Continuous Estrogen Replacement

Estrogen only Preparations
1. Status post Hysterectomy
Combination Estrogen Replacement in Late post-Menopause with intact Uterus
1. Continuous is preferred over Sequential Estrogen Replacement in intact Uterus
2. Continuous Replacement is associated with a lower risk of Endometrial Hyperplasia
3. Jaakkola (2009) Obstet Gynecol 114(6): 1197-1204 [PubMed]

Estrogen must be taken with Progesterone if Uterus is intact (Endometrial Hyperplasia risk)
Two pill regimen
1. Estrogen taken daily (see options below)
2. Progestin taken daily (see options below)
Combination Pill - Standard Estrogen and Progesterone
1. Activella (Estradiol + Norethindrone) 0.5 mg/0.1 mg or 1.0 mg/0.5 mg daily
2. Prefest (Estradiol + Norethindrone) 1 mg/0.09 mg
  1. Taken in 4 day cycles (Estradiol alone for 1 day, Estradiol/Norethindrone for 3 days)
3. Angeliq (Estradiol + Drospirenone) 0.5 mg/0.25 mg or 1.0 mg/0.5 mg daily
4. Fyavolv or FemHRT (Ethinyl Estradiol + Norethindrone) 2.5 mcg/0.5 mg daily (lower cost in 2023)
5. Jinetli (Ethinyl Estradiol + Norethindrone) 5 mcg/1 mg daily (lower cost in 2023)
6. Prempro (Conjugated Estrogen + Medroxyprogesterone) 0.625 mg/2.5 mg (or 0.3/1.5, 0.45/1.5, 0.625/5.0) daily
Combination Pills - Bioidentical Estrogen and Progesterone
1. Bioidenticals have no proven benefit over standard combination hormonal therapy
2. Bijuva (Estradiol 1 mg + Progesterone 100 mg)
  1. Cost for combined pill in 2019 is $215 compared with separate pills at $40 total
  2. (2019) Presc Lett 26(6)
Combination Pill - Estrogen and Selective Estrogen Receptor Modulator (SERM)
1. Duavee (Conjugated equine Estrogen + Bazedoxifene) 0.45/20 mg daily
Combination Transdermal Patch
1. Climara Pro (Estradiol + Levonorgestrel) 0.45/0.015 applied once weekly
2. Combipatch (Estradiol + Norethindrone) 0.05/0.14 or 0.05/0.25 applied twice weekly

Estrogen must be taken with Progesterone if Uterus is intact (Endometrial Hyperplasia risk)
Some protocols stop Estrogen for the last 5 to 7 days of the months
Oral
1. Estradiol (Estrace, bioidentical)
  1. Take 0.5 mg orally daily (up to 1.0 or 2.0 mg)
2. Conjugated Estrogen (Premarin, Enjuvia)
  1. Take 0.625 mg orally daily (or 0.3, 0.45, 0.9, 1.25 mg)
3. Estropipate (Ogen)
  1. Take 0.625 mg orally daily
4. Esterified Estrogen (Estratab, Menest)
  1. Take 0.625 mg orally daily (or 0.3, 1.25, 2.5 mg)
Transdermal Estrogen
1. Estradiol transdermal patch (Bioidentical; Estraderm, Alora, Climara, Minivelle)
  1. Apply 0.05 mg patch/week (or 0.025, 0.075 or 0.1)
2. Estradiol transdermal gel (Divigel, Elestrin, Estrogel)
  1. Apply 0.25, 0.5, 0.75 or 1.0 daily (depending on manufacturer)
3. Evamist transdermal spray (1.53 per spray)
  1. Start with 1 spray daily and advance to max of 3 sprays daily based on response

Decreased Libido: Consider Estratest instead of Premarin
1. Estrogen 1.25
2. Methyltestosterone 2.5
Recurrent Vaginal Bleeding
1. Rule-out Endometrial Cancer with Endometrial Biopsy
2. Change Estrogen Replacement regimen
  1. Estradiol 1 mg daily AND
  2. Norethindrone Acetate (NETA) 0.1 to 0.5 mg qd
    1. NETA 0.1 mg: No bleeding in 79% at 1 year
    2. NETA 0.25 mg: No bleeding in 84% at 1 year
    3. NETA 0.5 mg: No bleeding in 90% at 1 year
3. References
  1. Archer (1999) Obstet Gynecol 94:323-9 [PubMed]