What are the recommended starting dosages for body identical Hormone Replacement Therapy (HRT) and follow-up protocols?

Body-Identical HRT Dosing Recommendations

For postmenopausal women initiating body-identical HRT, start with transdermal 17β-estradiol 50 μg/day (via twice-weekly patches) combined with oral micronized progesterone 200 mg daily for 12-14 days per month if using sequential therapy, or 100 mg daily if using continuous therapy. 1, 2

Starting Estrogen Dosages

Transdermal Estradiol (Preferred Route)

• Initial dose: 50-100 μg/day via patches changed twice weekly or weekly depending on product 2
• Transdermal administration demonstrates superior bone mass accrual and cardiovascular risk profiles compared to oral formulations 2
• This route avoids hepatic first-pass metabolism, reducing risks of venous thromboembolism and coagulation activation 3, 4

Oral Estradiol (Alternative)

• Initial dose: 1-2 mg daily of 17β-estradiol 2, 5
• The FDA label specifies starting at the lowest dose for the indication, with 1-2 mg daily as the usual initial range 5
• Oral administration may be preferred in women with insulin resistance or metabolic syndrome 4

Starting Progesterone Dosages (For Women With Intact Uterus)

Progestin must be added to estrogen therapy to reduce endometrial cancer risk in women with a uterus 2

Sequential Regimens (Preferred for Perimenopause/Early Menopause)

• Micronized progesterone: 200 mg daily for 12-14 days per 28-day cycle 1
• Alternative: Dydrogesterone 10 mg daily for 12-14 days per month 1
• Alternative: Medroxyprogesterone acetate 10 mg daily for 12-14 days per month 1
• Vaginal route option: 200 mg micronized progesterone daily for 12-14 days per month 1

Continuous Combined Regimens (For Established Menopause)

• Micronized progesterone: 100 mg daily 1
• Alternative: Dydrogesterone 5 mg daily 1
• Alternative: Medroxyprogesterone acetate 2.5 mg daily 1
• Alternative: Norethisterone 1 mg daily 1

Micronized progesterone is strongly preferred over synthetic progestins due to significantly lower cardiovascular disease and venous thromboembolism risk 1, 2, 3

Follow-Up Protocol

Initial Assessment Period

• Reevaluate at 3-month intervals initially to determine if treatment is still necessary and assess symptom control 5
• Adjust dose according to the woman's tolerance and feeling of wellbeing 1
• The minimal effective dose should be determined by titration 5

Ongoing Monitoring

• Annual clinical review to assess compliance and side effects 1
• No routine monitoring tests are required unless prompted by specific symptoms 1
• Attempts to discontinue or taper medication should be made at 3-6 month intervals 5
• For women with undiagnosed persistent or recurring abnormal vaginal bleeding, endometrial sampling should be undertaken 5

Duration Considerations

• Use the lowest effective dose for the shortest duration consistent with treatment goals 5
• The guideline consensus recommends using HRT for menopausal symptoms rather than chronic disease prevention 6
• Risks such as venous thromboembolism, CHD, and stroke occur within the first 1-2 years of therapy, while breast cancer risk increases with longer-term use 6

Critical Dosing Principles

"Start Low, Go Slow" Approach

• Lower post-menopausal doses have more favorable risk-benefit profiles 2
• Recent evidence supports low-dose HRT as safe and effective for preventing postmenopausal bone loss while potentially improving compliance and reducing breast cancer risk 7
• Serum estradiol levels should be maintained at appropriate levels for benefits without being excessively high to prevent side effects 7

Administration Timing

• Cyclic administration (e.g., 3 weeks on and 1 week off) may be used for estrogen 5
• Sequential progestin regimens typically result in higher rates of amenorrhea and better endometrial protection compared to lower doses 7

Common Pitfalls to Avoid

• Never prescribe estrogen alone in women with an intact uterus - this dramatically increases endometrial cancer risk 2, 5
• Avoid starting with high doses - the evidence shows no additional benefit and increased harm 6
• Do not use HRT routinely for chronic disease prevention - the WHI study demonstrated that for 10,000 women taking estrogen and progestin for 1 year, there would be 7 additional CHD events, 8 more strokes, 8 more pulmonary emboli, and 8 more invasive breast cancers 6
• Do not ignore route of administration - transdermal estradiol combined with micronized progesterone appears most effective and relatively safe when elementary precautions are taken 3