What alternative hormone replacement therapy regimen can be used instead of sublingual (under the tongue) troche formulation?

Alternative to Sublingual Troche Hormone Replacement Therapy

The best alternative to sublingual troche formulations is transdermal 17β-estradiol patches (50-100 μg daily), which should be your first-line choice for hormone replacement therapy. 1

Primary Recommendation: Transdermal Estradiol

Transdermal 17β-estradiol patches are superior to oral or sublingual formulations because they:

• Avoid first-pass hepatic metabolism, reducing cardiovascular and thrombotic risks 1
• Provide more physiologic estrogen delivery with better bone mineral density outcomes 1
• Show lower odds ratio for venous thromboembolism (OR 0.9) compared to oral estrogen (OR 4.2) 1
• Release 50-100 μg of 17β-estradiol per 24 hours, changed twice weekly or weekly depending on brand 1

Required Progestin Opposition (For Intact Uterus)

You must add progestin for endometrial protection if the patient has a uterus. The hierarchy of options is:

First Choice: Combined Transdermal Patches

• 17β-estradiol + levonorgestrel patches provide the best compliance 1
• Sequential regimen: 50 μg estradiol alone for 2 weeks, then 50 μg estradiol + 10 μg levonorgestrel for 2 weeks 1
• Continuous regimen: 50 μg estradiol + 7 μg levonorgestrel daily without interruption (avoids withdrawal bleeding) 1

Second Choice: Transdermal Estradiol + Oral/Vaginal Progestin

If combined patches are unavailable:

• Micronized progesterone (MP) 200 mg is the preferred progestin due to lower cardiovascular and thrombotic risk 1
• Administer for 12-14 days every 28 days (sequential regimen) 1, 2, 3
• Can be given orally or vaginally 1, 2
• Alternative progestins: medroxyprogesterone acetate (MPA) 10 mg daily for 12-14 days, or dydrogesterone 10 mg daily for 12-14 days 1, 3

Continuous Regimen Option (No Withdrawal Bleeding)

• Oral norethisterone 1 mg daily, MPA 2.5 mg daily, or dydrogesterone 5 mg daily 1

Alternative Estrogen Route: Vaginal Gel

If patches are contraindicated (e.g., chronic skin conditions, patient refusal):

• Vaginal 17β-estradiol gel 0.5-1 mg daily provides systemic absorption 1
• Still requires progestin opposition as outlined above 1

Third-Line Option: Oral 17β-Estradiol

Only use oral formulations when transdermal/vaginal routes are impossible:

• Oral 17β-estradiol 1-2 mg daily 1
• Combined tablets available: 17β-estradiol + dydrogesterone or 17β-estradiol + MPA 1
• Sequential or continuous formulations available 1
• Higher thrombotic risk than transdermal route 1

Critical Monitoring Requirements

Before initiating any regimen:

• Perform baseline transvaginal ultrasound to document endometrial thickness 2, 3

During treatment:

• Adjust estradiol dose based on symptom relief and tolerance 1
• Consider annual endometrial thickness monitoring 3
• Continue therapy until average age of natural menopause (45-55 years) 1

Important Caveats

Avoid progestins with anti-androgenic effects in patients with hypoandrogenism or sexual dysfunction, as they may worsen symptoms 1

For patients requiring contraception: Consider 17β-estradiol-based combined oral contraceptives (17β-estradiol + nomegestrol acetate or dienogest) as first choice over ethinylestradiol formulations 1

Contraindications to transdermal administration include diffuse cutaneous disorders such as chronic skin graft-versus-host disease 1