginal Estrogen

Aka: Vaginal Estrogen, Topical Estrogen, Estrogen Vaginal Preparation, Estradiol Vaginal Ring, Estrogen Ring, FemRing, Estring, Estradiol Vaginal Tablet, Vagifem, Estrogen Cream, Premarin Cream, Estrace Cream, Prasterone, Intrarosa

1. See Also
   1. Menopause
   2. Estrogen Replacement
   3. Continuous Estrogen Replacement
   4. Sequential Estrogen Replacement
   5. Transdermal Estrogen
2. Indications
   1. Atrophic Vaginitis in Menopause
   2. Postmenopausal Dyspareunia
3. Precautions
   1. Higher dose Topical Estrogens require concurrent Progesterone if Uterus intact (risk of Endometrial Hyperplasia)
   2. Lower dose Topical Estrogens do not require systemic Progesterone (in intact Uterus) if used <1 year
      1. Obtain Transvaginal Ultrasound (endometrial stripe) and Endometrial Biopsy if vaginal spotting or bleeding
      2. Some guidelines allow use of low dose Topical Estrogens indefinately
      3. No consistent guidelines as whether low dose agents require Progesterone with prolonged use >1 year
      4. Krause (2009) J Pelvic Med Surg 15(3): 105–14 [PubMed]
4. Preparations: High Dose Topical Estrogens
   1. Indicated for vasomotor symptoms AND Genitourinary Syndrome of Menopause (Vaginal Atrophy)
   2. Requires concurrent progesteron use
   3. Estradiol acetate vaginal ring (FemRing)
      1. Placed in vagina and replaced every 90 days
      2. Available as 0.05 and 0.1 mg/day rings
      3. Requires opposing Progesterone if Uterus intact (risk of Endometrial Hyperplasia)
5. Preparations: Low Dose Topical Estrogens
   1. Indicated for Genitourinary Syndrome of Menopause
   2. Estradiol Vaginal Ring (Estring)
      1. Placed in vagina and replaced every 90 days
      2. Available as 2 mg rings (releases 7.5 mcg estradiol per day)
   3. Estradiol Vaginal Tablet (Vagifem, Yuvafem)
      1. Initial: One tablet intravaginally daily for 2 weeks
      2. Later: One tablet intravaginally twice weekly
      3. Available in 10 mcg and 25 mcg applicators
      4. May be safe at low dose, low frequency use despite history of Breast Cancer
         1. Low systemic absorption at low dose
         2. Requires Informed Consent regarding potential risks and lack of safety studies following Breast Cancer
         3. Pruthi (2012) Mayo POIM Conference, Rochester
   4. Estradiol vaginal soft gel (Imvexxy)
      1. Released in 2018 at $180/month or twice the cost of generic vaginal creams
      2. Gel is applied manually (without applicator) twice weekly
      3. (2018) Presc Lett 25(9): 53
   5. Estrogen Cream (Premarin or Estrace Creams)
      1. Premarin (Conjugated Estrogen 0.625 mg per 1 g cream)
         1. Apply 0.5 g (up to 2 g) daily for 21 of every 28 days OR
         2. Apply 0.5 g applied intravaginally twice weekly
      2. Estrace (Estradiol)
         1. Apply 2-4 g daily for 2 weeks, then reduce to 0.5 g twice weekly
   6. Prasterone or DHEA (Intrarosa)
      1. Although marketed as non-Estrogen, it is DHEA which converts to Estrogens and androgens in vaginal tissue
      2. Released in U.S. in 2017
      3. (2017) Presc Lett 24(9): 53
6. References
   1. Hill (2016) Am Fam Physician 94(11): 884-9 [PubMed]
   2. Ringel (2020) Am Fam Physician 102(9):550-7 [PubMed]