Best Regimen for Starting Hormone Replacement Therapy (HRT) in Women

Estrogen Component Selection

The American College of Obstetricians and Gynecologists recommends transdermal 17β-estradiol as the preferred estrogen due to its ability to mimic physiological serum estradiol concentrations, providing a better safety profile by avoiding hepatic first-pass effect, minimizing impact on hemostatic factors, and having more beneficial effects on lipid profiles, inflammation markers, and blood pressure 1, 2
Transdermal 17β-estradiol is particularly recommended for women with hypertension, as it has a more favorable cardiovascular risk profile 3, 4
The recommended starting dose for transdermal estradiol is 50-100 μg/day, with adjustments based on symptom control 1
17β-estradiol is preferred over ethinylestradiol or conjugated equine estrogens for all routes of administration due to its more favorable safety profile and efficacy 6, 7, 3

The Endocrine Society recommends micronized natural progesterone as the first-choice progestogen due to its more favorable cardiovascular risk profile, neutral or beneficial effects on blood pressure, and better safety profile regarding thrombotic risk 2, 8
Alternative progestogens, such as medroxyprogesterone acetate or dydrogesterone, can be considered if micronized progesterone is not tolerated 5, 8

For women with hypertension, transdermal estradiol is strongly preferred due to its more favorable cardiovascular risk profile 3, 4
For women with a history of migraine, HRT is not contraindicated, but dose/route adjustments may be needed if migraines worsen 7, 3
For women with a history of endometriosis, combined estrogen/progestogen therapy is recommended 6, 3
For women with BRCA1/2 mutations without breast cancer, HRT is a treatment option 6, 3
For breast cancer survivors, HRT is generally contraindicated 6, 3

A sequential regimen is recommended, with continuous estrogen administration and progestogen added for 12-14 days every 28 days, resulting in regular withdrawal bleeding 8, 5
Continuous combined regimens can be considered when the woman prefers to avoid withdrawal bleeding or at least 12 months have passed since the last menstrual period 5, 8

Annual clinical review is recommended once therapy is established, with particular attention to compliance 6, 7
No routine monitoring tests are required, but may be prompted by specific symptoms or concerns 6, 7
Patient preference for route and method of administration should be considered when prescribing, as should contraceptive needs 6, 7