What is the preparation process for a Hormone Replacement Therapy (HRT) cycle?

HRT Cycle Preparation Protocol

The recommended approach for Hormone Replacement Therapy (HRT) cycle preparation is a sequential regimen with continuous estrogen administration and progestogen added for 12-14 days every 28 days, resulting in regular withdrawal bleeding. 1

Estrogen Component Selection

• Transdermal 17β-estradiol is the preferred estrogen due to its ability to mimic physiological serum estradiol concentrations, providing a better safety profile by avoiding hepatic first-pass effect 1
• 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 1, 2
• For oral administration, the usual initial dosage range is 1 to 2 mg daily of estradiol, adjusted as necessary to control symptoms 3

Progestogen Component (for women with intact uterus)

• Micronized natural progesterone is recommended as the first-choice progestogen due to its more favorable cardiovascular risk profile and better safety profile regarding thrombotic risk 1, 2
• Alternative progestogens include medroxyprogesterone acetate (MPA) or dydrogesterone if micronized progesterone is not tolerated 2, 1
• Progestogen is essential for women with an intact uterus to reduce the risk of endometrial cancer 3, 2

Administration Regimens

Sequential/Cyclic Regimen (Preferred for Initial Therapy)

• Continuous estrogen administration with progestogen added for 12-14 days every 28 days 1
• This regimen results in regular withdrawal bleeding, which allows earlier recognition of pregnancy in women who may still ovulate 2
• Cyclic therapy using low-dose estrogen offers advantages including minimal progestin exposure and lower rate of withdrawal bleeding 4

Continuous Combined Regimen

• Can be considered when the woman prefers to avoid withdrawal bleeding or at least 12 months have passed since the last menstrual period 1
• Designed to minimize bleeding but may have different effects on lipid profiles due to daily progestin use 4

Special Considerations

• Administration should be cyclic (e.g., 3 weeks on and 1 week off) for certain indications 3
• The lowest effective dose should be used for the shortest duration consistent with treatment goals and risks 3
• Patients should be reevaluated periodically (every 3-6 months) to determine if treatment is still necessary 3
• For women with hypertension, transdermal estradiol is strongly preferred due to its more favorable cardiovascular risk profile 1

Common Pitfalls and Caveats

• Using HRT solely for prevention of chronic conditions is not recommended based on risk-benefit analysis 2
• Failure to add progestogen for women with an intact uterus increases risk of endometrial cancer 3
• Using too high doses of estrogen increases risks of adverse effects without proportional increase in benefits 3
• Not recognizing that risks of HRT differ depending on type, dose, duration, route of administration, and timing of initiation 5
• Not considering that women with POI may spontaneously ovulate, making cyclic administration advantageous for pregnancy recognition 2

By following these evidence-based recommendations for HRT cycle preparation, clinicians can optimize the benefit-risk ratio for their patients while effectively managing menopausal symptoms.